Cellular Uptake of Cell-Penetrating Peptides Activated by Amphiphilic p-Sulfonatocalix[4]arenes.

We report the synthesis of a series of amphiphilic p-sulfonatocalix[4]arenes with varying alkyl chain lengths (CX4-Cn) and their application as efficient counterion activators for membrane transport of cell-penetrating peptides (CPPs). The enhanced membrane activity is confirmed with the carboxyfluorescein (CF) assay in vesicles and by the direct cytosolic delivery of CPPs into CHO-K1, HCT 116, and KTC-1 cells enabling excellent cellular uptake of the CPPs into two cancer cell lines. Intracellular delivery was confirmed by fluorescence microscopy after CPP entry into live cells mediated by CX4-Cn, which was also quantified after cell lysis by fluorescence spectroscopy. The results present the first systematic exploration of structure-activity relationships for calixarene-based counterion activators and show that CX4-Cn are exceptionally effective in cellular delivery of CPPs. The dodecyl derivative, CX4-C12, serves as best activator. A first mechanistic insight is provided by efficient CPP uptake at 4 °C and in the presence of the endocytosis inhibitor dynasore, which indicates a direct translocation of the CPP-counterion complexes into the cytosol and highlights the potential benefits of CX4-Cn for efficient and direct translocation of CPPs and CPP-conjugated cargo molecules into the cytosol of live cells.

Sex differences in the association between obesity and albuminuria among Korean adults: a cross-sectional study using the Korea National Health and Nutrition Examination Survey data.

BACKGROUND: The association between obesity and albuminuria in the general population remains unclear. We aimed to identify the association between obesity and albuminuria as well as sex differences regarding the associations using several obesity indices, including waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHR). METHODS: This study included 3841 subjects (1730 males and 2111 females; age 20-80 years) who participated in the Fifth Korea National Health and Nutrition Examination Survey conducted in 2011. Subjects with hypertension, diabetes, renal failure, or a malignant tumor and those who were pregnant or menstruating were excluded. Albuminuria was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g. Anthropometric parameters were categorized into sex-specific quartiles. Logistic regression models were used to assess the associations between each anthropometric parameter and albuminuria. RESULTS: All of the obesity indices of the fourth quartile group of females showed a twofold higher risk for albuminuria than the second quartile group, and it was persistently significant after adjusting for age, smoking, and physical activity. After further adjustment for high blood pressure and impaired fasting glucose and triglyceride levels, WC and BMI of the fourth quartile group of females still showed a significantly higher risk for albuminuria than the second quartile group (odds ratios 1.96 and 2.24; 95 % confidence intervals 1.03-3.74 and 1.15-4.37). None of the associations between albuminuria and the obesity indices were significant in males. CONCLUSION: Higher WC and BMI were significantly associated with the risk of albuminuria among females, but not males.

Hospital consultations and jurisdiction over patients: consequences for the medical profession.

Advances in biomedical technologies and the increased specialisation of the medical profession have made collaborations among specialty physicians integral to care delivery. As physicians increasingly must share patients, how does this shape the jurisdiction that physicians hold? The sociological literature has extensively documented inter-professional jurisdictional claims and conflicts to maintain the professional power of physicians in relation to allied occupational groups. However, less is known of intra-professional avoidance and resolution of conflict over jurisdiction. This case study considers how jurisdictions are shared, maintained and challenged in a single profession. Drawing from ethnographic and interview data collected from September 2010 to October 2012 on the internal medicine service of a teaching hospital in the USA, I demonstrate the variation in jurisdictional conflicts that emerge between internal medicine and other specialties during the consultation process. Ignoring shared jurisdictions and refusing to accept jurisdiction of patients generate disputes among the principal medical and specialist teams. These disputes ensue due to blurred boundaries dividing the various specialties. To avoid conflicts, internal medicine physicians adopt strategies behind the scenes to facilitate smooth consultations.

Consumerism in action: how patients and physicians negotiate payment in health care.

