GULP1 deficiency reduces adipogenesis and glucose uptake via downregulation of PPAR signaling and disturbing of insulin/ERK signaling in 3T3-L1 cells.

Obesity and metabolic disorders caused by alterations in lipid metabolism are major health issues in developed, affluent societies. Adipose tissue is the only organ that stores lipids and prevents lipotoxicity in other organs. Mature adipocytes can affect themselves and distant metabolism-related tissues by producing various adipokines, including adiponectin and leptin. The engulfment adaptor phosphotyrosine-binding domain-containing 1 (GULP1) regulates intracellular trafficking of glycosphingolipids and cholesterol, suggesting its close association with lipid metabolism. However, the role of GULP1 in adipocytes remains unknown. Therefore, this study aimed to investigate the function of GULP1 in adipogenesis, glucose uptake, and the insulin signaling pathway in adipocytes. A 3T3-L1 cell line with Gulp1 knockdown (shGulp1) and a 3T3-L1 control group (U6) were established. Changes in shGulp1 cells due to GULP1 deficiency were examined and compared to those in U6 cells using microarray analysis. Glucose uptake was monitored via insulin stimulation in shGulp1 and U6 cells using a 2-NBDG glucose uptake assay, and the insulin signaling pathway was investigated by western blot analysis. Adipogenesis was significantly delayed, lipid metabolism was altered, and several adipogenesis-related genes were downregulated in shGulp1 cells compared to those in U6 cells. Microarray analysis revealed significant inhibition of peroxisome proliferator-activated receptor signaling in shGulp1 cells compared with U6 cells. The production and secretion of adiponectin as well as the expression of adiponectin receptor were decreased in shGulp1 cells. In particular, compared with U6 cells, glucose uptake via insulin stimulation was significantly decreased in shGulp1 cells through the disturbance of ERK1/2 phosphorylation. This is the first study to identify the role of GULP1 in adipogenesis and insulin-stimulated glucose uptake by adipocytes, thereby providing new insights into the differentiation and functions of adipocytes and the metabolism of lipids and glucose, which can help better understand metabolic diseases.

Unique cartilage matrix-associated protein inhibits osteoclast differentiation by alleviating RANKL-induced reactive oxygen species.

Unique cartilage matrix-associated protein (UCMA) is a γ-carboxyglutamic acid-rich secretory protein primarily expressed in adult cartilage. UCMA promotes osteoblast differentiation and reduces high glucose-induced reactive oxygen species (ROS) production in osteoblasts; however, its role in osteoclasts remains unclear. Since Ucma is not expressed in osteoclasts, treatment with recombinant UCMA protein (rUCMA) was employed to investigate the effect of UCMA on osteoclasts. The rUCMA-treated osteoclasts exhibited significantly reduced osteoclast differentiation, resorption activity, and osteoclast-specific gene expression. Moreover, rUCMA treatment reduced RANKL-induced ROS production and increased the expression of antioxidant genes in osteoclasts. This study demonstrates that UCMA effectively inhibits RANKL-stimulated osteoclast differentiation and oxidative stress.

Sarcopenia, a Risk Predictor of Postoperative Acute Kidney Injury in Elderly Patients after Hip Fracture Surgery: A Retrospective Analysis.

Background and Objectives: Hip fracture surgery, which affects quality of life, can be a major challenge in geriatric populations. Although sarcopenia is known to be associated with postoperative outcomes, there are few studies on the association between sarcopenia and postoperative acute kidney injury (AKI) in this population. We investigated the association between sarcopenia and postoperative AKI in elderly patients following hip fracture surgery. Materials and Methods: We retrospectively reviewed the records of patients who underwent hip fracture surgery at our institution from March 2019 to December 2021. Patients under the age of 65, patients with no preoperative computed tomography (CT) scans and patients with inappropriate cross-sectional images for measurement were excluded. The psoas-lumbar vertebral index (PLVI), which is the ratio of the average area of both psoas muscles to the area of the fourth lumbar vertebral body, was measured from preoperative CT scans. Sarcopenia was defined as a PLVI within the lowest 25% for each sex, and patients were categorized into sarcopenic and nonsarcopenic groups. The occurrence of AKI was determined based on the serum creatinine level within postoperative day 7 using the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and the occurrence of AKI. Results: Among the 348 enrolled patients, 92 patients were excluded, and 256 patients were analyzed. The PLVI cutoff values for defining sarcopenia lower than 25% for male and female patients were 0.57 and 0.43, respectively. The overall incidence of AKI was 18.4% (47 patients), and AKI occurred more frequently in sarcopenic patients than in nonsarcopenic patients (29.7% vs. 14.6%, p = 0.007). According to the multivariate logistic regression, which included all variables with a p value < 0.05 in the univariate analysis and adjusted for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) physical status, sarcopenia was revealed to be an independent predictor of postoperative AKI (odds ratio = 5.10, 95% confidence interval = 1.77-14.77; p = 0.003). Conclusions: Preoperative sarcopenia, which corresponds to the lowest quartile of PLVI values, is associated with postoperative AKI among elderly patients who underwent hip fracture surgery.

