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Taking the β-Hex release rate of the model group as the base, the release rate of SD and POG in high dose groups were 43.79% and 57.01%, respectively, which were significantly lower than model group (

 < 0.01), and significantly lower than KF group (63.83%,

 < 0.01,

 < 0.05). SD and POG could down-regulate the expression of related proteins in the Lyn/Syk, PI3K/AKT and MAPK signalling pathways.

could inhibit IgE-induced degranulation of mast cells, providing a scientific basis for further research and clinical applications of SD in TIA treatment.

Saposhnikovia divaricata could inhibit IgE-induced degranulation of mast cells, providing a scientific basis for further research and clinical applications of SD in TIA treatment.

Advance (anticipatory) care planning (ACP) requires discussions between patients and healthcare professionals about planning for future deterioration in health. ACP improves care coordination but uptake is limited and often deferred.

To assess the feasibility and acceptability to patients, carers, and GPs of a primary care ACP intervention for people with incurable oesophageal, gastric, or pancreatic cancer.

A 12-month feasibility randomised controlled trial (RCT) in a Scottish Cancer Network.

Patients aged ≥18 years starting palliative oncology treatment were randomised 11 to an ACP intervention or standard care. Patients in the intervention group received an oncologist letter supporting them to request a GP review along with a patient information leaflet about ACP. Pre-specified analyses with masking included trial recruitment and retention, ACP completion, and quality-of-life questionnaires (EuroQol EQ-5D-5L and ICECAP Supportive Care Measure) at baseline, 6, 12, 24, and 48 weeks. Qualitative interviews with purposive sampling explored patient, carer, and GP experiences.

Of 99 eligible participants (269 screened), 46% were recruited (

= 46) and randomised; 25 to intervention and 21 to control. By 12 weeks, 45% (

= 9/20) of the individuals in the intervention and 59% (

= 10/17) in the control group had a documented ACP plan. By 24 weeks, 30% (

= 14) had died; in the remaining participants quality of life was maintained at 24 weeks except for physical symptoms. Social norms associating ACP with dying were prevalent among 23 participants interviewed. No psychological or clinical harms were identified.

An RCT of ACP for people with incurable cancer in primary care is feasible. Patient, carer, and GP attitudes and behaviours determined acceptability and timing of care planning.

An RCT of ACP for people with incurable cancer in primary care is feasible. Patient, carer, and GP attitudes and behaviours determined acceptability and timing of care planning.

Non-acute abdominal pain in primary care is diagnostically challenging.

To quantify the 1-year cumulative incidence of 35 non-malignant diagnoses and nine cancers in adults after newly recorded abdominal pain in primary care.

Observational cohort study of 125 793 Clinical Practice Research Datalink GOLD records.

Participants, aged ≥40 years, had newly recorded abdominal pain between 1 January 2009 and 31 December 2013. Age- and sex-stratified 1-year cumulative incidence by diagnosis is reported.

Most (>70%) participants had no pre-specified diagnoses after newly recorded abdominal pain. Non-malignant diagnoses were most common upper gastrointestinal problems (gastro-oesophageal reflux disease, hiatus hernia, gastritis, oesophagitis, and gastric/duodenal ulcer) in males and urinary tract infection in females. The incidence of upper gastrointestinal problems plateaued at age ≥60 years (aged 40-59 years males 4.9%, 95% confidence interval [CI] = 4.6 to 5.1, females 4.0%, 95% CI = 3.8 to 4.2; aged 60-69 years males 5.8%, 95% CI = 5.4 to 6.2, females 5.4%, 95% CI = 5.1 to 5.8). Urinary tract infection incidence increased with age (aged 40-59 years females 5.1%, 95% CI = 4.8 to 5.3, males 1.1%, 95% CI = 1.0 to 1.2; aged ≥70 years females 8.0%, 95% CI = 7.6 to 8.4, males 3.3%, 95% CI = 3.0 to 3.6%). Diverticular disease incidence rose with age, plateauing at 4.2% (95% CI = 3.9 to 4.6) in males aged ≥60 years, increasing to 6.1% (95% CI = 5.8 to 6.4) in females aged ≥70 years. Irritable bowel syndrome incidence was higher in females (aged 40-59 years 2.9%, 95% CI = 2.7 to 3.1) than males (aged 40-59 years 2.1%, 95% CI = 1.9 to 2.3), decreasing with age to 1.3% (95% CI = 1.2 to 1.5) in females and 0.6% (95% CI = 0.5 to 0.8) in males aged ≥70 years.

