Pediatric Critical Care Illness Severity Toolkit: Stata Commands for Calculation of Pediatric Index of Mortality and Pediatric Logistic Organ Dysfunction Scores.

Introduction: Illness severity scoring tools, such as PRISM III/IV, PIM-3, and PELOD-2, are widely used in pediatric critical care research. However, their application is hindered by complex calculation processes, privacy concerns with third-party online calculators, and challenges in accurate implementation within statistical packages. Methods: We have developed a comprehensive, open-source toolkit for implementing the PIM-3, Simplified PIM-3, and PELOD-2 scores. The toolkit includes the pim3 and pelod2 commands and is compatible with Stata versions 12 and above. It features robust data validation, error messaging, a graphical interface, and support for SI and Imperial units. The toolkit's accuracy was validated through unit testing and synthetic data, comparing results with existing implementations. Results: In performance tests, the toolkit exhibited a median processing time of 21.82 seconds for PELOD-2, 14.06 seconds for PIM-3, and 9.74 seconds for Simplified PIM-3, when applied to datasets of 10,000,000 records. It consistently achieved 100% accuracy in both synthetic data tests and manual spot checks. Conclusion: The toolkit decreases processing time and improves accuracy in calculating pediatric critical care severity scores such as PELOD-2, PIM-3, and Simplified PIM-3. Its application in large datasets and validation highlights its utility as a tool for streamlining pediatric critical care research.

Racial and ethnic disparities in potentially inappropriate medication use in patients with dementia.

INTRODUCTION: Racial and ethnic disparities in potentially inappropriate medication (PIM) use among older adults with dementia are unclear. METHODS: Data were drawn from the baseline visits of participants who were ≥60 years old and diagnosed with dementia in the National Alzheimer's Coordinating Center Uniform Data Set (NACCUDS) recruited from National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADCs) throughout the United States. PIM utilization was evaluated using the 2019 American Geriatrics Society Beers Criteria for PIM Use in Older Adults. We estimated the association between race and ethnicity and the following outcomes and estimation models: (1) any PIM use, any PIM in each drug class, and any PIM best avoided in dementia patients using logistic regression models, (2) total number of medications, total number of PIMs, and anticholinergic burden scale (ACBS) using Poisson or negative binomial regression models, and (3) proportion of total medications that were PIMs using generalized linear models (GLM). RESULTS: Compared to White participants, Black, Hispanic, and Asian participants reported taking fewer total medications (incidence rate ratio [IRR] ± standard error[SE] = 0.903 ± 0.017, 0.875 ± 0.021, and 0.912 ± 0.041, respectively, all p < 0.01). Asian participants were less likely to be exposed to any PIM (odds ratio [OR] ± SE = 0.619 ± 0.118, p < 0.05). Compared to White participants, Black participants were less likely to be exposed to benzodiazepine (OR ± SE = 0.609 ± 0.094, p < 0.01) and antidepressant (OR ± SE = 0.416 ± 0.103, p < 0.001) PIMs, but greater antipsychotic (OR ± SE = 1.496 ± 0.204, p < 0.01), cardiovascular (OR ± SE = 2.193 ± 0.255, p < 0.001), and skeletal muscle relaxant (OR ± SE = 2.977 ± 0.860, p < 0.001) PIMs. Hispanic participants were exposed to greater skeletal muscle relaxant PIMs and had lower anticholinergic burden. Asian participants were exposed to fewer benzodiazepine PIMs. DISCUSSION: Significant racial and ethnic disparities in exposure to PIMs and PIMs by medication category in dementia research participants who have access to dementia experts found in the study suggest that disparities may be wider in the larger community.

Multi-Objectives Optimization of Plastic Injection Molding Process Parameters Based on Numerical DNN-GA-MCS Strategy.