Gulp1 deficiency augments bone mass in male mice by affecting osteoclasts due to elevated 17ß-estradiol levels.

The engulfment adaptor phosphotyrosine-binding domain containing 1 (GULP1) is an adaptor protein involved in the engulfment of apoptotic cells via phagocytosis. Gulp1 was first found to promote the phagocytosis of apoptotic cells by macrophages, and its role in various tissues, including neurons and ovaries, has been well studied. However, the expression and function of GULP1 in bone tissue are poorly understood. Consequently, to determine whether GULP1 plays a role in the regulation of bone remodeling in vitro and in vivo, we generated Gulp1 knockout (KO) mice. Gulp1 was expressed in bone tissue, mainly in osteoblasts, while its expression is very low in osteoclasts. Microcomputed tomography and histomorphometry analysis in 8-week-old male Gulp1 KO mice revealed a high bone mass in comparison with male wild-type (WT) mice. This was a result of decreased osteoclast differentiation and function in vivo and in vitro as confirmed by a reduced actin ring and microtubule formation in osteoclasts. Gas chromatography-mass spectrometry analysis further showed that both 17ß-estradiol (E2) and 2-hydroxyestradiol levels, and the E2/testosterone metabolic ratio, reflecting aromatase activity, were also higher in the bone marrow of male Gulp1 KO mice than in male WT mice. Consistent with mass spectrometry analysis, aromatase enzymatic activity was significantly higher in the bone marrow of male Gulp1 KO mice. Altogether, our results suggest that GULP1 deficiency decreases the differentiation and function of osteoclasts themselves and increases sex steroid hormone-mediated inhibition of osteoclast differentiation and function, rather than affecting osteoblasts, resulting in a high bone mass in male mice. To the best of our knowledge, this is the first study to explore the direct and indirect roles of GULP1 in bone remodeling, providing new insights into its regulation.

Impact of fiber-fortified food consumption on anthropometric measurements and cardiometabolic outcomes: A systematic review, meta-analyses, and meta-regressions of randomized controlled trials.

The consumption of processed and refined food lacking in fiber has led to global prevalence of obesity and cardiometabolic diseases. Fiber-fortification into these foods can yield potential health improvements to reduce disease risk. This meta-analyses aimed to evaluate how fiber-fortified food consumption changes body composition, blood pressure, blood lipid-lipoprotein panel, and glycemic-related markers. Searches were performed from 5 databases, with 31 randomized controlled trial eventually analyzed. Hedges' g values (95% confidence interval [CI]) attained from outcome change values were calculated using random-effects model. Fiber-fortified food significantly reduced body weight (-0.31 [-0.59, -0.03]), fat mass (-0.49 [-0.72, -0.26]), total cholesterol (-0.54 [-0.71, -0.36]), low-density lipoprotein cholesterol (-0.49 [-0.65, -0.33]), triglycerides (-0.24 [-0.36, -0.12]), fasting glucose (-0.30 [-0.49, -0.12]), and HbA1c (-0.44 [-0.74, -0.13]). Subgroup analysis differentiated soluble fiber as significantly reducing triglycerides and insulin while insoluble fiber significantly reduced body weight, BMI, and HbA1c. Greater outcome improvements were observed with solid/semi-solid food state than liquid state. Additionally, fiber fortification of <15 g/day induced more health outcome benefits compared to ≥15 g/day, although meta-regression found a dose-dependent improvement to waist circumference (p-value = 0.036). Findings from this study suggest that consuming food fortified with dietary fiber can improve anthropometric and cardiometabolic outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2053658.

