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Patients with hypertension in Nepal are often known to have poor medication adherence and quality of life. This randomised controlled trial aimed to evaluate the impact of a hospital pharmacist-delivered individualised pharmaceutical service (P-DIPS) intervention on blood pressure, medication adherence and health-related quality of life (HRQoL) among patients with hypertension in a hospital setting in Nepal.

In an open trial, 56 adult patients with hypertension who had been receiving antihypertensive medication for ≥6 months were randomly allocated to a control group (n=28) which received the usual care and an intervention group (n=28) which received a P-DIPS along with the usual care. The difference in blood pressure, medication adherence and HRQoL between the two groups at baseline, 2 and 4 months was compared using the Mann-Whitney U test, independent t-test or χ

tests.

Participants were mostly ≥40 years (86%) and female (57%). There were no significant differences in the baseline characteristics bificant potential to improve blood pressure, medication adherence and HRQoL in patients with hypertension.Growth factor independence-1 (GFI1) is a transcriptional repressor and master regulator of normal and malignant hematopoiesis. Repression by GFI1 is attributable to recruitment of LSD1-containing protein complexes via its SNAG domain. However, the full complement of GFI1 partners in transcriptional control is not known. We show that in T-acute lymphoblastic leukemia (ALL) cells, GFI1 and IKAROS are transcriptional partners that co-occupy regulatory regions of hallmark T-cell development genes. Transcriptional profiling reveals a subset of genes directly transactivated through the GFI1-IKAROS partnership. Among these is NOTCH3, a key factor in T-ALL pathogenesis. Surprisingly, NOTCH3 expression by GFI1 and IKAROS requires the GFI1 SNAG domain but occurs independent of SNAG-LSD1 binding. GFI1 variants deficient in LSD1 binding fail to activate NOTCH3, but conversely, small molecules that disrupt the SNAG-LSD1 interaction while leaving the SNAG primary structure intact stimulate NOTCH3 expression. These results identify a noncanonical transcriptional control mechanism in T-ALL which supports GFI1-mediated transactivation in partnership with IKAROS and suggest competition between LSD1-containing repressive complexes and others favoring transactivation.

Combinatorial diversity and cooperation between DNA binding proteins and complexes assembled by them can direct context-dependent transcriptional outputs to control cell fate and may offer new insights for therapeutic targeting in cancer.

Combinatorial diversity and cooperation between DNA binding proteins and complexes assembled by them can direct context-dependent transcriptional outputs to control cell fate and may offer new insights for therapeutic targeting in cancer.Radiotherapy is the most widely used cancer treatment and improvements in its efficacy and safety are highly sought-after. Peposertib (also known as M3814), a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, effectively suppresses the repair of radiation-induced DNA double-strand breaks (DSB) and regresses human xenograft tumors in preclinical models. Irradiated cancer cells devoid of p53 activity are especially sensitive to the DNA-PK inhibitor, as they lose a key cell-cycle checkpoint circuit and enter mitosis with unrepaired DSBs, leading to catastrophic consequences. Here, we show that inhibiting the repair of DSBs induced by ionizing radiation with peposertib offers a powerful new way for improving radiotherapy by simultaneously enhancing cancer cell killing and response to a bifunctional TGFβ "trap"/anti-PD-L1 cancer immunotherapy. By promoting chromosome misalignment and missegregation in p53-deficient cancer cells with unrepaired DSBs, DNA-PK inhibitor accelerated micronuclei formation, a key generator of cytosolic DNA and activator of cGAS/STING-dependent inflammatory signaling as it elevated PD-L1 expression in irradiated cancer cells. Triple combination of radiation, peposertib, and bintrafusp alfa, a fusion protein simultaneously inhibiting the profibrotic TGFβ and immunosuppressive PD-L1 pathways was superior to dual combinations and suggested a novel approach to more efficacious radioimmunotherapy of cancer.

Selective inhibition of DNA-PK in irradiated cancer cells enhances inflammatory signaling and activity of dual TGFβ/PD-L1 targeted therapy and may offer a more efficacious combination option for the treatment of locally advanced solid tumors.

Selective inhibition of DNA-PK in irradiated cancer cells enhances inflammatory signaling and activity of dual TGFβ/PD-L1 targeted therapy and may offer a more efficacious combination option for the treatment of locally advanced solid tumors.

