Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.

Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and 6) are approved for the treatment of subsets of patients with hormone receptor positive (HR+) breast cancer (BC). In metastatic disease, strategies involving endocrine therapy combined with CDK4 and 6 inhibitors (CDK4 and 6i) improve clinical outcomes in HR+ BCs. CDK4 and 6i prevent retinoblastoma tumor suppressor protein phosphorylation, thereby blocking the transcription of E2F target genes, which in turn inhibits both mitogen and estrogen-mediated cell proliferation. In this review, we summarize preclinical data pertaining to the use of CDK4 and 6i in BC, with a particular focus on several of the unique chemical, pharmacologic, and mechanistic properties of abemaciclib. As research efforts elucidate the novel mechanisms underlying abemaciclib activity, potential new applications are being identified. For example, preclinical studies have demonstrated abemaciclib can exert antitumor activity against multiple tumor types and can cross the blood-brain barrier. Abemaciclib has also demonstrated distinct activity as a monotherapeutic in the treatment of BC. Accordingly, we also discuss how a greater understanding of mechanisms related to CDK4 and 6 blockade highlight abemaciclib's unique in-class properties, and could pave new avenues for enhancing its therapeutic efficacy.

The validation of contemporary body composition methods in various races and ethnicities.

Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94-2·37 %; FFM: TE = 0·72-1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52-2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21-2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3-4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.

Effects of adiposity and body composition on adjusted resting energy expenditure in women.

OBJECTIVES: Fat-free mass (FFM) accounts for ~80% of the variance in resting energy expenditure (REE), and this relationship is complicated by adiposity. The objective was to compare adjusted REE and contributions of skeletal lean mass and fat mass (FM) to adjusted REE in women with varying adiposity levels using a novel approach. METHODS: Women were divided into tertiles by body fat percent (%fat): Tertile 1 (T1): %fat = 18.5%-28.4%; Tertile 2 (T2): %fat = 28.5%-33.8%; Tertile 3 (T3): %fat = 34.0%-61.0%. Outcome measures were measured and adjusted REE, body composition (skeletal lean mass, FM, %fat) from dual-energy X-ray absorptiometry, and percent contribution of skeletal lean mass and FM to adjusted REE. RESULTS: The main effect for tertiles (T1 vs. T2 vs. T3) was significant (p = .001); REE was significantly higher in T3 versus both T1 by 281 kcal/day (p = .001) and T2 by 215 kcal/day (p = .001). Expenditure from skeletal lean mass in T1 was significantly higher than T3 by 3.2% (p = .001). T3 had a significantly higher FM contribution than T1 by 5.1% (p = .001) and T2 by 3.9% (p = .001). CONCLUSIONS: Women with elevated %fat experienced lower skeletal lean mass contribution and higher FM contribution to adjusted REE. FM may explain more of the variance in REE between women of different levels of adiposity.

PDE5 inhibition rescues mitochondrial dysfunction and angiogenic responses induced by Akt3 inhibition by promotion of PRC expression.

Akt3 regulates mitochondrial content in endothelial cells through the inhibition of PGC-1α nuclear localization and is also required for angiogenesis. However, whether there is a direct link between mitochondrial function and angiogenesis is unknown. Here we show that Akt3 depletion in primary endothelial cells results in decreased uncoupled oxygen consumption, increased fission, decreased membrane potential, and increased expression of the mitochondria-specific protein chaperones, HSP60 and HSP10, suggesting that Akt3 is required for mitochondrial homeostasis. Direct inhibition of mitochondrial homeostasis by the model oxidant paraquat results in decreased angiogenesis, showing a direct link between angiogenesis and mitochondrial function. Next, in exploring functional links to PGC-1α, the master regulator of mitochondrial biogenesis, we searched for compounds that induce this process. We found that, sildenafil, a phosphodiesterase 5 inhibitor, induced mitochondrial biogenesis as measured by increased uncoupled oxygen consumption, mitochondrial DNA content, and voltage-dependent anion channel protein expression. Sildenafil rescued the effects on mitochondria by Akt3 depletion or pharmacological inhibition and promoted angiogenesis, further supporting that mitochondrial homeostasis is required for angiogenesis. Sildenafil also induces the expression of PGC-1 family member PRC and can compensate for PGC-1α activity during mitochondrial stress by an Akt3-independent mechanism. The induction of PRC by sildenafil depends upon cAMP and the transcription factor CREB. Thus, PRC can functionally substitute during Akt3 depletion for absent PGC-1α activity to restore mitochondrial homeostasis and promote angiogenesis. These findings show that mitochondrial homeostasis as controlled by the PGC family of transcriptional activators is required for angiogenic responses.