An intelligent optimization technique has been presented to enhance the multiple structural performance of PA6-20CF carbon fiber-reinforced polymer (CFRP) plastic injection molding (PIM) products. This approach integrates a deep neural network (DNN), Non-dominated Sorting Genetic Algorithm II (NSGA-II), and Monte Carlo simulation (MCS), collectively referred to as the DNN-GA-MCS strategy. The main objective is to ascertain complex process parameters while elucidating the intrinsic relationships between processing methods and material properties. To realize this, a numerical study on the PIM structural performance of an automotive front engine hood panel was conducted, considering fiber orientation tensor (FOT), warpage, and equivalent plastic strain (PEEQ). The mold temperature, melt temperature, packing pressure, packing time, injection time, cooling temperature, and cooling time were employed as design variables. Subsequently, multiple objective optimizations of the molding process parameters were employed by GA. The utilization of Z-score normalization metrics provided a robust framework for evaluating the comprehensive objective function. The numerical target response in PIM is extremely intricate, but the stability offered by the DNN-GA-MCS strategy ensures precision for accurate results. The enhancement effect of global and local multi-objectives on the molded polymer-metal hybrid (PMH) front hood panel was verified, and the numerical results showed that this strategy can quickly and accurately select the optimal process parameter settings. Compared with the training set mean value, the objectives were increased by 8.63%, 6.61%, and 9.75%, respectively. Compared to the full AA 5083 hood panel scenario, our design reduces weight by 16.67%, and achievements of 92.54%, 93.75%, and 106.85% were obtained in lateral, longitudinal, and torsional strain energy, respectively. In summary, our proposed methodology demonstrates considerable potential in improving the, highlighting its significant impact on the optimization of structural performance.

Benzohydroxamate and nitrobenzohydroxamate affect membrane order: Correlations between spectroscopic and molecular dynamics to approach tuberculosis.

This work correlates the effects of benzohydroxamate (BH) and nitrobenzohydroxamate (NBH) anions in two membrane models which may be used for anti-tuberculosis (anti-TB) spectroscopic studies and/or computational studies. Firstly, the BH and NBH influence in the physico-chemical properties of soy asolectin (ASO)-based large multilamellar vesicles (MLVs) were evaluated by spectroscopic and calorimetric studies. In parallel, the BH and NBH interaction with a Mycobacterium tuberculosis (Mtb) inner membrane model, composed of phosphatidyl-myo-inositol-dimannoside (PIM2), was investigated by molecular dynamics (MD) simulations. Spectroscopic data showed a localization of BH close to the lipid phosphate group, while NBH was found close to the choline region. The BH ordered the ASO choline, phosphate and carbonyl regions and disrupted the acyl methylenes, reducing the membrane packing of the lipid hydrophobic region. On the other hand, NBH showed an ordering effect in all the lipid groups (polar, interface and hydrophobic ones). By MD studies, it was found that NBH enhanced the stability of the PIM2 membrane more than BH, while also being positioned closer to its mannosyl oxygens. As in ASO MLVs, BH was localized close to the PIM2 phosphate group and disrupted its acyl chains. However, higher values of lateral diffusion were observed for NBH than BH. Despite this, BH and NBH increased the membrane thickness by 35 %, which suggests a global ordering effect of both drugs. Findings of this work reinforce the accordance and complementarity between MLVs based on ASO and the PIM2 MD model results to study the drug effects in Mtb membrane properties.

Risk of falls or fall-related injuries associated with potentially inappropriate medication use among older adults with dementia.

BACKGROUND: Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. METHODS: The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. RESULTS: During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39-1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1-14 days: IRR = 2.76, 95% CI = 2.31-3.28; 15-28 days: IRR = 1.95, 95% CI = 1.48-2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01-1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. CONCLUSION: Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls.

National patterns of paroxetine use among US Medicare patients from 2015-2020.

Introduction: Paroxetine is an older "selective" serotonin reuptake inhibitor (SSRI) that is notable for its lack of selectivity, resulting in an anticholinergic adverse-effect profile, especially among older adults (65+). Methods: Paroxetine prescription rates and costs per state were ascertained from the Medicare Specialty Utilization and Payment Data. States' annual prescription rate, corrected per thousand Part D enrollees, outside a 95% confidence interval were considered significantly different from the average. Results: Nationally, there was a steady decrease in population-corrected paroxetine prescriptions (-34.52%) and spending (-29.55%) from 2015-2020 but a consistent, five-fold state-level difference. From 2015-2020, Kentucky (194.9, 195.3, 182.7, 165.1, 143.3, 132.5) showed significantly higher prescriptions rates relative to the national average, and Hawaii (42.1, 37.9, 34.3, 31.7, 27.7, 26.6) showed significantly lower prescription rates. North Dakota was often a frequently elevated prescriber of paroxetine (2016: 170.7, 2018: 143.3), relative to the average. Neuropsychiatry and geriatric medicine frequently prescribed the most paroxetine, relative to the number of providers in that specialty, from 2015-2020. Discussion: Despite the American Geriatrics Society's prohibition against paroxetine use in older adults and many effective treatment alternatives, paroxetine was still commonly used in the US in this population, especially in Kentucky and North Dakota and by neuropsychiatry and geriatric medicine. These findings provide information on the specialty types and states where education and policy reform would likely have the greatest impact on improving adherence to the paroxetine prescription recommendations.

