Epidemiologic Trends of Cleft Lip and Palate in a Southern State: A 30-Year Follow-Up.

OBJECTIVES: Children's of Mississippi at the University of Mississippi Medical Center serves as the state's only American Cleft Palate-Craniofacial Association-approved cleft team at the only pediatric hospital in the state. The goal of this study is to report geographic and demographic patterns of patients with orofacial cleft (OFC) treated at Children's of Mississippi, which are lacking. METHODS: Patients with OFC treated at Children's of Mississippi from 2015 to 2020 were included. Demographic data were collected, including birth county and total live births from state data. Significant differences between incidence of OFC among public health regions of Mississippi were examined using analysis of variance (P < 0.05). Cases were compared with historical data from 1980 to 1989. RESULTS: There were 184 patients who presented with OFC, with a statewide incidence of 0.83 per 1000 live births among 222,819 live births in the state across 6 years. The incidence of OFC was 0.83/1000 for Whites and 0.82/1000 for non-Whites versus a historical rate of 1.36 and 0.54, respectively. Significantly fewer children in the northern region (0.25/1000) were born with OFC than in central (1.21; P < 0.001) and southern (0.86; P < 0.001) regions. CONCLUSIONS: Results from this study suggest changing regional patterns of OFC in Mississippi. Although rates increased among non-White infants, the overall incidence of OFC has decreased compared with historical data. The findings may reflect actual incidence patterns in the state or the proximity of certain regions to Children's of Mississippi. Further study may reveal regional differences in risk factors underlying OFC incidence, and/or issues with access to cleft care for different regions in the state.

B1-B2 transition in shock-compressed MgO.

Magnesium oxide (MgO) is a major component of the Earth's mantle and is expected to play a similar role in the mantles of large rocky exoplanets. At extreme pressures, MgO transitions from the NaCl B1 crystal structure to a CsCl B2 structure, which may have implications for exoplanetary deep mantle dynamics. In this study, we constrain the phase diagram of MgO with laser-compression along the shock Hugoniot, with simultaneous measurements of crystal structure, density, pressure, and temperature. We identify the B1 to B2 phase transition between 397 and 425 gigapascal (around 9700 kelvin), in agreement with recent theory that accounts for phonon anharmonicity. From 425 to 493 gigapascal, we observe a mixed-phase region of B1 and B2 coexistence. The transformation follows the Watanabe-Tokonami-Morimoto mechanism. Our data are consistent with B2-liquid coexistence above 500 gigapascal and complete melting at 634 gigapascal. This study bridges the gap between previous theoretical and experimental studies, providing insights into the timescale of this phase transition.

Control of Physiologic Glucose Homeostasis via the Hypothalamic Modulation of Gluconeogenic Substrate Availability.

The brain augments glucose production during fasting, but the mechanisms are poorly understood. Here, we show that Cckbr-expressing neurons in the ventromedial hypothalamic nucleus (VMNCckbr cells) prevent low blood glucose during fasting through sympathetic nervous system (SNS)-mediated augmentation of adipose tissue lipolysis and substrate release. Activating VMNCckbr neurons mobilized gluconeogenic substrates without altering glycogenolysis or gluconeogenic enzyme expression. Silencing these cells (CckbrTetTox animals) reduced fasting blood glucose, impaired lipolysis, and decreased circulating glycerol (but not other gluconeogenic substrates) despite normal insulin, counterregulatory hormones, liver glycogen, and liver gluconeogenic gene expression. Furthermore, ß3-adrenergic adipose tissue stimulation in CckbrTetTox animals restored lipolysis and blood glucose. Hence, VMNCckbr neurons impact blood glucose not by controlling islet or liver physiology, but rather by mobilizing gluconeogenic substrates. These findings establish a central role for hypothalamic and SNS signaling during normal glucose homeostasis and highlight the importance of gluconeogenic substrate mobilization during physiologic fasting.

Association of Smartwatch-Based Heart Rate and Physical Activity With Cardiorespiratory Fitness Measures in the Community: Cohort Study.