Endothelial progenitor cells as an emerging cardiovascular risk factor in the field of food and nutrition research: advances and challenges.

Dietary modifications can help prevent many cardiovascular disease (CVD) events. Endothelial progenitor cells (EPCs) actively contribute to cardiovascular system maintenance and could function as surrogate markers for evaluating improvement in cardiovascular health resulting from nutritional interventions. This review summarizes the latest research progress on the impact of food and nutrients on EPCs, drawing on evidence from human, animal, and in vitro studies. Additionally, current trends and challenges faced in the field are highlighted. Findings from studies examining cells as EPCs are generally consistent, demonstrating that a healthy diet, such as the Mediterranean diet or a supervised diet for overweight people, specific foods like olive oil, fruit, vegetables, red wine, tea, chia, and nutraceuticals, and certain nutrients such as polyphenols, unsaturated fats, inorganic nitrate, and vitamins, generally promote higher EPC numbers and enhanced EPC function. Conversely, an unhealthy diet, such as one high in sugar substitutes, salt, or fructose, impairs EPC function. Research on outgrowth EPCs has revealed that various pathways are involved in the modulation effects of food and nutrients. The potential of EPCs as a biomarker for assessing the effectiveness of nutritional interventions in preventing CVDs is immense, while further clarification on definition and characterization of EPCs is required.

Measures of carbohydrate quality and their association with diet quality and cardiometabolic health outcomes in Singapore middle-aged and older adults.

BACKGROUND AND AIMS: Carbohydrate quality may play a key role in cardiometabolic health and disease risk. This study aimed to assess the dietary carbohydrate quality of the free-living middle-aged and older adults in Singapore, and its association with overall diet quality and cardiometabolic health. METHODS AND RESULTS: This cross-sectional study examined the diet and cardiometabolic disease risk indicators of middle-aged and older adults in Singapore (n = 104). Dietary carbohydrate quality was assessed as the pass and fail rate of the population to four measures of carbohydrate quality: (i) dietary fiber recommended daily allowance (RDA), (ii) whole-grain recommendation, (iii) free sugar recommendation, and (iv) carbohydrate metrics. The association between each carbohydrate quality measure and diet quality, as well as cardiometabolic health, was assessed. Except for free sugar recommendation, the carbohydrate quality of the population was found to be poor with a low adherence (20-36%) to three measures. Subjects meeting these measures had generally higher intakes of fiber, protein, and most micronutrients compared with subjects who failed. Meeting different variants of the carbohydrate metrics was associated with 60% lower odds of pre-hypertensive blood pressure (p = 0.037; p = 0.047), and meeting the dietary fiber RDA was associated with lower waist circumference (p = 0.021). CONCLUSION: An improvement in carbohydrate quality is warranted among free-living middle-aged and older adults in Singapore. Not all measures of carbohydrate quality were equally effective in preserving overall diet quality; the carbohydrate metrics and dietary fiber RDA can be identified as effective measures in relation to cardiometabolic disease risk. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ CLINICAL TRIAL REGISTRATION: NCT03554954, 13 Sept. 2018.

GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone.

Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor ß (TGF-ß) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality of Gdf11 null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show that Gdf11 null mice, despite significantly down-regulating Mstn expression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed in Mstn null mice that display enhanced bone mass. Mechanistically, Mstn deletion up-regulates Gdf11 expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlike Mstn null mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.

Effects of different fats on postprandial appetite responses: a randomised crossover trial.

Overconsumption of fat is considered a major driver of the prevalence of obesity globally. While fat type and emulsification have been suggested to play roles in appetite control, very limited data exist. This study aimed to investigate the impacts of type and emulsification of fat on postprandial appetite responses. Sixteen healthy subjects participated in a 4-arm, randomised, crossover study. The net iAUC of hunger visual analogue scales (VAS) (mean ± SE) was observed higher with emulsified fat (-512 ± 137 cm × 300 min) than with non-emulsified fat (-785 ± 133 cm × 300 min) (p < 0.05), but the difference became insignificant over time. Compared to olive oil, coconut oil resulted in higher fullness VAS iAUC (olive oil: 1369 ± 306 cm × 600 min; coconut oil: 1786 ± 311 cm × 600 mi, p < 0.05). Findings from this study support the potential effects of fat in appetite regulation.

