Notes

Oncological as well as functional outcomes of supratotal resection regarding IDH1 wild-type glioblastoma according to 11C-methionine Puppy: a retrospective, single-center study.
need to consider reducing barriers for caregivers in obtaining food for themselves during their child's admission.
Self-harm in young people is a growing public health concern. Young people commonly present to their GP for help with self-harm, and thus general practice may be a key setting to support young people who have self-harmed.

To examine the potential of general practice to support young people aged 10-25 years who have harmed themselves.

A narrative review of published and grey literature.

The Scale for the Assessment of Narrative Review Articles (SANRA) was used to guide a narrative review to examine the potential of general practice to support young people who have self-harmed. The evidence is presented textually.

The included evidence showed that GPs have a key role in supporting young people, and they sometimes relied on gut feeling when handling uncertainty on how to help young people who had self-harmed. Young people described the importance of initial clinician responses after disclosing self-harm, and if they were perceived to be negative, the self-harm could become worse.

In context of the evidence included, this review found that general practice is a key setting for the identification and management of self-harm in young people; but improvements are needed to enhance general practice care for young people to fulfil its potential.
In context of the evidence included, this review found that general practice is a key setting for the identification and management of self-harm in young people; but improvements are needed to enhance general practice care for young people to fulfil its potential.
In Sweden, patients receiving Home Care (HC) are older people with frailty and multimorbidity, and are often treated with many medicines. Their perspectives on polypharmacy have been sparsely explored.

To investigate HC patients' experiences and perceptions regarding polypharmacy.

Semi-structured interviews with 17 patients with HC in Stockholm, Sweden.

The interview questions were open and aimed to encourage participants to speak freely about their personal experiences of living with polypharmacy. https://www.selleckchem.com/products/climbazole.html Data were analysed using an inductive thematic analysis.

The participants' median age was 83.5 years (range 74-97 years) and the median number of prescribed medicines was 11 (range 5-30). The following two themes were identified (1) experiences from daily life with polypharmacy; and (2) dependency on the relationship to healthcare professionals. The first theme contains the main finding, which was the diversity in how older people experienced polypharmacy and how they coped with polypharmacy in everyday life. While some were satisfied despite having multiple medicines, others experienced such psychological unease owing to polypharmacy that it led to reduced quality of life. The second theme reflects the importance of the relationship between the older person and healthcare professionals for medicine-related ideas and attitudes.

The individual variation in experiences regarding polypharmacy points to the value of interprofessional teamwork with the patient as an active partner. Therefore, healthcare professionals need to adapt a more person-centred approach where the patient's perspectives are respected and considered in medicine-related decisionmaking.
The individual variation in experiences regarding polypharmacy points to the value of interprofessional teamwork with the patient as an active partner. Therefore, healthcare professionals need to adapt a more person-centred approach where the patient's perspectives are respected and considered in medicine-related decisionmaking.
Primary care plays an important role in the conception and delivery of transformational research but GP engagement is lacking, prompting calls for the promotion of academic opportunities in primary care.

To identify potential barriers and facilitators among GP trainees and trainers in primary care research to inform support given by Local Clinical Research Networks (LCRNs).

A cross-sectional online survey was developed and distributed by the CRN to GP trainees and trainers in the North East and North West.

The survey covered areas including demographics, career intentions, current and potential engagement with research, as well as their general understanding of research in primary care, which included barriers and facilitators to primary care research.

Trainees had low intentionality to pursue research and half of trainees did not engage with any research activity. Despite one in five trainees reporting intentions to include research in their career, only 1% would undertake a solely academic career. Medical school region was the only strongly associated factor with academic career intention. Just under 30% of trainers reported engagement in research, but far fewer (8.6%) were interested in contributing to research, and only 10% felt prepared to mentor in research.

Among trainees, there is limited engagement in and intentionality to pursue research, and this was crucially reflected by responses from trainers. This study identified the need for LCRNs to assist with training in research mentoring and skills, funding opportunities, and to develop resources to promote research in primary care.
Among trainees, there is limited engagement in and intentionality to pursue research, and this was crucially reflected by responses from trainers. This study identified the need for LCRNs to assist with training in research mentoring and skills, funding opportunities, and to develop resources to promote research in primary care.
Care for patients with chronic kidney disease (CKD) necessitates tailored pathways between primary and secondary care. It is unknown if back referring patients with CKD is safe and effective.

To study the feasibility of discharging patients with stable moderate-to-advanced CKD from secondary to primary care, and to evaluate quality of care (QoC) and patients' and GPs' experiences.

A monocentre prospective mixed-method study in the Netherlands.

Patients were included who met pre-determined back-referral (BR) criteria. Patients were discharged with personalised information guides and transfer letters. GPs had the option of consulting a nephrologist by telenephrology. Renal outcomes, QoC, and experiences were collected after 1 year.

