Initial Studies Research Articles

Direct modulation of TRPC ion channels by Gα proteins.

GPCR-Gi protein pathways are involved in the regulation of vagus muscarinic pathway under physiological conditions and are closely associated with the regulation of internal visceral organs. The muscarinic receptor-operated cationic channel is important in GPCR-Gi protein signal transduction as it decreases heart rate and increases GI rhythm frequency. In the SA node of the heart, acetylcholine binds to the M2 receptor and the released Gβγ activates GIRK (I(K,ACh)) channel, inducing a negative chronotropic action. In gastric smooth muscle, there are two muscarinic acetylcholine receptor (mAChR) subtypes, M2 and M3. M2 receptor activates the muscarinic receptor-operated nonselective cationic current (mIcat, NSCC(ACh)) and induces positive chronotropic effect. Meanwhile, M3 receptor induces hydrolysis of PIP2 and releases DAG and IP3. This IP3 increases intracellular Ca2+ and then leads to contraction of GI smooth muscles. The activation of mIcat is inhibited by anti-Gi/o protein antibodies in GI smooth muscle, indicating the involvement of Gαi/o protein in the activation of mIcat. TRPC4 channel is a molecular candidate for mIcat and can be directly activated by constitutively active Gαi QL proteins. TRPC4 and TRPC5 belong to the same subfamily and both are activated by Gi/o proteins. Initial studies suggested that the binding sites for G protein exist at the rib helix or the CIRB domain of TRPC4/5 channels. However, recent cryo-EM structure showed that IYY58-60 amino acids at ARD of TRPC5 binds with Gi3 protein. Considering the expression of TRPC4/5 in the brain, the direct G protein activation on TRPC4/5 is important in terms of neurophysiology. TRPC4/5 channels are also suggested as a coincidence detector for Gi and Gq pathway as Gq pathway increases intracellular Ca2+ and the increased Ca2+ facilitates the activation of TRPC4/5 channels. More complicated situation would occur when GIRK, KCNQ2/3 (IM) and TRPC4/5 channels are co-activated by stimulation of muscarinic receptors at the acetylcholine-releasing nerve terminals. This review highlights the effects of GPCR-Gi protein pathway, including dopamine, μ-opioid, serotonin, glutamate, GABA, on various oragns, and it emphasizes the importance of considering TRPC4/5 channels as crucial players in the field of neuroscience.

Placing the keystone: the LIMBIC Military and Tactical Athlete Research Study

ABSTRACT Objective The LIMBIC Military and Tactical Athletic Research Study (MATARS) framework was established to confirm and extend understanding of concussion with initial studies driven by clinical data collected between 2015 and 2020 in a collegiate sports setting. The LIMBIC MATARS framework will be leveraged to apply gold-standard and innovative research designs to advance the science of concussion. This manuscript provides the background, methodology, and initial demographic data associated with the LIMBIC MATARS. Methods Consensus-based common data elements were used to conduct a retrospective chart review, specific to collegiate athletes diagnosed with concussions between 2015 and 2020 at 11 universities. Results A final sample of 1,311 (47.8% female) concussions were diagnosed during the five-year study period from athletes participating in a variety of National Collegiate Athlete Association (NCAA) sports. The LIMBIC MATARS demographic data, align with the NCAA and other pioneering multi-site concussion-related studies in terms of biological sex, race and ethnicity, and sport participation. Conclusion This pragmatic, methodological approach was used to address several a priori hypotheses related to concussion, align with other multi-site studies of concussion, and establish a consortium for future investigations.

Thermal analysis of AISI 1020 low carbon steel plate agglutinated by gas tungsten arc welding technique: a computational study of weld dilution using finite element method

