Phthalate and phthalate replacement concentrations in relationship to adiposity in a multi-racial cohort of children.

BACKGROUND/OBJECTIVE: Phthalates and phthalate replacements are used in multiple everyday products, making many of them bioavailable to children. Experimental studies suggest that phthalates and their replacements may be obesogenic, however, epidemiologic studies remain inconsistent. Therefore, our objective was to examine the association between phthalates, phthalate replacements and childhood adiposity/obesity markers in children. SUBJECTS/METHODS: A cross-sectional study was conducted in 630 racial/ethnically diverse children ages 4-8 years. Urinary oxidative metabolites of DINCH and DEHTP, three low molecular weight (LMW) phthalates, and eleven high molecular weight (HMW) phthalates were measured. Weight, height, waist circumference and % body fat were measured. Composite molar sum groups (nmol/ml) were natural log-transformed. Linear regression models adjusted for urine specific gravity, sex, age, race-ethnicity, birthweight, breastfeeding, reported activity level, mother's education and pre-pregnancy BMI. RESULTS: All children had LMW and HMW phthalate metabolites and 88% had DINCH levels above the limit of detection. One unit higher in the log of DINCH was associated with 0.106 units lower BMI z-score [ß = -0.106 (95% CI: -0.181, -0.031)], 0.119 units lower waist circumference z-score [ß = -0.119 (95% CI: -0.189, -0.050)], and 0.012 units lower percent body fat [ß = -0.012 (95% CI: -0.019, -0.005)]. LMW and HMW group values were not associated with adiposity/obesity. CONCLUSIONS: We report an inverse association between child urinary DINCH levels, a non-phthalate plasticizer that has replaced DEHP in several applications, and BMI z-score, waist circumference z-score and % body fat in children. Few prior studies of phthalates and their replacements in children have been conducted in diverse populations. Moreover, DINCH has not received a great deal of attention or regulation, but it is a common exposure. In summary, understanding the ubiquitous nature of these chemical exposures and ultimately their sources will contribute to our understanding of their relationship with obesity.

Napa Valley Cabernet Sauvignon Proanthocyanidin Changes During Fruit Ripening: A Multi-Appellation Survey.

In 2015, an experiment was designed to investigate the distribution and variance of in winegrape flavonoids across the ripening phase in the Napa Valley. This Cabernet Sauvignon experiment was intended to evaluate the polyphenol differences across Napa Valley in order to understand parameters controlling "proanthocyanidin activity." This method has shown promise in understanding proanthocyanidin (PA) astringency based on size distribution, pigmentation, conformation, and composition. Results from whole berry partial extractions showed that seed PA material was driving PA activity early in the ripening phase, while the formation of the pigmented polymer led to a decrease later in the growing season. Multivariate analysis showed that the main drivers of changes across the ripening phase were the molecular masses of PAs and the amount of pigmentation. Given the high amount of variability seen in the experiment between sites in such a small geographical area, the results suggest that manipulation of PA activity may be possible in the vineyard, perhaps explaining variations in wine mouthfeel attributes between locations. These results can be used to develop furthermore controlled experiments targeting the variables responsible for PA activity changes.

Dietary inflammatory index (DII) and sleep quality, duration, and timing: A systematic review.

Sleep has strong inflammatory underpinnings and diet is one of the primary determinants of systemic inflammation. A systematic literature review was conducted to synthesize current research associating dietary inflammatory potential, as measured by the dietary inflammatory index (DII®) or the energy-adjusted DII (E-DII™) and sleep quality and duration. The National Library of Medicine (Medline), Web of Science, and PsycInfo databases were searched through March 2023. Studies must have used the DII/E-DII as the independent variable and sleep outcomes as dependent variables. Study characteristics, based on STROBE guidelines, were scored based on the presence of the recommendation. Out of the initial 14 studies identified, a total of 12 studies were included for data synthesis. In all 12 studies, more anti-inflammatory diets (i.e., low DII/E-DII scores) were associated with better sleep in at least one sleep domain (most often sleep efficiency and wake-after-sleep-onset). Among those studies with more rigorous diet and sleep measurements, such as dietary recalls and actigraphy, associations between DII/E-DII and sleep outcomes were stronger and more consistent compared to studies using primarily subjective assessments. More rigorous measurement of diet and sleep, especially those relating to sleep stage structure, should be considered in future studies with prospective designs.

Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer.

Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor-node-metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.

Functional Outcomes After the Sacrifice of Mandibular Condyle Using Fibula Free Flap for Immediate Surgical Reconstruction.

Introduction Head and neck cancer with mandibular invasion often necessitates composite resection, leading to defects requiring reconstruction. Microvascular fibula free flap (FFF) surgery is a common approach for this purpose. In this study, we focus on our experience with condyle sacrifice, emphasizing treatment outcomes and functional results. Additionally, we highlight a contemporary perspective by discussing surgical techniques and radiographic outcomes based on a 3D analysis of neo-condyle placement on CT imaging. Methods We studied 23 patients who had undergone segmental mandibulectomy requiring FFF reconstruction between 2009 and 2020. These were all performed by the same surgeon (M.M.) at an academic tertiary care center. Twenty-three reconstructions included condyle sacrifice. Retrospective chart review was performed with a focus on treatment, functional outcomes, and surgical technique. Results A total of 23 patients were included in the study group (13 females and 10 males) with a mean age of 58.1 years. The most common surgical indication was for oncologic purposes (n=9; 39.1%). Twenty (87%) patients required tracheostomy, and all were decannulated. In terms of surgical complications, two (8.7%) patients had a degree of arterial insufficiency and two (8.7%) developed delayed infections. The average inpatient stay was 5.61 days, with a subsequent average clinic follow-up after 16.9 days. CT or MRI imaging was available for 21 (91.3%) patients, showing 14 (66.7%) neo-condyles within the glenoid fossa. Fifteen (71.4%) patients had some element of anterior displacement (average=6.27 mm), and seven (33.3%) patients had a component of lateral displacement (average=2.23 mm). Three (13%) patients died during the follow-up period. Eighteen (90%) of the surviving patients returned to an oral diet within an average of 24.9 days. All patients returned to normal interincisal distance by 12 months. All FFFs, with and without complications, remained viable. Conclusion We achieved favorable oral function outcomes in the majority of our patients. Intriguingly, although radiographic evidence revealed anterior and/or lateral displacement of the neo-condyle, there was no observed correlation with the resumption of oral diet, trismus, or crossbite among these patients.

The evolution of raw data archiving and the growth of its importance in crystallography.

The hardware for data archiving has expanded capacities for digital storage enormously in the past decade or more. The IUCr evaluated the costs and benefits of this within an official working group which advised that raw data archiving would allow ground truth reproducibility in published studies. Consultations of the IUCr's Commissions ensued via a newly constituted standing advisory committee, the Committee on Data. At all stages, the IUCr financed workshops to facilitate community discussions and possible methods of raw data archiving implementation. The recent launch of the IUCrData journal's Raw Data Letters is a milestone in the implementation of raw data archiving beyond the currently published studies: it includes diffraction patterns that have not been fully interpreted, if at all. The IUCr 75th Congress in Melbourne included a workshop on raw data reuse, discussing the successes and ongoing challenges of raw data reuse. This article charts the efforts of the IUCr to facilitate discussions and plans relating to raw data archiving and reuse within the various communities of crystallography, diffraction and scattering.

Total Elbow Arthroplasty Versus Open Reduction and Internal Fixation for Distal Humerus Fractures: A Propensity Score Matched Analysis of 30-Day Postoperative Complications.