Eighteen patients were included. The mean age was 73 years; the mean estimated glomerular filtration rate (eGFR) was 33.2 ml/min/1.73 m
at baseline. After 1 year, four patients had received either no or incomplete monitoring, and one patients' blood pressure was too high. The remaining 13 had stable eGFR, proteinuria, and metabolic parameters. Patients were satisfied with information provision and treatment by GPs but expected more frequent monitoring. In one-third of cases, monitoring frequency was decreased by GPs for several reasons. GPs believed they had sufficient knowledge to treat patients with CKD, but indicated they needed support besides a transfer letter.

BR seems safe and feasible for patients with stable moderate-to-advanced CKD who meet specific criteria. Patients have good renal outcomes after 1 year and are satisfied with treatment. GP QoC can be improved, particularly completeness and monitoring frequency.
BR seems safe and feasible for patients with stable moderate-to-advanced CKD who meet specific criteria. Patients have good renal outcomes after 1 year and are satisfied with treatment. GP QoC can be improved, particularly completeness and monitoring frequency.Lactate is an abundant oncometabolite in the tumor environment. In prostate cancer, cancer-associated fibroblasts (CAF) are major contributors of secreted lactate, which can be taken up by cancer cells to sustain mitochondrial metabolism. However, how lactate impacts transcriptional regulation in tumors has yet to be fully elucidated. Here, we describe a mechanism by which CAF-secreted lactate is able to increase the expression of genes involved in lipid metabolism in prostate cancer cells. This regulation enhanced intracellular lipid accumulation in lipid droplets (LD) and provided acetyl moieties for histone acetylation, establishing a regulatory loop between metabolites and epigenetic modification. Inhibition of this loop by targeting the bromodomain and extraterminal protein family of histone acetylation readers suppressed the expression of perilipin 2 (PLIN2), a crucial component of LDs, disrupting lactate-dependent lipid metabolic rewiring. Inhibition of this CAF-induced metabolic-epigenetic regulatory loop in vivo reduced growth and metastasis of prostate cancer cells, demonstrating its translational relevance as a therapeutic target in prostate cancer. Clinically, PLIN2 expression was elevated in tumors with a higher Gleason grade and in castration-resistant prostate cancer compared with primary prostate cancer. Overall, these findings show that lactate has both a metabolic and an epigenetic role in promoting prostate cancer progression.
This work shows that stromal-derived lactate induces accumulation of lipid droplets, stimulates epigenetic rewiring, and fosters metastatic potential in prostate cancer.
This work shows that stromal-derived lactate induces accumulation of lipid droplets, stimulates epigenetic rewiring, and fosters metastatic potential in prostate cancer.The combination of the synthetic TLR9 ligand CpG and agnostic OX40 antibody can trigger systemic antitumor immune responses upon co-injection into the tumor microenvironment, eradicating simultaneous untreated sites of metastatic disease. Here we explore the application of this in situ immunotherapy to the neoadjuvant setting. Current neoadjuvant checkpoint blockade therapy is delivered systemically, resulting in off-target adverse effects. In contrast, intratumoral immunotherapy minimizes the potential for toxicities and allows for greater development of combination therapies. In two metastatic solid tumor models, neoadjuvant intratumoral immunotherapy generated a local T-cell antitumor response that then acted systemically to attack cancer throughout the body. In addition, the importance of timing between neoadjuvant immunotherapy and surgical resection was established, as well as the increased therapeutic power of adding systemic anti-PD1 antibody. The combination of local and systemic immunotherapy generated an additional survival benefit due to synergistic inhibitory effect on tumor-associated macrophages. These results provide a strong rationale for translating this neoadjuvant intratumoral immunotherapy to the clinical setting, especially in conjunction with established checkpoint inhibitors.
This work demonstrates the ability of neoadjuvant intratumoral immunotherapy to target local and distant metastatic disease and consequently improve survival.
This work demonstrates the ability of neoadjuvant intratumoral immunotherapy to target local and distant metastatic disease and consequently improve survival.Macrophages perform key and distinct functions in maintaining tissue homeostasis by finely tuning their activation state. Within the tumor microenvironment, macrophages are reshaped to drive tumor progression. Here we report that tumor necrosis factor α-induced protein 8-like 1 (TIPE1) is highly expressed in macrophages and that depletion of TIPE1 impedes alternative activation of macrophages. TIPE1 enhanced activation of the PI3K/Akt pathway in macrophages by directly binding with and regulating the metabolism of phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). Accordingly, inhibition of the PI3K/Akt pathway significantly attenuated the effect of TIPE1 on macrophage alternative activation. Tumor-associated macrophages (TAM) in human liver cancer and melanoma tissues showed significantly upregulated TIPE1 expression that negatively correlated with patient survival. In vitro and in vivo, TIPE1 knockdown in macrophages retarded the growth and metastasis of liver cancer and melanoma.
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