Mechanical lengthening of porcine small intestine with decreased forces

Introductionshort bowel syndrome is marked by inadequate intestinal surface area to absorb nutrients. Current treatments are focused on medical management and surgical reconfiguration of the dilated intestine. We propose the use of spring-mediated distraction enterogenesis as a novel intervention to increase intestinal length. Given our previous success lengthening intestinal segments using springs with spring constant ~7 N/m that exerts 0.46 N or higher, we sought to determine the minimal force needed to lengthen porcine small intestinal segments, and to explore effects on intestine over time.MethodsJuvenile Yucatan pigs underwent laparotomy with enterotomy to introduce nitinol springs intraluminally (n = 21 springs). Bowel segments (control, spring-distracted) were retrieved on post-operative day (POD) 7 and 14, and lengths measured. Thickness of cross-sectional intestinal layers were measured using H&E, and submucosal collagen fiber orientation measured using trichrome stained sections.Resultsall pigs survived to POD7 and 14. Spring constants of at least 2 N/m exerting a minimum force of 0.10 N significantly lengthened intestinal segments (p <0.0001). The stronger the spring force, the greater the induced thickness of various intestinal layers at POD7 and 14. Collagen fiber orientation was also more disordered because of stronger springs.Conclusiona spring constant of approximately 2 N/m exerting 0.10 N and greater significantly lengthens intestinal segments and stimulates intestinal structural changes at POD7 and 14. This suggests a decreased force is capable of inducing spring-mediated distraction enterogenesis.     

Evaluating the safety and efficacy of the 1,440‐nm laser in the treatment of photodamage in Asian skin

Background and Objective

As the demand for diminished procedure‐associated downtime continues to increase, nonablative fractional laser resurfacing is becoming a more popular intervention in the progression of photoaging. Patients with pigmented skin and a mild degree of photodamage may be particularly suited for a less intensive laser treatment. In this study, we have evaluated the safety and efficacy of a low energy, low density 1,440‐nm fractional laser in the treatment of multiple signs of photoaging including dyspigmentation, wrinkling, tissue laxity, enlarged pores, and skin roughness in Asians.

Study Design/Materials and Methods

Ten Chinese subjects with Fitzpatrick skin types III–V and visible signs of photodamage participated in this study. Patients received four treatments at 2‐week intervals with a 1,440‐nm diode‐based fractional laser. Photographs were taken at baseline, 2 weeks after each of the first three treatments and 4 weeks after the final treatment. Images were evaluated independently by two physicians. Clinical improvement and adverse events were analyzed. Discomfort, heat sensation and overall patient satisfaction associated with the procedure were also quantified.

Results

In this prospective single‐arm study, signs of photoaging were examined after treatment with the 1,440‐nm laser. Here we show that a series of four treatments with this device produced a mild improvement in skin texture, pigmentation, and wrinkling. Changes in pore size and skin laxity failed to reach statistical significance. Immediate after‐effects of the procedure included erythema and edema which were transient and left no permanent sequela. A significant proportion of patients reported some degree of discomfort during the procedure despite use of a topical anesthetic. One patient developed a discrete, localized area of post‐inflammatory hyperpigmentation which completely resolved by the final follow up visit.

Conclusion

The low energy, low density nonablative 1,440‐nm fractional laser produces a mild improvement in select signs of photodamage after four treatments without any long‐term adverse effects. Lasers Surg. Med. 46:375–379, 2014. © 2014 Wiley Periodicals, Inc.     

The Montreal Cognitive Assessment is superior to the Mini-Mental State Examination in detecting patients at higher risk of dementia

