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Synthesis, Characterization, and Anti-Plasmodium falciparum Activity of a New Copper(II) Complex Containing 2-(Tert-Butoxy)-6-(1H-imidazol-1-yl)pyridine
Patiño-Cubides, Alexander; Velasco-Pareja, María Camila; Macías, Mario A; Yasnot-Acosta, María F; Rodriguez, Ana; Valderrama-Aguirre, Augusto; Hurtado, John J
This work describes the synthesis, characterization, and preliminary evaluation of the anti-Plasmodium falciparum activity of a copper(II) coordination-complex derived from an imidazole-based ligand. This compound was characterized by Infrared, UV-Vis, Raman, high resolution mass spectrometry, fluorescence, Thermogravimetric analysis, and electrical conductivity allowing the elucidation of their structure and which was also confirmed by single-crystal X-ray diffraction. From the crystallographic analysis, it was found that the copper atom is situated in an octahedral environment, with both carboxylate ligands occupying equatorial positions and the ligands L located axially. Interestingly, the acetate ions act as bidentate ligands, but in an anisobidentate binding mode, where the oxygen atoms exhibit different bond distances to the metal center, resulting in asymmetric coordination. This phenomenon is attributed to strong hydrogen bonding within the crystal packing. Biological assays performed to test the complex revealed low hemocytotoxicity, with values ≤20% at concentrations above 500 µg/mL. When evaluated in vitro against Plasmodium falciparum (3D7 strain, chloroquine-sensitive), the complex exhibited significantly higher activity than the free ligand. These findings indicate that coordination to the metal center plays a substantial role in enhancing antiparasitic-activity, providing a solid foundation for future investigations aimed at elucidating the underlying mechanisms and advancing research on the anti-Plasmodium falciparum activity of metal complexes.
PMCID:13243347
PMID: 42252480
ISSN: 1860-7187
CID: 6047982
Meckel's cartilage and SOX9/Scx expression during morphogenesis of the mouse mylohyoid attachment site
Koresawa, Toshihisa; Nagakura, Ryotaro; Jeong, Juhee; Kitamura, Kei; Yotsuya, Mamoru; Sato, Masaki; Chang, Wei-Jen; Abe, Shinichi; Yamamoto, Masahito
Meckel's cartilage is a central structure in mandibular morphogenesis, but how developing muscles establish their attachment to the mandible in relation to Meckel's cartilage remains unclear. In this study, we investigated the fetal development of the mouse mylohyoid attachment site using histological analysis, immunohistochemistry, in situ hybridization, and three-dimensional reconstruction, with particular attention to SOX9 and Scleraxis (Scx), markers associated with cartilage and tendon development. At E13.5, the mylohyoid attachment site was located close to the inferior aspect of Meckel's cartilage, and SOX9-positive mesenchymal cells were observed between the mylohyoid muscle bundle and Meckel's cartilage. During subsequent development, the intramembranous mandibular bone extended into the space between Meckel's cartilage and the mylohyoid attachment site. By E17.5, the mylohyoid attachment site was closely associated with the mandibular bone. SOX9 expression was detected at the developing attachment site from E13.5 to E17.5, whereas Scx mRNA expression was detected transiently and became progressively reduced during this period. Three-dimensional reconstruction further supported the developmental shift in the spatial relationship among Meckel's cartilage, the mandibular bone, and the mylohyoid attachment site. These findings suggest that Meckel's cartilage may serve as a transient anatomical framework associated with early organization of the mylohyoid attachment site before definitive attachment to the mandibular bone is established.
