Health and job-related factors associated with work ability in older working populations of Korea.

BACKGROUND: Knowledge about determinants of workability is crucial for designing interventions to increase the participation of older employees in the workforce and maintain or increase their productivity levels at work. AIMS: This study explored the impact of health conditions and job characteristics on poor work ability. METHODS: This study used data from the Korean Longitudinal Study of Aging (KLoSA) from 2014 to 2020, which is a nationally representative population-based panel study of Korean citizens aged ≥45 years. The KLoSA survey assessed subjective work ability using work ability score. The participants were asked if they had been diagnosed with any underlying diseases by a physician. The job characteristics were assessed in terms of working conditions and satisfaction. Generalized estimating equations were used to calculate the odds ratios (ORs) and 95% confidence intervals for workers' health-related variables and job characteristics associated with poor work ability. RESULTS: The results showed that workers' health-related factors were associated with poor work ability; poor vision (OR = 1.52) and bad hearing ability (OR = 2.37); low gripping strength (OR = 2.29); poor self-rated health (OR = 3.77) and various diseases such as hypertension, diabetes, cancer, chronic lung disease, liver disease, heart disease, cerebrovascular disease, mental illness, arthritis, prostate disease, gastrointestinal disease and disc disease. Additionally, high physical work demands (OR = 1.51) and low job satisfaction (OR = 4.23) were highly correlated with poor work ability. CONCLUSIONS: The findings addressing poor work abilities caused by individuals' health- and job-related factors can help prioritize worker health management and the development of more effective human capital investment strategies at the workplace.

Hormonal stimulation reduces numbers and impairs function of human uterine natural killer cells during implantation.

STUDY QUESTION: How does an altered maternal hormonal environment, such as that seen during superovulation with gonadotropins in ART, impact human uterine immune cell distribution and function during the window of implantation? SUMMARY ANSWER: Hormonal stimulation with gonadotropins alters abundance of maternal immune cells including uterine natural killer (uNK) cells and reduces uNK cell ability to promote extravillous trophoblast (EVT) invasion. WHAT IS KNOWN ALREADY: An altered maternal hormonal environment, seen following ART, can lead to increased risk for adverse perinatal outcomes associated with disordered placentation. Maternal immune cells play an essential role in invasion of EVTs, a process required for proper establishment of the placenta, and adverse perinatal outcomes have been associated with altered immune cell populations. How ART impacts maternal immune cells and whether this can in turn affect implantation and placentation in humans remain unknown. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out between 2018 and 2021 on 51 subjects: 20 from natural cycles 8 days after LH surge; and 31 from stimulated IVF cycles 7 days after egg retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies and peripheral blood samples were collected during the window of implantation in subjects with regular menstrual cycles or undergoing superovulation. Serum estradiol and progesterone levels were measured by chemiluminescent competitive immunoassay. Immune cell populations in blood and endometrium were analyzed using flow cytometry. uNK cells were purified using fluorescence-activated cell sorting and were subjected to RNA sequencing (RNA-seq). Functional changes in uNK cells due to hormonal stimulation were evaluated using the implantation-on-a-chip (IOC) device, a novel bioengineered platform using human primary cells that mimics early processes that occur during pregnancy in a physiologically relevant manner. Unpaired t-tests, one-way ANOVA, and pairwise multiple comparison tests were used to statistically evaluate differences. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were comparable for both groups. As expected, serum estradiol levels on the day of biopsy were significantly higher in stimulated (superovulated) patients (P = 0.0005). In the setting of superovulation, we found an endometrium-specific reduction in the density of bulk CD56+ uNK cells (P < 0.05), as well as in the uNK3 subpopulation (P = 0.025) specifically (CD103+ NK cells). In stimulated samples, we also found that the proportion of endometrial B cells was increased (P < 0.0001). Our findings were specific to the endometrium and not seen in peripheral blood. On the IOC device, uNK cells from naturally cycling secretory endometrium promote EVT invasion (P = 0.03). However, uNK cells from hormonally stimulated endometrium were unable to significantly promote EVT invasion, as measured by area of invasion, depth of invasion, and number of invaded EVTs by area. Bulk RNA-seq of sorted uNK cells from stimulated and unstimulated endometrium revealed changes in signaling pathways associated with immune cell trafficking/movement and inflammation. LIMITATIONS, REASONS FOR CAUTION: Patient numbers utilized for the study were low but were enough to identify significant overall population differences in select immune cell types. With additional power and deeper immune phenotyping, we may detect additional differences in immune cell composition of blood and endometrium in the setting of hormonal stimulation. Flow cytometry was performed on targeted immune cell populations that have shown involvement in early pregnancy. A more unbiased approach might identify changes in novel maternal immune cells not investigated in this study. We performed RNA-seq only on uNK cells, which demonstrated differences in gene expression. Ovarian stimulation may also impact gene expression and function of other subsets of immune cells, as well as other cell types within the endometrium. Finally, the IOC device, while a major improvement over existing in vitro methods to study early pregnancy, does not include all possible maternal cells present during early pregnancy, which could impact functional effects seen. Immune cells other than uNK cells may impact invasion of EVTs in vitro and in vivo, though these remain to be tested. WIDER IMPLICATIONS OF THE FINDINGS: These findings demonstrate that hormonal stimulation affects the distribution of uNK cells during the implantation window and reduces the proinvasive effects of uNK cells during early pregnancy. Our results provide a potential mechanism by which fresh IVF cycles may increase risk of disorders of placentation, previously linked to adverse perinatal outcomes. STUDY FUNDING/COMPETING INTEREST(S): Research reported in this publication was supported by the University of Pennsylvania University Research Funding (to M.M.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD068157 to M.M., S.S., and S.M.), National Center for Advancing Translational Sciences of the National Institutes of Health (TL1TR001880 to J.K.), the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania, the Children's Hospital of Philadelphia Research Institute (to S.M.G.), and the National Institute of Allergy and Infectious Diseases (K08AI151265 to S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial.