BACKGROUND: Resting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. OBJECTIVE: This study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. METHODS: Electronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. RESULTS: We included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)-adjusted P values <.001 for all. Reductions of 2.4 beats per minute in nonactive HR, or increases of nearly 1000 daily steps, corresponded to a 1.3 mL/kg/min higher peak VO2. In addition, ventilatory efficiency (VE/VCO2; FDR-adjusted P=.009), % predicted maximum HR (FDR-adjusted P<.001), and systolic blood pressure-to-workload slope (FDR-adjusted P=.01) were associated with nonactive HR but not associated with daily steps. CONCLUSIONS: Our findings suggest that smartwatch-based assessments are associated with a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise. Metrics captured by wearable devices offer a valuable opportunity to use extensive data on health factors and behaviors to provide a window into individual cardiovascular fitness levels.

Multimodal, PSMA-Targeted, PAMAM Dendrimer-Drug Conjugates for Treatment of Prostate Cancer: Preclinical Evaluation.

Introduction: Prostate cancer (PC) is the second most common cancer and the fifth most frequent cause of cancer death among men. Prostate-specific membrane antigen (PSMA) expression is associated with aggressive PC, with expression in over 90% of patients with metastatic disease. Those characteristics have led to its use for PC diagnosis and therapies with radiopharmaceuticals, antibody-drug conjugates, and nanoparticles. Despite these advancements, none of the current therapeutics are curative and show some degree of toxicity. Here we present the synthesis and preclinical evaluation of a multimodal, PSMA-targeted dendrimer-drug conjugate (PT-DDC), synthesized using poly(amidoamine) (PAMAM) dendrimers. PT-DDC was designed to enable imaging of drug delivery, providing valuable insights to understand and enhance therapeutic response. Methods: The PT-DDC was synthesized through consecutive conjugation of generation-4 PAMAM dendrimers with maytansinoid-1 (DM1) a highly potent antimitotic agent, Cy5 infrared dye for optical imaging, 2,2',2"-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) chelator for radiolabeling with copper-64 and positron emission tomography tomography/computed tomography (PET/CT), lysine-urea-glutamate (KEU) PSMA-targeting moiety and the remaining terminal primary amines were capped with butane-1,2-diol. Non-targeted control dendrimer-drug conjugate (Ctrl-DDC) was formulated without conjugation of KEU. PT-DDC and Ctrl-DDC were characterized using high-performance liquid chromatography, matrix assisted laser desorption ionization mass spectrometry and dynamic light scattering. In vitro and in vivo evaluation of PT-DDC and Ctrl-DDC were carried out in isogenic human prostate cancer PSMA+ PC3 PIP and PSMA- PC3 flu cell lines, and in mice bearing the corresponding xenografts. Results: PT-DDC was stable in 1×PBS and human blood plasma and required glutathione for DM1 release. Optical, PET/CT and biodistribution studies confirmed the in vivo PSMA-specificity of PT-DDC. PT-DDC demonstrated dose-dependent accumulation and cytotoxicity in PSMA+ PC3 PIP cells, and also showed growth inhibition of the corresponding tumors. PT-DDC did not accumulate in PSMA- PC3 flu tumors and did not inhibit their growth. Ctrl-DDC did not show PSMA specificity. Conclusion: In this study, we synthesized a multimodal theranostic agent capable of delivering DM1 and a radionuclide to PSMA+ tumors. This approach holds promise for enhancing image-guided treatment of aggressive, metastatic subtypes of prostate cancer.

ERK3 is involved in regulating cardiac fibroblast function.

ERK3/MAPK6 activates MAP kinase-activated protein kinase (MK)-5 in selected cell types. Male MK5 haplodeficient mice show reduced hypertrophy and attenuated increase in Col1a1 mRNA in response to increased cardiac afterload. In addition, MK5 deficiency impairs cardiac fibroblast function. This study determined the effect of reduced ERK3 on cardiac hypertrophy following transverse aortic constriction (TAC) and fibroblast biology in male mice. Three weeks post-surgery, ERK3, but not ERK4 or p38α, co-immunoprecipitated with MK5 from both sham and TAC heart lysates. The increase in left ventricular mass and myocyte diameter was lower in TAC-ERK3+/- than TAC-ERK3+/+ hearts, whereas ERK3 haploinsufficiency did not alter systolic or diastolic function. Furthermore, the TAC-induced increase in Col1a1 mRNA abundance was diminished in ERK3+/- hearts. ERK3 immunoreactivity was detected in atrial and ventricular fibroblasts but not myocytes. In both quiescent fibroblasts and "activated" myofibroblasts isolated from adult mouse heart, siRNA-mediated knockdown of ERK3 reduced the TGF-ß-induced increase in Col1a1 mRNA. In addition, intracellular type 1 collagen immunoreactivity was reduced following ERK3 depletion in quiescent fibroblasts but not myofibroblasts. Finally, knocking down ERK3 impaired motility in both atrial and ventricular myofibroblasts. These results suggest that ERK3 plays an important role in multiple aspects of cardiac fibroblast biology.