An important goal in a number of optimization studies is a high-quality weld joint. Thermal analysis of AISI 1020 low carbon steel plate agglutinated by gas tungsten arc welding technique was carried out using S 2021 version. With SOLIDWORKS Premium, the simulation was run. The simulation was performed using the Thermal Simulation programme with 20 weld runs. With the findings of the initial study serving as a sensor, a design study was conducted. A total of 15 runs were completed, and the weld dilution and thermal conductivity responses were available. A range of welding temperatures including 3397 to 3688 °C were experimentally applied in the joining process of AISI 1020 low carbon steel plate of 10 mm thickness, and a strain gauge indicator was used to measure the thermal stresses induced in the steel plate. However, minimum and maximum weld dilution values of 73.1 and 46.8% were obtained with FEM at an input of arc heat of 66.4 and 37.2 J/mm, while the minimum and maximum weld dilution values of 71.55 and 45.5% were computed using experimental approach at the same heat input. On the other hand, maximum and minimum weld dilution of 71.55 and 44.5% were computed from experimental process at minimum and maximum welding current of 199.77 and 250.23 A, while 73.1 and 46.8% were obtained for the maximum and minimum weld dilution through FEM procedure at the same welding input variables. Hence, gas tungsten arc welding input parameters should be properly selected and controlled during welding operation, in order to minimize thermal effects and welding flaws such as high dilution rate.

Spectroscopic Study on the Complexation of trivalent Actinide and Lanthanide ions with TEDGA in Solution

AbstractNMR spectroscopy studies on the complexation of La(III), Sm(III), Lu(III), Y(III) and Am(III) with N,N,N′,N′‐tetraethyldiglycolamide (TEDGA) have been performed. Initial studies concerning the stoichiometry of the complexes prove the formation of [M(TEDGA)3]3+ in D2O and [M(TEDGA)1‐3]3+ in CD3CN. Decreasing the solvent polarity translates to an increase of the complex stability as shown by complementary TRLFS studies with Cm(III). Due to delocalization of the lone electron pair of the amide nitrogen atom, the M(III)−O interaction has been studied indirectly by collecting 13C and 15N NMR data. The observed chemical shifts prove that the interaction of the trivalent ions, An(III) and Ln(III), and TEDGA is almost identical.

Quality Initiative Program to Improve the Percentage of Very Preterm Neonates Receiving Expressed Breast Milk Within 24 Hours of Birth in a Tertiary Care (Level III-B) NICU

Background There is often a delay in the initiation of feeding in preterm babies and more dependence on PDHM milk due to the non-availability of the mother’s own milk. This study aimed to increase the percentage of very preterm neonates receiving expressed breast milk (EBM) within 24 hours of birth. Methods A quality improvement (QI) initiative study was conducted from May 2022 to August 2022 in a tertiary care (Level III-B) NICU. A QI support team was formed. The reasons for the delay in the initiation of expression of breastmilk were evaluated. We included preterm neonates (<32 weeks gestation) born within the study period. Antenatal and postnatal counseling regarding the expression of breast milk, using leaflets and video, frequent visits, telephonic reminders, and emphasizing Kangaroo Mother Care through various Plan-Do-Study-Act cycles were done. Results A total of 17 very preterm babies were studied over a period of 3 months. The percentage of preterm receiving EBM within 24 hours of birth, increased from 20% (observation phase) to 83.3% (initiation phase) and maintained to 90% in the continuation phase. The time of receiving the first EBM reduced from a median of 32.5 hours (1.35 days) in the retrospective phase to 17 hours (0.7 days) during the initiation phase and it was sustained later on. Mothers were able to express as early as within 4.5 hours. Conclusion A simple QI intervention showed early expression and sustenance of breast milk in mothers of preterm neonates.

Improving polygenic risk prediction in admixed populations by explicitly modeling ancestral-differential effects via GAUDI

Polygenic risk scores (PRS) have shown successes in clinics, but most PRS methods focus only on participants with distinct primary continental ancestry without accommodating recently-admixed individuals with mosaic continental ancestry backgrounds for different segments of their genomes. Here, we develop GAUDI, a novel penalized-regression-based method specifically designed for admixed individuals. GAUDI explicitly models ancestry-differential effects while borrowing information across segments with shared ancestry in admixed genomes. We demonstrate marked advantages of GAUDI over other methods through comprehensive simulation and real data analyses for traits with associated variants exhibiting ancestral-differential effects. Leveraging data from the Women’s Health Initiative study, we show that GAUDI improves PRS prediction of white blood cell count and C-reactive protein in African Americans by > 64% compared to alternative methods, and even outperforms PRS-CSx with large European GWAS for some scenarios. We believe GAUDI will be a valuable tool to mitigate disparities in PRS performance in admixed individuals.

The Role of FNDC5/Irisin in Cardiovascular Disease.