An Automated High-Throughput Screening (HTS) Spotter for 3D Tumor Spheroid Formation.

Three-dimensional (3D) culture platforms have been adopted in a high-throughput screening (HTS) system to mimic in vivo physiological microenvironments. The automated dispenser has been established commercially to enable spotting or distributing non-viscous or viscous biomaterials onto microplates. However, there are still challenges to the precise and accurate dispensation of cells embedded in hydrogels such as Alginate- and Matrigel-extracellular matrices. We developed and improved an automated contact-free dispensing machine, the ASFA SPOTTER (V5 and V6), which is compatible with 96- and 384-pillar/well plates and 330- and 532-micropillar/well chips for the support of 3D spheroid/organoid models using bioprinting techniques. This enables the distribution of non-viscous and viscous biosamples, including chemical drugs and cancer cells, for large-scale drug screening at high speed and small volumes (20 to 4000 nanoliters) with no damage to cells. The ASFA SPOTTER (V5 and V6) utilizes a contact-free method that minimizes cross-contamination for the dispensation of encapsulated tissue cells with highly viscous scaffolds (over 70%). In particular, the SPOTTER V6 does not require a washing process and offers the advantage of almost no dead volume (defined as additional required sample volume, including a pre-shot and flushing shot for dispensing). It can be successfully applied for the achievement of an organoid culture in automation, with rapid and easy operation, as well as miniaturization for high-throughput screening. In this study, we report the advantages of the ASFA SPOTTER, which distributes standard-sized cell spots with hydrogels onto a 384-pillar/well plate with a fast dispensing speed, small-scale volume, accuracy, and precision.

Interactions between Malassezia and New Therapeutic Agents in Atopic Dermatitis Affecting Skin Barrier and Inflammation in Recombinant Human Epidermis Model.

Several studies have reported the pathogenic role of Malassezia in atopic dermatitis (AD); the significance of Malassezia's influence on AD needs to be further investigated. Dupilumab, a monoclonal antibody to anti-Interleukin (IL) 4Rα, and ruxolitinib, a Janus kinase (JAK)1/2 inhibitor, are the first approved biologics and inhibitors widely used for AD treatment. In this study, we aimed to investigate how Malassezia Restricta (M. restricta) affects the skin barrier and inflammation in AD and interacts with the AD therapeutic agents ruxolitinib and anti-IL4Rα. To induce an in vitro AD model, a reconstructed human epidermis (RHE) was treated with IL-4 and IL-13. M. restricta was inoculated on the surface of RHE, and anti-IL4Rα or ruxolitinib was supplemented to model treated AD lesions. Histological and molecular analyses were performed. Skin barrier and ceramide-related molecules were downregulated by M. restricta and reverted by anti-IL4Rα and ruxolitinib. Antimicrobial peptides, VEGF, Th2-related, and JAK/STAT pathway molecules were upregulated by M. restricta and suppressed by anti-IL4Rα and ruxolitinib. These findings show that M. restricta aggravated skin barrier function and Th2 inflammation and decreased the efficacy of anti-IL4Rα and ruxolitinib.

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

Estradiol-17 ß levels as a tool for sex determination in Farmed Anguilla japonica.

In this study, the levels of plasma estradiol-17ß (E2) in farmed Anguilla japonica were measured to determine their sex. The analyses were performed for two different size groups (large group, Total length (TL): 61-69 cm; small group, TL: 53-60 cm). The anatomical and histological observations showed that the large group consisted of 29% males and 71% females; the small group, 54% males and 45% females. The gonad histology showed that in the large group, 88% of the eels had immature gonads with ongoing sexual differentiation, 12% were mature with completed sexual differentiation. In the small group, 87% of the eels had immature gonads. The plasma E2 hormone levels were higher in the females of both sizes. In the large group, the average plasma E2 in females was 415 pg/ml, which was significantly higher than the average of 109 pg/ml in males (P < 0.05). In the small group, the average plasma E2 hormone level was 618 pg/ml, which was much higher than the average of 108 pg/ml in males. Quantitative real-time PCR showed that zygote arrest 1 (zar 1) and zona pellucida glycoprotein 3 (zp3) were more highly expressed in females than male. In the H-E staining, an eel in the oil droplet containing ovary stage had a high level of plasma E2 (1500 pg/ml), while an eel with testis in the spermatocyte stage had a low (60 pg/ml). E2 is a potentially useful tool and could play an important role in sex determination in broodstocks.