Drawing from the medical sociology literature on the patient-doctor relationship and microeconomic sociological scholarship about the role of money in personal relationships, I examined patient-physician interactions within a clinic that offered eye health and cosmetic facial services in the United States. Relying on ethnographic observations conducted in 2008, I evaluated how financial pressures shape the patient-physician relationship during the clinical encounter. To gain a financial advantage, patients attempted to reshape the relationship toward a socially intimate one, where favor and gift exchanges are more common. To ensure the rendering of services, the physician in turn allied herself with the patient, demonstrating how external parties are the barriers to affordable care. This allied relationship was tested when conflicts emerged, primarily because of the role of financial intermediaries in the clinical encounter. These conflicts resulted in the disintegration of the personal relationship, with patient and physician pitted against one another.

Effectiveness of tailored screening for multidrug-resistant organisms upon admission to an intensive care unit in the United Arab Emirates.

BACKGROUND: Multidrug-resistant organism (MDRO) screening may identify high-risk patients for MDRO infection and curb the spread of these resistant pathogens. However, the heterogeneous practices in MDRO screening and the diversity of MDRO risk factors necessitate a tailored approach for successful implementation. This study aimed to evaluate the performance of tailored MDRO screening in predicting MDRO carriage compared to universal screening. METHODS: Critically ill patients who underwent MDRO screening tests upon intensive care unit admission between September 2015 and December 2019 were included in the study. A risk-predicting model was developed using risk factors identified through multivariable logistic regression analysis. If an individual had one or more identified risk factors, the individual was deemed to be at risk of MDRO carriage and undergo tailored screening. The sensitivity of tailored screening was compared with universal screening for methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Gram-negative bacilli (carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales). RESULTS: The use of tracheostomy or endotracheal tubes, previous antibiotic exposure, previous multidrug-resistant Gram-negative bacilli carriage history, admission to the medical department, peripheral vascular disease, and liver disease were associated with positive screening for multidrug-resistant Gram-negative bacilli. These six risk factors accounted for all positive screening for multidrug-resistant Gram-negative bacilli, requiring 38.6% of all tests. Notably, MRSA had different risk factor profiles, and the risk factor-based screening approach detected only 43.1% (31 out of 72) of MRSA-positive cases. CONCLUSIONS: Tailored screening based on identified risk factors showed variable sensitivities to individual MDROs compared to universal screening. A tailored screening approach for individual MDROs may enhance the overall effectiveness of MDRO screening programs.

Effect of pre-fragmentation on efficacy and safety for phacoemulsification in femtosecond laser-assisted cataract surgery: a non-randomized clinical trial.

Background: Ultrasound energy during phacoemulsification results in the endothelial cell loss of cornea. Crystallin lens fragmentation with softening before phacoemulsification can be used with femtosecond laser-assisted cataract surgery (FLACS) device. Methods: This non-randomized clinical trial included patients who underwent cataract surgery and not had corneal opacity. Patients who were not possible to apply the interface on the ocular surface, were excluded. Each subject was allowed to decide the surgical method by himself/herself. Cataract surgery was performed with FLACS (groups I and II) or conventional surgical technique (group III). The FLACS group was further subdivided into two groups according to whether a lens softening procedure was performed (group I) or not (group II). The nuclear density of cataract was objectively classified by Pentacam nuclear staging (PNS), preoperatively. Surgical parameters including total phacoemulsification time (TPT), cumulative dissipated energy (CDE), and the balanced salt solution (BSS) volume consumed, were measured during the surgery. Postoperative visual outcomes were evaluated at three months after the surgery, and corneal endothelial cell count (ECC) loss were calculated based on ECC measured before the surgery and two months after the surgery. Results: Eighty-nine eyes from 89 patients were enrolled. Fifty-three were treated using FLACS (groups I; quadrant pattern with softening of pre-fragmentation, n=31 and II; sextant pattern without softening of pre-fragmentation, n=22) and 36 (group III) with the conventional manual technique. The FLACS groups (groups I and II) had statistically significant lower TPT (P<0.001), CDE (P<0.001), and BSS volumes (P<0.001) used in the nucleus removal step compared to group III. Furthermore, ECC loss in groups I (4.59%±2.57%) and II (6.10%±3.30%) were also statistically lower compared to group III (13.49%±10.55%, P<0.001). From subgroup analysis with the PNS 2, group I showed lower pre-fragmentation time, lower CDE, lower BSS volume used during nucleus removal, and lower ECC loss compared to group II (all P<0.001). Conclusions: Pre-fragmentation using FLACS may reduce intraoperative ultrasound energy and intraocular manipulations compared to conventional cataract surgery.