Disorders of cardiomyocyte metabolism play a crucial role in many cardiovascular diseases, such as myocardial infarction, heart failure and ischemia-reperfusion injury. In myocardial infarction, cardiomyocyte metabolism is regulated by mitochondrial changes and biogenesis, which allows energy homeostasis. There are many proteins in cells that regulate and control metabolic processes. One of them is irisin (Ir), which is released from the transmembrane protein FNDC5. Initial studies indicated that Ir is a myokine secreted mainly by skeletal muscles. Further studies showed that Ir was also present in various tissues. However, its highest levels were observed in cardiomyocytes. Ir is responsible for many processes, including the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) by increasing the expression of thermogenin (UCP1). In addition, Ir affects mitochondrial biogenesis. Therefore, the levels of FNDC5/Ir in the blood and myocardium may be important in cardiovascular disease. This review discusses the current knowledge about the role of FNDC5/Ir in cardiovascular disease.

Proposing an Approach for the Diffusion of Building Integrated Photovoltaics (BIPVs)—A Case Study

Consistent probing into building integrity has led to the exploration of clean energy options such as building integrated photovoltaic (BIPV). BIPV has proven to be aesthetically pleasing, architecturally feasible, and capable of making buildings energy producers instead of mere energy consumers. Despite the enormous benefits of BIPV, its adoption and diffusion have been relatively sluggish and remain far below expectations, especially in developing countries like Ghana. This empirical study aims to assess the impact of advertising on BIPV awareness in Ghana. It also highlights the aesthetic preferences of various respondents. The study uses online surveys to gather quantitative data from 412 respondents across all 16 regions of the country. An initial study conducted on the awareness of BIPV in Ghana indicated a low rate of awareness. Therefore, a sensitisation poster and architectural visualization (AV) were adopted to boost awareness across all 16 regions of the country. Awareness of BIPV increased from 18% to 79.5% after the introduction of the sensitisation poster. Also, 88.8% of the respondents preferred BIPV to Building Applied Photovoltaic (BAPV) mainly because of aesthetics (beauty) and the cost benefits. The respondents indicated that aesthetics is paramount when choosing solar panels for their homes. This study therefore recommends high investment in awareness creation, development of specific design guidelines for BIPV applications and establishment of demo projects in developing countries. The findings of this study contribute to the existing literature on BIPV adoption and may be useful for BIPV manufacturers, marketers, government, and other stakeholders as it provides evidence on the often-neglected approach to BIPV diffusion.

A novel computational workflow to holistically assess total knee arthroplasty biomechanics identifies subject-specific effects of joint mechanics on implant fixation

Computational studies of total knee arthroplasty (TKA) often focus on either joint mechanics (kinematics and forces) or implant fixation mechanics. However, such disconnect between joint and fixation mechanics hinders our understanding of overall TKA biomechanical function by preventing identification of key relationships between these two levels of TKA mechanics. We developed a computational workflow to holistically assess TKA biomechanics by integrating musculoskeletal and finite element (FE) models. For our initial study using the workflow, we investigated how tibiofemoral contact mechanics affected the risk of failure due to debonding at the implant-cement interface using the four available subjects from the Grand Challenge Competitions to Predict In Vivo Knee Loads. We used a musculoskeletal model with a 12 degrees-of-freedom knee joint to simulate the stance phase of gait for each subject. The computed tibiofemoral joint forces at each node in contact were direct inputs to FE simulations of the same subjects. We found that the peak risk of failure did not coincide with the peak joint forces or the extreme tibiofemoral contact positions. Moreover, despite the consistency of joint forces across subjects, we observed important variability in the profile of the risk of failure during gait. Thus, by a combined evaluation of the joint and implant fixation mechanics of TKA, we could identify subject-specific effects of joint kinematics and forces on implant fixation that would otherwise have gone unnoticed. We intend to apply our workflow to evaluate the impact of implant alignment and design on TKA biomechanics.