Introduction: Open reduction and internal fixation (ORIF) is an established surgical procedure for distal humeral fractures; however, total elbow arthroplasty (TEA) has become an increasingly popular alternative for elderly patients with these injuries. Using a large sample of recent patient data, this study compares the rates of short-term complications between ORIF and TEA and evaluates complication risk factors. Methods: Patients who underwent primary TEA or ORIF from 2012 to 2021 were identified by Current Procedural Terminology codes in the American College of Surgeons National Surgical Quality Improvement Program database. Propensity score matching controlled for demographic and comorbid differences. The rates of 30-day postoperative complications were compared. Results: A total of 1539 patients were identified, with 1365 (88.7%) and 174 (11.3%) undergoing ORIF and TEA, respectively. Patients undergoing TEA were older on average (ORIF: 56.2 ± 19.8 years, TEA: 74.3 ± 11.0 years, P < .001). 348 patients were included in the matched analysis, with 174 patients in each group. TEA was associated with an increased risk for postoperative transfusion (OR = 6.808, 95% CI = 1.355 - 34.199, P = .020). There were no significant differences in any adverse event (AAE) between procedures (P = .259). A multivariate analysis indicated age was the only independent risk factor for the development of AAE across both groups (OR = 1.068, 95% CI = 1.011 - 1.128, P = .018). Conclusion: The risk of short-term complications within 30-days of ORIF or TEA procedures are similar when patient characteristics are controlled. TEA, however, was found to increase the risk of postoperative transfusions. Risks associated with increasing patient age should be considered prior to either procedure. These findings suggest that long-term functional outcomes can be prioritized in the management of distal humerus fractures.

A folding motif formed with an expanded genetic alphabet.

Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ-:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ-:dZ pairs join parallel strands in a four-stranded compact down-up-down-up fold. These have two possible structures: one with intercalated dZ-:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.

The art of establishing mineral tolerances of dogs and cats.

For over six decades, nutritional science has provided well-developed, peer-reviewed nutrient recommendations to support the health of dogs and cats. These guidelines are updated based on new scientifically valid research and appropriate peer-review. Recent regulatory and scientific positions around health issues have resulted in strong opinions and desires for rapid regulatory action surrounding mineral nutrition, but with limited and conflicting scientific evidence. Pet Food Institute nutrition experts have come together to jointly author an article on the complexities of establishing mineral tolerances of dogs and cats to illustrate the limitations in defining mineral tolerances. This discussion covers how mineral requirements were determined, including the opportunities and pitfalls encountered. Scientific councils must review and clarify any proposed changes in conducting mineral nutrition research that might impact complete and balanced foods and surrounding regulations. It is important to clarify the multiple issues in mineral nutrition research and the necessity for thorough evaluation of data while avoiding arbitrary and potentially harmful guidelines.

Dogs and cats are living longer and healthier lives due, in part, to the scientific development of nutritional information. This information has allowed the building of many new types of foods, treats, and supplements that promote life, health, and enjoyment by the pet. There are several organizations that have provided helpful reviews of nutritional data through scientific councils that help identify safe and healthy criteria for all pet food products. These are readily available for those who want to learn more about pet nutrition. For many nutrients, there is a large database of information to help build products. Nutrients that are called macro- or micro-/trace minerals (e.g., sodium, potassium, zinc, copper, etc.) often have more limited information. Recently, strong opinions about pet health as related to mineral nutrition have been shared and robustly communicated without adequate scientific research to support the hypotheses. This has led to misinformation, concerns, and fear. To safeguard the health of companion animals and provide assistance to regulatory bodies regarding the nutritional welfare of dogs and cats, scientific panels have come together from industry, government, and academia to review, approve, and challenge nutritional guidelines. This overview provides the reader context into the rigor needed to establish safe mineral tolerances for dogs and cats.

Innovative Ideas, Strategies, and Resources to Attract Students to the Pharmacy Profession: Report of the 2023-2024 AACP Student Affairs Committee.

Over the past two decades, the academy has witnessed an increase in new colleges and schools of pharmacy and simultaneously a decrease in student applications, resulting in a decline in enrollment across most institutions. Although the number of students pursuing a Doctor of Pharmacy (PharmD) degree has been dropping, the academy is responsible for bolstering recruitment to effectively prepare a robust pharmacy workforce to care for our ever-growing and complex patient populations. The 2023-2024 Student Affairs Committee (SAC) was convened to explore new ideas, develop innovative strategies, and gather supportive resources that can be utilized by colleges and schools of pharmacy to attract students to the pharmacy profession. The SAC was charged with developing a framework for a video mini-series that utilizes the art of storytelling to promote the pharmacy profession to prospective students. Secondarily, the SAC was charged with developing a plan to engage with students who apply but do not ultimately get accepted into non-pharmacy health professions programs and consider recommendations for targeting pharmacy technicians to pursue a PharmD degree. To accomplish this work, we created videos and proposed other innovative tools and flexible pathways to assist in recruiting students into the pharmacy profession. We also conducted a literature and website review, engaged in professional networking across the academy, and proposed best practices to enhance student recruitment. Additionally, we offered eight recommendations to AACP and seven suggestions to colleges and schools of pharmacy to attract students to the pharmacy profession. EXECUTIVE SUMMARY: The academy has seen a decrease in student applications, leading to lower enrollment at most institutions. The 2023-2024 Student Affairs Committee (SAC) was chargedto develop new strategies and resources to attract students to pharmacy programs. We created videos and other tools, proposing flexible pathways to aid recruitment. We provided eight recommendations to AACP and seven suggestions to colleges and schools of pharmacy to help attract students to the profession.