The role of Pim-1 kinases in inflammatory signaling pathways.

OBJECTIVE AND DESIGN: This observational study investigated the regulatory mechanism of Pim-1 in inflammatory signaling pathways. MATERIALS: THP-1, RAW 264.7, BV2, and Jurkat human T cell lines were used. TREATMENT: None. METHODS: Lipopolysaccharide (LPS) was used to induce inflammation, followed by PIM1 knockdown. Western blot, immunoprecipitation, immunofluorescence, and RT-PCR assays were used to assess the effect of PIM1 knockdown on LPS-induced inflammation. RESULTS: PIM1 knockdown in macrophage-like THP-1 cells suppressed LPS-induced upregulation of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B p65 (NF-κB p65). It also suppressed upregulation of inhibitor of NF-κB kinase α/ß and enhanced the nuclear translocation of NF-κB p65. Moreover, it inhibited the upregulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and cleavage of caspase-1 induced by co-treatment of LPS with adenosine triphosphate. Additionally, p-transforming growth factor-ß-activated kinase 1 (TAK1) interacted with Pim-1. All three members of Pim kinases (Pim-1, Pim-2, and Pim-3) were required for LPS-mediated inflammation in macrophages; however, unlike Pim-1 and Pim-3, Pim-2 functioned as a negative regulator of T cell activity. CONCLUSIONS: Pim-1 interacts with TAK1 in LPS-induced inflammatory responses and is involved in MAPK/NF-κB/NLRP3 signaling pathways. Additionally, considering the negative regulatory role of Pim-2 in T cells, further in-depth studies on their respective functions are needed.

Facile Polymer of Intrinsic Microporosity-Modified Separator with Quite-Low Loading for Enhanced-Performance Lithium Metal Batteries.

Lithium metal batteries (LMBs) using Li metals as anodes are conspicuous for high-energy-density energy-storage devices. However, the nonuniform deposition of Li+ ions leading to uncontrolled Li dendrite growth, which adversely affects electrochemical performance and safety, has impeded the practical application of lithium metal batteries (LMBs). Herein, PIM-1, a type of polymer of intrinsic microporosity (PIM), was utilized for surface engineering of conventional polyolefin separators. This process resulted in the formation of a continuous and homogeneous coating across the separator, facilitating uniform Li+ ion flux and deposition, and consequently reducing dendrite formation. Notably, the loading mass was quite low (0.6 g/m2) through the convenient dipping method. The intrinsic micropores and polar groups (cyano and ether groups) of PIM-1 greatly improved the electrolyte wettability and ionic conductivity of commercial polypropylene (PP) separators. And the PIM-1 coating guided Li+ flux to achieve uniform Li deposition. Moreover, the polar groups (cyano and ether groups) of PIM-1 are beneficial to the desolvation of Li+-solvates. As a result, the synergetic effect of uniform Li+ flux, desolvation, and enhanced mechanical strength of separators brings about considerable improvement in cycle life, suppression of Li dendrite, and Coulombic efficiency for LMBs. As this surface engineering is simple, relatively low-cost, and effective, this work provides fresh insights into separators for LMBs.

Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.

A key step in platelet production is the migration of megakaryocytes to the vascular sinusoids within the bone marrow. This homing is mediated by the chemokine CXCL12 and its receptor CXCR4. CXCR4 is also a positive regulator of platelet activation and thrombosis. Pim-1 kinase has been shown to regulate CXCR4 signalling in other cell types, and we have previously described how Pim kinase inhibitors attenuate platelet aggregation to CXCL12. However, the mechanism by which Pim-1 regulates CXCR4 signalling in platelets and megakaryocytes has yet to be elucidated. Using human platelets, murine bone marrow-derived megakaryocytes, and the megakaryocyte cell line MEG-01, we demonstrate that pharmacological Pim kinase inhibition leads to reduced megakaryocyte and platelet function responses to CXCL12, including reduced megakaryocyte migration and platelet granule secretion. Attenuation of CXCL12 signalling was found to be attributed to the reduced surface expression of CXCR4. The decrease in CXCR4 surface levels was found to be mediated by rapid receptor internalisation, in the absence of agonist stimulation. We demonstrate that pharmacological Pim kinase inhibition disrupts megakaryocyte and platelet function by reducing constitutive CXCR4 surface expression, decreasing the number of receptors available for agonist stimulation and signalling. These findings have implications for the development and use of Pim kinase inhibitors for the treatment of conditions associated with elevated circulating levels of CXCL12/SDF1α and increased thrombotic risk.

