A coalition-driven examination of organization capacity to address food insecurity in Greater Houston: a qualitative research study.

Background: Economic and social hardships have worsened food insecurity, particularly among low income and racial-ethnic minority groups. Given the core goal of the 150+ member Houston Health Equity Collective (HEC) to reduce food insecurity by 5% in 2025, we explored member organizations' capacity and challenges faced in screening and responding to food insecurity through care coordination efforts. Methods: A twice-administered Qualtrics XM survey (Provo, Utah) with 76 organizations, followed by five focus groups with 22 of these organizations, explored reach and response efforts to food insecurity. Qualitative assessments lasted between 0.5 to 1.5 h, were audio-recorded, cleaned, coded, and thematically analyzed using NVivo, version 11 (Burlington, Massachusetts). The qualitative study was guided by a general inductive approach. In total, over 6 h of audiovisual recording were extracted, and over 100 pages of text exported to NVivo for data analysis. The research team read and coded transcripts independently using the codebook, and met routinely to discuss and resolve codes -resulting in numerous revisions to the codebook. Coding structure was discussed at multiple meetings and differences were addressed through consensus. Predominant qualitative themes impacting food insecurity screening were "stigma and cultural-related barriers", "clinic capacity and attitudes", "need to focus on upstream influences of food insecurity and SDOH needs", "impact of COVID-19", and "need for HEC system responses". Main recommendations to enhance screening and reach included improving staff culture, enhancing cultural sensitivity across organizational practices, and using shared technology to coordinate care. Respondents stated that the HEC can drive these recommendations through networking opportunities, use of shared resource directory, and placing focus on upstream factors. Conclusions: Recommendations to target food insecurity must focus on organizational staff responsiveness and sensitivity to patients' needs. Of equal importance is the need for increased attention to the upstream influencers and integration of systems-level interventions to holistically target the barriers impacting food insecurity.

How is food variety conceptualised and measured as a diet quality indicator in developed settings? Protocol for a systematic scoping review.

OBJECTIVES: Dietary diversity (DD) is a pillar of healthy eating guidance and can be used to assess diet quality. Despite being an established nutrition concept, many inconsistencies in its definition and measurement exist and meanings vary across the development spectrum. This protocol outlines a research trajectory, whereby a scoping review will be undertaken to illustrate and map the methodological approaches that have been utilised to measure diversity as a marker of diet quality in the general population. It seeks to determine the most common and less used methodological approaches to measure DD in the diet of healthy adults. METHODS AND ANALYSIS: Scoping review of peer-reviewed and grey literature from five bibliographic databases, supplemented by handsearching of reviews and reference lists. Search terms will include DD, food variety, mixed diet, balanced diet and food group variety. Eligible articles must include a measure for DD as an indicator of diet quality in the general population living in developed settings. Two independent reviewers will screen titles or abstracts, and read full-texts. Consensus will resolve any disagreements on study eligibility with a third reviewer consulted if needed. Data will be extracted using a standardised evidence table and analysed using a narrative synthesis approach. Data will be managed using Covidence. ETHICS AND DISSEMINATION: No ethics is required for this study using public documents. Results will be disseminated through peer-reviewed papers and scientific conferences. DISCUSSION: This scoping review will help to map, classify and assess the methodological approaches used in the nutrition literature to measure DD as a diet quality indicator. We anticipate a wide range of DD measures and expect to identify the most prevalent DD measures used to assess diet quality. Our findings will inform standardisation to improve future research on this nutritional concept.

Characterizing the role and associated stakeholder perceptions of a novel pharmacy experiential education facilitator role within the inpatient practice setting.