Teachers’ digital literacy overview in secondary school

<span lang="EN-US">This study explored the teachers’ digital literacy in secondary school and deciphered the most suggested way of enhancing secondary teachers’ digital literacy, overview levels, and the trends factors in the last five years of research. The methodologies in this study employed the traditional systematic literature review (SLR), which compiled some previous studies to be examined. The initial studies were only selected from an article published in a reputable journal indexed by Scopus. Of the 118 articles reviewed, 46 were selected to be included in the analysis. Significant findings summarize the fact that most of the last five-year research about teachers in secondary schools was impacted by the rapid development of technology and the demand for 21st-century skills. To summarize, as it is at the intermediate level, most secondary school teachers are digitally literate. However, future research may evaluate digital literacy training programs for teachers to assess what improvements should be made to delivery as well as existing frameworks used to test teachers’ digital literacy.</span>

Ad libitum feeding systems for lactating sows: effects on productivity and welfare of sows and piglets

The nutritional requirements of sows change during lactation and thus require adapted and dynamic feeding regimes that consider the sows’ behavioral needs and production traits. The present study evaluated the effect of four different feeding systems on productivity and aspects of the welfare of 61 sows and their piglets during lactation. A non-ad libitum system (CON) was compared with two computer-monitored (COMP, COMP + ) ad libitum feeding systems, that allowed sows to access feed via displacement of an electronic sensor, as well as a third purely mechanical ad libitum feeding system (MECH). Daily feed disappearance, piglet growth, piglet growth per feed disappearance as well as sows’ weight and conception rate were recorded. Health indicators of sows and piglets were scored as well as sow behavior analyzed for a total of 96 hours/sow from video recordings taken on days 2–4 and 23 postfarrowing (n = 35 sows). Sows from all three ad libitum systems (COMP, COMP+, MECH) showed a lower feed disappearance than CON (P < 0.01). Additionally, average daily piglet growth tended to be higher (P = 0.05) and piglet growth per sow feed disappearance was significantly higher in all three ad libitum systems than in CON (P < 0.01). Piglet mortality, sow weight loss and subsequent conception rates did not differ between treatment groups. Piglets in COMP and COMP + had fewer head lesions (P = 0.01). Sows in all three ad libitum systems spent more time with their head in the trough than in the non-ad libitum system (P < 0.01). Occurrence of sow stereotypies (vacuum chewing, biting fixtures) was rare (typically < 2% of scans) and did not differ between treatments. Our data suggest that sows fed ad libitum eat what they need and can convert feed more efficiently into the piglets’ growth without additional weight loss. Furthermore, the increased time sows spent in ad libitum systems with their head in the trough points toward longer feeding times, which might be beneficial in terms of meeting pigs’ behavioral need to forage. Taken together, our initial studies on sow feeding behavior and feed efficiency will benefit the development of new lactation feeding systems that promise to improve animal welfare and productivity while reducing feed costs.

Street Art as a Tool for Social Dialogue: A Case Study of Tula

This article is a comprehensive study of the role of street art as a tool of social dialogue, focusing primarily on the urban environment of Tula. Starting with an in-depth study of the historical roots and modern consequences of street art, the evolution of this art form is considered in the context of social dynamics and change. Street art emerges as a hybrid space balancing personal self-expression with public interests, emphasizing its importance in the development of public discourse, generating social transformations and consolidating historical memory. A detailed study of specific artistic initiatives, works in Tula sheds light on a variety of topics. The research touches on both the historical roots of street art in Tula and its modern manifestations, covering various aspects, from reflecting the urban spirit to its role in shaping public discourse and preserving historical memory. The methodology is based on a comprehensive analysis of street art works, as well as the study of the social and historical contexts of street art in Tula. This study presents a new perspective on street art as a tool for social dialogue and cultural interaction. It reveals how Tula's street art contributes to social change by expressing and strengthening the city's collective identity. The article emphasizes that street art not only reflects current social sentiments, but also serves as a catalyst for social transformation, turning into a living archive of urban history and culture. Special attention is paid to the interaction of art with urban residents, its influence on public opinion and the ability to form a new urban environment conducive to cultural and social development. Specific examples of murals and graffiti, their historical and cultural contexts, as well as the role of these works in creating a dialogue between different social groups are analyzed.