Life's Essential 8 Cardiovascular Health Score and Cardiorespiratory Fitness in the Community.

BACKGROUND: The relation of cardiorespiratory fitness (CRF) to lifestyle behaviors and factors linked with cardiovascular health remains unclear. We aimed to understand how the American Heart Association's Life's Essential 8 (LE8) score (and its changes over time) relate to CRF and complementary exercise measures in community-dwelling adults. METHODS AND RESULTS: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise testing for direct quantification of peak oxygen uptake (V̇O2). A 100-point LE8 score was constructed as the average across 8 factors: diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure. We related total LE8 score, score components, and change in LE8 score over 8 years with peak V̇O2 (log-transformed) and complementary CRF measures. In age- and sex-adjusted linear models (N=1838, age 54±9 years, 54% women, LE8 score 76±12), a higher LE8 score was associated favorably with peak V̇O2, ventilatory efficiency, resting heart rate, and blood pressure response to exercise (all P<0.0001). A clinically meaningful 5-point higher LE8 score was associated with a 6.0% greater peak V̇O2 (≈1.4 mL/kg per minute at sample mean). All LE8 components were significantly associated with peak V̇O2 in models adjusted for age and sex, but blood lipids, diet, and sleep health were no longer statistically significant after adjustment for all LE8 components. Over an ≈8-year interval, a 5-unit increase in LE8 score was associated with a 3.7% higher peak V̇O2 (P<0.0001). CONCLUSIONS: Higher LE8 score and improvement in LE8 over time was associated with greater CRF, highlighting the importance of the LE8 factors in maintaining CRF.

Educational Limitations of ChatGPT in Neurosurgery Board Preparation.

Objective This study evaluated the potential of Chat Generative Pre-trained Transformer (ChatGPT) as an educational tool for neurosurgery residents preparing for the American Board of Neurological Surgery (ABNS) primary examination. Methods Non-imaging questions from the Congress of Neurological Surgeons (CNS) Self-Assessment in Neurological Surgery (SANS) online question bank were input into ChatGPT. Accuracy was evaluated and compared to human performance across subcategories. To quantify ChatGPT's educational potential, the concordance and insight of explanations were assessed by multiple neurosurgical faculty. Associations among these metrics as well as question length were evaluated. Results ChatGPT had an accuracy of 50.4% (1,068/2,120), with the highest and lowest accuracies in the pharmacology (81.2%, 13/16) and vascular (32.9%, 91/277) subcategories, respectively. ChatGPT performed worse than humans overall, as well as in the functional, other, peripheral, radiology, spine, trauma, tumor, and vascular subcategories. There were no subjects in which ChatGPT performed better than humans and its accuracy was below that required to pass the exam. The mean concordance was 93.4% (198/212) and the mean insight score was 2.7. Accuracy was negatively associated with question length (R2=0.29, p=0.03) but positively associated with both concordance (p<0.001, q<0.001) and insight (p<0.001, q<0.001). Conclusions The current study provides the largest and most comprehensive assessment of the accuracy and explanatory quality of ChatGPT in answering ABNS primary exam questions. The findings demonstrate shortcomings regarding ChatGPT's ability to pass, let alone teach, the neurosurgical boards.

The cutting edge: Promising oncology radiotracers in clinical development.