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.

Survival of oral mucosal melanoma according to treatment, tumour resection margin, and metastases.

Because of the poor prognosis and of oral mucosal melanoma, and patients' short survival, large, randomised, clinical studies are difficult. We have investigated its demographic characteristics and analysed the effect of treatment, resection margins, and metastases on survival. We recorded age, sex, site of primary tumour, and types of treatment, survival, and metastases in 74 patients treated at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital. Survival was analysed based on bony invasion, depth of invasion, and resection margins, and we found that it varied depending on the primary site (p=0.002), and declined with liver (p=0.001) or brain (p=0.033) metastases. The two-year survival according to the primary site was as follows: palate 85% (n=32), anterior maxillary gingiva 53% (n=13), mandible 58% (n=13), and posterior maxillary gingival 74% (n=10) and buccal mucosa 50% (n=4). The two-year survival was 34% (n=8) in patients with liver metastases and 23% (n=7) in patients with brain metastases. In cases of bony invasion (p=0.005), depth of invasion (p=0.042), unclear resection margin (p=0.023), or higher T stages (p=0.009), the survival declined considerably. Neck dissection did not affect survival (p=0.343). Survival of the patients given chemotherapy was significantly lower (p=0.013) and the two-year survival was 54.0%. The patients given radiotherapy showed no significant difference in survival compared with those not given radiotherapy (p=0.107). In conclusion, primary site, bony invasion, resection margins, depth of invasion and systemic metastases were critical to predict prognosis and selection of treatment of oral mucosal melanoma.

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer.

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

Akt1-Mediated Phosphorylation of RBP-Jk Controls Notch1 Signaling.

The Notch1 signaling pathway plays a crucial role in determining cell fate, including cell growth and differentiation. In this study, we demonstrated that the antagonistic action of RTK (receptor tyrosine kinase) signaling pathway on the Notch1 signaling pathway is mediated via Ras-PI3K-Akt1. The PI3K-Akt1 signaling pathway was shown to inhibit Notch1 signaling via phosphorylation of RBP-Jk. We observed not only reduced association between Notch1 and RBP-Jk, but also suppression of the Notch1 transcriptional activity. Our results demonstrated that Akt1 functions as a natural inhibitor of the Notch1 signaling pathway via phosphorylation of RBP-Jk.

Comparison of open and pneumovesical approaches for Politano-Leadbetter ureteric reimplantation: a single-center long-term follow-up study.