Impact of long-term quorum sensing inhibition on uropathogenic Escherichia coli.

BACKGROUND: Quorum sensing is an extracellular bacterial communication system used in the density-dependent regulation of gene expression and development of biofilms. Biofilm formation has been implicated in the establishment of catheter-associated urinary tract infections and therefore quorum sensing inhibitors (QSIs) have been suggested as anti-biofilm catheter coating agents. The long-term effects of QSIs in uropathogens is, however, not clearly understood. OBJECTIVES: We evaluated the effects of repeated exposure to the QSIs cinnamaldehyde, (Z)-4-bromo-5(bromomethylene)-2(5H)-furanone-C30 (furanone-C30) and 4-fluoro-5-hydroxypentane-2,3-dione (F-DPD) on antimicrobial susceptibility, biofilm formation and relative pathogenicity in eight uropathogenic Escherichia coli (UPEC) isolates. METHODS: MICs, MBCs and minimum biofilm eradication concentrations and antibiotic susceptibility were determined. Biofilm formation was quantified using crystal violet. Relative pathogenicity was assessed in a Galleria mellonella model. To correlate changes in phenotype to gene expression, transcriptomic profiles were created through RNA sequencing and variant analysis of genomes was performed in strain EC958. RESULTS: Cinnamaldehyde and furanone-C30 led to increases in susceptibility in planktonic and biofilm-associated UPEC. Relative pathogenicity increased after cinnamaldehyde exposure (4/8 isolates), decreased after furanone-C30 exposure (6/8 isolates) and varied after F-DPD exposure (one increased and one decreased). A total of 9/96 cases of putative antibiotic cross-resistance were generated. Exposure to cinnamaldehyde or F-DPD reduced expression of genes associated with locomotion, whilst cinnamaldehyde caused an increase in genes encoding fimbrial and afimbrial-like adhesins. Furanone-C30 caused a reduction in genes involved in cellular biosynthetic processes, likely though impaired ribonucleoprotein assembly. CONCLUSIONS: The multiple phenotypic adaptations induced during QSI exposure in UPEC should be considered when selecting an anti-infective catheter coating agent.

Technician-Scored Stool Consistency Spans the Full Range of the Bristol Scale in a Healthy US Population and Differs by Diet and Chronic Stress Load.