PMID: 42250060
ISSN: 1447-073x
CID: 6047852
Comparative diagnostic accuracy of panic provocation tests: A meta-analysis
Tural, Umit; Shannon, Sara Rose; Iosifescu, Dan V
Panic provocation tests have been widely used to investigate the biological underpinnings of panic disorder (PD). However, their diagnostic specificity remains uncertain, as several agents can also induce panic-like reactions in healthy individuals. This meta-analysis estimated and compared diagnostic odds ratios (DORs) across different provocation methods. Random-effects meta-analyses were conducted using the Hartung-Knapp adjustment. Based on 123 studies including 5693 participants, sodium lactate infusion showed the highest pooled DOR (24.77, 95% CI 19.03-32.25, GRADE certainty = High), followed by isoproterenol (18.85, 95% CI 12.39-28.66, GRADE certainty = Moderate), cholecystokinin tetrapeptide (CCK-4; 15.03, 95% CI 7.83-28.84, GRADE certainty = Moderate), meta-chlorophenyl piperazine (m-CPP; 14.51, 95% CI 4.67-45.07, GRADE certainty = Low), caffeine (14.11, 95% CI 4.79-41.54, GRADE certainty = Moderate), hyperventilation (11.89, 95% CI 6.51-21.73, GRADE certainty = High), carbon dioxide inhalation (CO2; 11.12, 95% CI 8.63-14.32, GRADE certainty = High), and yohimbine (7.87, 95% CI 1.12-55.13, GRADE certainty = Very low). Breath holding, fenfluramine and flumazenil did not demonstrate statistically significant discriminative ability. Meta-regression analysis confirmed that sodium lactate yielded significantly higher DORs than m-CPP, hyperventilation, CO2, fenfluramine, flumazenil, and yohimbine. No substantial between-study heterogeneity or publication bias was identified across the pooled analyses. These findings suggest that provocation methods targeting acid-base balance, especially sodium lactate infusion, are associated with superior diagnostic discrimination between individuals with PD and healthy controls.
PMID: 42190597
ISSN: 1879-1379
CID: 6047962
Acute healthcare and palliative care utilization among hospitalized patients with different levels of functional impairment
Xu, Luyi; Zeng, Li; Bollens-Lund, Evan; Singer, Joshua; Chai, Emily; Sean Morrison, R; Gelfman, Laura P
BACKGROUND:Preadmission functional status has important predictive values for outcomes among hospitalized patients, and may facilitate healthcare resource allocation including early palliative care referral. OBJECTIVES/OBJECTIVE:To compare acute healthcare and palliative care utilization among hospitalized patients with different levels of baseline functional impairment. METHODS:We conducted a retrospective cohort study of adult patients ≥ 18 years discharged from a quaternary academic hospital between July 1, 2022, and December 31, 2024, with baseline functional status assessed on admission via Karnofsky Performance Status (KPS) scale. Using electronic health records and billing data, we collected patients' socio-demographic information, clinical characteristics, and utilization of acute healthcare and palliative care. RESULTS:Among 18,049 patients, baseline functional impairment was classified as mild (KPS 70%-100%): 13,411 (74.3%), moderate (KPS 50%-60%): 2953 (16.4%), severe (KPS30%-40%): 974 (5.4%) and very severe (KPS 10%-20%): 711 (3.9%). Overall, 2089 (11.6%) patients had a intensive care unit (ICU) admission, 1574 (8.7%) received palliative care consultation, and 1021 (5.6%) died in the hospital. In generalized linear models stratified by functional status category, increasing severity of functional impairment was significantly associated with increasing ICU admission, ICU and hospital length of stay, in-hospital mortality, and receipt of palliative care intervention. Mean number of days between admission and palliative care consultation was significantly decreased among patients with very severe impairment when compared with those with mild impairment (5.3 vs. 6.7 days, p < .001). CONCLUSIONS:Baseline functional status assessment may offer an easy-to-measure guide for timely inpatient palliative care intervention among patients at elevated risk for in-hospital morbidity and mortality.