PURPOSE: To report our experience with the laparoscopic pneumovesical approach for Politano-Leadbetter ureteric reimplantation and to compare the results to those obtained using a traditional open approach. METHODS: We retrospectively reviewed the medical records of 52 patients who underwent Politano-Leadbetter ureteral reimplantation between 2012 and 2017. The peri-operative parameters, postoperative outcomes, and complication rates of patients who underwent the open approach for the Politano-Leadbetter procedure and those who underwent the laparoscopic pneumovesical approach were compared. RESULTS: During the study period, 52 ureteric reimplantation procedures were analyzed. Among these, 28 and 24 patients underwent surgery using the open and pneumovesical approaches, respectively. The mean operative time did not differ between the groups (143.64 min vs. 128.12 min, P = 0.092). However, the pneumovesical group had a shorter duration of hospital stay (5.08 days vs 7.43 days, P = 0.001) and required less morphine analgesic for pain than did the open group (7.7% vs 32.1%, P = 0.027). No significant differences in the success rates (94.9% vs 92.5%, P = 0.512) or procedure-related complications were noted between the pneumovesical and open techniques. CONCLUSIONS: The transvesicoscopic Politano-Leadbetter technique with pneumovesicum is safe and effective for ureteric reimplantation and is comparable to the open approach.

The effect of low body mass index on the development of chronic obstructive pulmonary disease and mortality.

BACKGROUND: Sarcopenia may worsen disease progression and lead to poor outcomes in chronic obstructive pulmonary disease (COPD). OBJECTIVES: We aimed to determine the effect of BMI on the development of COPD and mortality. METHODS: We enrolled 437 584 participants registered in the physical health check-up cohort database of the Korean National Health Interview Survey from 2002 to 2003, and we defined COPD diagnosis based on the ICD-10 code and prescribed medication. BMI (kg m-2 ) classified them to five groups (low BMI < 18.5, normal BMI 18.5-23, overweight 23-25, obesity 25-30, severe obesity ≥30) at baseline. RESULTS: Participants in the low BMI group had a significantly higher rate of COPD development for 13 years (7.6%) than those in other groups (3.4-4.1%, P < 0.0001). Amongst never or light smokers, COPD development in the low BMI group (5.6-6.7%) was significantly higher than that in other groups (2.8-4.7%). Similarly, amongst participants with a smoking history of ≥30 years, COPD development in the low BMI group (20.1%) was higher than those in other groups (8.4-12.4%). On multivariable analysis, normal or higher than normal body weight was significantly protective against the development of COPD (hazard ratio [HR], 0.609-0.739,) compared to low BMI. COPD-free-survival (HR, 0.491-0.622) and overall survival (HR, 0.440-0.585) were also better in them compared to those with low BMI (all P < 0.0001). CONCLUSIONS: Low BMI is an important risk factor for COPD development and mortality. Maintaining adequate body weight may reduce the risk for COPD development and mortality.

Biomarkers and new therapeutic targets in renal cell carcinoma.

OBJECTIVE: Renal Cell Carcinoma (RCC) is the most common malignancy in adult kidneys. The American Cancer Society estimated 62,700 new cases and 14,240 deaths in 2018. Although early detection has improved in recent years, the treatment remains a challenge and reliable biomarkers for poor outcomes become necessary for the prevention of metastases and improve the quality of patients' life during and after treatment. Then, the current status of the search for new RCC biomarkers was discussed, as well as the latest discoveries in the RCC risk and metastatic treatment were discussed in this review. MATERIALS AND METHODS: Extensive research was carried out in the online databases and full-free text articles published in the last 5 years, or more when convenient, were evaluated. Articles were included that addressed the proposed theme and were published in the English language. RESULTS: The present state of knowledge on biomarkers for RCC carcinogenesis and progression is still much to be understood about RCC risk factors and molecular pathways resulting in metastatic progression. Newest RCC target therapies were discussed, mainly in relation to immunological therapy, and vaccines that have been tested in numerous trials with different cancer types. CONCLUSIONS: The development of targeted therapies has revolutionized the treatment of advanced and metastatic cancers or non-responder patients. Combined therapy between classical chemotherapy and adjuvant immunotherapies has been modifying the cancer patients prognosis and bringing the hope of a cure in many cases.

Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures.

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs.

Predictors of failure to detect early hepatocellular carcinoma in patients with chronic hepatitis B who received regular surveillance.

BACKGROUND: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance. AIMS: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance. METHODS: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C. RESULTS: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure. CONCLUSIONS: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.

Bronchial angles are associated with nodular bronchiectatic non-tuberculous mycobacteria lung disease.