BACKGROUND: Prior studies of adults with constipation or diarrhea suggest that dietary intake, physical activity, and stress may affect stool consistency. However, the influence of these factors is unresolved and has not been investigated in healthy adults. OBJECTIVES: We assessed the relations of technician-scored stool consistency in healthy adults with self-reported diet, objectively monitored physical activity, and quantifiable markers of stress. METHODS: Stool consistency was scored by an independent technician using the Bristol Stool Form Scale (BSFS) to analyze samples provided by healthy adults, aged 18-65 y, BMI 18-44 kg/m2, in the USDA Nutritional Phenotyping Study (n = 364). A subset of participants (n = 109) were also asked to rate their sample using the BSFS. Dietary intake was assessed with two to three 24-h recalls completed at home and energy expenditure from physical activity was monitored using an accelerometer in the 7-d period preceding the stool collection. Stress was measured using the Wheaton Chronic Stress Inventory and allostatic load (AL). Statistical and machine learning analyses were conducted to determine which dietary, physiological, lifestyle, and stress factors differed by stool form. RESULTS: Technician-scored BSFS scores were significantly further (P = 0.003) from the central score (mean ± SEM distance: 1.41 ± 0.089) than the self-reported score (1.06 ± 0.086). Hard stool was associated with higher (P = 0.005) intake of saturated fat (13.8 ± 0.40 g/1000 kcal) than was normal stool (12.5 ± 0.30 g/1000 kcal). AL scores were lower for normal stool (2.49 ± 0.15) than for hard (3.07 ± 0.18) (P = 0.009) or soft stool (2.89 ± 0.18) (P = 0.049). Machine learning analyses revealed that various dietary components, physiological characteristics, and stress hormones predicted stool consistency. CONCLUSIONS: Technician-scored stool consistency differed by dietary intake and stress hormones, but not by physical activity, in healthy adults.This trial was registered at clincialtrials.gov as NCT02367287.

Acute feeding has minimal effect on the validity of body composition and metabolic measures: dual-energy X-ray absorptiometry and a multi-compartment model.

Understanding the effects of acute feeding on body composition and metabolic measures is essential to the translational component and practical application of measurement and clinical use. To investigate the influence of acute feeding on the validity of dual-energy X-ray absorptiometry (DXA), a four-compartment model (4C) and indirect calorimetry metabolic outcomes, thirty-nine healthy young adults (n 19 females; age: 21·8 (sd 3·1) years, weight; 71·5 (sd 10·0) kg) participated in a randomised cross-over study. Subjects were provided one of four randomised meals on separate occasions (high carbohydrate, high protein, ad libitum or fasted baseline) prior to body composition and metabolic assessments. Regardless of macronutrient content, acute feeding increased DXA percent body fat (%fat) for the total sample and females (average constant error (CE):-0·30 %; total error (TE): 2·34 %), although not significant (P = 0·062); the error in males was minimal (CE: 0·11 %; TE: 0·86 %). DXA fat mass (CE: 0·26 kg; TE: 0·75 kg) and lean mass (LM) (CE: 0·83 kg; TE: 1·23 kg) were not altered beyond measurement error for the total sample. 4C %fat was significantly impacted from all acute feedings (avg CE: 0·46 %; TE: 3·7 %). 4C fat mass (CE: 0·71 kg; TE: 3·38 kg) and fat-free mass (CE: 0·55 kg; TE: 3·05 kg) exceeded measurement error for the total sample. RMR was increased for each feeding condition (TE: 1666·9 kJ/d; 398 kcal/d). Standard pre-testing fasting guidelines may be important when evaluating DXA and 4C %fat, whereas additional DXA variables (fat mass and LM) may not be significantly impacted by an acute meal. Measuring body composition via DXA under less stringent pre-testing guidelines may be valid and increase feasibility of testing in clinical settings.

Ensemble-level energy transfer measurements can reveal the spatial distribution of defect sites in semiconductor nanocrystals.

Energy transfer measurements are widely used to measure the distance between donors and acceptors in heterogeneous environments. In nanocrystal (NC)-molecule donor-acceptor systems, NC defects can participate in electronic energy transfer (EnT) in a defect-mediated EnT process. Here, we explore whether ensemble-level spectroscopy measurements can quantify the distance between the donor defect sites in the NC and acceptor molecules. We studied defect-mediated EnT between ZnO NCs and Alexa Fluor 555 (A555) because EnT occurs via emissive NC defect sites, such as oxygen vacancies. We synthesized a size series of ZnO NCs and characterized their radii, concentration, photoluminescence (PL) lifetime, and defect PL quantum yield using a combination of transmission electron microscopy, elemental analysis, and time-resolved PL spectroscopy. The ZnO defect PL decay kinetics were analyzed using the stochastic binding (SB) and restricted geometry (RG) models. Both models assume the Förster point dipole approximation, but the RG model considers the geometry of the NC donor in the presence of multiple acceptors. The RG model revealed that the emissive defect sites are separated, on average, 0.5 nm from the A555 acceptor molecules. That is, the emissive defect sites are predominantly located at or near the surface of large NCs. The SB model revealed the average number of A555 molecules per NC and the equilibrium binding constant but did not provide meaningful information regarding the defect-acceptor distance. We conclude that ensemble-level EnT measurements can reveal the spatial distribution of defect sites in NCs without the need for interrogating the sample with a microscope.