INTRODUCTION: To address practicum challenges commonly reported in inpatient pharmacy practice settings, a novel experiential education facilitator (EEF) role was created and implemented to provide on-the-ground support for students and practice educators (PEs). This article characterizes the daily activities of the EEF and associated perceptions of their role by students and PEs. METHODS: In this prospective, descriptive study, EEFs, students, and PEs involved with inpatient advanced pharmacy practice experiences (APPEs) participated. Day-to-day activities were captured by EEFs through completion of logs, and student and PE perceptions of the EEF role were collected through surveys. RESULTS: Seven EEFs, 14 students, and 20 PEs participated. During the practicum, EEFs frequently organized student activities, provided education to PEs, assisted with student evaluations, and provided logistical support. Orienting students to the site and providing teaching sessions took the greatest amount of time. These activities were perceived to be beneficial by students and PEs, and 12 of 14 (86%) students stated that they felt more confident in their clinical skills after working with their EEF. The majority of students and PEs did not experience challenges with the EEF role. The main challenge identified by both groups was inaccessibility to the EEF due to illness, vacation, or competing clinical responsibilities. CONCLUSIONS: EEFs within inpatient practice settings are valued for their involvement in providing on-site support for students and PEs. Orientating students to the site, facilitating teaching sessions, and supporting student evaluation were perceived as beneficial and addressed some of the key needs identified by inpatient stakeholders.

A selective anticoagulation policy for splanchnic vein thrombosis in acute pancreatitis is associated with favourable outcomes: experience from a UK tertiary referral centre.

INTRODUCTION: There is a paucity of data on the incidence, risk factors, and treatment of splanchnic vein thrombosis (SVT) in acute pancreatitis (AP). METHODS: All AP admissions between 2018 and 2021 across North East of England were included. Anticoagulation was considered in the presence of superior mesenteric vein/portal vein (SMV/PV) thrombus or progressive splenic vein thrombus (SpVT). The impact of such a selective anticoagulation policy, on vein recanalisation rates and bleeding complications were explored. RESULTS: 401 patients (median age 58) were admitted with AP. 109 patients (27.2%) developed SVT. The splenic vein in isolation was the most common site (n = 46) followed by SMV/PV (n = 36) and combined SMV/PV and SpVT (n = 27). On multivariate logistic regression alcohol aetiology (OR 2.64, 95% CI [1.43-5.01]) and >50% necrosis of the pancreas (OR 14.6, 95% CI [1.43-383.9]) increased the risk of developing SVT. The rate of recanalization with anticoagulation was higher for PVT (66.7%; 42/63) than in SpVT (2/11; p = 0.003). 5/74 of anticoagulated patients developed bleeding complications while 0/35 patients not anticoagulated had bleeding complications (p = 0.4). CONCLUSION: The risk of SVT increases with AP severity and with extent of pancreatic necrosis. A selective anticoagulation policy for PVT and progressive SpVT in AP is associated with favourable outcomes with no increased risk of bleeding complications.

Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α.

Inositol requiring enzyme 1 (IRE1) mitigates endoplasmic-reticulum (ER) stress by orchestrating the unfolded-protein response (UPR). IRE1 spans the ER membrane, and signals through a cytosolic kinase-endoribonuclease module. The endoribonuclease generates the transcription factor XBP1s by intron excision between similar RNA stem-loop endomotifs, and depletes select cellular mRNAs through regulated IRE1-dependent decay (RIDD). Paradoxically, in mammals RIDD seems to target only mRNAs with XBP1-like endomotifs, while in flies RIDD exhibits little sequence restriction. By comparing nascent and total IRE1α-controlled mRNAs in human cells, we identify not only canonical endomotif-containing RIDD substrates, but also targets without such motifs-degraded by a process we coin RIDDLE, for RIDD lacking endomotif. IRE1α displays two basic endoribonuclease modalities: highly specific, endomotif-directed cleavage, minimally requiring dimers; and more promiscuous, endomotif-independent processing, requiring phospho-oligomers. An oligomer-deficient IRE1α mutant fails to support RIDDLE in vitro and in cells. Our results advance current mechanistic understanding of the UPR.

ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses.

Cytosolic double-stranded RNA (dsRNA) initiates type I IFN responses. Endogenous retroelements, notably Alu elements, constitute a source of dsRNA. Adenosine-to-inosine (A-to-I) editing by ADAR induces mismatches in dsRNA and prevents recognition by MDA5 and autoinflammation. To identify additional endogenous dsRNA checkpoints, we conducted a candidate screen in THP-1 monocytes and found that hnRNPC and ADAR deficiency resulted in synergistic induction of MDA5-dependent IFN responses. RNA-seq analysis demonstrated dysregulation of Alu-containing introns in hnRNPC-deficient cells via utilization of unmasked cryptic splice sites, including introns containing ADAR-dependent A-to-I editing clusters. These putative MDA5 ligands showed reduced editing in the absence of ADAR, providing a plausible mechanism for the combined effects of hnRNPC and ADAR. This study contributes to our understanding of the control of repetitive element-induced autoinflammation and suggests that patients with hnRNPC-mutated tumors might maximally benefit from ADAR inhibition-based immunotherapy.

