LIM Group Research Articles

Effects of riboflavin/ultraviolet-A(UVA) scleral crosslinking on the mechanical behavior of the scleral fibroblasts of lens-induced myopia Guinea pigs

Myopia is becoming increasingly severe, and studies have shown that the cellular mechanics of scleral fibroblasts are altered following myopia. Scleral UVA-Riboflavin Collagen Crosslinking（sCXL） is a promising treatment for myopia prevention and control of axial growth. Understanding the mechanical properties of scleral fibroblasts is crucial, as it influences the cellular response and limits the extent of molecular deformation triggered. Thus, our study aimed to investigate the effect of mechanical properties of scleral fibroblasts in a lens-induced myopic guinea pig model following sCXL. For this purpose, we performed the 0.1% riboflavin/UVA scleral crosslinking (365 nm,3 mW/cm2,30 min) in the right eyes of guinea pigs in Group CXL. In Group LIM, the right eyes were only administrated negative lens for 6 weeks. No treatment was performed in both eyes of the guinea pigs in group Control. The scleral fibroblasts were isolated and cultured from the scleral tissue at the cross-linking area in Group CXL and the corresponding area in Group LIM and control. The curve of the length of microtubules inhaled by cells under negative pressure was measured by a microaspiration-based isolation technique, and the equilibrium Young's modulus and apparent viscosity of scleral fibroblasts were calculated by formula fitting. The equilibrium Young's modulus of scleral fibroblasts in group CXL was significantly lower than that in the LIM group (P < 0.01, two-sample t-test between pairs）, and there was no significant difference between groups CXL and control. The results show that sCXL can effectively moderate the phenomenon that scleral fibroblasts are not easy to deform after myopia. The apparent viscosity modulus in the CXL group was higher than the groups' control and LIM. Taken together, our data demonstrate the biomechanics of the scleral fibroblasts altered after Riboflavin/UVA scleral collagen cross-linking in a lens-induced myopia model.

Myomectomy in adult women of reproductive age: a propensity score-matched study for pregnancy rates.

To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. 40years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. Patients aged over 40years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.

Paragreen v Lim Group Holdings Pty Ltd

Paragreen v Lim Group Holdings Pty Ltd

Sirolimus-eluting BiOSS LIM dedicated bifurcation stent in the treatment of unprotected distal left main stenosis.

Proximal optimization technique (POT) has been proposed to adapt the conventional drug-eluting stent (DES) with the fractal anatomy of the bifurcation. However, only few DES are labeled for post-expansion beyond 5.0 mm. Furthermore, recrossing in the side branch (SB) through the main vessel (MV) stent cells may be challenging. To compare the sirolimus-eluting, balloon-expandable dedicated bifurcation stent BiOSS LIM DES versus the second generation DES in the treatment of distal unprotected left main coronary arteries (ULMCAs) lesions. Forty-two consecutive patients with distal ULMCA lesions were treated with the BiOSS LIM (BiOSS LIM group) in our center. A matched-group of patients treated with second-generation DES was selected from our database (Control group). The primary endpoint was the procedural complication rate, including (a) SB occlusion, defined as intraprocedural TIMI flow grade <3 immediately after MV stenting; and/or (b) trouble in SB access, defined as the need of ≥2 guidewires or a failure to recross in the SB trough the MV stent cells. The need of POT in the two groups was also analyzed. The primary endpoint occurred in four (9.5%) patients in the BiOSS LIM group and in 13 (31%) in the Control group (p = 0.028; OR = 4.25; 95% confidence interval: 1.25-14.43). POT was performed more often in the Control group (71% vs. 35%; p = 0.004). Compared to conventional DES, the BiOSS LIM stent (1) facilitates SB recrossing and (2) fits well with the fractal anatomy of the left main bifurcation.

Lever-elevating vs. liquid-isolating maneuvers during microwave ablation of high-risk benign thyroid nodules: a prospective single-center study