To optimize type 1 diabetes mellitus self-management, experts recommend a person-centered approach, in which care is tailored to meet people's needs and preferences. Existing tools for tailoring type 1 diabetes mellitus education and support are limited by narrow focus, lack of strong association with meaningful outcomes like A1c, or having been developed before widespread use of modern diabetes technology. To facilitate comprehensive, effective tailoring for today's working-aged adults with type 1 diabetes mellitus, we developed and validated the Barriers and Supports Evaluation (BASES).

Participants 25-64 years of age with type 1 diabetes mellitus were recruited from clinics and a population-based registry. Content analysis of semistructured interviews (n=33) yielded a pool of 136 items, further refined to 70 candidate items on a 5-point Likert scale through cognitive interviewing and piloting. To develop and validate the tool, factor analyses were applied to responses to candidate items (n=392). Additi success in achieving HbA1c goals and optimal QOL.

The BASES is a valid, comprehensive, person-centered tool that can tailor diabetes support and education to individuals' needs in a modern practice environment, improving effectiveness and uptake of services. Clinicians could use the tool to uncover patient-specific barriers that limit success in achieving HbA1c goals and optimal QOL.

Healthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population.

We conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data.

Overall, PA had a weak inverse association (β=-0.00033, p=0.049) and carbohydrate intake had a strt that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with hemoglobin A1c (A1c) among patients with type 2 diabetes mellitus (T2DM); however, there is a paucity of data evaluating its association with microvascular complications. We conducted this systematic review to examine the association between TIR and microvascular complications of diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). TVB-3166 We conducted a comprehensive literature search on PubMed, Scopus, and Web of Science online databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Full-text original articles that evaluated the association between CGM-derived TIR and risk of microvascular complications and were published between 2010 and June 2021 were included in our systematic review. The quality of the included studies was evaluated using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Se diverse participants is warranted to further validate the utility of TIR as a predictor of diabetic microvascular complications.

Hospital accreditation by an international organisation can play an important role in health quality and safety. However, little is known about how managers and front-line employees experience and perceive the effects of accreditation. Their views could inform quality improvement processes and procedures.

To explore perceptions of employees at the managerial level on the Joint Commission International (JCI) accreditation process and its impact on quality of patient care in Saudi Arabian JCI-accredited hospitals.

We undertook a qualitative study using semi-structured interviews to explore the perspectives of senior staff from three accredited public hospitals in Saudi Arabia. Interviews were transcribed prior to thematic analysis.

Twenty managers participated in the interviews. The following inter-related themes emerged concerning the JCI accreditation process and its impact on quality of patient care drivers for the change; the plan for the change; the process of the change; maintaining changes post-aimprovements to care continue beyond the accreditation period.

Proper sedation is integral to ensuring the safety and comfort of children on mechanical ventilation (MV). Sedation protocols help to achieve this goal and reduce the duration of MV. We have observed varied sedation approaches, sedation score targets and sedative use by our physicians, which were manifested as oversedation and undersedation with associated accidental extubation. Hence, we aimed to implement a standardised sedation protocol and assess its impact on mechanically ventilated paediatric patients.

A multidisciplinary quality improvement team was formed to develop and implement a standardised sedation protocol for mechanically ventilated paediatric patients. COMFORT-Behaviour (COMFORT-B) Scale score was used to assess the sedation targets and define undersedation, oversedation or adequate sedation. Our goal was to achieve adequate sedation during 90% of the sedation period. Based on the model for improvement methodology, we used plan-do-study-act cycles to develop, test and implement the new sedation protocol.

There was an immediate percentage increase in COMFORT-B Scale scores within the target sedation level, which was associated with a gradual decrease in the need for intermittent sedation doses over sedation infusion in the preimplementation, improvement and control phases (6.3, 4.9 and 3.1 sedation doses/12 hours/patient, respectively) to achieve adequate sedation target.

The standardisation of sedation protocols was safe and efficient, and improved the sedation quality in mechanically ventilated paediatric patients.

The standardisation of sedation protocols was safe and efficient, and improved the sedation quality in mechanically ventilated paediatric patients.