Notes

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COVID-19 is a respiratory tract infection that can affect multiple organ systems. Predicting the severity and clinical outcome of individual patients is a major unmet clinical need that remains challenging due to intra- and inter-patient variability. Here, we longitudinally profiled and integrated more than 150 clinical, laboratory, and immunological parameters of 173 patients with mild to fatal COVID-19. Using systems biology, we detected progressive dysregulation of multiple parameters indicative of organ damage that correlated with disease severity, particularly affecting kidneys, hepatobiliary system, and immune landscape. By performing unsupervised clustering and trajectory analysis, we identified T and B cell depletion as early indicators of a complicated disease course. In addition, markers of hepatobiliary damage emerged as robust predictor of lethal outcome in critically ill patients. This allowed us to propose a novel clinical COVID-19 SeveriTy (COST) score that distinguishes complicated disease trajectories and predicts lethal outcome in critically ill patients.Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct pathological states during severe disease remains unknown. Here, we leveraged 96 publicly available single-cell RNA sequencing datasets to elucidate common and compartment-specific features of severe to critical COVID-19 at the levels of transcript expression, biological pathways, and ligand-receptor signaling networks. Comparing severe patients to milder and healthy donors, we identified distinct differential gene expression signatures between compartments and a core set of co-directionally regulated surface markers. A majority of severity-enriched pathways were shared, whereas TNF and interferon responses were polarized. Severity-specific ligand-receptor networks appeared to be differentially active in both compartments. Overall, our results describe a nuanced response during severe COVID-19 where compartment plays a role in dictating the pathological state of immune cells.
This study aimed to review and pilot-test feedback from childbearing women who completed the German short version of the Childbirth Self-Efficacy Inventory (CBSEI-C32), which is widely used and validated in different languages.

Ten pregnant nulliparas, who planned a natural childbirth, completed the German CBSEI-C32 and provided comments about the comprehensibility of the tool.

When applying the standardized translated German CBSEI-C32, we discovered that women generally gave positive feedback, and reported that the items made them think about coping strategies for labor and birth. Some pregnant woman had problems in understanding two items 'Mich beherrschen' (original English item 'Keep myself in control'), and 'Mich ruhig halten' (original English item 'Keep myself calm'). Some of the items were not comprehensible for pregnant women and might not represent contemporary concepts of childbirth self-efficacy.

Two items of the German CBSEI-C32 were interpreted ambiguously by the pilot testers. The CBSEIrather than restrain women. For measuring self-efficacy beliefs in childbirth nowadays, it appears that health-oriented aspects, such as concentrating on the pauses between contractions or mentally staying in the present moment, are more important for women than focusing on control during childbirth.
Continuity models of midwifery care are significant factors in facilitating a positive childbirth experience for birthing women. A knowledge gap exists regarding partners' experiences of continuity of midwifery care during pregnancy, birth, and after birth, although it is essential to understand the experiences of both parents in relation to continuity of care. Thus, the aim of this study was to highlight partners' expectations and experiences of having participated in a continuity of midwifery care project.

A qualitative interview study using thematic analysis was carried out. Thirty-six partners in a rural area in northern Sweden were recruited after the closure of the local labor ward. Interviews were conducted in October 2019 and in May 2020.

An overarching theme 'A partner-midwife relationship facilitated a sense of security'; and two themes 'The concept of availability' and 'The midwife's competence and professionalism' reflect partners' expectations and experiences after participating in a contin to gain access to continuity models of midwifery care and to have a possibility to give birth closer to their residence. The results of this qualitative study further strengthen the growing evidence of the positive effects of continuity models of midwifery care.
Prior studies documenting more frequent and problematic use among young adults who have acquired medical marijuana (MM) cards have broadly compared those who use medically to those who use recreationally. An chemical Gaining a better picture of how health symptoms and problematic use vary both within those who have a MM card for specific condition domains and between those who do not have a MM card can provide key information for medical practitioners and states interested in adopting or updating MM policies.