Aim: To compare the effects of the liquid-isolating maneuver and the lever-elevating maneuver in protecting cervical structures during microwave ablation for treating high-risk benign thyroid nodules.Methods: This prospectively study was approved by the Medical Ethics Committee of Panzhihua Central Hospital. A total of 174 patients were enrolled and randomly assigned to a liquid-isolating maneuver group (LIM, n = 87) or a lever-elevating maneuver group (LEM, n = 87). Operation time, postoperative voice change, time to recovery of baseline voice, peri-thyroid hematoma, neck tension, and intraoperative vasovagal reaction were assessed.Results: Operation time was greater in the LIM group than in the LEM group (44.75 ± 13.14 vs. 32.87 ± 10.84 min; p = .017).Voice changes were observed in 6 patients in the LIM group and 2 in the LEM group (6.9% vs. 2.3%, p = .278). The time to recovery of baseline voice was significantly greater in the LIM group compared with the LEM group (36.15 ± 10.24 vs. 24.48 ± 11.53 days, p = .014). The incidences of peri-thyroid hematoma and neck tension were higher in the LIM than in the LEM group (11.5% vs. 3.4%, 10.3% vs. 2.3%, p = .044 and p = .029). One patient (1.1%) in the LEM group and none of the patients in the LIM group experienced a vasovagal response (p = 1.000).Conclusion: The lever-elevating method is feasible and effective for the microwave ablation of benign thyroid nodules, with better protection of neck structures than observed with the liquid-isolating method.

12-month intravascular ultrasound observations from BiOSS® first-in-man studies.

The aim of this study was to analyze the difference in neointima pattern assessed by intravascular ultrasound (IVUS) between two dedicated bifurcation stents, BiOSS® Expert and BiOSS® LIM at 12-month follow-up. This manuscript reports IVUS findings obtained from the analysis of patients enrolled into first-in-man registries initially assessing the BiOSS Expert® (paclitaxel) and BiOSS LIM® (sirolimus) stents. Quantitative angiographic analysis was performed pre, post-stenting, and at follow-up. IVUS examination was performed at 12 months. There were analyzed 34 cases (BiOSS Expert® 11 patients, BiOSS LIM® 23 patients). Procedural characteristics in the two groups were similar, except for rates of main vessel predilatation and FKB/POT, which were higher in BiOSS® LIM group, 54.5 % vs 73.9 % (P < 0.05) and 0 % vs 39.1 % (P < 0.05), respectively. When comparing late lumen loss (LLL) for both stents there were significantly bigger values for main vessel and main branch in the BiOSS® Expert group, but not in side branch. Intravascular ultrasound examination showed that in the BiOSS LIM® group comparing with the BiOSS Expert® group there was lower neointima burden in the whole stent (24.7 ± 7.5 % vs 19.4 ± 8.6 %, P < 0.05) as well as in main vessel (22.8 ± 5.6 % vs 16.9 ± 6.1 %, P < 0.05) and main branch (36.1 ± 6.5 % vs 27.6 ± 8.7 %, P < 0.05), but not at the level of bifurcation (15.1 ± 3.8 % vs 13.6 ± 5.4 %, P = NS). In addition, we found that final kissing balloon/proximal optimization technique (FKB/POT) was associated with significantly smaller value of LLL in main vessel (0.24 ± 0.09 mm vs 0.32 ± 0.14 mm, P < 0.05), which in IVUS analysis resulted in smaller neointima burden in main vessel (13.7 ± 3.9 % vs 18.9 ± 4.45 %, P < 0.05) as well as at the bifurcation site (12.6 ± 4.1 % vs 14.1 ± 2.4 %, P < 0.05). The obtained results suggest that neointima proliferation was the largest in main branches of both stents assessed in quantitative angiography (LLL) as well as in IVUS (neointima burden) and the neointima increase was smaller in BiOSS LIM® stents than in BiOSS Expert® stents. Moreover, the middle part of the stent seems to not to be associated with excessive neointima proliferation and more aggressive protocol of implantation with the use FKB/POT seems to decrease this process.Electronic supplementary materialThe online version of this article (doi:10.1007/s10554-016-0926-9) contains supplementary material, which is available to authorized users.

Validity of Accelerometer Methods to Estimate Activity Energy Cost in Adults With and Without Functional Limitations

PURPOSE: The purpose of this study was to evaluate the validity of two published accelerometer analysis methods to estimate energy cost of physical activities in adults with and without functional limitations. METHODS: 62 healthy and functionally limited ambulatory adults underwent measures of strength and functional testing to cluster into 1) no functional limitations [HLTHY], or 2) lower and/or upper body limitations [LIM]. All subjects completed a variety of simulated activities while wearing accelerometers and a portable metabolic system. Estimated METs were derived from a hip-worn accelerometer (Freedson et al.(HIP)), and a wrist-worn accelerometer (Staudenmayer et al.(WRIST)). Model predictions were compared to measured METs and evaluated on the types of activities for which they were developed (HIP=locomotion, WRIST=all activities). Statistical significance was assessed with a linear mixed model. RESULTS: Mean (95% CI) measured METs across all activities were HLTHY (n=17, 48.1 ± 16.7 yrs) 3.17 (1.59) and LIM (n=45, 61.0 ±12.9 yrs) 2.32 (1.08). Fig.1. Accelerometer Model Prediction Performance. Mean (95% CI). Fig.1. shows neither the HIP nor the WRIST methods are significantly biased for the HLTHY group, and both methods are biased for the LIM group. Estimates for the LIM group are significantly different from the HLTHY group for both methods. The HIP and WRIST methods under- and over-estimate respectively for the LIM group. CONCLUSION: Accelerometer energy cost model performance is influenced by whether or not an individual has functional limitations. Future research efforts should examine how to improve accelerometer model performance within individuals with functional limitations. Supported by NIH-1R21HD080828.