Association of Homologous and Heterologous Vaccine Boosters With SARS-CoV-2 Infection in BBIBP-CorV Vaccinated Healthcare Personnel.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a crucial role in mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, few studies have addressed the optimal booster vaccine type in recipients of the primary series of BBIBP-CorV (an inactivated virus vaccine developed by Sinopharm). This study aimed to estimate the association between the heterologous or homologous COVID-19 vaccination and SARS-CoV-2 infection. The study enrolled healthcare personnel (HCP) who had completed two doses of BBIBP-CorV between November 2020 and September 2021. The associations between SARS-CoV-2 infection and boosters were measured using multivariable logistic regression, comparing the odds of a positive COVID-19 test result between the no booster group and booster groups (BNT162b2 {Pfizer-BioNTech COVID-19 vaccine} group and BBIBP-CorV group, respectively). A total of 495 HCP comprising 326 (65.9%) in the BNT162b2 group, 121 (24.4%) in the no booster group, and 48 (9.7%) in the BBIBP-CorV group enrolled. One hundred thirty-six cases (27.5%) tested positive for COVID-19. The odds ratios for testing positive after booster dose were 0.401 (95% CI: 0.187-0.860, p = 0.019) and 0.446 (95% CI: 0.170-1.167, p = 0.100) for BNT162b2 and BBIBP-CorV group, respectively. The BNT162b2 booster in HCP after a second dose of BBIBP-CorV, relative to no booster, and the BBIBP-CorV booster, was associated with protection against laboratory-confirmed COVID-19.

Follow-up COVID-19 PCR result up to day 5 with clinical features predicts positivity for inconclusive results.

Introduction: False-positive inconclusive polymerase chain reaction (PCR) results against severe acute respiratory syndrome coronavirus 2 were not low and have potentially harmful effects. We aimed to find parameters to differentiate positive cases from false-positive ones, and suggest an optimal scheme and follow-up period for inconclusive results. Methods: Cases with inconclusive PCR tests among healthcare personnel from February 2020 to June 2021 were classified as confirmed positive, clinically positive, and clinically negative groups, which were compared. The diagnostic accuracy of follow-up tests and composites of clinical and laboratory data were analyzed. Results: Symptoms, contact history, and lower cycle threshold of the N gene were more common in the COVID-19 positive group. The scoring schemes combining symptom and contact history with follow-up PCR results had higher sensitivities than the PCR tests only modality. Follow-up tests up to 5 days combined with symptoms and contact history could discriminate between positive and negative cases. Conclusion: A follow-up PCR test up to day 5 with clinical features might predict positivity and shorten the quarantine period in most healthcare personnel.

Menstrual Cycle Variation in MRI-Based Quantification of Intraluminal Gas in Women With and Without Dysmenorrhea.

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MRI) to determine colonic gas volumes throughout the menstrual cycle. To avoid dietary influence, the participants were instructed to avoid gas-producing foods before their scheduled MRI. We verified the measurement repeatability across the reviewers and obtained an intraclass correlation coefficient of 0.92. There were no significant differences in intraluminal gas volume between menses and non-menses scans (p = 0.679). Even among the women with dysmenorrhea, there was no significant difference in the intraluminal gas volume between menses and non-menses (p = 0.753). During menstruation, the participants with dysmenorrhea had less intraluminal gas than participants without dysmenorrhea (p = 0.044). However, the correlation between the bowel gas volume and the pain symptoms were not significant (p > 0.05). Although increased bowel symptoms and bloating are reported in the women with dysmenorrhea during menses, our results do not support the hypothesis that increased intraluminal gas is a contributing factor. Although dietary treatment has been shown in other studies to improve menstrual pain, the mechanism responsible for abdominal symptoms requires further investigation. Our findings demonstrate that the intraluminal bowel gas volume measurements are feasible and are unaffected by menses under a controlled diet. The method described might prove helpful in future mechanistic studies in clarifying the role of intraluminal bowel gas in other conditions.

Assessment for Macular Thickness after Uncomplicated Phacoemulsification Using Optical Coherence Tomography.

PURPOSE: Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study. METHODS: Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT. RESULTS: A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range. CONCLUSIONS: The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.

The continued social transformation of the medical profession.