BACKGROUND: The nodular bronchiectatic (NB) form of non-tuberculous mycobacteria (NTM) lung disease usually involves the right middle lobe (RML) and the left upper lobe lingular segment. However, the reason underlying this preference is not known. METHODS: Fifty patients with NB NTM lung disease who had both positive NTM culture(s) and NB lesions in the RML or lingular segment on computed tomography (CT) of the chest, and 100 healthy subjects matched for sex, age, height and body weight with normal chest CT, were randomly selected. Using reconstructed curved multiplanar reformation (MPR) images, the lengths, diameters and angles of the RML and lingular bronchi were measured. RESULTS: Of the 150 individuals, 64% were female; the mean age was 55 years. The angles of the bronchi were significantly more acute in patients than in healthy subjects, both in the RML (patients, mean 46.75° ± standard deviation 8.87° vs. healthy subjects, mean 51.73° ± 7.76°; P = 0.001) and in the lingular segments (patients, mean 26.94° ± 8.16° vs. healthy subjects, mean 34.65° ± 9.75°; P < 0.001). In addition, the angles of the bronchi in the involved segments were more acute than those in the non-involved segments, both in the RML and the lingular segments. There were no differences in the lengths and bronchi diameters between groups. CONCLUSIONS: An acute angle (obtuse slope) of RML/lingular bronchi could be an anatomical risk factor for NB NTM lung disease.

Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

Cannabinoid receptor 1 (CNR1) gene variant moderates neural index of cognitive disruption during nicotine withdrawal.

Nicotine withdrawal-related disruption of cognitive control may contribute to the reinforcement of tobacco use. Identification of gene variants that predict this withdrawal phenotype may lead to tailored pharmacotherapy for smoking cessation. Variation on the cannabinoid receptor 1 gene (CNR1) has been related to nicotine dependence, and CNR1 antagonists may increase attention and memory functioning. We targeted CNR1 variants as moderators of a validated neural marker of nicotine withdrawal-related cognitive disruption. CNR1 polymorphisms comprising the 'TAG' haplotype (rs806379, rs1535255 and rs2023239) were tested independently, as no participants in this sample possessed this haplotype. Nicotine withdrawal-related cognitive disruption was indexed as increased resting electroencephalogram (EEG) alpha-1 power density across 17 electrodes. Seventy-three Caucasian Non-Hispanic smokers (≥15 cigarettes per day) visited the laboratory on two occasions following overnight smoking/nicotine deprivation. Either two nicotine or two placebo cigarettes were smoked prior to collecting EEG data at each session. Analyses showed that rs806379 moderated the effects of nicotine deprivation increasing slow wave EEG (P = 0.004). Smokers homozygous for the major allele exhibited greater nicotine withdrawal-related cognitive disruption. The current findings suggest potential efficacy of cannabinoid receptor antagonism as a pharmacotherapy approach for smoking cessation among individuals who exhibit greater nicotine withdrawal-related cognitive disruption.

Efficacy and possible mechanisms of topical tranexamic acid in melasma.

BACKGROUND: Tranexamic acid (TA) has been suggested as an effective treatment for melasma. AIM: To investigate the effects and mechanism of action of topical TA in the treatment of melasma. METHODS: In this study, 23 participants with melasma applied a 2% TA formulation to the whole face for 12 weeks. Clinical effects were evaluated using the modified Melasma Area and Severity Index (mMASI) and a chromameter. Skin biopsies were obtained from 10 participants to evaluate pigmentation, vascularity and the expression levels of possible paracrine factors contributing to the effect of TA. RESULTS: Most of the participants had mild melasma, with mMASI of < 5. The mMASI scores significantly improved in 22 of 23 participants after application. The L* values were increased and the a* values were decreased in both lesional and perilesional normal skin. Fontana-Masson staining showed a significant decrease in melanin content in the epidermis. The number of CD31-positive vessels and the expression of the vascular endothelial growth factor both tended to decrease. Endothelin (ET)-1 was found to be downregulated with TA. CONCLUSIONS: Topical TA is effective for melasma. This immunohistochemical study found that suppression of ET-1 could be one of the mechanisms of action of TA on melasma.

Initial experiences of laparoscopic intravesical detrusorraphy using the Politano-Leadbetter technique.