Effects of hepatocyte growth factor on MMP-2 expression in scleral fibroblasts from a guinea pig myopia model.

To investigate the effects of hepatocyte growth factor (HGF) on MMP-2 expression in scleral fibroblasts from guinea pig with LIM. Sixty 1-week-old guinea pigs were chosen for the study. The right eyes were treated with -10.0 D lenses as the LIM group; the left eyes remained untreated as the control group. The refraction and axial length were measured by streak retinoscopy and A-scan ultrasonography respectively prior to and 4 weeks after the experiment. Four weeks later, the guinea pigs were sacrificed and primary scleral fibroblasts were taken for tissue culture. The 3rd-5th generation scleral fibroblasts were chosen for the experiments. The expression levels of HGF and MMP-2 protein in the scleral fibroblasts were analyzed by Western blotting. After HGF with different doses acted on the scleral fibroblasts of the control group, MMP-2 protein expression in the scleral fibroblasts was analyzed by Western blotting. HGF siRNA was transfected into the scleral fibroblasts of the LIM group and the protein expressions of HGF and MMP-2 were analyzed by Western blotting. The LIM group became myopic with a significant increase in axial length (7.97±0.29 mm vs 7.01±0.26 mm, P<0.05), and a significant decrease in refraction (-5.06±0.31 D vs 0.55±0.25 D, P<0.05) compared with the control group. The protein expression of HGF in the scleral fibroblasts of the LIM group was significantly higher compared with the control group ( 1.26±0.04 vs 0.32 ±0.04, P<0.05). The protein expression of MMP-2 in the scleral fibroblasts of the LIM group was significantly higher compared with the control group (0.89±0.06 vs 0.42±0.05, P<0.05). In the scleral fibroblasts of the control group, HGF(0, 0.1, 1, 10 ng/mL) upregulated MMP-2 protein expression in a dose-dependent manner (0.35±0.03, 0.44±0.02, 0.91±0.03, 1.33±0.04, all P<0.05). In the scleral fibroblasts of the LIM group transfected with HGF siRNA, MMP-2 protein expressions were significantly decreased compared with the negative control group (0.29±0.03 vs 0.81±0.05, P<0.05). HGF is a upstream mediator of MMP-2 in scleral fibroblasts from guinea pig.

Effects of Maternal Exposure to Cow's Milk High or Low in Isoflavones on Carcinogen-Induced Mammary Tumorigenesis among Rat Offspring

We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin-like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis in female rat offspring. Pregnant Sprague-Dawley rats were given HIM, LIM, or tap water (control) from gestational day (GD) 11 until birth; hereafter all rats received tap water. Mammary tumorigenesis was induced by administrating 7,12-dimethylbenz[a]anthracene (DMBA) on postnatal day 50. No differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM group than in the HIM group. Puberty onset occurred earlier in the LIM offspring than in controls (P = 0.03). Although the high isoflavone content seemed to prevent the effect on circulating estradiol and IGF-1 levels and advanced puberty onset seen in the LIM group, HIM increased DMBA-DNA adducts in the mammary gland and tended to increase mammary tumorigenesis. In contrast, offspring exposed to LIM in utero, did not exhibit increased breast cancer risk, despite having higher estradiol and IGF-1 environment and consequently earlier puberty onset. These results indicate that the phytochemical content in the cow's milk, consumed by a pregnant dam, determines how milk affects the offspring.

Characteristic Differences between Patients Who Have Undergone Surgical Treatment for Lung Metastasis or Hepatic Metastasis From Colorectal Cancer