Targeting prostate cancer via therapeutic targeting of PIM-1 kinase by Naringenin and Quercetin.

PIM-1 kinase belongs to the Ser/Thr kinases family, an attractive therapeutic target for prostate cancer. Here, we screened about 100 natural substances to find potential PIM-1 inhibitors. Two natural compounds, Naringenin and Quercetin, were finally selected based on their PIM-1 inhibitory potential and binding affinities. The docking score of Naringenin and Quercetin with PIM-1 is -8.4 and - 8.1 kcal/mol, respectively. Fluorescence binding studies revealed a strong affinity (Ka values, 3.1 × 104 M-1 and 4.6 × 107 M-1 for Naringenin and Quercetin, respectively) with excellent IC50 values for Naringenin and Quercetin (28.6 µM and 34.9 µM, respectively). Both compounds inhibited the growth of prostate cancer cells (LNCaP) in a dose-dependent manner, with the IC50 value of Naringenin at 17.5 µM and Quercetin at 8.88 µM. To obtain deeper insights into the PIM-1 inhibitory effect of Naringenin and Quercetin, we performed extensive molecular dynamics simulation studies, which provided insights into the binding mechanisms of PIM-1 inhibitors. Finally, Naringenin and Quercetin were suggested to serve as potent PIM-1 inhibitors, offering targeted treatments of prostate cancer. In addition, our findings may help to design novel Naringenin and Quercetin derivatives that could be effective in therapeutic targeting of prostate cancer.

High rate of potentially inappropriate medication use in older people: a case-control study.

Annually, 172 million fall events cause temporary or permanent impairment in older adults, and this number is increasing. Contributing factors that increase the risk for falls include age, polypharmacy, and malnutrition. This study evaluated medications mainly included in the EU(7)-PIM (potentially inappropriate medication) list. From March 21, 2022, to July 6, 2022, 945 patients who experienced a fall and visited the Department of Emergency Medicine at the Albert Szent-Györgyi Health Centre of the University of Szeged in Hungary. Data from 886 patients were collected (study group). The control group included 1364 patient data collected from three general practice in Hungary. The use of ≥ 2 EU(7)-PIM drugs was found to be associated with increased risk for falls (adjusted odds ratio [AOR], 1.38; 95% confidence interval [CI] 1.01-1.88). Piracetam (AOR, 1.81; 95% CI, 1.28-2.57) and trimetazidine (AOR, 1.62; 95% CI, 1.17-2.24) were associated with increased risk for falls. Doxazosin was associated with a low risk for falls (AOR, 0.59; 95% CI, 0.41-0.86). Tiapride (AOR, 3.54; 95% CI, 1.75-7.17), gliclazide (AOR, 1.57; 95% CI, 1.02-2.43), and vinpocetine (AOR, 1.95; 95% CI, 1.29-2.95) are not included in the EU(7)-PIM list; however, they are associated with increased risk for falls. Long-acting benzodiazepines (AOR, 1.79; 95% CI, 1.20-2.68), antidepressants (AOR, 1.89; 95% 95% CI, 1.37-2.61), serotonin-norepinephrine reuptake inhibitor (AOR, 2.82; 95% CI, 1.41-5.67; p < 0.01), and selective serotonin reuptake inhibitor (AOR, 1.88; 95% CI, 1.24-2.85) were also associated with increased risk for falls. However, Z-drugs were associated with a low risk for falls (AOR, 0.57; 95% CI, 0.36-0.92). With the help of this tool, trimetazidine and piracetam are filtered as EU(7)-PIM drugs associated with increased risk for falls.

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification.

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

Efficient Data Transfer and Multi-Bit Multiplier Design in Processing in Memory.