Prognostic value of nocturnal blood pressure dipping on cardiovascular outcomes in Chinese patients with hypertension in primary care.

Meta-analyses showed that non-dipping of nocturnal blood pressure on ambulatory blood pressure monitoring (ABPM) was associated with adverse cardiovascular prognosis. However, these prognostic studies were mainly conducted in Caucasian and Japanese populations. Whether this association applies to Chinese patients remained uninvestigated. A total of 1199 Chinese patients with hypertension undergoing ABPM between January 2012 and December 2014 were recruited retrospectively from five public hypertension referral clinics in Hong Kong. Patients were followed up for a mean 6.42 years for cardiovascular morbidity and mortality and all-cause mortality. Time to event of different dipping patterns was compared by Kaplan-Meier curves. Hazard ratios (HR) were obtained by Cox proportional hazard models with patient demographics and confounding factors adjusted in multivariate regression. A total of 163 end point events occurred in the period. Normal dipping was observed in 446 patients (37.2%), non-dipping in 490 (40.9%), reverse dipping in 161 (13.4%), and extreme dipping in 102 (8.5%). Kaplan-Meier analyses showed inferior survival in non-dippers and reverse dippers for total cardiovascular events and coronary events but not cerebrovascular events. After adjusting for confounding factors, Cox regressions showed HRs 1.166 (CI 0.770-1.764) and 1.173 (CI 0.681-2.021) in non-dippers and reverse dippers for total cardiovascular events, and HRs 1.320 (CI 0.814-2.141) and 1.476 (CI 0.783-2.784) for coronary events. Nocturnal blood pressure non-dipping, and to a greater extent reverse dipping, demonstrated adverse cardiovascular prognosis in a cohort of Chinese patients with hypertension in Hong Kong. Further focused studies on cerebrovascular events and reverse dippers were warranted to refine risk stratification.

Postoperative Pain Relief after Pancreatic Resection: Systematic Review and Meta-Analysis of Analgesic Modalities.

BACKGROUND: This systematic review explored the efficacy of different pain relief modalities used in the management of postoperative pain following pancreatoduodenectomy (PD) and distal pancreatectomy (DP) and impact on perioperative outcomes. METHODS: MEDLINE (OVID), Embase, Pubmed, Web of Science and CENTRAL databases were searched using PRISMA framework. Primary outcomes included pain on postoperative day 2 and 4 and respiratory morbidity. Secondary outcomes included operation time, bile leak, delayed gastric emptying, postoperative pancreatic fistula, length of stay, and opioid use. RESULTS: Five randomized controlled trials and seven retrospective cohort studies (1313 patients) were included in the systematic review. Studies compared epidural analgesia (EDA) (n = 845), patient controlled analgesia (PCA) (n = 425) and transabdominal wound catheters (TAWC) (n = 43). EDA versus PCA following PD was compared in eight studies (1004 patients) in the quantitative meta-analysis. Pain scores on day 2 (p = 0.19) and 4 (p = 0.18) and respiratory morbidity (p = 0.42) were comparable between EDA and PCA. Operative times, bile leak, delayed gastric emptying, pancreatic fistula, opioid use, and length of stay also were comparable between EDA and PCA. Pain scores and perioperative outcomes were comparable between EDA and PCA following DP and EDA and TAWC following PD. CONCLUSIONS: EDA, PCA and TAWC are the most frequently used analgesic modalities in pancreatic surgery. Pain relief and other perioperative outcomes are comparable between them. Further larger randomized controlled trials are warranted to explore the relative merits of each analgesic modality on postoperative outcomes with emphasis on postoperative complications.

Hospital pharmacists understanding of available health literacy assessment tools and their perceived barriers for incorporation in patient education - a survey study.