The current study categorizes young adults authorized to use MM into three mutually exclusive groups based on endorsements of qualifying conditions (1) Physical Health only (e.g., AIDS, arthritis, cancer;
= 34); (2) Behavioral Health only (e.g., anxiety, depression, sleep problems;
= 75); and (3) Multiple Conditions (a physical and behavioral health condition;
= 71). Multiple and logistic regression models examined differences across marijuana use, problems, mental health, physical health, and sleep quaons.
Findings emphasize the importance of providers conducting a careful assessment of reasons for needing a card, along with use, to reduce potential harms while adding credibility to a medical movement with genuine promise of relief for many medical conditions.We generated self-adjuvanted protein nanoparticles of conserved influenza antigens and immunized mice via skin vaccination with dissolvable microneedle patches (MNPs) to increase the strength and breadth of immune responses. We produced M2e nanoparticles via ethanol desolvation, and double-layered NA1/M2e (shell/core), NA1-FliC/M2e, NA2/M2e, and NA2-FliC/M2e protein nanoparticles by chemically crosslinking influenza NA and flagellin (FliC) onto the surfaces of the M2e nanoparticles. The resulting nanoparticles retained FliC TLR5 innate signaling activity and significantly increased antigen-uptake and dendritic cell maturation in vitro. We incorporated the nanoparticles into MNPs for skin vaccination in mice. The nanoparticle MNPs significantly increased M2e and NA-specific antibody levels, the numbers of germinal center B cells, and IL-4 positive splenocytes. Double-layered nanoparticle MNP skin vaccination protected mice against homologous and heterosubtypic influenza viruses. Our results demonstrated that MNP skin vaccination of NA-FliC/M2e nanoparticles could be developed into a standalone or synergistic component of a universal influenza vaccine strategy.Advances in synthetic biology, nanotechnology, and genetic engineering are allowing parallel advances in areas such as drug delivery and rapid diagnostics. Although our current visions of nanobots may be far off, a generation of nanobots synthesized by engineering viruses is approaching. Such tools can be used to solve complex problems where current methods do not meet current demands. Assuring safe drinking water is crucial for minimizing the spread of waterborne illnesses. Although extremely low levels of fecal contamination in drinking water are sufficient to cause a public health risk, it remains challenging to rapidly detect Escherichia coli, the standard fecal indicator organism. Current methods sensitive enough to meet regulatory standards suffer from either prohibitively long incubation times or requirement of expensive, impractical equipment. Bacteriophages, tuned by billions of years of evolution to bind viable bacteria and readily engineered to produce custom proteins, are uniquely suited to bacterial detection. We have developed a biosensor platform based on magnetized phages encoding luminescent reporter enzymes. This system utilizes bio-orthogonally functionalized phages to enable site-specific conjugation to magnetic nanoparticles. The resulting phage-based nanobots, when combined with standard, portable field equipment, allow for detection of less then 10 cfu/100 mL of viable E. coli within 7 h, faster than any methods published to date.Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide with a low 5-year survival rate. More effective chemotherapeutic drugs, either new or repurposing ones, are urgently needed. Disulfiram (DSF) is a safe and public domain drug for alcohol addiction treatment and later shown to have anti-cancer capability, especially when administrated together with copper. The present study is to test the hypothesis that a newly developed copper-cysteamine (Cu-Cy) nanoparticles (NPs) can enhance the anti-tumor effect of DSF on esophageal cancer with reduced risk of copper poisoning. Our results showed that Cu-Cy NPs could greatly facilitate DSF to inhibit cell proliferation in cultured human esophageal cancer cells. Interestingly, the combined inhibitory function could be further enhanced when DSF and Cu-Cy NPs were present at an optimal molar ratio of 14. The results of the change in physical color, UV-vis absorption and fluorescence spectra, X-ray diffraction patterns, and FTIR spectra from a mixture of DSF and Cu-Cy NPs suggest a possible reaction between DSF and Cu-Cy NPs and the formation of new materials. Furthermore, cellular mechanistic studies revealed that the combination of DSF and Cu-Cy NPs resulted in reactive oxygen species (ROS) accumulation, and blocked nuclear translocation of NF-ƙB (p65) in esophageal cancer cells. Moreover, in xenograft nude mice, combined administration of DSF and Cu-Cy NPs greatly inhibited tumor growth without noticeable histological toxicity, while any single agent at the same doses presented no inhibitory function. Together, this study demonstrates an effective anti-cancer function of combined treatment of DSF and Cu-Cy NPs in vitro and in vivo, which could be a promising new chemotherapy for esophageal cancer patients.Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The metabolic disease type 2 diabetes (T2D) significantly increases the risk of developing active TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication. Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection, injury and neoplastic changes. Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients. In this study, using a diet-induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility, we investigated how the intestinal microbiota may impact the development of T2D, and how the gut microbial composition changes following a very low-dose aerosol infection with Mycobacterium tuberculosis (Mtb). Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non-diabetic animals.
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