Molecular imaging moves forward with the development of new imaging agents, and among these are new radiotracers for nuclear medicine applications, particularly positron emission tomography (PET). A number of new targets are becoming accessible for use in oncologic applications. In this review, major new radiotracers in clinical development are discussed. Prominent among these is the family of fibroblast-activation protein-targeted agents that interact with the tumor microenvironment and may show superiority to 2-deoxy-2-[18F]fluoro-d-glucose in a subset of different tumor histologies. Additionally, carbonic anhydrase IX (CAIX) inhibitors are directed at clear cell renal cell carcinoma, which has long lacked an effective PET imaging agent. Those CAIX agents may also have utility in hypoxic tumors. Pentixafor, which binds to a transmembrane receptor, may similarly allow for visualization by PET of low-grade lymphomas, as well as being a second agent for multiple myeloma that opens theranostic possibilities. There are new adrenergic agents aimed at providing a PET-visible replacement to the single-photon-emitting radiotracer meta-[123I]iodobenzylguanidine (MIBG). Finally, in response to a major development in oncologic chemotherapy, there are new radiotracers targeted at assessing the suitability or use of immunotherapeutic agents. All of these and the existing evidence for their utility are discussed.

Association between suicidal behavior and symptoms of other mental health problems in Mexican adolescents.

BACKGROUND: Suicidal behavior in adolescents is a growing public health problem. Knowing its risk factors is key for reducing it. OBJECTIVE: To identify the relationship between two suicidal behaviors (ideation and attempt) and eight mental health problems (MHPs) in Mexican adolescents. MATERIAL AND METHODS: Through an online survey of adolescent students from 20 states, the following information was screened: symptomatology of six MHPs (affective problems/depression, behavioral problems, somatic problems, inattention and hyperactivity problems, oppositional defiant problems and anxiety problems) and suicidal behavior (suicidal ideation and suicide attempts). MHP and suicidal behavior frequencies and percentages were analyzed, and associations were sought using binary logistic regression. RESULTS: Six-thousand seven hundred sixty-six adolescents completed the survey, out of whom 61.02% were females, with ages ranging between 11 and 19 years (16.38 ± 1.33); 10% reported suicidal behavior, and between 3 and 5%, MHPs. The predictors (χ2(8) = 387.13, p < 0.001) of suicidal behavior were affective problems/depression, behavioral problems, somatic problems, oppositional defiant problems and anxiety problems. CONCLUSION: Five mental health problems increased the risk of reporting suicidal behaviors.

ANTECEDENTES: Las conductas suicidas en adolescentes son un problema de salud pública que va en aumento. Conocer sus factores de riesgo es clave para reducirlas. OBJETIVO: Identificar la relación entre dos conductas suicidas (ideación e intento) y ocho problemas de salud mental (PSM) en adolescentes mexicanos. MATERIAL Y MÉTODOS: Mediante una encuesta en línea a adolescentes escolarizados de 20 estados, se tamizó la siguiente información: sintomatología de seis PSM (problemas afectivos/depresión, problemas conductuales, problemas somáticos, problemas de inatención e hiperactividad, problemas oposicionistas desafianes y problemas de ansiedad) y conducta suicida (ideación e intentos de suicidio). Se analizaron frecuencias y porcentajes y se indagó asociación mediante regresión logística binaria. RESULTADOS: Completaron la encuesta 6766 adolescentes entre 11 y 19 años (16.38 ± 1.33), 61.02 % del sexo femenino. El 10 % reportó conducta suicida y entre 3 y 5 %, PSM. Los factores predictivos (χ2(8) = 387.13, p < 0.001) de la conducta suicida fueron problemas afectivos/depresión, problemas conductuales, problemas somáticos, problemas oposicionistas desafiantes y problemas de ansiedad. CONCLUSIÓN: Cinco problemas de salud mental incrementaron el riesgo de reportar conductas suicidas.

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy.