Studies of C2H2F4 and SF6 alternative gas mixtures for HPL RPC detectors for High Energy Physics applications

This research investigates the viability of replacing greenhouse gases C2H2F4 and SF6 with eco-friendly gas mixtures in Resistive Plate Chamber (RPC) detectors used at CERN LHC experiments. The study focuses on the addition of CO2 as a substitute of C2H2F4 to minimize greenhouse gas emissions and reduce operational costs. Initial performance studies with cosmic muons evaluate key parameters such as efficiency, current, streamer probability, prompt charge, cluster size, and time resolution of the detectors. Subsequent assessments take place at the CERN Gamma Irradiation Facility, emulating the LHC experiment background radiation. Furthermore, the study explores alternatives to SF6, including 3M NOVECTM 4710 and AMOLEATM 1224yd, presenting perforances results about these gas alternatives in High Pressure Laminate RPCs.

Abstract IA019: Multiscale systems approach to target tumor ecosystem responses for therapeutic benefit

Abstract Breast tumors arise and progress via processes that involve intrinsic deregulation of epithelial cells and that also alter the composition and function of associated stromal and immune cells. Together, these tumor-intrinsic and microenvironmental changes enable malignant epithelial cells in the tumor to acquire key cancer hallmarks, including proliferation, migration, immune evasion and further evolution. The resulting collection of cancer and stromal cells comprise a complex, adaptive tumor ecosystem. Long-term therapeutic success will require that drugs attack malignant cells, favorably activate the immune system, and create a tumor microenvironment that does not support tumor (re)growth. Creating a process for treatment selection will require an integrated systems biology approach to develop, test and refine a robust computational framework that takes into account the states, signaling relationships, and spatial organization that determine the emergent properties inherent in complex interacting systems. Toward this goal, we have developed a coordinated experimental-computational approach designed to enable identification of effective treatment strategies. To examine therapeutic responses of diverse aspects of the tumor ecosystem, we have deployed a novel drug delivery microdevice that enables rapid, high-throughput assessment of the effects of multiple therapies on tumor cells and the surrounding microenvironment. When coupled with multiplex tissue imaging, this platform provides a comprehensive assessment of the state and spatial organization of the tumor ecosystem as it adapts to therapy. Initial studies demonstrated that many drugs designed to target malignant epithelial cells strongly impact stromal and immune cells, providing new insights into the importance of considering multiple aspects of the tumor ecosystem when designing effective therapeutic strategies. The resultant data are being used to guide development of a multiscale computational model that considers the functional relationships between different tumor components and can be used to predict the effects of therapies on diverse aspects of tumor ecosystems. In total, our approach has the potential to transform cancer treatments through rational identification of effective therapeutic strategies that lead to long-term durable control of tumors. Citation Format: Laura M. Heiser. Multiscale systems approach to target tumor ecosystem responses for therapeutic benefit [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA019.

Diagnostic Validity of Chronic Kidney Disease in Health Claims Data Over Time: Results from a Cohort of Community-Dwelling Older Adults in Germany.

The validity of ICD-10 diagnostic codes for chronic kidney disease (CKD) in health claims data has not been sufficiently studied in the general population and over time. We used data from the Berlin Initiative Study (BIS), a prospective longitudinal cohort of community-dwelling individuals aged ≥70 years in Berlin, Germany. With estimated glomerular filtration rate (eGFR) as reference, we assessed the diagnostic validity (sensitivity, specificity, positive [PPV], and negative predictive values [NPV]) of different claims-based ICD-10 codes for CKD stages G3-5 (eGFR <60mL/min/1.73m²: ICD-10 N18.x-N19), G3 (eGFR 30-<60mL/min/1.73m²: N18.3), and G4-5 (eGFR <30mL/min/1.73m²: N18.4-5). We analysed trends over five study visits (2009-2019). We included data of 2068 participants at baseline (2009-2011) and 870 at follow-up 4 (2018-2019), of whom 784 (38.9%) and 440 (50.6%) had CKD G3-5, respectively. At baseline, sensitivity for CKD in claims data ranged from 0.25 (95%-confidence interval [CI] 0.22-0.28) to 0.51 (95%-CI 0.48-0.55) for G3-5, depending on the included ICD-10 codes, 0.20 (95%-CI 0.18-0.24) for G3, and 0.36 (95%-CI 0.25-0.49) for G4-5. Over the course of 10 years, sensitivity increased by 0.17 to 0.29 in all groups. Specificity, PPVs, and NPVs remained mostly stable over time and ranged from 0.82-0.99, 0.47-0.89, and 0.66-0.98 across all study visits, respectively. German claims data showed overall agreeable performance in identifying older adults with CKD, while differentiation between stages was limited. Our results suggest increasing sensitivity over time possibly attributable to improved CKD diagnosis and awareness.