A pressing concern in contemporary health policy is whether the medical profession's mandate to take care of clients has been undermined by the influx of money into health care. We examine the medical profession's transformation over the past decades. First, we review how sociologists have viewed the medical profession over the past half-century as one stakeholder among other stakeholders vying for market share and power in the health care field. We then examine three recent challenges to the profession that exemplify the tension between self-interest and collective altruism to act in the best interest of patients: (1) the rise of patient consumerism, (2) the advent of evidence-based medicine, and (3) the increasing power of the pharmaceutical industry. We show the resilience of the medical profession as it adapts and transforms in response to these challenges. We conclude with implications to help inform policy makers' assessments of how the medical profession will react to policy initiatives.

Inter-rater agreement among multiple examiners for the assessment of plaque scores between quantitative light-induced fluorescence-digital and two-tone disclosing solution-stained digital images.

BACKGROUND: To utilize plaque scoring indices as objective measures, a certain standard of intra-rater and inter-rater agreement must be met. Achievement of high consistency among several examiners in the assessment of images from Q-ray cam (for quantitative light-induced fluorescence-digital imaging) and digital single-lens reflex camera of stained tooth surfaces might enable more efficient undertaking of large epidemiological studies and oral tests. METHODS: Second-year dental hygiene students and registered dental hygienists 40 examiners were randomly selected, all of whom provided informed consent. Multiple examiners assessed plaque scoring indices from the two types of images of the same 30 patients. The images were observed on a computer monitor, and the area with dental plaque was assessed using the Patient Hygiene Performance Index. The intra-class correlation coefficient was determined to evaluate the agreement among examiners and test methods for dental plaque Q-ray cam and digital single-lens reflex camera measurements were compared using a Bland-Altman plot. The intra-class correlation coefficient was analyzed using SPSS version 24 software (SPSS Inc., Chicago, IL, USA), and the exploratory graph was analyzed with MedCalc. RESULTS: Agreement among 40 examiners was excellent with an intra-class correlation coefficient of 0.990 when the Q-ray cam was used. The intra-class correlation coefficient for the registered dental hygienists group was 0.987 and that for the dental hygiene students group was 0.980. CONCLUSIONS: The study was high agreement in the assessment of Q-ray cam images and digital single-lens reflex camera images of stained dental plaque by multiple examiners, confirming that the two methods are validated both independently and with high mutual agreement.

Relationship between Mammographic Density and Age in the United Arab Emirates Population.

OBJECTIVE: Higher breast density is a strong, independent risk factor for breast cancer. Breast density varies by age, ethnicity, and geographic area although dense breast tissue has been associated with younger age and premenopausal status. The relationship between breast density and age in women in the United Arab Emirates (UAE) has not been determined. This study evaluated breast density in the UAE population and its relationship with age. METHODS: Women participating in the national cancer screening program from August 2015 to May 2018 who underwent screening mammography were included. Breast parenchymal density was classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) from category a (almost entirely fatty) through d (extremely dense). Subjects were divided into six age groups, and the association between age and breast density was evaluated. RESULTS: Of the 4911 women included, 1604 (32.7%), 2149 (43.8%), 1055 (21.5%), and 103 (2.1%) were classified as having categories a-d breast density, respectively. A significant negative correlation was observed between age and breast density category (p < 0.001). Women of mean age 44 ± 7 years had the highest breast density, whereas those of mean age 56 ± 14 years had the lowest breast density. Comparisons of Emirati women with Lebanese and Western women showed that breast density was lower in Emirati women than in the other populations. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between mammographic breast density and age in UAE women. As in other populations, age was inversely related to breast density, but the proportion of Emirati women with dense breasts was lower than in other populations. Because this study lacked demographic, clinical, and histopathological data, further evaluation is required.

Resisting Throughput Pressures: Physicians' and Patients' Strategies to Manage Hospital Discharge.

In recent years, quickly discharging patients has become a collective goal at hospitals, as excessive medical workups and extended hospital stays have been associated with unnecessary healthcare spending. Physicians, however, frequently encounter numerous barriers when trying to discharge patients. Presenting ethnographic and interview data collected from September 2010 to September 2013, this paper examines one of the most difficult discharge cases physicians encounter on the internal medicine service at a U.S. teaching hospital: resistant patients-patients and families who refuse to leave the hospital. As physicians try to discharge resistant patients, they are met with conflicting financial and professional incentives. Drawing from the sociological literature on professions, managerialism, and consumerism, I analyze the strategies physicians develop to manage these difficult discharge cases.