ABSTRACT: Prostate cancer (PCa) is the most common noncutaneous malignancy in men. Until recent years, accurate imaging of men with newly diagnosed PCa, or recurrent or low-volume metastatic disease, was limited. Further, therapeutic options for men with advanced, metastatic, castration-resistant disease were increasingly limited as a result of increasing numbers of systemic therapies being combined in the upfront metastatic setting. The advent of urea-based, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) has partially addressed those shortcomings in diagnosis and therapy of PCa. On the diagnostic side, there are multiple pivotal phase III trials with several different agents having demonstrated utility in the initial staging setting, with generally modest sensitivity but very high specificity for determining otherwise-occult pelvic nodal involvement. That latter statistic drives the utility of the scan by allowing imaging interpreters to read with very high sensitivity while maintaining a robust specificity. Other pivotal phase III trials have demonstrated high detection efficiency in patients with biochemical failure, with high positive predictive value at the lesion level, opening up possible new avenues of therapy such as metastasis-directed therapy. Beyond the diagnostic aspects of PSMA-targeted radiotracers, the same urea-based chemical scaffolds can be altered to deliver therapeutic isotopes to PCa cells that express PSMA. To date, one such agent, when combined with best standard-of-care therapy, has demonstrated an ability to improve overall survival, progression-free survival, and freedom from skeletal events relative to best standard-of-care therapy alone in men with metastatic, castration-resistant PCa who are post chemotherapy. Within the current milieu, there are a number of important future directions including the use of artificial intelligence to better leverage diagnostic findings, further medicinal chemistry refinements to the urea-based structure that may allow improved tumor targeting and decreased toxicities, and the incorporation of new radionuclides that may better balance efficacy with toxicities than those nuclides that are available.

Total Syntheses of the Structures Assigned to Denigrins A, B, C, F, and G, 3,4-Diaryl-Pyrrole and -Pyrrolidinone Alkaloids, and the Conversion of Congener B into the Co-metabolite Spirodactylone.

The title marine natural products have been prepared by total synthesis and in the case of congeners 3, 6, and 7 for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (2). The structure, 3, assigned to denigrin C is shown to be incorrect. Reaction of compound 2 with DDQ has led, in high yield, to the related natural product spirodactylone (16), while treating the corresponding permethyl ether 15 with PIFA/BF3·Et2O provides compound 20, embodying an isomeric framework.

Protocol for the 'Supporting Young Cancer Survivors who Smoke' study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England.

BACKGROUND: Childhood, adolescent and young adult (CAYA) cancer survivors are vulnerable to adverse late-effects. For CAYA cancer survivors, tobacco smoking is the most important preventable cause of ill-health and early death. Yet, effective strategies to support smoking cessation in this group are lacking. The PRISM study aims to undertake multi-method formative research to explore the need for, and if appropriate, inform the future development of an evidence-based and theory-informed tobacco smoking cessation intervention for CAYA cancer survivors. MATERIALS AND METHODS: PRISM involves three phases of: 1) an environmental scan using multiple strategies to identify and examine a) smoking cessation interventions for CAYA cancer survivors that are published in the international literature and b) current smoking cessation services in England that may be available to, or tailorable to, CAYA cancer survivors; 2) a qualitative study involving semi-structured interviews with CAYA cancer survivors (aged 16-29 years and who are current or recent ex-smokers and/or current vapers) to explore their views and experiences of smoking, smoking cessation and vaping; and 3) stakeholder workshops with survivors, healthcare professionals and other stakeholders to consider the potential for a smoking cessation intervention for CAYA cancer survivors and what such an intervention would need to target and change. Findings will be disseminated to patient groups, healthcare professionals and researchers, through conference presentations, journal papers, plain English summaries and social media. DISCUSSION: PRISM will explore current delivery of, perceived need for, and barriers and facilitators to, smoking cessation advice and support to CAYA cancer survivors from the perspective of both survivors and healthcare professionals. A key strength of PRISM is the user involvement throughout the study and the additional exploration of survivors' views on vaping, a behaviour which often co-occurs with smoking. PRISM is the first step in the development of a person-centred, evidence- and theory-based smoking cessation intervention for CAYA cancer survivors who smoke, which if effective, will reduce morbidity and mortality in the CAYA cancer survivor population.

Deinonychosaur trackways in southeastern China record a possible giant troodontid.