PMID: 42252756
ISSN: 1553-5606
CID: 6048012
Breaking barriers: Validation of a Spanish oral health knowledge tool to enhance patient-provider communication
Spivakovsky, Silvia; Figueroa, Joyce; Ruff, Ryan Richard
OBJECTIVES/OBJECTIVE:This study aimed to develop and validate the Knowledge Related to Oral Health Literacy Spanish (KROHL- S) instrument to assess oral health knowledge among Spanish-speaking adults in the United States, a population facing significant oral health disparities. DESIGN/METHODS:A cross-sectional study was conducted at NYU College of Dentistry. A convenience sample of 175 self-identified Spanish-speaking adults (70% female, mean age 49. 79 years) completed the orally administered KROHL- S questionnaire. Participants, mainly born outside the US (91. 9%), also completed the Comprehensive Measure of Oral Health Knowledge (CMOHK) and a single-item literacy screening tool in Spanish (SILS). Psychometric properties of the KROHL- S, including internal consistency (Cronbach's alpha), discriminant validity (correlation with CMOHK), and known-group validity (comparison across education levels), were evaluated. Confirmatory factor analysis was used to test the original factor structure. RESULTS:The mean KROHL- S score was 8.34 (SD = 5.82), indicating a low level of oral health knowledge in the sample. Internal consistency for the overall KROHL- S was good (Cronbach's alpha = 0.75), and interrater agreement was high. A moderate positive correlation was found between KROHL- S and CMOHK scores (r = 0.49, p < .0001). Participants with higher education levels showed significantly greater oral health knowledge on the KROHL- S. Confirmatory factor analysis suggested an average fit to the data (RMSEA = 0.064, CFI = 0.86, TLI = 0.83). CONCLUSION/CONCLUSIONS:The KROHL- S could be used to assess oral health knowledge among Spanish-speaking adults and incorporates cultural and linguistic aspects, making it suitable for a wider range of individuals. KROHL-S offers a valuable tool for healthcare providers by not only helping identify individuals' knowledge gaps to guide customized educational interventions but also helping enhance patient-provider communications.
PMCID:13241004
PMID: 42247452
ISSN: 1932-6203
CID: 6047842
The Role of Hospitality in Neurosurgery
Dastagirzada, Yosef M; Weiner, Howard L
BACKGROUND:"Business, like life, is all about how you make people feel. It's that simple and it's that hard" says Danny Meyer, the restauranteur and CEO of the Union Square Hospitality Group in New York. Similarly, Maya Angelou famously said that people will never forget how you made them feel, though they may forget what you said or did. In neurosurgery, we are doing two things at once: something very technical and something very human. The core thesis of this hospitality philosophy is that whereas the technical aspect of our job is critically important, it represents 49% of our success. The human aspect of our work represents 51%, ever so slightly more important. SUMMARY/CONCLUSIONS:We will explore how hospitality has impacted the practice of and a career in neurosurgery over a 35-year period, based on the principles outlined by Danny Meyer in his 2006 book Setting the Table. We will define the difference between service, the technical delivery of a product (e.g., a surgical procedure), and hospitality, how the delivery of that service makes someone feel; if someone feels you are on their side, hospitality is present. We will also define the 51% rule for hiring: one is invited onto our team based 49% on technical skill and 51% on these hospitality-related human qualities (optimistic warmth, intelligence, work ethic, empathy, self-awareness, and integrity). KEY MESSAGES/CONCLUSIONS:Hospitality has played a transformative role in a neurosurgery career: in developing a destination academic practice, managing complications, overcoming challenges, and in building an outstanding team. In our opinion, hospitality plays a significant role in pediatric neurosurgery, driving growth in activity and excellence. As Danny says "it takes both great service and great hospitality to rise to the top."
PMCID:13245946
PMID: 41296670
ISSN: 1423-0305
CID: 6047952
T1 Over Squared Proton Density Ratio to Characterize Multiple Sclerosis Lesions
Wright, Sarah J; McKay, Scotty G; Bou, Jean Ramos; Bao, Fen; Truong, Vivian B; Li, Chenyang; Jiang, Li; Memon, Anza B; Haacke, E Mark; Ge, Yulin; Chen, Yongsheng
OBJECTIVE:ratio (TPR) imaging approach and evaluates its ability to characterize MS lesions alongside other quantitative MRI (qMRI) metrics. METHODS:and PD values were used to illustrate TPR contrast. Statistical analyses included Wilcoxon rank-sum tests and Spearman correlations (p < 0.05). RESULTS:* (92 ms) values but lower MTR (37.3%) and MTsat (1.57%) compared to hypointense lesions (1085 ms; 0.88 a.u.; 64 ms; 46%; 2.48%, respectively). QSM values varied across lesion types. INTERPRETATION/CONCLUSIONS:, PD, and MT metrics, consistent with demyelination. In contrast, hypointense lesions may reflect tissue changes associated with repair processes such as remyelination.