Improving the competency of dental hygiene students in detecting dental restorations using quantitative light-induced fluorescence technology.

OBJECTIVES: The purpose of this study was to determine the usefulness of a quantitative light-induced fluorescence (QLF) technology in detecting dental restorations by comparing the detection ability of dental hygiene students between using conventional visual inspection alone and visual inspection combined with QLF technology. METHODS: The subjects of this study comprised 92 dental hygiene students. The students assigned to the control group only used white-light images to visually assess the mouth environment, while those in the experimental group additionally used fluorescence images. Using the test results of an experienced inspector as a reference value, the agreement between the reference value and the evaluation results of the students in the experimental and control groups was evaluated using Cohen's kappa and the percentage agreement. The subjects were then classified into groups covering three percentage ranges according to the score distribution and agreement values of the three groups were compared. The percentage agreement was calculated according to the type of dental restorations. RESULTS: The mean kappa value was significantly higher in the experimental group than the control group (0.70 vs 0.60, p<0.001), as was the percentage agreement (80.06% vs 72.64%, p<0.001). The agreement rate when using QLF technology increased by 8% more in the middle and bottom percentage groups than in the top percentage group (p<0.001). The agreement rate also varied with the type of restoration, being significantly higher for a sound tooth or tooth-colored restoration in the experimental group (p<0.001). CONCLUSIONS: Combining QLF technology with conventional visual inspections could improve the ability to detect dental restorations and distinguish sound teeth from aesthetic restorations.

Time to First Cigarette and Hypertension in Korean Male Smokers.

BACKGROUND: Morning blood pressure surge affects to cardiovascular disease risk. Short time to first cigarette (TTFC) after waking can enhance morning blood pressure surge, and accelerate atherosclerosis. METHODS: We investigated that the relationship between TTFC and blood pressure. The study subjects included male current smokers (n=211) who had health check-up in Hallym University Sacred Heart Hospital from July to September, 2014. We categorized the subjects into 2 groups according to TTFC; early TTFC (TTFC <30 minutes) and late TTFC (TTFC ≥30 minutes), and the subjects who were taking antihypertensive medications or had a high blood pressure (>140 mm Hg or 90 mm Hg) were defined as hypertensive group. Multivariate logistic regression was performed to estimate the odds ratio and 95% confidence interval to investigate the association between TTFC and hypertensive group. RESULTS: Compared with late TTFC, early TTFC had higher odds (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.89-7.94) for hypertensive group. After adjusting confounding factors, early TTFC was significantly associated with an increased risk of hypertension (OR, 4.43; 95% CI, 1.84-10.70). CONCLUSION: early TTFC after waking is associated with hypertension. It suggests delaying TTFC might help to control of blood pressure among the current smokers who are not ready to immediately quit smoking.

Association between High Blood Pressure and Intakes of Sodium and Potassium among Korean Adults: Korean National Health and Nutrition Examination Survey, 2007-2012.

BACKGROUND: The association between dietary sodium and potassium, the ratio of sodium to potassium, and blood pressure remains unclear. OBJECTIVE: We evaluated the associations between blood pressure and dietary sodium and potassium intake in terms of the amount and ratio in Korean adults. DESIGN: This cross-sectional study was based on data from the fourth and fifth Korean National Health and Nutrition Examination Survey, 2007-2012. PARTICIPANTS/SETTING: A total of 24,096 adults (aged ≥19 years) without history of antihypertensive medication use were selected. The 24-hour recall method was used for dietary assessment. We categorized the subjects into four groups using median intakes of sodium and potassium, and defined the low sodium/high potassium intake group as the reference group. MAIN OUTCOME MEASURES: High blood pressure (HBP) was defined as mean systolic or diastolic blood pressures of ≥140 or ≥90 mm Hg, respectively. STATISTICAL ANALYSES PERFORMED: Multivariate logistic regression was performed to estimate the odds ratio and 95% CI to investigate the association between the four groups of sodium and potassium intakes and HBP. RESULTS: Sodium intake was positively associated with diastolic blood pressure, with an increase of 0.21 mm Hg per 1 mg/kcal increase in sodium (P<0.001). In contrast, potassium intake was negatively associated with systolic blood pressure, with a decrease of 1.01 mm Hg per 1 mg/kcal increase in potassium (P<0.001). After adjusting for confounders, the high sodium/low potassium (odds ratio 1.21, 95% CI 1.02 to 1.44) and low sodium/low potassium intake groups (odds ratio 1.19, 95% CI 1.01 to 1.40) were at higher risk of HBP than the reference group. The risk of HBP in the high sodium/high potassium group did not differ from that in the reference group. CONCLUSIONS: Low potassium intake was associated with an increased risk of hypertension. These results suggest that increasing potassium intake might be beneficial for hypertension control among populations with low-potassium diets.