Metabolic effects of high-intensity interval training and essential amino acids.

High-intensity interval training (HIIT) promotes positive cardiometabolic and body composition changes. Essential amino acids (EAA) may support changes associated with HIIT, but evaluation of potential synergistic effects is lacking. The purpose of this study was to compare independent and combined effects of HIIT and EAA on total body composition and metabolism in men and women considered overweight/obese; an exploratory aim was to evaluate the modulatory effects of sex. Sixty-six healthy adults (50% female; Age: 36.7 ± 6.0 years; BMI: 32.0 ± 4.2 kg/m2) completed 8 weeks of: (1) HIIT, 2 days/weeks; (2) EAA supplementation, 3.6 g twice daily; (3) HIIT + EAA; or (4) control. Body composition, resting metabolic rate (RMR), substrate metabolism (respiratory exchange ratio; RER), and cardiorespiratory fitness were measured at baseline, 4 weeks, and 8 weeks; cardiometabolic blood markers were measured at baseline and 8 weeks. Differences between groups were assessed by linear mixed models covaried for baseline values, followed by 95% confidence intervals (CI) on adjusted mean change scores. There were no significant changes in body composition (p > 0.05) for any group. Changes in RER, but not RMR, occurred with HIIT (mean change; [95% CI]: - 0.04; [- 0.07, - 0.02]) and EAA (- 0.03; [- 0.06, - 0.01]) after 8 weeks. Cardiorespiratory fitness increased following 8 weeks of HIIT (+ 5.1 ml/kg/min [3.3,6.8]) and HIIT + EAA (+ 4.1 ml/kg/min [1.0,6.4]). Changes with HIIT + EAA were not significantly different from HIIT. There were no changes in cardiometabolic markers (p > 0.05) and no sex interaction (p > 0.05). HIIT is efficacious for promoting positive changes in cardiorespiratory fitness and resting substrate metabolism in adults considered overweight/obese. Addition of EAA did not significantly enhance HIIT-induced adaptations. ClinicalTrials.gov ID#NCT04080102.

White Cord Syndrome after Thoracic Cord Decompression in a Pediatric Patient.

INTRODUCTION: White cord syndrome (WCS) is a rare phenomenon which causes acute neurologic deterioration after a chronically compressed spinal cord is surgically decompressed, resulting in a T2-hyperintense signal to appear in the cord. We present the first case of pediatric WCS in the thoracic spine and the first to show complete resolution of symptoms. CASE PRESENTATION: A 3-year-old girl presented with difficulty ambulating due to pain caused by T4-8 spinal cord compression from a mass of ganglioneuromatous tissue, consistent with her previously treated mediastinal neuroblastoma. She underwent laminoplasty and microsurgical debulking of the mass. She developed severe bilateral leg weakness on postoperative day 1. Magnetic resonance imaging (MRI) showed T2 hyperintensity in the spinal cord from T1 to T10 without enhancement, concerning for WCS. She was started on high-dose steroids and monitored. Her strength improved to 3/5 in both legs prior to discharge to inpatient rehabilitation. On the latest follow-up, 4 months after surgery, she did not demonstrate any neurologic deficits and was ambulating well. Follow-up MRIs have showed continued improvement in the T2 hyperintensity. DISCUSSION/CONCLUSION: Most cases in the literature occur in older adults with chronic cervical compression. Only 1 pediatric case, caused by a cervical arachnoid cyst, has been reported and only resulted in partial improvement. Our case is the first pediatric case of WCS to occur in the thoracic spine, the first pediatric case to demonstrate complete resolution, and the first case of any age to start to establish a length of time the compression is needed to be at risk for WCS.