Processing in Memory based on memristors is considered the most effective solution to overcome the Von Neumann bottleneck issue and has become a hot research topic. The execution efficiency of logical computation and in-memory data transmission is crucial for Processing in Memory. This paper presents a design scheme for data transmission and multi-bit multipliers within MAT (a data storage set in MPU) based on the memristive alternating crossbar array structure. Firstly, to improve the data transfer efficiency, we reserve the edge row and column of the array as assistant cells for OR AND (OA) and AND data transmission logic operations to reduce the data transfer steps. Furthermore, we convert the multipliers into multi-bit addition operations via Multiple Input Multiple Output (MIMO) logical operations, which effectively improves the execution efficiency of multipliers. PSpice simulation shows that the proposed data transmission and multi-bit multiplier solution has lower latency and power consumption and higher efficiency and flexibility.

PIM kinase inhibitors: an updated patent review (2016-present).

INTRODUCTION: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer. AREAS COVERED: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted. EXPERT OPINION: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

UM171 suppresses breast cancer progression by inducing KLF2.

PURPOSE: Breast cancer is the most frequent cancer in women with significant death rate. Morbidity is associated with drug resistance and metastasis. Development of novel drugs is unmet need. The aim of this study is to show potent anti-neoplastic activity of the UM171 compound on breast cancer cells and its mechanism of action. METHODS: The inhibitory effect of UM171 on several breast cancer (BC) cell lines was examined using MTT and colony-forming assays. Cell cycle and apoptosis assays were utilized to determine the effect of UM171 on BC cell proliferation and survival. Wound healing scratch and transwell migration assays were used to examine the migration of BC cell lines in culture. Xenograft of mouse model with 4T1 cells was used to determine inhibitory effect of UM171 in vivo. Q-RT-PCR and western blotting were used to determine the expression level of genes effected by UM171. Lentivirus-mediated shRNAs were used to knockdown the expression of KLF2 in BC cells. RESULTS: UM171 was previously identified as a potent agonist of human hematopoietic stem cell renewal and inhibitor of leukemia. In this study, UM171 was shown to inhibit the growth of multiple breast cancer cell lines in culture. UM171-mediated growth inhibition was associated with the induction of apoptosis, G2/M cell cycle arrest, lower colony-forming capacity, and reduced motility. In a xenotransplantation model of mouse triple-negative breast cancer 4T1 cells injected into syngeneic BALB/c mice, UM171 strongly inhibited tumor growth at a level comparable to control paclitaxel. UM171 increased the expression of the three PIM genes (PIM1-3) in breast cancer cells. Moreover, UM171 strongly induced the expression of the tumor suppressor gene KLF2 and cell cycle inhibitor P21CIP1. Accordingly, knockdown of KLF2 using lentivirus-mediated shRNA significantly attenuated the growth suppressor activity of UM171. As PIM1-3 act as oncogenes and are involved in breast cancer progression, induction of these kinases likely impedes the inhibitory effect of KLF2 induction by UM171. Accordingly, combination of UM171 with a PAN-PIM inhibitor LGH447 significantly reduced tumor growth in culture. CONCLUSION: These results suggested that UM171 inhibited breast cancer progression in part through activation of KLF2 and P21. Combination of UM171 with a PAN-PIM inhibitor offer a novel therapy for aggressive forms of breast cancer.

Participatory irrigation management, social capital, and efficiency in rice production. Understanding the linkage in the case of irrigated rice farms in Northern Thailand.

Enforcement of rules to increase farmers' involvement in participatory irrigation management (PIM) has been ineffective given the non-exclusivity nature of surface irrigation. In this study, we investigated the interrelationship of the social capital's role in higher participation in PIM and the effects towards farmers' efficiency using the case of rice farmers in Northern Thailand. We found that higher intention to participate in PIM collective activities is largely driven by the water user's social capital endowments. Farmers' efficiency level is positively associated with PIM participation and the condition of the collective irrigation management. Our findings suggest the importance of complementing current government efforts with policy interventions focusing on strengthening water user groups' social capital, such as improving group cohesion and their capacity for networking in compensating for various impediments faced by farmers.

Enhancing Medication Safety through Implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in Ambulatory Older Adults.