An Experimental Infection Model in Sheep and Goats to Evaluate Salmonella Colonization in Deep Tissue Lymph Nodes and after Carcass Vascular Rinsing with Bacteriophages in Goats.

An animal infection model was evaluated on sheep and goats to confirm which species infected with Salmonella enterica serovar Enteritidis C StR (SE13) would provide a consistent and high frequency of Salmonella colonization in lymph nodes (LNs) without causing undue animal morbidity. Sheep and goats (n=5) were intradermally inoculated with Salmonella, post-incubated for 7 days, and euthanized. Superficial cervical, medial iliac, subiliac, mammary, and popliteal LNs were excised from each carcass. Goat LNs had approximately 53% greater Salmonella level compared to sheep. Also, Salmonella was inconsistently recovered from the sheep LNs. Thus, goats were selected to determine the ability of carcass vascular rinsing (with and without bacteriophages) to reduce Salmonella in infected LNs. Goats with similar characteristics were grouped together before being randomly assigned to 3 post-harvest treatments; control (CN, not vascularly rinsed; n=10), vascularly rinsed with a standard Rinse & Chill® solution (RC; 98.5% water and a blend of saccharides and phosphates; n=10), or vascularly rinsed with a standard Rinse & Chill® solution plus the addition of bacteriophages (BP; n=10). Rinse & Chill® system was able to successfully deliver a mean 7.0 log PFU/g to the S. Enteritidis-infected LNs (mean 3.5 log CFU/g). However, neither Rinse & Chill® without bacteriophages nor with bacteriophages caused Salmonella reduction (P>0.05) compared to the non-rinsed goat carcasses.

Using a broadband long-wavelength channel to increase the capture range of segment piston phase retrieval for segmented-aperture systems.

Segmented-aperture systems, such as the James Webb Space Telescope (JWST), require fine piston alignment between primary mirror segments. Computer simulation experiments show that using a broadband long-wavelength channel, illustrated with the Mid Infrared Instrument (MIRI) onboard the JWST, can extend the capture range of segment piston phase retrieval significantly (in the case of JWST with MIRI, up to hundreds of microns), greatly reducing the requirements on coarse phasing.

Chemo- and regio-selective differential modification of native cysteines on an antibody via the use of dehydroalanine forming reagents.

Protein modification has garnered increasing interest over the past few decades and has become an important tool in many aspects of chemical biology. In recent years, much effort has focused on site-selective modification strategies that generate more homogenous bioconjugates, and this is particularly so in the antibody modification space. Modifying native antibodies by targeting solvent-accessible cysteines liberated by interchain disulfide reduction is, perhaps, the predominant strategy for achieving more site-selectivity on an antibody scaffold. This is evidenced by numerous approved antibody therapeutics that have utilised cysteine-directed conjugation reagents and the plethora of methods/strategies focused on antibody cysteine modification. However, all of these methods have a common feature in that after the reduction of native solvent-accessible cystines, the liberated cysteines are all reacted in the same manner. Herein, we report the discovery and application of dehydroalanine forming reagents (including novel reagents) capable of regio- and chemo-selectively modifying these cysteines (differentially) on a clinically relevant antibody fragment and a full antibody. We discovered that these reagents could enable differential reactivity between light chain C-terminal cysteines, heavy chain hinge region cysteines (cysteines with an adjacent proline residue, Cys-Pro), and other heavy chain internal cysteines. This differential reactivity was also showcased on small molecules and on the peptide somatostatin. The application of these dehydroalanine forming reagents was exemplified in the preparation of a dually modified antibody fragment and full antibody. Additionally, we discovered that readily available amide coupling agents can be repurposed as dehydroalanine forming reagents, which could be of interest to the broader field of chemical biology.