The characteristic differences between patients with lung or liver metastases from colorectal carcinoma (CRC) have not yet been clarified. A small group of these patients demonstrate a better prognosis, and the selection criteria for resection of liver and/or lung metastasis are not well defined. It is important to compare and analyze the most common metastatic sites, which include liver metastases and lung metastases. The objective of this study was to compare the characteristics of the two groups in order to identify patients who benefitted from surgical resection of CRC. We retrospectively reviewed the medical charts of 80 patients who had undergone resection for liver or lung metastasis from CRC in Fukuoka University Hospital between June 1991 and December 2004. These patients were grouped according to surgical therapy received for the metastases, and separated into two groups, as follows: LUM, lung metastases resection; LIM, liver metastases resection. We evaluated these groups for a set of several factors. The characteristic factors between the two groups (LUM vs. LIM) demonstrated significant differences according to histological differentiation, venous invasion, and lymphatic permeation. There was a statistical difference in the disease-free interval (DFI) between the two groups (947.06 +/- 840.39 days in LUM vs. 246.03 +/- 229.26 days in LIM). Although serum CEA levels at resection of metastasis showed significant differences between the groups (LUM, 13.25 +/- 31.55 ng/ml; LIM, 55.21 +/- 99.52 ng/ml), the primary serum CEA levels were not significantly different. Overall survival rates at 5 years were 37.0 % for LUM and 42.8 % for LIM. There was no significant difference in the survival rate of the LUM vs. the LIM group after resection of metastasis. The Cox proportional hazards regression model was used to determine serum CEA status at the time of the metastases and showed a significant difference indicating poor prognosis for patients with LUM, but the results were not significant for LIM cases. Candidates for surgical treatment for lung or liver metastases from CRC may be an acceptable for the same valuable approach, even if characteristic differences were observed in each group.

Detection of Group B Streptococcus by immunoassay following enrichment in LIM-selective broth medium

Rapid immunoassays have been developed to decrease the time to detection of Group B Streptococcus (GBS) carriage in pregnant women. In this study, a total of 162 pregnant women, considered to be high-risk obstetric patients, were seen in the Family Care Center at Memorial Hospital of Rhode Island, a 300-bed teaching hospital associated with Brown University Medical School. Vaginal and rectal specimens were taken and tested for GBS by using two rapid enzyme immunoassays (EIAs) that were compared with culture. Quidel and Hybritech ICON Group B strep tests were run following 4 h incubation in the selective enrichment LIM Group B strep broth; cultures were done both directly and after enrichment. Results with both EIAs were identical, with overall sensitivity, specificity, and positive and negative predictive values of 38%, 98%, 88%, and 84% respectively. However, when women having positive cultures were separated into moderately to heavily colonized (≥3 + ) and lightly colonized (≤2 + ) populations, the sensitivities were 82% and 19%, respectively. Although GBS assays are useful in the rapid diagnosis of heavily colonized women, culture following enrichment remains the most sensitive method for a lightly colonized population.

Lim group B Strep Broth and coagglutination for rapid identification of group B streptococci in preterm pregnant women.

A total of 147 preterm pregnant women at Orlando Regional Medical Center were screened for group B streptococci by using Lim Group B Strep Broth (GIBCO Laboratories, Madison, Wis.) and the Phadebact Strep B Test (Pharmacia Diagnostics, Piscataway, N.J.). Test results were available within 20 h of culture and, in the case of heavily colonized women, within 5 h. This procedure is useful in rapid diagnosis of preterm pregnant women for group B streptococcal colonization.

Reduction of morbidity and mortality rates for neonatal group B streptococcal disease through early diagnosis and chemoprophylaxis.

Pregnant women, part of the term service population at Orlando Regional Medical Center, were screened for group B streptococci (GBS), using Lim Group B Strep Broth (GIBCO Laboratories, Madison, Wis.) and the Phadebact Strep B Test (Pharmacia Diagnostics, Piscataway, N.J.). Of the 803 women screened, 173 were confirmed as colonized with GBS at the time of admission in labor. Eighty of these women were treated with ampicillin at least 6 h prior to delivery. The remaining 93 women received no ampicillin. None of the infants born to the treated women was colonized with GBS at surface culture sites. Forty-three of the infants born to untreated women were colonized. Rapid identification of GBS colonization in women, combined with ampicillin chemoprophylaxis, significantly reduced vertical transmission of GBS.

Group B streptococcal colonization patterns in mothers and their infants.

Maternity patients and their newborn infants were cultured for group B streptococci (GBS) at Tampa General Hospital, Tampa, Fla., from September 1982 to May 1983. Culture swabs were placed into Lim Group B Strep Broth (GIBCO Laboratories, Madison, Wis.) and quantitated for GBS. A strong correlation was found between the numbers of GBS in the maternal vagina and the infant rectum. Infants symptomatic for early-onset GBS disease were delivered by mothers heavily colonized (greater than or equal to 3 X 10(4) GBS per swab) at the vagina. Such mothers were identified as GBS carriers by slide coagglutination and latex agglutination after their broth cultures had been incubated for 5 h. These data indicate that maternity patients at high risk of delivering infants heavily colonized with GBS and potentially symptomatic for early-onset GBS disease can be rapidly and selectively identified.