The Function of KDEL Receptors as UPR Genes in Disease.

The KDEL receptor retrieval pathway is essential for maintaining resident proteins in the endoplasmic reticulum (ER) lumen. ER resident proteins serve a variety of functions, including protein folding and maturation. Perturbations to the lumenal ER microenvironment, such as calcium depletion, can cause protein misfolding and activation of the unfolded protein response (UPR). Additionally, ER resident proteins are secreted from the cell by overwhelming the KDEL receptor retrieval pathway. Recent data show that KDEL receptors are also activated during the UPR through the IRE1/XBP1 signaling pathway as an adaptive response to cellular stress set forth to reduce the loss of ER resident proteins. This review will discuss the emerging connection between UPR activation and KDEL receptors as it pertains to ER proteostasis and disease states.

Exploring the "Athlete's Paradox": Division I Cross-Country Runners Demonstrate Similar Muscle Characteristics to Recreationally Trained Young Adults.

ABSTRACT: Cabre, HE, Greenwalt, CE, Gould, LM, Hirsch, KR, Blue, MNM, and Smith-Ryan, AE. Exploring the "Athlete's Paradox": Division I cross-country runners demonstrate similar muscle characteristics to recreationally trained young adults. J Strength Cond Res 35(11): 3213-3217, 2021-Endurance training can influence body composition and muscle characteristics. Endurance athletes have demonstrated elevated intramuscular fat (IMF), yet individuals with greater body fat also demonstrate elevated IMF. The purpose of this study was to examine differences in muscle characteristics (echo intensity [EI] and muscle cross-sectional area [mCSA]) and body composition between Division I collegiate athletes and college-age adults matched for percent fat (%fat). Thirty cross-country athletes (XC) and 30 normal-weight (NW) recreationally active college students (male athletes: n = 30; female athletes: n = 30; mean ± SD: age: 19.2 ± 1.1 years; body mass: 61.7 ± 8.7 kg; %fat: 18.0 ± 5.2%) underwent a panoramic ultrasound scan of the vastus lateralis to evaluate EI and mCSA. A full-body dual-energy x-ray absorptiometry scan was used to assess fat mass (FM), lean mass (LM), and %fat. Independent t-tests were used to evaluate mCSA, EI, and body composition. Significance level was set at ≤ 0.05. There were no significant differences between the XC and NW cohorts in mCSA (mean difference [MD; XC - NW], -1.30 ± -0.40 cm3; p = 0.340) or EI (MD: 3.97 ± 2.66 a.u.; p = 0.478). Body composition was not different between the groups: FM (MD: -0.14 ± -0.54 kg; p = 0.848), LM (-3.07 ± 1.25 kg; p = 0.268), or bone mineral content (-0.21 ± 0.03 kg; p = 0.120). There were also no significant differences for any outcome variables when stratified by male athletes (p = 0.097-0.468) or female athletes (p = 0.055-0.700). These results suggest that XC athletes may have similar muscle characteristics to NW individuals when matched for %fat. Understanding and tracking muscle characteristics in XC athletes may be important for performance, injury prevention, and the transition to retirement.

Uterine perforation secondary to metritis and placenta percreta in a postpartum bitch.

A 3-year-old intact female Labradoodle bitch was referred due to fever and lethargy 4 days postpartum. The dog was reported to have had prolonged labor that required assistance and fetal membranes were retained. Physical examination and diagnostics led to a suspicion of metritis and uterine perforation. Ovariohysterectomy was performed. Gross and histopathology findings revealed multifocal uterine perforation, necrosuppurative metritis, and placenta percreta. Post-operative antibiotic therapy and supportive care resulted in an uneventful clinical recovery. This is the first reported case of placenta percreta in a bitch. It is presumed that this pathology was paramount in the patient's development of metritis and subsequent uterine rupture. Key clinical message: Placenta percreta may lead to more severe clinical consequences of metritis, including uterine rupture.