Although abdominal pain commonly remains unexplained, non-malignant diagnosis are more likely than cancer.

Although abdominal pain commonly remains unexplained, non-malignant diagnosis are more likely than cancer.

NHS England has introduced a new structured medication review (SMR) service within primary care networks (PCNs) forming during the COVID-19 pandemic. Policy drivers are addressing problematic polypharmacy, reducing avoidable hospitalisations, and delivering better value from medicines spending. This study explores early implementation of the SMR from the perspective of the primary care clinical pharmacist workforce.

To identify factors affecting the early implementation of the SMR service.

Qualitative interview study in general practice between September 2020 and June 2021.

Two semi-structured interviews were carried out with each of 10 newly appointed pharmacists (20 in total) in 10 PCNs in Northern England; and one interview was carried out with 10 pharmacists already established in GP practices in 10 other PCNs across England. Audiorecordings were transcribed verbatim and a modified framework method supported a constructionist thematic analysis.

SMRs were not yet a PCN priority and SMR implementaentation without prior adequate skills development, testing, and refining.

Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia's certification, by the World Health Organization in 2014, of the elimination of measles.

Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status.

Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalonal borders reopen.The advent of massively parallel sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long noncoding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Expression of lncRNAs is strongly linked with adjacent protein-coding gene expression, suggesting potential cis-regulatory functions. A more detailed understanding of these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes. Despite the diversity of reported lncRNA regulatory mechanisms, where causal cis-regulatory relationships exist, lncRNA transcription is expected to precede changes in target gene expression. Using a high temporal resolution RNA-seq time course, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal that lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells. Our findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. WP1066 in vivo The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.Clinical exome sequencing has yielded extensive disease-related missense single-nucleotide variants (SNVs) of uncertain significance, leading to diagnostic uncertainty. KCNQ4 is one of the most commonly responsible genes for autosomal dominant nonsyndromic hearing loss. According to the gnomAD cohort, approximately one in 100 people harbors missense variants in KCNQ4 (missense variants with minor allele frequency > 0.1% were excluded), but most are of unknown consequence. To prospectively characterize the function of all 4085 possible missense SNVs of human KCNQ4, we recorded the whole-cell currents using the patch-clamp technique and categorized 1068 missense SNVs as loss of function, as well as 728 loss-of-function SNVs located in the transmembrane domains. Further, to mimic the heterozygous condition in Deafness nonsyndromic autosomal dominant 2 (DFNA2) patients caused by KCNQ4 variants, we coexpressed loss-of-function variants with wild-type KCNQ4 and found 516 variants showed impaired or only partially rescued heterogeneous channel function. Overall, our functional classification is highly concordant with the auditory phenotypes in Kcnq4 mutant mice and the assessments of pathogenicity in clinical variant interpretations. Taken together, our results provide strong functional evidence to support the pathogenicity classification of newly discovered KCNQ4 missense variants in clinical genetic testing.Variation within human genomes is unevenly distributed, and variants show spatial clustering. DNA-replication-related template switching is a poorly known mutational mechanism capable of causing major chromosomal rearrangements as well as creating short inverted sequence copies that appear as local mutation clusters in sequence comparisons. I reanalyzed haplotype-resolved genome assemblies representing 25 human populations and multinucleotide variants aggregated from 140,000 human sequencing experiments. Local template switching could explain thousands of complex mutation clusters across the human genome, the loci segregating within and between populations. I developed computational tools for identification of template switch events using both short-read sequencing data and genotype data, and for genotyping candidate loci using short-read data. The characteristics of template-switch mutations complicate their detection, and widely used analysis pipelines for short-read sequencing data, normally capable of identifying single nucleotide changes, were found to miss template-switch mutations of tens of base pairs, potentially invalidating medical genetic studies searching for a causative allele behind genetic diseases. Combined with the massive sequencing data now available for humans, the novel tools described here enable building catalogs of affected loci and studying the cellular mechanisms behind template switching in both healthy organisms and disease.