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Harnessing immunological objectives pertaining to COVID-19 immunotherapy.
Sialin interacts with nitrate and participates in the regulation of NO production and cell biological functions for body homeostasis. The interactions between nitrate and NO or sialin is an important mechanism by which homeostasis is regulated.
There is consistent evidence of social inequalities in dementia but the mechanisms underlying this association remain unclear. We examined the role of smoking in midlife in socioeconomic differences in dementia at older ages.

Analyses were based on 9951 (67% men) participants, median age 44.3 [IQR=39.6, 50.3] years at baseline in 1985-1988, from the Whitehall II cohort study. Socioeconomic position (SEP) and smoking (smoking status (current, ex-, never-smoker), pack years of smoking, and smoking history score (combining status and pack-years)) were measured at baseline. Counterfactual mediation analysis was used to examine the contribution of smoking to the association between SEP and dementia.

During a median follow-up of 31.6 (IQR 31.1, 32.6) years, 628 participants were diagnosed with dementia and 2110 died. Analyses adjusted for age, sex, ethnicity, education, and SEP showed smokers (hazard ratio [HR] 1.36 [95% CI 1.10-1.68]) but not ex-smokers (HR 0.95 [95% CI 0.79-1.14]) to have a higher risk of dementia compared to never-smokers; similar results for smoking were obtained for pack-years of smoking and smoking history score. Mediation analysis showed low SEP to be associated with higher risk of dementia (HRs between 1.97 and 2.02, depending on the measure of smoking in the model); estimate for the mediation effect was 16% for smoking status (Indirect Effect HR 1.09 [95% CI 1.03-1.15]), 7% for pack-years of smoking (Indirect Effect HR 1.03 [95% CI 1.01-1.06]) and 11% for smoking history score (Indirect Effect HR 1.06 [95% CI 1.02-1.10]).

Our findings suggest that part of the social inequalities in dementia is mediated by smoking.

NIH.
NIH.
The two-dose BNT162b2 (Pfizer-BioNTech) vaccine has demonstrated high efficacy against COVID-19 disease in clinical trials of children and young people (CYP). Consequently, we investigated the uptake, safety, effectiveness and waning of the protective effect of the BNT162b2 against symptomatic COVID-19 in CYP aged 12-17 years in Scotland.

The analysis of the vaccine uptake was based on information from the Turas Vaccination Management Tool, inclusive of Mar 1, 2022. Vaccine safety was evaluated using national data on hospital admissions and General Practice (GP) consultations, through a self-controlled case series (SCCS) design, investigating 17 health outcomes of interest. Vaccine effectiveness (VE) against symptomatic COVID-19 disease for Delta and Omicron variants was estimated using a test-negative design (TND) and S-gene status in a prospective cohort study using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. The waning of the VE fol Studies - Data and Connectivity.
UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Chief Scientist's Office of the Scottish Government; Health Data Research UK; National Core Studies - Data and Connectivity.Antisense RNA technology is a strategy for the treatment of Duchenne muscular dystrophy (DMD), a progressive and universally fatal X-linked neuromuscular disease caused by frameshift mutations in the gene encoding dystrophin. Phosphorodiamidate morpholino oligomers (PMOs) are an antisense RNA platform that is used clinically in patients with DMD to facilitate exon skipping and production of an internally truncated, yet functional, dystrophin protein. Peptide-conjugated PMOs (PPMOs) are a next-generation platform in which a cell-penetrating peptide is conjugated to the PMO backbone, with the goal of increasing cellular uptake. RC-1001 is a PPMO that contains a proprietary cell-penetrating peptide and targets the Dmd mutation in mdx mice. It was evaluated in mdx mice for exon 23 skipping, dystrophin production, and functional efficacy. Single-dose RC-1001 dose dependently increased exon skipping and dystrophin protein levels in striated muscle and is associated with improvements in muscle function. Dystrophin protein levels were durable for 60 days. Three doses, each given 1 month apart, increased exon skipping to 99% in quadriceps and 43% in heart, with dystrophin protein levels at 39% and 9% of wild type, respectively. These findings support clinical development of PPMO therapies for the treatment of DMD.The gut fermentation product butyrate displays anti-cancer properties in the human proximal colon, including the ability to inhibit proliferation and induce apoptosis in colorectal cancer (CRC) cells. A natural histone deacetylase inhibitor (HDACi), butyrate can alter histone acetylation patterns in CRC cells, and thereby regulate global gene expression, including the non-coding transcriptome and microRNAs (miRNAs). Dysregulated miRNA expression affects CRC development and progression; however, the interplay between miRNA activity and butyrate response remains to be elucidated. check details A high-throughput functional screen was employed to identify miRNAs that can act as enhancers of the anti-cancer properties of butyrate. Validation studies confirmed that several miRNAs, including miR-125b, miR-181a, miR-593, and miR-1227, enhanced apoptosis, decreased proliferation, and promoted cell-cycle arrest in the presence of butyrate. Pathway analyses of predicted miRNA target genes highlighted their likely involvement in critical cancer-related growth pathways, including WNT and PI3K signaling. Several cancer-associated miRNA targets, including TRIM29, COX2, PIK3R3, CCND1, MET, EEF2K, DVL3, and NUP62 were synergistically regulated by the combination of cognate miRNAs and butyrate. Overall, this study has exposed the potential of miRNAs to act as enhancers of the anti-cancer effects of HDAC inhibition and identifies specific miRNAs that might be exploited for therapeutic benefit.Kirsten rat sarcoma virus (KRAS) mutations are frequently detected in many cancers and are major driver genes. Therefore, KRAS inhibitors have been the subject of extensive research. We developed chemically modified MIR143-3p (MIR143#12), which exhibits higher anticancer activity and nuclease resistance than other commercial inhibitors. MIR143#12 potently suppressed cell growth in colorectal and pancreatic cancer cell lines via apoptosis induced by repression of the entire rat sarcoma virus (RAS) network, which was achieved by silencing KRAS, Son of sevenless homolog 1 ( SOS1 ), AKT, and extracellular signal-regulated kinase (ERK). We investigated the mechanistic advantages of MIR143#12 in various KRAS mutant colorectal cancer cell lines. Its effects were stronger than those of knockdown of KRAS alone in colon cancer cells because silencing of KRAS by small interfering RNA (siRNA) did not decrease the protein expression levels of AKT or ERKs. The KRAS mRNA recruitment system, called the "positive circuit" under effector signaling pathways, may contribute to insensitivity of KRAS mutant cancers to MIR143#12 and siRNAs. In an in vivo study, we newly demonstrated that MIR143#12 induced neoangiogenesis in the tumor microenvironment with growth suppression. Based on the present results, it is crucial to down-regulate not only KRAS but also the entire KRAS signaling network, which may be accomplished by MIR143#12.[This retracts the article DOI 10.1016/j.omtn.2021.02.020.].
Breast cancer is the second leading cause of cancer death in women worldwide. The significantly higher mortality rate has been considered due to poor knowledge of women, delay in diagnosis, and initiation of treatment. Therefore, this hospital-based cross-sectional study aimed to understand the knowledge and perception of women with breast cancer in Bangladesh.