Reactivation of Bone Lining Cells are Attenuated Over Repeated Anti-sclerostin Antibody Administration.

Reactivation of bone lining cells (BLCs) is a crucial mechanism governing the anabolic action of anti-sclerostin antibody (Scl-Ab) via modeling-based bone formation; however, it remains unclear whether this reactivation can be attenuated after persistent administration of Scl-Ab. Here, we aimed to investigate the reproducibility of persistent Scl-Ab administration for the reactivation of BLCs, and to elucidate the relationship between the activity of BLCs and serum levels of N-terminal procollagen type I (P1NP) during chronic Scl-Ab administration. We conducted an osteoblast lineage tracing study. Briefly, Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen weekly from postnatal weeks four to eight. Mice were treated twice with either vehicle or Scl-Ab (25 mg/kg) at weeks 12, 16, and 20, and were euthanized at weeks 8, 12, 13, 16, 17, 20, and 21 (4-6 mice in each group). After euthanization, the number and thickness of X-gal (+) cells on the periosteum of the femoral bones and the serum levels of P1NP were quantified at each time point. Scl-Ab induced a significant increase in the thickness of X-gal (+) cells on periosteal bone surfaces at postnatal weeks 13 (after 1st dose), 17 (after 2nd dose), and 21 (after 3rd dose) compared to that in vehicle-treated mice (all P < 0.001). In the Scl-Ab group, significant increases in the thickness of labeled cells were observed between weeks 16 and 17 and weeks 20 and 21 (both P < 0.001). The percentage increase in X-gal (+) cell thickness was 108.9% from week 12 to week 13, 54.6% from week 16 to week 17, and 49.2% from week 20 to week 21 in the Scl-Ab group. Although Scl-Ab treatment increased the serum levels of P1NP at postnatal weeks 13 and 17 compared with those at week 12 (P = 0.017 and P = 0.038, respectively), the same was not observed at week 21 (P = 0.296). A significant increase in P1NP levels was observed between weeks 16 and 17 and weeks 20 and 21 in the Scl-Ab group (P = 0.005 and P = 0.007, respectively). The percentage increase in P1NP levels was 141.7% from weeks 12 to 13, 114.8% from weeks 16 to 17, and 99.4% from weeks 20 to 21. Serum P1NP levels were positively correlated with X-gal (+) cell thickness (R2 = 0.732, P < 0.001). Reactivation of BLCs is modestly attenuated, but reproducible, during persistent Scl-Ab administration. Serum P1NP levels appear to be an indicator of the impact of Scl-Ab on the conversion of BLCs into mature osteoblasts on periosteal bone surfaces, thus contributing to modeling-based bone formation.