PMID: 42252607
ISSN: 2328-9503
CID: 6047992
Understanding sugar-sweetened beverage tax implementation globally: a 34-year, population-based observational study in 183 countries
Loaeza, Lizbeth Moreno; Lara-Castor, Laura; Sharib, Julia R; Cudhea, Frederick; Wang, Meng; Li, Peizhi; Mozaffarian, Dariush; ,
BACKGROUND:Taxes on sugar-sweetened beverages can improve public health. We aimed to characterise the extent and types of sugar-sweetened beverage taxes implemented worldwide and the national characteristics predicting implementation, such as sugar-sweetened beverage intake amounts, disease rates, or economic development. METHODS:This longitudinal analysis aggregated serial global datasets (including the Global Dietary Database, Non-Communicable Diseases Risk Factor Collaboration, Global Burden of Disease study, and World Bank data) from 1990 to 2024 in 183 countries to assess sugar-sweetened beverage tax characteristics and national predictors of policy adoption. Sugar-sweetened beverage taxes for public health purposes were identified and characterised, including amounts, fiscal instruments, structures, and covered beverages. Sugar-sweetened beverage consumption, obesity and diabetes prevalence, gross domestic product (GDP), and sociodemographic index (SDI) were assessed as predictors of tax implementation using Cox proportional hazards models with time-varying covariates. FINDINGS/RESULTS:From 1990 to 2024, 64 countries implemented sugar-sweetened beverage taxes, accelerating over time and covering 3·5 billion people globally. South Asia led in adoption (50% of countries; median tax rate 7·5%), followed by southeast and east Asia (47·8%; 5·0%), the Middle East and North Africa (30·0%; 17·0%), and Latin America and the Caribbean (31·3%; 7·0%). Taxes were ad valorem (ie, based on price; 45%), volume-based (44%), sugar-content-based (5%), or mixed (6%), and 13% of countries earmarked revenue for public health. Multivariable-adjusted predictors of tax implementation included diabetes prevalence (hazard ratio [HR]=1·22 [95% CI 1·05-1·43]), obesity prevalence (1·14 [1·00-1·29]), GDP per capita (HR per $10 000: 1·19 [1·06-1·34]), and SDI (0·70 [0·57-0·86]), but not sugar-sweetened beverage intake (0·77 [0·42-1·39]). INTERPRETATION/CONCLUSIONS:Global adoption of sugar-sweetened beverage taxes has rapidly accelerated since 1990; however, there is important heterogeneity by region and tax structure, and the taxes are shaped by a country's economic capacity, social development, and health conditions. FUNDING/BACKGROUND:This work was supported by the National Institutes of Health (R01HL115189).
PMID: 42259348
ISSN: 2214-109x
CID: 6047882
Effects of ethanol exposure in neonatal mice on retinoic acid signaling in forebrain neurons and astrocytes
Saito, Mariko; Park, Jungann; Nalluri, Anusha; Marino, Brandon; Williams, Colin R O; Wilson, Donald A; Das, Bhaskar C; Smiley, John F
Toxicity of prenatal ethanol leading to fetal alcohol spectrum disorders (FASDs) has been linked to disturbances in retinoic acid (RA) signaling necessary for embryonic development. While ethanol exposure in the postnatal day 7 (P7) mice, which induces immediate neurodegeneration and long-lasting GABAergic cell loss and behavioral deficits, has been used for the third trimester FASD model, involvement of RA signaling in the process has not been well explored. Using RARE-LacZ reporter mice that express β-galactosidase (β-Gal) under the control of retinoic acid response element (RARE), we examined RA signaling activity of the forebrains of P8 and P30 mice with or without P7 ethanol treatment. In all experimental groups, β-Gal was expressed mainly in the hippocampus with the strongest expression in the granule cell layer of dentate gyrus. In addition, β-Gal was expressed in pyramidal neurons and parvalbumin (PV) neurons in CA1-3 pyramidal layer and in astrocytes scattered around the CA1-3 region although PV neurons were only examined at P30 because of the low PV expression at P8. β-Gal was also expressed in the anteroventral/anteromedial (AV/AM) thalamus and the retrosplenial (Rs) and Tbr1-positive (+) layer 6 cortices. β-Gal-expressing PV neurons were also found in the cortex such as Rs, while β-Gal was barely detected in somatostatin neurons in any brain regions examined. Such region and cell specific β-Gal expression was significantly higher in P8 brains than P30 brains in various brain regions. P7 ethanol reduced β-Gal expression in the CA1-3 pyramidal layer, Tbr1 + cortical layer 6, and the AV/AM thalamus at P8 or P30 or both. Although P7 ethanol decreased PV cells in CA2-3 pyramidal layers as reported, it decreased β-Gal+ PV cells more drastically. The active RA signaling found in PV neurons and the effects of P7 ethanol on the signaling suggest that reduced RA signaling by P7 ethanol may disturb PV cell maturation and enhance long-lasting brain abnormalities.