Synaptic vesicle release regulates pre-myelinating oligodendrocyte-axon interactions in a neuron subtype-specific manner.

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron-glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.

The Association of Dietary Inflammatory Index and Cognitive Function in Iranian Elders.

BACKGROUND: Cognitive impairment is amongst the most substantial mental health problems in elderly people, and inflammation is an underlying mechanism for cognitive impairment. The dietary inflammatory index (DII®) reflects the overall inflammatory potential of individuals' diets. The current study aimed to assess the relationship between the DII and cognitive function among the Iranian old population. METHODS: This cross-sectional study was conducted on 221 subjects≥65 years old in healthcare centers in five socioeconomically distinct districts of Tehran, Iran. Dietary intake data were obtained using a validated food frequency questionnaire (FFQ). Energy-adjusted-DII (E-DIITM) scores were calculated for each participant according to a total of 35 food parameters, which were available from the FFQ. Mini mental state examination (MMSE), a brief screening questionnaire was used to assess cognitive function. RESULTS: E-DII scores were not significantly associated with cognitive function, both in the crude model (ß=-0.04, p-value=0.82) and after adjusting for potential confounders (ß=0.22, pvalue= 0.14). Additionally, in the unadjusted model, individuals in the highest tertile of E-DII score had increased odds of mild cognitive impairment (OR=1.13, p-trend=0.01) compared to those older adults in the lowest tertile of E-DII score. However, after controlling for potential confounders, these relationships faded (AOR=1.46, p-trend=0.12). CONCLUSION: The findings of the present study showed no significant relationship between E- DII and cognitive function among the Iranian elderly. Future prospective studies should be undertaken to explore the association between diet-associated inflammation and cognitive decline in the elderly.

NSQIP data collection up to 30 postoperative days is sufficient to capture some complications in orthopedic surgeries.

PURPOSE: The primary aim of this study is to determine if the 30-day follow-up period used by the National Surgical Quality Improvement Program (NSIQP) is an appropriate timeframe to capture complications after orthopedic surgeries. METHODS: The 2019 NSQIP data were used. The independent variables were complication type. The dependent variable was days to complication. A Shapiro-Wilk test was used to determine if the data were normally distributed. RESULTS: 271,397 orthopedic cases were included. Myocardial infarction, pneumonia, ventilator over 48 h, progressive renal insufficiency, acute renal failure, stroke, and cardiac arrest had positive skewness and positive kurtosis. Deep incisional surgical site infection (SSI), organ/space SSI, wound disruption, unplanned reoperation one, unplanned reoperation two, readmission two, and readmission three had negative kurtosis and negative skewness. Complications with positive kurtosis and positive skewness are more likely to be confined to the 30-day postoperative period, whereas complications with negative skewness and negative kurtosis may be underreported within the 30-day follow-up. CONCLUSIONS: These findings are useful in their ability to inform future orthopedic research using NSQIP which continues to generate new data for surgeons to consider for their postoperative care and complication management.

Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment.

Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and the modulation of gastric carcinogenesis.

Ribosomal DNA copy number is associated with body mass in humans and other mammals.

Body mass results from a complex interplay between genetics and environment. Previous studies of the genetic contribution to body mass have excluded repetitive regions due to the technical limitations of platforms used for population scale studies. Here we apply genome-wide approaches, identifying an association between adult body mass and the copy number (CN) of 47S-ribosomal DNA (rDNA). rDNA codes for the 18 S, 5.8 S and 28 S ribosomal RNA (rRNA) components of the ribosome. In mammals, there are hundreds of copies of these genes. Inter-individual variation in the rDNA CN has not previously been associated with a mammalian phenotype. Here, we show that rDNA CN variation associates with post-pubertal growth rate in rats and body mass index in adult humans. rDNA CN is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This aligns with the observation that the association emerges by early adulthood.