Havana Syndrome: A Mysterious Illness or a New Domain of Warfare

Abstract: Havana syndrome cases increased in Cuba at the end of 2016 and early 2017, and the consequences ranged from minor to severe health concerns. In almost all affected individuals, symptoms like difficulty-concentrating, visual issues, brain-fog, memory problems, tinnitus, and sleep-related complaints were reported. Some initial studies pointed the causative possibility towards energy weapons, ultrasound, microwaves, microbes and chemicals. However, to date, no study has provided a comprehensive explanation of this sudden mysterious syndrome, and the root cause remains unexplained.

The risk of prostate cancer diagnosis in men with an elevated PSA but low IsoPSA.

292 Background: IsoPSA is a structure-based serum assay. Initial studies demonstrated that it outperformed total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (i.e., grade group (GG) ≥2) on biopsy. This led to an overall reduction in invasive testing and magnetic resonance imaging (MRI). We sought to compare the risk of csPCa in patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients (n=1578) who underwent IsoPSA testing from November 2016 to August 2022. Data was dichotomized into patients with normal (≤6) and high IsoPSA (&gt;6). We collected the outcomes of any follow-up IsoPSA, prostate biopsy, MRI, and diagnosis of prostate cancer. In the case of multiple follow-up tests, the most recent one was recorded. Results: The median follow-up time of 1578 patients who underwent IsoPSA testing was 24 months (IQR 16-29). Among 541 patients with an initial normal IsoPSA, 60 (11.1%) had a subsequent high IsoPSA, 23 (4.3%) had csPCa on a subsequent biopsy, and 48 (8.9%) had suspicious lesions on MRI (PI-RADS 4-5). Among 1037 patients with an initial high IsoPSA, 366 (35.3%) had csPCa on a subsequent biopsy and 342 (33%) had suspicious lesions on MRI. The sensitivity of IsoPSA to predict csPCa was 94.1%, and its negative predictive value was 89.3%. Conclusions: With 24-month follow-up, 4.3% of patients with normal IsoPSA developed csPCa, suggesting that a low baseline IsoPSA provides durable information about the 2-year risk of csPCa.[Table: see text]

Predictors of Mortality in Methanol Poisoning: A Systematic Review and Meta-analysis

Background: Today, methanol intoxication is increasing. Identifying mortality predictors has a significant correlation with poisoning progress. This meta-analysis study aimed to identify and evaluate mortality predictors for methanol poisoning. Methods: In this study, we searched electronic databases for case-control and cohort studies related to methanol poisoning. The quality of the studies was evaluated using the STROBE checklist. Comprehensive meta-analysis 3 was used to calculate the odds ratio (OR) and 95% CI of the factors present, as well as to perform heterogeneity, sensitivity, and publication bias assessments. Results: In this meta-analysis study, 14 out of 945 initial studies were included. The results identified 15 mortality predictors of methanol poisoning. The risk factors were ranked by the integrated OR values and included venous blood pH (OR=3.79, 95% CI, 2.42%, 5.19%), methanol concentration (OR=1.64, 95% CI, 1.05%, 2.55%), venous carbon dioxide pressure (PCO2) (OR=9.993, 95% CI, 5.80%, 17.18%), base deficit (OR=2.943, 95% CI, 1.20%, 7.165%), hemodialysis time (OR=2.69, 95% CI, 1.35%, 5.35%), blood sugar (OR=9.84, 95% CI=3.86, 25.09), venous bicarbonate (HCO3) (OR=2.97, 95% CI, 1.68%, 5.26%), creatinine (OR=13.10, 95% CI, 2.68%, 64.04%), potassium (K) (OR=3.51, 95% CI, 1.66%, 7.43%), alanine aminotransferase (OR=7.57, 95% CI, 1.03%, 55.57%), sodium (OR=6.69, 95% CI, 1.78%, 25.12%), white blood cells (OR=7.16, 95% CI, 1.42%, 36.16%), coma (OR=32.73, 95% CI, 18.59%, 56.70%), visual disturbances (OR=3.37, 95% CI, 1.59%, 7.16%), and gastrointestinal symptoms (OR=1.94, 95% CI, 1.16%, 3.22%). Conclusion: Identifying mortality predictors and disease progression in methanol intoxication patients can help doctors diagnose patients at risk better and faster to provide effective treatment interventions for them.