PMCID:13240825
PMID: 42254759
ISSN: 2667-2421
CID: 6048042
Alpha DaRT source activity confirmation using a reentrant well-type ionization chamber
Deufel, Christopher L; Ordog, Jasmine L; Underwood, Kyle; Cohen, Yadin; Cohen, Gil'ad N; Damato, Antonio L; Malouff, Timothy D
BACKGROUND:Alpha-emitting radionuclides enable precise cancer therapy through high linear energy transfer and limited tissue penetration, damaging tumor cells while sparing healthy tissue. Diffusing Alpha-emitters Radiation Therapy (Alpha DaRT) features Ra-224 sources that are implanted directly into the tumor and emit alpha particles during radioactive decay. Alpha DaRT has demonstrated efficacy and safety in preclinical and early clinical trials across multiple tumor types, including skin, head and neck, and pancreatic cancers. PURPOSE/OBJECTIVE:Reliable and efficient methods for verifying Alpha DaRT source activity prior to treatment can help support accurate and consistent radiation delivery. The direct measurement of alpha particles from sources within an Alpha DaRT applicator is impractical due to their short range; however, gamma emissions from the Ra-224 sources can be used to infer radioactivity. This study established a protocol for verifying the source activity within Ra-224 Alpha DaRT applicators using a reentrant well-type ionization chamber, providing users with a practical method for detecting errors in source manufacturing or certificate paperwork without compromising applicator sterility. METHODS:Ra-224 Alpha DaRT sources in sterile packaging (Flex and Needle applicators with 1-4 sources) were assessed. Source energy spectra and activities were verified using a high-purity germanium (HPGe) radiation detector. Calibration factors (kBq/pA) were established using an IVB1000 well-type ionization chamber with measurements conducted by placing single applicator sterile packages into the chamber with sources centered in the chamber's sweet spot and corrected for temperature, pressure, and leakage current. Quality assurance was performed on 26 Flex applicators using the established calibrations before the first clinical procedure. RESULTS:HPGe measurements agreed with vendor-stated activities. The average calibration coefficient using the IVB1000 chamber was 233 ± 3 kBq/pA for Flex and 597 ± 7 kBq/pA for Needle applicators. Calibration coefficients were consistent across two IVB1000 chambers. Source number dependence was observed, with calibration factors increasing by 1.7% ± 0.7% per source (Needle) and 2.7% ± 0.6% per source (Flex). Measurement repeatability was 3.3%. Applying the calibration to 26 Flex applicators before the first patient treatment yielded a 1.1 ± 5.8% (range: -7.5% to 11.4%) difference relative to the vendor's stated activity. CONCLUSION/CONCLUSIONS:A reentrant well-type ionization chamber is suitable for pre-treatment quality assurance of Ra-224 Alpha DaRT applicators, enabling verification of the vendor-stated activity while maintaining sterility within sealed packaging.
PMID: 42253233
ISSN: 2473-4209
CID: 6048022