Cardiovascular disease risk reduction with wolfberry consumption: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Wolfberry is rich in bioactive compounds which may lower cardiovascular disease risk. This meta-analysis aimed to systematically evaluate the effects of wolfberry-based randomized controlled trials (RCTs) on overall cardiovascular health. METHODS: Four online databases (PubMed, CINAHL Plus, Medline and Cochrane Library) were searched to shortlist relevant RCTs. Outcomes of interests included blood lipids and lipoproteins, blood pressure, biomarkers of oxidative stress, inflammation and other cardiovascular health-related indicators. Random-effects models were used to provide a weighted mean difference (WMD) and/or Hedges' g for quantitative synthesis. This was coupled with subcategory analyses which stratified RCTs according to the form in which wolfberry was administered (whole wolfberry versus wolfberry extract). RESULTS: From the 785 articles identified, 10 were selected for meta-analysis. Compared to the control, groups which consumed wolfberry showed a reduction in blood triglycerides [WMDpooled (95% confidence interval): - 0.14 (- 0.19, - 0.09) mmol/L] and increased blood high-density lipoprotein cholesterol [WMDpooled: 0.06 (0.02, 0.09) mmol/L]. Notably, effects for both triglycerides [WMDwhole: - 0.14 (- 0.19, - 0.09) mmol/L; WMDextract: - 0.07 (- 0.30, 0.16) mmol/L] and high-density lipoprotein cholesterol [WMDwhole: 0.06 (0.02, 0.09) mmol/L; WMDextract: 0.05 (- 0.02, 0.13) mmol/L] were more prominent after whole wolfberry interventions. Additionally, blood malondialdehyde equivalents were also significantly decreased in wolfberry consuming groups [Hedges' gpooled: - 1.45 (- 2.75, - 0.16)]. No changes were observed for the other lipids and lipoproteins as well as blood pressure. CONCLUSIONS: Wolfberry consumption is effective in improving blood lipids and lipoproteins profile and lowering oxidative stress. This supports the incorporation of wolfberry, particularly as whole fruits, into dietary patterns targeted at improving cardiovascular health.

Correlation between craniofacial changes and respiratory improvement after nasomaxillary skeletal expansion in pediatric obstructive sleep apnea patients.

PURPOSE: The aim of this study was to investigate the correlation between the changes in respiratory function and dimensions of the nasomaxillary complex (NMC) and upper airway (UA) compartments after nasomaxillary skeletal expansion (NMSE) treatment for pediatric patients with obstructive sleep apnea (OSA). METHODS: Nonobese OSA patients (mean age, 13.6 ± 2.9 years; mean body mass index, 18.1 ± 3.0 kg/m2); mean apnea-hypopnea index (AHI, 7.0 ± 5.4 events/h) presenting with transverse nasomaxillary constriction were evaluated before and after NMSE using cone-beam computed tomography (CBCT), home sleep test, and modified pediatric sleep questionnaire (m-PSQ). Paired t tests were performed to examine the treatment-related changes in all the parameters, and a multiple regression analysis adjusted for age and sagittal and vertical skeletal patterns was conducted to determine the dimensional parameters to affect the functional improvement. RESULTS: Among 26 patients, NMSE treatment significantly increased NMC dimensions at all tested levels and all UA compartments in CBCT, except glossopharyngeal airway. Concurrently, AHI, oxygen desaturation index, the lowest oxygen saturation (LSaO2), flow limitation (FL), snoring, and m-PSQ were significantly improved. AHI reduction was correlated with UA enlargement with no correlation with NMC expansion, whereas FL reduction was affected by NMC expansion. The minimal cross-sectional area was the most predictive of functional improvement, presenting correlations with AHI, LSaO2, and m-PSQ. CONCLUSION: NMSE can be a good treatment for pediatric OSA patients when applied to enhance the nasal and pharyngeal airway patencies beyond the NMC, ultimately to improve pharyngeal collapsibility as well as nasal airflow.

Effects of head-elevated position on tracheal intubation using a McGrath MAC videolaryngoscope in patients with a simulated difficult airway: a prospective randomized crossover study.