Clinical Characteristics and Metabolic Health Status of Obese Korean Children and Adolescents.

BACKGROUND: This study aimed to determine the prevalence of metabolically healthy and unhealthy obesity (MHO and MUO, respectively) and examine the demographic, anthropometric, and lifestyle predictors of metabolic health status in Korean children and adolescents. METHODS: This study was based on data collected from the Korean Children-Adolescent Study in 2010. A total of 1,700 children (846 boys and 854 girls) were included in the primary cohort and classified into metabolically healthy and unhealthy groups according to factors related to the metabolic syndrome. Demographic and biochemical features were evaluated in study participants. Logistic regression estimated the odds ratios of having more fat mass among MUO compared with MHO children after adjusting for confounding factors. RESULTS: Mean body mass index was higher in the MUO group than in the MHO group (24.83 vs. 23.02 kg/m(2), respectively). The proportion of obese participants was also higher in the MUO group (59.4%) than in the MHO group (20.7%). MHO children were more likely to have parents with better socioeconomic status and a higher fruit and vegetable intake compared with MUO children. Higher fat mass and percent fat was associated with MUO according to multiple logistic regression analysis. CONCLUSION: Fat mass and percent fat are associated with metabolically healthy phenotypes of obesity among children and adolescents.

Biphasic effects of the flavonoids quercetin and naringenin on the metabolic activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline by Salmonella typhimurium TA1538 co-expressing human cytochrome P450 1A2, NADPH-cytochrome P450 reductase, and cytochrome b5.

Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 microM, respectively, but suppressed 82 and 96% at 50 and 100 microM. Naringenin also increased the MeIQ-induced mutation about 37 and 22% at 0.1 and 1 microM, but suppressed it 32 and 63% at 50 and 100 microM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. These results indicate that quercetin and naringenin can exhibit inhibitory or stimulating effects on CYP1A2 mediated mutagenesis by MeIQ, depending on their concentrations.

Cytokine deposition alters leukocyte morphology and initial recruitment of monocytes and γδT cells after corneal injury.

PURPOSE: An in vivo mouse model reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously 2 weeks after a single 1.5-mm corneal debridement wound made with a dulled blade. When 1.5-mm wounds are made by a rotating burr so that the corneal epithelial basement membrane is removed, corneas heal without developing erosions. Here, we characterize differences in cytokine deposition and changes in leukocytes between 0 and 6 hours after dulled-blade and rotating-burr wounding. METHODS: BALB/c mice were used to study 1.5-mm corneal wounds made using a dulled blade or a rotating burr. Mice were studied immediately after wounding (0 hour) and at 6 hours in vivo and in vitro in organ culture. Corneas, corneal extracts, and collagenase digests from naïve and wounded mice were used for three-dimensional (3D) confocal imaging, cytokine arrays, and flow cytometry. RESULTS: Confocal imaging showed CD45, a protein derived from leukocytes, accumulates at the wound edge by 3 and 6 hours after wounding in vivo but not in vitro with more CD45 accumulating after dulled-blade compared with rotating-burr wounds. Morphologic changes occurred in CD45+ leukocytes and higher levels for several cytokines were detected in the stromal wound bed within minutes following dulled-blade wounds. Flow cytometry showed significantly more monocytes (CD45+/CD11b+/Ly6C+) and γδT cells (CD45+/GL3+) recruited into the corneas of mice with dulled-blade wounds by 6 hours. CONCLUSIONS: Differences in cytokine-driven leukocyte responses are seen after dulled-blade debridement compared with rotating-burr injury.