INTRODUCTION: To promote optimal healthcare delivery, safeguarding older adults from the risks associated with inappropriate medication use is paramount. OBJECTIVE: This study aims to evaluate the effectiveness of implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in ambulatory older adults to enhance medication safety. METHOD: The QTRIM was developed by an expert consensus panel using the Beers Criteria and contained a list of potentially inappropriate medications (PIMs) based on the local formulary. Using quality improvement methodology, it was piloted and implemented in two outpatient pharmacy settings serving geriatric medicine and dermatology clinics at Rumailah Hospital, Qatar. Key performance indicators (KPIs) using implementation documentation as a process measure and the percentage reduction in PIM prescriptions as an outcome measure were assessed before and after QTRIM implementation. This study was conducted between July 2022 and September 2023. RESULTS: In the outpatient department (OPD) geriatric pharmacy, the prescription rate of PIMs was reduced from an average of 1.2 ± 0.7 PIMs per 1000 orders in 2022 to an average of 0.8 ± 0.2 PIMs per 1000 orders in 2023. In the OPD geriatric pharmacy, the results showed a 66.6% reduction in tricyclic antidepressants (TCAs) (from 30 to 10), a reduction in first-generation antihistamines by 51.7% (29 to 14), and muscle relaxants by 33.3% (36 to 24). While in dermatology, the older adult prescription rate of PIMs was reduced from an average of 8 ± 3 PIMs per 1000 orders in 2022 to a rate of 5 ± 3 PIMs per 1000 orders in 2023; the most PIM reductions were (49.4%) in antihistamines (from 89 to 45), while muscle relaxants and TCAs showed a minimal reduction. CONCLUSIONS: Implementing QTRIM with pharmacy documentation monitoring markedly reduced the PIMs dispensed from two specialized outpatient pharmacies serving older adults. It may be a promising effective strategy to enhance medication safety in outpatient pharmacy settings.

NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation.

INTRODUCTION: Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown. MATERIALS AND METHODS: To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline-inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T-ALL cells. RESULTS: NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto-oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB-induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T-ALL cells by inactivating the pro-apoptotic protein BCL2-associated agonist of cell death (BAD). CONCLUSION: We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion-positive leukemia.

PVDF-HFP-based polymer inclusion membrane functionalized with D2EHPA for the selective extraction of bismuth(III) from sulfate media.

This study is the first application of a PVDF-HFP-based polymer inclusion membrane incorporating the poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and di(2-ethylhexyl)phosphoric acid (D2EHPA) as the base polymer and extractant for the extraction of bismuth(III), respectively. It is demonstrated that the PIM comprised of 60 wt% PVDF-HFP and 40 wt% D2EHPA is the most effective in the extraction of bismuth(III) from feed solution containing 20 mg L-1 bismuth(III) and 0.2 mol L-1 sulfate adjusted to pH 1.4. The extracted bismuth(III) ions are back-extracted quantitatively to the receiving solution containing 1 mol L-1 sulfuric acid. The stoichiometry experiments reveal that the Bi: D2EHPA ratio in the bismuth(III) extracted complex is 1:6, and D2EHPA is dimer. Moreover, it is shown that the studied PIM has high selectivity in the extraction of bismuth(III) over other interfering ions such as Mo(VI), Cr(III), Al(III), Fe(III), Ni(II), Zn(II), Cd(II), Co(II), Cu(II), and Mn(II). The interference of Fe(III) is also eliminated by masking with fluoride, leading finally to a nearly pure extraction of bismuth(III).

Nutritional status and clinical outcomes of brain tumor surgery in pediatric intensive care unit: A prospective cohort study.

BACKGROUND: To determine whether nutritional status affects mortality and length of stay in the pediatric intensive care unit (PICU) after brain tumor surgery. METHODS: Subjects aged 2 months to 13 years with brain tumor surgery were included in the study. Z-scores of BMI for age, weight for age, and weight for length were calculated at admission. Undernutrition was defined as Z-score < -2. Nutritional intake was measured daily by a clinical nutritionist. Outcomes to be measured included duration of hospitalization and mortality. Regression analyses was used to investigate the relationship between nutritional variables and outcomes. RESULTS: A total of 63 patients met the inclusion criteria. Undernutrition at admission was found in 33% of subjects based on Z-scores of BMI and weight for length. The mortality rate was 17.5%. Calorie and protein intake was <50% of the target in 50.7% and 42.8 % of children, respectively. Undernutrition by weight for age Z-score, BMI for age and weight for length Z-scores, and low protein intake increased mortality risk by 5, 5.9 and 4.7 times, respectively. The risk of shorter PICU-free days was independently 80% and 90% lower in those receiving <50% of protein and calorie requirements. CONCLUSION: Undernutrition at admission is prevalent in children undergoing brain tumor surgery and is associated with a higher risk of mortality. Caloric and protein intake during hospitalization is generally low, leading to longer PICU stay.