Perforation utérine secondaire à une métrite et un placenta percreta chez une chienne en période post-partum. Une femelle Labradoodle intacte âgée de 3 ans fut référée pour cause de fièvre et léthargie 4 jours post-partum. Il fut rapporté que la chienne avait eu un travail long qui demanda de l'assistance et qu'il y avait eu rétention des membranes foetales. L'examen physique et le diagnostic mena à un doute de métrite et de perforation utérine. Une ovario-hystérectomie fut réalisée. Les trouvailles de pathologie macroscopique et d'histopathologie révélèrent des perforations utérines multifocales, une métrite nécro-suppurative et un placenta percreta. Une antibiothérapie post-opératoire et des soins de support ont résulté en une guérison clinique sans conséquence. Ceci représente le premier cas rapporté de placenta percreta chez une chienne. Il est présumé que chez cette chienne cette pathologie était vitale dans le développement de la métrite et de la rupture utérine subséquente.Message clinique clé :Un placenta percreta peut mener à des conséquences cliniques plus sévères de métrite, incluant la rupture utérine.(Traduit par Dr Serge Messier).

Biocide Exposure Induces Changes in Susceptibility, Pathogenicity, and Biofilm Formation in Uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is a frequent cause of catheter-associated urinary tract infection (CAUTI). Biocides have been incorporated into catheter coatings to inhibit bacterial colonization while, ideally, exhibiting low cytotoxicity and mitigating the selection of resistant bacterial populations. We compared the effects of long-term biocide exposure on susceptibility, biofilm formation, and relative pathogenicity in eight UPEC isolates. MICs, minimum bactericidal concentrations (MBCs), minimum biofilm eradication concentrations (MBECs), and antibiotic susceptibilities were determined before and after long-term exposure to triclosan, polyhexamethylene biguanide (PHMB), benzalkonium chloride (BAC), and silver nitrate. Biofilm formation was quantified using a crystal violet assay, and relative pathogenicity was assessed via a Galleria mellonella waxworm model. Cytotoxicity and the resulting biocompatibility index values were determined by use of an L929 murine fibroblast cell line. Biocide exposure resulted in multiple decreases in biocide susceptibility in planktonic and biofilm-associated UPEC. Triclosan exposure induced the largest frequency and magnitude of susceptibility decreases at the MIC, MBC, and MBEC, which correlated with an increase in biofilm biomass in all isolates. Induction of antibiotic cross-resistance occurred in 6/84 possible combinations of bacteria, biocide, and antibiotic. Relative pathogenicity significantly decreased after triclosan exposure (5/8 isolates), increased after silver nitrate exposure (2/8 isolates), and varied between isolates for PHMB and BAC. The biocompatibility index ranked the antiseptic potential as PHMB > triclosan > BAC > silver nitrate. Biocide exposure in UPEC may lead to reductions in biocide and antibiotic susceptibility, changes in biofilm formation, and alterations in relative pathogenicity. These data indicate the multiple consequences of biocide adaptation that should be considered when selecting an anti-infective catheter-coating agent.

Prenatal Iron Deficiency and Replete Iron Status Are Associated with Adverse Birth Outcomes, but Associations Differ in Ghana and Malawi.

