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.

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.

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.

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.

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.

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.

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.