ABSTRACT Background: To examine the discriminant validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting patients with cognitive impairment at higher risk for dementia at a memory clinic setting. Methods: Memory clinic patients were administered the MoCA, MMSE, and a comprehensive formal neuropsychological battery. Mild cognitive impairment (MCI) subtypes were dichotomized into two groups: single domain-MCI (sd-MCI) and multiple domain-MCI (md-MCI). Area under the receiver operating characteristic curve (ROC) analysis was used to compare the discriminatory ability of the MoCA and the MMSE. Results: Two hundred thirty patients were recruited, of which 136 (59.1%) were diagnosed with dementia, 61 (26.5%) with MCI, and 33 (14.3%) with no cognitive impairment (NCI). The majority of MCI patients had md-MCI (n = 36, 59%). The MoCA had significantly larger AUCs than the MMSE in discriminating md-MCI from the lower risk group for incident dementia (NCI and sd-MCI) [MoCA 0.92 (95% CI, 0.86-0.98) vs. MMSE 0.84 (95% CI, 0.75-0.92), p = 0.02). At their optimal cut-off points, the MoCA (19/20) remained superior to the MMSE (23/24) in detecting md-MCI [sensitivity: 0.83 vs. 0.72; specificity: 0.86 vs. 0.83; PPV: 0.79 vs. 0.72; NPV: 0.89 vs. 0.83; correctly classified: 85.1% vs. 78.7%]. Conclusion: The MoCA is superior to the MMSE in the detection of patients with cognitive impairment at higher risk for incident dementia at a memory clinic setting.     

A survival-stratification model of human colorectal carcinomas with beta-catenin and p27kip1

BACKGROUND: The stabilization and nuclear translocation of beta-catenin are early events in the majority of sporadic colorectal carcinomas (CRC). beta-catenin up-regulates c-Myc and cyclin D1, which antagonize the association of the cyclin-dependent kinase (Cdk) inhibitor, p27(kip1), with Cdk2, thus allowing cell cycle progression through G1 to S-phase. Lack of p27 is a significant predictor of poor survival in a series of 136 CRC specimens. A combination of molecules in the same pathway may be a better prognostic factor. METHODS: The expression of beta-catenin, c-Myc, and cyclin D1 in relation to patients' survival and clinicopathologic parameters in the same series was evaluated by immunohistochemistry. RESULTS: Intense nuclear overexpression of beta-catenin, but not a lack of cell membrane or cytoplasmic expression, is a significant predictor of poor survival by both univariate (P = 0.0029) and multivariate analyses (P = 0.004, risk ratio =3.8), suggesting that beta-catenin is retained in the nucleus to function as an oncogene. None of the patients with high nuclear beta-catenin and low p27 expression survived 5 years or more whereas 65% of patients with all other combinations of the two markers survived (P < 0.0001). This combination is also a significant and independent prognostic factor (P = 0.001; risk ratio = 9.7). Overexpression of c-Myc is associated with higher mortality rates, but the expression of cyclin D1 has no prognostic significance. CONCLUSIONS: The combined expression of beta-catenin and p27 can stratify patients into markedly different survival groups, possibly via their antagonistic effects on metastasis promotion.     

Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2

Purpose

To perform Preimplantation Genetic Diagnosis (PGD) on a paternal Brca2 unknown mutation carrier with early-onset breast cancer, whose paternal grandmother and mother had breast cancer at 60s.

Method

Elucidating the linkage via single sperm haplotyping on patient''s carrier brother, and identifying the genomic deletion via BLAST followed by PCR screening. PGD was subsequently conducted.

Result

The mutant allele was found by using 4 microsatellite and 2 intragenic SNP markers. Recombination was detected in 8 % of sperms. BLAST was utilized to locate putative hairpin structure(s), followed by PCR screening with seven sets of primers. A novel 2,596 bp deletion containing exon 15 ~ 16 was identified. Due to the severity of phenotype and the integrity of exon 11 encoding RAD51 binding domain, and the fact that the patient''s mother also had breast cancer at her 60s, we speculate a possible coexistence of maternal breast cancer risk allele(s). Embryo biopsy was performed on day 3. Unaffected morula and blastocyst were replaced on day 5, resulting in a singleton livebirth. A breast lump appeared in the patient after delivery without the presence of malignant cells.

Conclusion

Concerning the assisted reproductive option for breast cancer patients, the possibility of coexistence of multiple familial risk alleles and the significance of each mutation to the phenotype should be evaluated. To eliminate misdiagnosis resulting from recombination and/or allelic drop-out, both direct mutation detection and linkage analysis approaches may be necessary. BLAST is a very useful and cost-effective tool for identifying large genomic deletion.     

亮氨酸脑啡肽的电子结构及构效关系研究

对亮氨酸脑啡肽进行了量子化学(INDO)计算,研究其电子结构特征,讨论其活性部位、作用机理及构效关系。同吗啡和R31833进行了活性部位的电子结构与空间结构比较,推断它们的活性药效结构具有共同特点,与阿片受体相互作用时作用方式相同,作用部位有对应关系,因而具有相同的药理性质。