BACKGROUND: Previous literature suggests a U-shaped relation between hemoglobin concentration and adverse birth outcomes. There is less evidence on associations between iron status and birth outcomes. OBJECTIVE: Our objective was to determine the associations of maternal hemoglobin concentration and iron status with birth outcomes. METHODS: We conducted a secondary data analysis of data from 2 cohorts of pregnant women receiving iron-containing nutritional supplements (20-60 mg ferrous sulfate) in Ghana (n = 1137) and Malawi (n = 1243). Hemoglobin concentration and 2 markers of iron status [zinc protoporphyrin and soluble transferrin receptor (sTfR)] were measured at ≤20 weeks and 36 weeks of gestation. We used linear and Poisson regression models and birth outcomes included preterm birth (PTB), newborn stunting, low birth weight (LBW), and small-for-gestational-age. RESULTS: Prevalence of iron deficiency (sTfR >6.0 mg/L) at enrollment was 9% in Ghana and 20% in Malawi. In early pregnancy, iron deficiency was associated with PTB (9% compared with 17%, adjusted RR: 1.63; 95% CI: 1.14, 2.33) and stunting (15% compared with 23%, adjusted RR: 1.44; 95% CI: 1.09, 1.94) in Malawi but not Ghana, and was not associated with LBW in either country; replete iron status (sTfR <10th percentile) was associated with stunting (9% compared with 15%, adjusted RR: 1.71; 95% CI: 1.06, 2.77) in Ghana, but not PTB or LBW, and was not associated with any birth outcomes in Malawi. In late pregnancy, iron deficiency was not related to birth outcomes in either country and iron-replete status was associated with higher risk of LBW (8% compared with 16%, adjusted RR: 1.90; 95% CI: 1.17, 3.09) and stunting (6% compared with 13%, adjusted RR: 2.14; 95% CI: 1.21, 3.77) in Ghana, but was not associated with birth outcomes in Malawi. CONCLUSIONS: The associations of low or replete iron status with birth outcomes are population specific. Research to replicate and extend these findings would be beneficial. These trials were registered at clinicaltrials.gov as NCT00970866 (Ghana) and NCT01239693 (Malawi).

Effect of print layer height on the assessment of 3D-printed models.

INTRODUCTION: Many variables can affect the accuracy of 3D-printed orthodontic models, and the effects of different printing parameters on the clinical utility of the printed models are just beginning to be understood. The objective of this study was to investigate the effect of print layer height on the assessment of 3D-printed orthodontic models with the use of the American Board of Orthodontics Cast-Radiograph Evaluation grading system. METHODS: Twelve cases were scanned using a desktop model scanner and 3D-printed using a stereolithography-based printer at three different layer heights (25, 50, and 100-µm; n = 12 per group). All models were scored by eleven graders using the Cast-Radiograph Evaluation grading system. All models were scored a second time, at least two weeks later. RESULTS: No statistically significant effects of print layer height were found on the scoring of the models for any of the grading metrics or total score. 3D-printed models of each layer height were highly positively correlated with stone models for the total score, with the strongest correlation found with models printed at 100-µm. CONCLUSIONS: 100-µm layer height 3D-printed models are potentially clinically acceptable for the purposes of evaluation of treatment outcomes, diagnosis and treatment planning, and residency training.

Comparison of automated grading of digital orthodontic models and hand grading of 3-dimensionally printed models.

INTRODUCTION: Emerging workflows in orthodontics enable automated analysis of digital models and production of physical study models from digital files for the evaluation of treatment outcomes. The objective of this study was to compare the automated assessment of digital orthodontic models and the hand grading of 3D-printed models with the use of the American Board of Orthodontics cast-radiograph evaluation (ABO CRE) system. METHODS: Plaster models from 15 cases were scanned with the use of a desktop model scanner to create digital models from which physical models were produced with the use of a stereolithography-based 3D printer. All digital models from each case were graded with the use of an automated software tool (SureSmile), and 3D-printed models were scored by hand with the use of the ABO CRE grading system. All hand-graded models were scored a second time at least 2 weeks later. RESULTS: SureSmile gave statistically significantly higher scores to alignment and rotations (P < 0.001), overjet (P < 0.001), occlusal contacts (P < 0.001), and total score (P < 0.001). Hand grading scored higher in buccolingual inclination (P < 0.001). No significant differences were found in marginal ridges, occlusal relationships, and interproximal contacts. CONCLUSIONS: Scores assessed in an automated manner by SureSmile are generally significantly greater than those assessed by hand grading.