INTRODUCTION: Minimally invasive laparoscopic surgical procedures are increasingly being used for the management of vesicoureteral reflux. OBJECTIVE: We present our experience of the laparoscopic Politano-Leadbetter technique performed under pneumovesicum conditions, which allows an orthotopic ureteral location after vesicoureteral reflux correction. Our procedure recreates the new ureteric orifice in a normal anatomical position with potential less morbidity and better cosmesis. STUDY DESIGN: Our series comprises ten cases. The three 5 mm ports were introduced through bladder wall under cystoscopic vision. A 5-0 monofilament traction suture was used and dissection was carried out. After the ureteral mobilization, the location of the new hiatus was selected in a straight line superior to the original orifice. Dissection of the submucosal tunnel was started from the new hiatus and advanced to the original hiatus and the ureter was gently drawn passed through the tunnel. The ureter was rolled up and muscle fibers were incised until ureter could freely move from the base of the new hiatus. Finally, after spatulation of the terminal part of the ureter, ureterovesical anastomosis was performed with intracorporeal suturing using 5-0 monofilament sutures. RESULTS: The average operative time was 125 min, with an average of 93 min for unilateral and 133 min for bilateral reimplantation. Blood loss was minimal and drains were used selectively. Removal of urethral catheter was decided empirically after hematuria stopped. Mean catheterization time was 5.1 days. The mean postoperative hospital stay was 6.2 days. DISCUSSION: This study had limitations: the small number of cases, follow-up period is relatively short and data on the pre-operative bladder capacity, catheter-related morbidity, pain control and cosmesis are lacking. But most cases showed positive clinical results including acceptable operating time and good resolution rate with minimal complication. Our Politano-Leadbetter transvesicoscopic ureteric reimplantation is safe and useful in the resolution of VUR, even though the laparoscopic ureteric reimplantation is technically demanding even for experienced pediatric surgeons. Considering the main advantages of endoscopic surgery, our new vesicoscopic technique could be an optional treatment to the open reimplantation and has merits because whole the procedure are performed within the bladder, so there is no risk of intraperitoneal organ injury. CONCLUSION: Though the role of this new technique in the treatment of VUR remains to be determined, the technique could be an optional treatment to replace other surgical methods as a less invasive and effective therapeutic method.

Polysaccharides from Korean Citrus hallabong peels inhibit angiogenesis and breast cancer cell migration.

Although the peel of the hallabong (Citrus sphaerocarpa) fruit is rich in polysaccharides, which are valuable dietary ingredients for human health, it is normally wasted. The present study aimed to utilize the peel waste and identify properties it may have against breast cancer metastasis. Hallabong peel extract containing crude polysaccharides was fractionated by gel permeation chromatography to produce four different polysaccharide fractions (HBE-I, -II, -III, and -IV). The HBE polysaccharides significantly blocked tube formation of human umbilical vein vascular endothelial cells (HUVECs), at a concentration of 12.5 or 25 µg/mL. Tube formation appeared to be more sensitive to HBE-II than to other HBE polysaccharides. HBE-II also inhibited breast cancer cell migration, through downregulation of matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 triple-negative breast cancer cells. Therefore, inhibition of tube formation and MMP-9-mediated migration observed in HUVEC and MDA-MB-231 cells, respectively, are likely to be important therapeutic targets in triple-negative breast cancer metastasis.

In vivo time-sequential histological study focused on melanocytes: suggestion of golden time for intervention to prevent post-laser pigmentary changes.

BACKGROUND: Post-inflammatory pigmentary changes after laser treatments are challenging adverse effect. OBJECTIVE: To suggest an ideal time period with regard to intervention to prevent post-laser pigmentary changes, an in vivo time-sequential histological study focused on melanocytes was performed. METHODS: The back skin of four volunteers was irradiated with Q-switched alexandrite laser (QSAL). In one subject (subject 4), topical corticosteroid was applied onto the irradiated skin from the time of irradiation to day 28. In all subjects, time-sequential skin biopsies were performed at baseline, an immediate time after irradiation, day 2, day 7, and day 28. Histological and immunohistochemical analyses were conducted. RESULTS: Q-switched alexandrite laser led to the successful removal of pigments and most melanocytes from the epidermis in all subjects. At day 28, there was increased epidermal pigmentation in the skin of the subjects 1-3. It was noted that numerous activated melanocytes appeared on day 7, continued to be observed until day 28. However, in the subject 4, the melanocyte activation and post-laser pigmentary changes were not observed. CONCLUSION: In regard to intervene melanocyte activation, at least 1 week after laser treatment is suggested as a 'golden' time period to prevent pigmentary changes.

Review article: the global emergence of Helicobacter pylori antibiotic resistance.

BACKGROUND: Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. AIM: To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms. METHODS: A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. RESULTS: The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced. CONCLUSIONS: Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.