BACKGROUND: The head-elevated laryngoscopy position has been described to be optimal for intubation, particularly in obese patients and those with anticipated difficult airways. Horizontal alignment of the external auditory meatus and sternal notch (AM-S) can be used as endpoints for optimal positioning. Thus, we aligned the head-elevated position with the AM-S in the horizontal plane and evaluated its effect on laryngeal visualization and ease of intubation using a McGrath MAC videolaryngoscope in patients with a simulated difficult airway. METHODS: Sixty-four patients were included in this prospective, crossover, randomized controlled trial. A cervical collar was used to restrict neck movement and mouth opening. The head-elevated position was achieved by raising the back section of the operation room table and ensuring that the end point was horizontally aligned with the AM-S (table-ramp method). The laryngeal view was randomly assessed in both head-flat and head-elevated positions based on the percentage of glottic opening (POGO) score and modified Cormack-Lehane (MCL) grade. External laryngeal manipulation was not permitted when laryngeal visualization was scored. The trachea was intubated only once (in the second position). The ease of intubation was assessed based on the need for optimization maneuvers, intubation difficulty scale (IDS) scores and time to intubation. RESULTS: The mean table-ramp angle required to achieve the horizontal alignment of AM-S was 17.5 ± 4.1°. The mean POGO score improved significantly in the head-elevated position (59.4 ± 23.8%) when compared with the head-flat position (37.5 ± 24%) (P <  0.0001). MCL grade 1 or 2a was achieved in 56 (85.9%) and 28 (43.7%) of patients in the head-elevated and head-flat positions, respectively (P <  0.0001). Optimization maneuvers for intubation were required in 7 (21.9%) and 17 (53.1%) patients in the head-elevated and head-flat positions, respectively (P <  0.0001). The IDS scores and time to intubation did not differ significantly between the two positions. CONCLUSION: In the head-elevated position, aligning the AM-S in the horizontal plane consistently improved laryngeal visualization without worsening the view when the McGrath MAC videolaryngoscope was used in patients with simulated difficult airways. It also improved the ease of intubation, which reduced the need for optimization maneuvers. TRIAL REGISTRATION: This trial was registered with www. CLINICALTRIALS: gov , NCT04716218 , on 20/01/2021.

First Report of Pseudonectria buxi causing Volutella blight on Boxwood (Buxus microphylla) in the Republic of Korea.

Boxwood (Buxus spp.) are evergreen landscaping plants commonly used as hedges and fresh greenery. In July and August 2020, boxwood (Buxus microphylla Sieb. et Zucc) samples with blight symptoms were collected from the parterres of Seoul National University (Seoul, Republic of Korea). Diseased leaves and stem tissues were soaked in 1% sodium hypochlorite for 1 min, rinsed with sterile water, cultured on potato dextrose agar (PDA; Difco, Sparks, MD, USA) and incubated at 25 ℃ for 5 days. Four isolates (B2S72-1, B2S7-3, B3B2, and B4L3-3) were pure-cultured using the single-spore isolation method. Light pink-colored sporodochia containing one-celled, fusoid conidia were observed on PDA. Mean conidial size was 9.11 × 3.79 µm and ranged from 7.68 to 10.71 × 3.18 to 4.92 µm. Morphological features suggested that these isolates possessed the same characteristics as previously described for P. buxi (Bezerra, 1963, Yang et al., 2021). Genomic DNA was extracted from each isolate and the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA), ß-tubulin coding sequence, and D1/D2 region of the large subunit of the rDNA gene cluster (LSU) were amplified using the primer pairs ITS4/ITS5 (White et al., 1990), Btub4Rd/Btub2Fd (Woudenberg et al., 2009), and LR0R/LR5 (Rehner & Samuels, 1994, Vilgalys & Hester, 1990), respectively. The sequences were deposited in GenBank (GenBank accessions No. OM169273-OM169276, OM176571-OM176574, OM176566-OM176569). BLAST search showed high similarity to GenBank sequences of the ex-type strain of P. buxi for ITS (≥99.50%, MH892589.1 and MH892583.1). In addition, neighbor-joining (NJ) phylogeneticnalysis was performed using MEGA-X based on the combined sequences. The four isolates were clustered on the same clade with Pseudonectria buxi reference strains with a high bootstrap value (100 %). For the pathogenicity test, leaves of 1-year-old boxwood were given a single cut with a razor blade and a 5-mm PDA mycelial plug was placed on the wound site. Plants were kept in a transparent box at 25°C with a 12-h photoperiod. After 21 days, inoculated leaves had turned yellow and orange to pink sporodochia were observed. P. buxi was successfully reisolated from the symptomatic tissues but not from the control leaves, therefore Koch's postulates were completed. To our knowledge, this is the first report of Volutella blight caused by P. buxi in the Republic of Korea.

A Phase 3, Randomized, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Neu-BoNT/A in Treatment of Primary Axillary Hyperhidrosis.

BACKGROUND: Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis. METHODS: The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored. RESULTS: Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests. CONCLUSION: Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Osteoclastogenesis and Osteogenesis.

Bone is a highly dynamic tissue that is continuously remodeled to attain and maintain optimal bone integrity, mass, and strength [...].