The impact of measurement on clinical trials: Comparison of preliminary outcomes of a brief mobile intervention for autistic adults using multiple measurement approaches.

Initial studies of the emotional safety plan (ESP), a new, brief telehealth and mobile intervention to support autistic adults to cope with periods of distress, have reported feasibility and acceptability (Bal et al., 2023, Autism, 1-13). Herein we report the preliminary clinical outcomes of thirty-six autistic adults who developed a personalized ESP, with a specific interest in comparing "outcomes" demonstrated by different instruments and assessment frequencies in order to inform outcome measurement in future clinical trials. Comparison of pre-intervention baseline to post-monitoring outcome (pre-post) anxiety symptoms (Generalized Anxiety Disorder-7 [GAD-7]) and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) revealed medium effect sizes for reduction in symptoms, though, low effect sizes were observed for pre-post Adult Self-report Anxiety and Depressive Problems scales and the Emotion Dysregulation Inventory Reactivity and Dysphoria scales. Weekly assessments showed an initial decrease in GAD-7 anxiety symptoms but no effect on weekly PHQ-9 depressive ratings. Ecological momentary assessment (EMA) data suggested that, when participants reported feeling sad or agitated and used the ESP, reduced negative feelings and increased positive states were reported in subsequent EMA. Perhaps not surprisingly, preliminary outcomes of these feasibility trials differed depending on measure chosen. Implications for the design of clinical trials are discussed.

Utility of cystatin C and serum creatinine-based glomerular filtration rate equations in predicting vancomycin clearance: A population pharmacokinetics analysis in elderly Chinese patients.

Renal function is an important factor affecting the pharmacokinetics of vancomycin. The renal function in elderly patients gradually decreases with age. An accurate estimated glomerular filtration rate (GFR) is essential in drug dosing. The study aimed to determine the most appropriate renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients using population pharmacokinetic analysis. Data were obtained retrospectively from elderly patients aged ≥65years who received vancomycin for infection from September 2016 to January 2022. Renal function was estimated using the Cockcroft-Gault equation (CG), Modification of Diet in Renal Disease equation (MDRD), three Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPIcys-scr , CKD-EPIscr , and CKD-EPIcys ) and two Berlin Initiative Study equations (BIS-1 and BIS-2). The CKD-EPIcys-scr and BIS-2 equations were based on cystatin C (Cys C) and serum creatinine (Scr). The others were based on Cys C or Scr. A nonlinear mixed effects model (NONMEM) was used to develop the population pharmacokinetic model. A total of 471 serum concentrations from 313 elderly patients were used to develop the population pharmacokinetic model. Weight and GFR were identified as significant covariates affecting the pharmacokinetics of vancomycin. Cys C and Scr-based GFR (CKD-EPIcys-scr and BIS-2) yielded significant improvement performance compared with the other equations in model building. The interindividual variability of CL was reduced from 49.4% to 23.6% and 49.4% to 23.7% in CKD-EPIcys-scr and BIS-2 based models, respectively. However, greater interindividual variabilities of CL (from 26.6% to 29.0%) were represented in the other five models which were based on either Cys C or Scr. The GFR estimated by EPIcys-scr and BIS-2 equations and vancomycin CL exhibited a good correlation (r=0.834 and 0.833). In the external validation with 124 serum concentrations, the predictive performances of the CKD-EPIcys-scr and BIS-2 based models (the mean relative prediction errors were less than 1%, the mean relative absolute prediction errors were about 23%) were also superior to the other five models (the mean relative prediction errors were about 2%, the mean relative absolute prediction errors were greater than 25%) which are based on either Cys C or Scr. In this study, we determined that the equation used to estimate GFR can affect the population pharmacokinetic model fitting result. Population pharmacokinetics model with CKD-EPIcys-scr or BIS-2 can be used to optimize vancomycin dosage in elderly Chinese patients.