The Longxiang tracksite (lower Upper Cretaceous, Shanghang Basin) includes twelve didactyl deinonychosaur tracks that fall into two morphologies, differentiated by both size and form. The smaller tracks (∼11 cm long) are referable to the ichnogenus Velociraptorichnus. The larger tracks (∼36 cm long) establish the ichnotaxon Fujianipus yingliangi. Based on the size of the tracks, F. yingliangi has an estimated hip height of over 1.8 m, a size comparable to that of the largest known deinonychosaurs, i.e., Austroraptor and Utahraptor. The reduced form of digit IV, relative to digit III, indicates that F. yingliangi is a probable troodontid. Gigantism evidently evolved independently at least four times within the Deinonychosauria and within at least three major lineages: the Eudromaeosauria, Unenlagiidae, and Troodontidae. In the mid-Cretaceous of Asia, the evolution of F. yingliangi overlapped with that of early large-bodied tyrannosauroids and with previously established large allosaurids (although the latter may have been in decline).

Screening of Astec® CHIRALDEX™ G-PN and LIPODEX™ D gas chromatography columns for enantioseparation of amphetamine derivatives.

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-ß-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.

Exploring a Lux® i-Amylose-3 column in normal phase and polar-organic mode for chiral separation of cathinone derivatives and pyrovalerones using high-performance liquid chromatography.

Each year, new psychoactive substances appear on the global drug market leading to constant changes. Most of these compounds with stimulating effect possess a chiral center, thus leading to two enantiomers with presumably different pharmacological properties. Among them, synthetic cathinones, often misleadingly traded as "bath salts," play an important role. There is little knowledge about the distinct effect of the enantiomers. The aim of this study was to test a commercially available Lux® i-Amylose-3 column by HPLC-UV for enantiorecognition of cathinone derivatives. Overall, 80 compounds were tested in normal phase mode, where 75 substances were separated under initial conditions. After method optimization, at least partial separation was achieved for the remaining compounds. The same set of substances was measured in polar-organic mode, where 63 analytes were resolved into their enantiomers under initial conditions with very short retention times. Both modes showed complementary results for the individual compounds. Furthermore, the tested methods proved to be suitable for differentiation of positional isomers, which can be useful for drug checking programs. All measurements were carried out under isocratic conditions, and intraday and interday repeatability tests were performed.

Broadband photodetectors from silane-passivated CsPbBr3 nanocrystals by ultrasound-mediated synthesis.

Perovskite nanocrystals have excellent optical properties but suffer from environmental instability and production up-scaling which limit their commercial application. Here, we report the gram-scale ultrasound-mediated synthesis of silane passivated CsPbBr3 nanocrystals using (3-aminopropyl) triethoxysilane (APTS) as the primary surface ligand surface. The surface engineering endowed the CsPbBr3@SiOR NCs with extended environmental stability, a narrow emission bandwidth and a high photoluminescence quantum yield (PLQY > 75%). Thanks to these excellent optical properties, high-efficiency lateral and vertical photodetectors were fabricated. In particular, the layered vertical photodiode composed of ITO/Ga2O3/CsPbBr3/Au exhibited a broadband photoresponse from 350-700 nm with a responsivity peaking at 44.5.1 A W-1 and specific detectivity above 1013 Jones when illuminated at 470 nm wavelength and biased at +5 V. These results correspond to the best-in-class performance perovskite nanocrystal PD and confirm the extraordinary potential of CsPbBr3@SiOR for the development of efficient optoelectronic devices.

Investigating the Mechanism of Aluminum Fluoride Chelation.

Aluminum fluoride (AlF) complexes have been used over the past decade to incorporate [18F]fluoride into large biomolecules in a highly selective fashion by using relatively facile conditions. However, despite their widespread usage, there are a large number of variations in the reaction conditions, without a definitive discussion provided on the mechanism to understand how these changes would alter the end result. Herein, we report a detailed mechanistic investigation of the reaction, using a mixture of theoretical studies, fluorine-19 and fluorine-18 chemistry, and the consequences it has on the efficient clinical translation of AlF-containing imaging agents.

Short Formal Syntheses of Lycorine and Congeners Using a 5-Endo-Trig/6-Endo-Trig Radical Cyclization Sequence.

Here, we report a practical route to medicinally interesting lycorine congeners alongside formal syntheses of various lycorine-type natural products, including lycorine itself. The efficiency of our strategy derives from a back-to-back 5-endo-trig/6-endo-trig radical cyclization sequence, which we systematically studied both experimentally and computationally. The results of our work will facilitate future development of urgently needed antiviral therapeutics based on lycorine.

Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.