Survey for the presence of a vitronectin-like protein in micro- and macroalgae and cyanobacteria.

Vitronectin (Vn) is a glycoprotein that serves a wide variety of roles in multicellular organisms. It was first identified in multicellular animals but has also been isolated from land plants and some algae, where it appears to serve as an extracellular adhesive molecule. In order to further elucidate presence and localization of a Vn-like protein and its potential role in algae, we surveyed different morphological regions of 24 species of macro- and microalgae and three species of cyanobacteria for the presence of a Vn-like protein. Vn-like proteins were not detected in any of the species of cyanobacteria, microalgae or Rhodophyta investigated. They were detected in several species of the Phaeophyceae and Chlorophyta where their localization was limited to the holdfast and rhizoids of these organisms, respectively. Detection of a Vn-like protein (between 0.0125 and 0.097 µg · µL-1 protein extract) was therefore limited to locations associated with substrate attachment.

Silver diamine fluoride and bond strength to enamel in vitro: A pilot study.

PURPOSE: To evaluate if pre-treatment with silver diamine fluoride (SDF) adversely affects the bond strength of orthodontic brackets to enamel. METHODS: 30 extracted non-carious permanent molar teeth were embedded in acrylic resin cylinders with buccal surfaces exposed and randomly divided equally into two groups. The experimental enamel surfaces were treated with 38% SDF applied for 1 minute between phosphoric acid etch and metal orthodontic bracket bonding with Transbond XT Light Cure Adhesive. Control groups were treated with 37% phosphoric acid etch followed by bonding. All samples were subjected to 500 thermocycles between 5°C and 55°C prior to shear load testing. Mean values and standard deviations of shear bond strengths for each group were analyzed using a general linear model at P< 0.05. Characteristics of bond failure were also recorded via Adhesive Remnant Index (ARI) and analyzed using an ordinal logistic regression at P< 0.05. RESULTS: No significant difference in shear bond strength to enamel was observed between the control and experimental groups (P= 0.65). Comparison of ARI did demonstrate a significant difference between the groups (P= 0.013); SDF significantly altered the characteristic of bond failure, resulting in more adhesive remaining bonded to enamel after failure. No silver staining of treated surfaces was observed. CLINICAL SIGNIFICANCE: The application of SDF to etched non-carious enamel in vitro prior to orthodontic bracket bonding does not adversely affect bond strength.

Effects of lipid-based nutrient supplements or multiple micronutrient supplements compared with iron and folic acid supplements during pregnancy on maternal haemoglobin and iron status.

We examined the effect of three types of prenatal supplements containing different amounts of iron on haemoglobin (Hb) and iron status (zinc protoporphyrin [ZPP] and soluble transferrin receptor [sTfR]) in late pregnancy among 1,379 women in rural Malawi. Participants were recruited at ≤20 gestational weeks (gw) and randomly assigned to consume daily (1) 60-mg iron and folic acid (IFA); (2) 20-mg iron plus 17 micronutrients in a capsule (MMN); or (3) lipid-based nutrient supplement (LNS; 118 kcal) with 20-mg iron plus 21 micronutrients, protein, and fat. We analysed differences between intervention groups in mean Hb, ZPP, and sTfR at 36 gw, and the proportion with anaemia (Hb < 100 g L-1 ) and iron deficiency (ZPP > 60 µmol mol-1 haem or sTfR > 6 mg L-1 ) at 36 gw. Women in the IFA group had higher Hb at 36 gw than women in the LNS group (P = 0.030) and higher iron status (lower ZPP and sTfR) than women in both the LNS (P < 0.001 for both ZPP and sTfR) and MMN (P = 0.025 and P = 0.046) groups. Results for anaemia and iron deficiency showed similar trends. Further research is needed to elucidate the appropriate amount of iron to improve Hb and iron status, while improving birth outcomes.