BACKGROUND: Patients with low health literacy experience difficulty in understanding their medications leading to worse health outcomes. Pharmacists need to use formal assessment tools to be able to identify these patients, so they can better tailor their patient education. The objective of the study was to characterize hospital pharmacists understanding of health literacy and their use of screening and counselling strategies before and after completion of an educational module and to identify barriers that hospital pharmacists perceive to exist that prevent them from using health literacy tools. METHODS: Pharmacists in three health authorities were administered a pre-survey and then given access to an online 11 min educational video. The post-survey was distributed 1 month later. Descriptive statistics were used to quantify survey responses with comparisons made between pre and post responses. The main outcome measure was pharmacists' understanding of health literacy and their current practice related to health literacy. RESULTS: There were 131 respondents for the pre-survey and 39 for the post-survey. In the pre-module survey, 84% of pharmacists felt they understood what health literacy was, but only 53% currently assessed patients for their health literacy status and 40% were aware of what strategies to use in low health literacy patients. Lack of time (74%) was the biggest barrier in assessing patients' health literacy. In the post-module survey, 87% felt they understood what health literacy was and 64% incorporated health literacy status evaluation into their clinical practice. The educational module was helpful to the clinical practice of 74% of respondents. CONCLUSION: As health literacy can affect a patient's ability to adhere to their medications it is important for pharmacists to assess this in their patients. While pharmacists self-reported a high degree of understanding of health literacy, they are not regularly assessing their patients' health literacy status and are unaware of what strategies to use for low literacy patients.

Effect of patient size on image quality in radiotherapy kV planar verification imaging: a phantom study.

INTRODUCTION: This study aimed to determine a maximal pelvic separation and waist circumference in pelvic patients to guide radiation therapists in acquiring kilovoltage (kV) planar images of acceptable quality for treatment verification. METHODS: A pelvic anthropomorphic phantom modified with different bolus thicknesses was imaged at various default kV exposure settings. Radiation therapists rated image quality and acceptance/rejection of these images for treatment verification. RESULTS: Sixteen radiation therapists participated in the study. Image quality was inversely proportional to phantom size. AP and lateral kV images were acceptable for treatment verification up to a waist circumference of 143 cm. CONCLUSIONS: Exposure settings for kV image verification of large patients should be individualised to avoid unnecessary patient radiation dose through repeated imaging.

The tumor suppressor BAP1 cooperates with BRAFV600E to promote tumor formation in cutaneous melanoma.

The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low frequency. In addition, Bap1-null melanoma cells derived from mouse tumors are more aggressive and colonize and grow at distant sites more than their wild-type counterparts. Molecularly, Bap1-null melanoma cell lines have increased DNA damage measured by γH2aX and hyperubiquitination of histone H2a. Therapeutically, these Bap1-null tumors are completely responsive to BRAF- and MEK-targeted therapies. Therefore, BAP1 functions as a tumor suppressor and limits tumor progression in melanoma.

A method for manual and automated multiplex RNAscope in situ hybridization and immunocytochemistry on cytospin samples.

In situ analysis of biomarkers is essential for clinical diagnosis and research purposes. The increasing need to understand the molecular signature of pathologies has led to the blooming of ultrasensitive and multiplexable techniques that combine in situ hybridization (ISH) and immunohistochemistry or immunocytochemistry (IHC or ICC). Most protocols are tailored to formalin-fixed paraffin embedded (FFPE) tissue sections. However, methods to perform such assays on non-adherent cell samples, such as patient blood-derived PBMCs, rare tumor samples, effusions or other body fluids, dissociated or sorted cells, are limited. Typically, a laboratory would need to invest a significant amount of time and resources to establish one such assay. Here, we describe a method that combines ultrasensitive RNAscope-ISH with ICC on cytospin cell preparations. This method allows automated, sensitive, multiplex ISH-ICC on small numbers of non-adherent cells. We provide guidelines for both chromogenic and fluorescent ISH/ICC combinations that can be performed either in fully automated or in manual settings. By using a CD8+ T cells in vitro stimulation paradigm, we demonstrate that this protocol is sensitive enough to detect subtle differences in gene expression and compares well to commonly used methods such as RT-qPCR and flow cytometry with the added benefit of visualization at the cellular level.

Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain.

The E3 ubiquitin ligase CRL4COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1, Olig2, and Sox10. The mice had subtle morphological abnormalities in the cerebral cortex, hippocampus, and cerebellum by embryonic day 18 and died soon after birth. Elevated c-JUN, ETV5, and ETV1 contributed to the perinatal lethality, as several Cop1-deficient mice also lacking c-Jun and Etv5, or lacking Etv5 and heterozygous for Etv1, were viable.

AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs.

Molecularly targeted drug therapies have revolutionized cancer treatment; however, resistance remains a major limitation to their overall efficacy. Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance to tyrosine kinase inhibitors (TKI), independent of mutational resistance mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been implicated in drug resistance and has emerged as a candidate therapeutic target. Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly associated with a mesenchymal phenotype, particularly in triple-negative breast cancer and non-small cell lung cancer. In an unbiased screen of small-molecule inhibitors of cancer-relevant processes, we discovered that AXL inhibition was specifically synergistic with antimitotic agents in killing cancer cells that had undergone EMT and demonstrated associated TKI resistance. However, we did not find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in the EMT setting, as previously reported. These findings reveal a novel cotreatment strategy for tumors displaying mesenchymal features that otherwise render them treatment refractory.

PPM1H is a p27 phosphatase implicated in trastuzumab resistance.

The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2-positive cancer historically portends a poor prognosis, but the HER2-targeted therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless, some patients suffer disease recurrence despite trastuzumab, and metastatic disease remains largely incurable due to innate and acquired resistance. Thus, understanding trastuzumab resistance remains an unmet medical need. Through RNA interference screening, we discovered that knockdown of the serine/threonine phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels of the tumor suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus removing a signal for proteasomal degradation. We further determined that patients whose tumors express low levels of PPM1H trend towards worse clinical outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new insight into how cancer cells destabilize a well-recognized tumor suppressor. Furthermore, low PPM1H expression may identify a subset of HER2-positive tumors that are harder to treat.

Prostate-specific Klf6 inactivation impairs anterior prostate branching morphogenesis through increased activation of the Shh pathway.

Krüppel-like factor 6 (Klf6) belongs to a family of zinc finger transcription factors known to play a role in development and tumor suppression. Although Klf6 is highly mutated in prostate cancer, its function in prostate development is unknown. We have generated a prostate-specific Klf6-deficient mouse model and report here a novel role for Klf6 in the regulation of prostate branching morphogenesis. Importantly, our study reveals a novel relationship between Klf6 and the Shh pathway. Klf6-deficiency leads to elevated levels of hedgehog pathway components (Shh, Ptc, and Gli) and loss of their localized expression, which in turn causes impaired lateral branching.

Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas.

Melanoma inhibitor of apoptosis (ML-IAP) is a potent inhibitor of apoptosis, which is highly expressed in melanomas and likely contributes to their resistance to chemotherapeutic treatments. Herein, we show that the lineage survival oncogene microphthalmia-associated transcription factor (MITF) is a critical regulator of ML-IAP transcription in melanoma cells. The ML-IAP promoter contains two MITF consensus sites, and analysis of MITF and ML-IAP mRNA levels revealed a high correlation in melanoma tumor samples and cell lines. In reporter assays, MITF promoted a strong stimulation of transcriptional activity from the ML-IAP promoter, and MITF bound the endogenous ML-IAP promoter in melanoma cells by chromatin immunoprecipitation and electrophoretic mobility shift assay. Strikingly, small interfering RNA (siRNA)-mediated knockdown of MITF in melanoma cells led to a dramatic decrease in ML-IAP mRNA and protein levels, establishing that ML-IAP expression in melanoma cells is MITF dependent. Additionally, cyclic AMP-mediated induction of MITF expression in melanocytes resulted in increased ML-IAP expression, suggesting that melanocytes can express ML-IAP when MITF levels are heightened. Disruption of MITF by siRNA led to a decrease in melanoma cell viability, which could be rescued by ectopic expression of ML-IAP. Collectively, these findings implicate MITF as a major transcriptional regulator of ML-IAP expression in melanomas, and suggest that ML-IAP contributes to the prosurvival activity of MITF in melanoma progression.