Data was collected using a questionnaire-based interview from 357 women aged 15-49 years attending two tertiary care hospitals in Chattogram city of Bangladesh.

Neighbors (18.6%) and relatives (18.1%) were the leading sources of information on breast cancer. Among the total, 69.5% knew about breast cancer however, only 14% of them knew about screening tests and 61.5% were unaware of risk factors for developing breast cancer. Pain in the breast, painless lump, and nipple discharge were the most recognized clinical symptoms by the participants. Exercise and weight control, the practice of breastfeeding, and taking medicine were the three most known prevention practices. Women perceived wrong conceptions that Breast cancer is only found in older age (42.3%) and women (15.7%) and that it causes losing one's breast (3.1%). A significant correlation was found between the education level of participants and their knowledge of risk factors related to breast cancer.

Although the majority of the participants have heard about breast cancer, they do not possess enough knowledge regarding the risk factor, symptoms, and preventive methods of breast cancer. We suggest interventions targeting a community-based awareness program.
Although the majority of the participants have heard about breast cancer, they do not possess enough knowledge regarding the risk factor, symptoms, and preventive methods of breast cancer. We suggest interventions targeting a community-based awareness program.
Nurses are the largest group of health-care providers and their clinical decisions have an essential role in patients' clinical condition. Evidence-based nursing has been proposed as a health-care method based on the latest findings and evidence. Therefore, we aimed to determine the effect of evidence-based nursing education on dialysis nurses' clinical decision-making.

This single-blind experimental study conducted in 2021 at dialysis wards of teaching hospitals affiliated to Urmia University of Medical Sciences. In this study, a total of 60 dialysis nurses were recruited using convenience sampling and allocated to two groups of intervention (
 = 30) and control (
 = 30). Data were collected at three time points of before, 1 week after, and 1 month after the intervention using a demographic questionnaire and the Lauri and Salantera Clinical Decision-Making Questionnaire (LSCD-MQ). Nurses in the intervention group received 12 sessions of evidence-based nursing education, while nurses in the control grouidence-based workshops to update nurses' knowledge.
The study results indicate the positive effect of evidence-based education on nurses' clinical decision-making. Therefore, nurses are recommended to apply evidence-based education methods to improve their level of clinical decision-making. Health officials are also recommended to hold in-service evidence-based workshops to update nurses' knowledge.
Atypical wounds comprise about 20% of all chronic wounds. Their diagnosis and treatment are challenging and requiremultidisciplinary cooperation. More knowledge is needed about the clinical characteristics and comorbidities of atypical wounds to enhance the treatment of these wounds.

We studied clinical characteristics and comorbidities of the atypical wounds by using the patient data retrieved from the Oulu University Hospital patient database from the year 1996 to the end of 2019 with the following International Classification of Diseasescodes L88, L95.0, L95.8, L95.9, and L98.1.

In our data, there were 135 patients with atypical wound, more commonly seen in females (
 = 84, 62.2%) than in males (
 = 51, 37.8%) (
 < 0.05). The mean age of patients at the time of diagnosis was 57.3 years;those with pyoderma gangrenosum (PG) and factitious wounds were the youngest (53.1 and 53.0 years, respectively). The majority of subjects (
 = 126, 93.3%) were diagnosed with comorbidity at the time of the diagnosis.
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