Effect of benign prostatic hyperplasia on the development of spine, hip, and wrist fractures.

Benign prostatic hyperplasia is one of the most common diseases in the elderly male population. The urinary tract symptoms may increase the risk of falls and fractures. The results indicated that patients with benign prostatic hyperplasia could increase the risk of vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. INTRODUCTION: The relationship between benign prostatic hyperplasia and the development of fall-related fractures, especially vertebral compression fractures, has been seldom mentioned in the literature. This study aimed to evaluate the risk of developing vertebral compression fracture, hip fracture, and wrist fracture in patients with benign prostatic hyperplasia. METHODS: This study obtained claims data retrospectively from the National Health Insurance Research Database of Taiwan and identified 48,114 patients who were diagnosed as having benign prostatic hyperplasia. Subjects of the control cohort were individually matched at a ratio of 4:1 with those in the benign prostatic hyperplasia cohort according to age and the index day. Comorbidities were classified as those existing before the index day and included a previous fracture history, osteoporosis, myocardial infarction, congestive heart failure, diabetes mellitus, hypertension, cerebrovascular accident, etc. The end of the follow-up period of the analyses was the day when the patient developed new vertebral compression fractures, hip fractures, or wrist fractures, terminated enrollment from the National Health Insurance, or died or until the end of 2012. The study used the Cox proportion hazard model to determine the hazard ratio for developing new hip fractures. RESULTS: Patients with benign prostatic hyperplasia were significantly more likely than those in the control cohort to develop new vertebral compression fractures in the thoracic spine (0.43% vs. 0.40%, adjusted hazard ratio 3.03, confidence interval 2.12-4.31) and lumbar spine (1.26% vs. 1.23%, adjusted hazard ratio 4.12, confidence interval 3.39-5.01), and hip fracture (1.47% vs. 2.09%, adjusted hazard ratio 1.22, confidence interval 1.10-1.36), but does not increase the risk of wrist fracture (0.61% vs. 0.67%, adjusted hazard ratio 1.07, confidence interval 0.85-1.34). CONCLUSIONS: Patients with benign prostatic hyperplasia exhibited an increased risk of developing vertebral compression fractures in both the thoracic and lumbar spine and also hip fractures, but did not increase the risk of wrist fracture. However, more research is needed to confirm this trend in the clinical setting.

Targeting of Aberrant αvß6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells.

Expression of the αvß6 integrin is upregulated in several solid tumors. In contrast, physiologic expression of this epithelial-specific integrin is restricted to development and epithelial re-modeling. Here, we describe, for the first time, the development of a chimeric antigen receptor (CAR) that couples the recognition of this integrin to the delivery of potent therapeutic activity in a diverse repertoire of solid tumor models. Highly selective targeting αvß6 was achieved using a foot and mouth disease virus-derived A20 peptide, coupled to a fused CD28+CD3 endodomain. To achieve selective expansion of CAR T cells ex vivo, an IL-4-responsive fusion gene (4αß) was co-expressed, which delivers a selective mitogenic signal to engineered T cells only. In vivo efficacy was demonstrated in mice with established ovarian, breast, and pancreatic tumor xenografts, all of which express αvß6 at intermediate to high levels. SCID beige mice were used for these studies because they are susceptible to cytokine release syndrome, unlike more immune-compromised strains. Nonetheless, although the CAR also engages mouse αvß6, mild and reversible toxicity was only observed when supra-therapeutic doses of CAR T cells were administered parenterally. These data support the clinical evaluation of αvß6 re-targeted CAR T cell immunotherapy in solid tumors that express this integrin.

Betulinic acid enhances TGF-ß signaling by altering TGF-ß receptors partitioning between lipid-raft/caveolae and non-caveolae membrane microdomains in mink lung epithelial cells.

BACKGROUND: TGF-ß is a key modulator in the regulation of cell proliferation and migration, and is also involved in the process of cancer development and progression. Previous studies have indicated that TGF-ß responsiveness is determined by TGF-ß receptor partitioning between lipid raft/caveolae-mediated and clathrin-mediated endocytosis. Lipid raft/caveolae-mediated endocytosis facilitates TGF-ß degradation and thus suppressing TGF-ß responsiveness. By contrast, clathrin-mediated endocytosis results in Smad2/3-dependent endosomal signaling, thereby promoting TGF-ß responsiveness. Because betulinic acid shares a similar chemical structure with cholesterol and has been reported to insert into the plasma membrane, we speculate that betulinic acid changes the fluidity of the plasma membrane and modulates the signaling pathway associated with membrane microdomains. We propose that betulinic acid modulates TGF-ß responsiveness by changing the partitioning of TGF-ß receptor between lipid-raft/caveolae and non-caveolae microdomain on plasma membrane. METHODS: We employed sucrose-density gradient ultracentrifugation and confocal microscopy to determine membrane localization of TGF-ß receptors and used a luciferase assay to examine the effects of betulinic acid in TGF-ß-stimulated promoter activation. In addition, we perform western blotting to test TGF-ß-induced Smad2 phosphorylation and fibronectin production. RESULTS AND CONCLUSIONS: Betulinic acid induces translocation of TGF-ß receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-ß receptors. The betulinic acid-induced TGF-ß receptors translocation is rapid and correlate with the TGF-ß-induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells.

Identification of the chitinase genes from the diamondback moth, Plutella xylostella.

Chitinases have an indispensable function in chitin metabolism and are well characterized in numerous insect species. Although the diamondback moth (DBM) Plutella xylostella, which has a high reproductive potential, short generation time, and characteristic adaptation to adverse environments, has become one of the most serious pests of cruciferous plants worldwide, the information on the chitinases of the moth is presently limited. In the present study, using degenerated polymerase chain reaction (PCR) and rapid amplification of cDNA ends-PCR strategies, four chitinase genes of P. xylostella were cloned, and an exhaustive search was conducted for chitinase-like sequences from the P. xylostella genome and transcriptomic database. Based on the domain analysis of the deduced amino acid sequences and the phylogenetic analysis of the catalytic domain sequences, we identified 15 chitinase genes from P. xylostella. Two of the gut-specific chitinases did not cluster with any of the known phylogenetic groups of chitinases and might be in a new group of the chitinase family. Moreover, in our study, group VIII chitinase was not identified. The structures, classifications and expression patterns of the chitinases of P. xylostella were further delineated, and with this information, further investigations on the functions of chitinase genes in DBM could be facilitated.

Anti-inflammatory effects of platelet biomaterials in a macrophage cellular model.

BACKGROUND AND OBJECTIVES: Recent clinical data suggested that platelet materials used in regenerative medicine exert anti-inflammatory effects. One must understand whether functionality varies among platelet preparations and also the role of the various protein compartments. MATERIALS AND METHODS: Platelet-poor-plasma (PPP), platelet lysate with cell debris (PL) or cell-free (CFPL), platelet gel releasate (PGR) and solvent/detergent-treated PL (SDPL) were prepared from four apheresis platelet donations. Protein profile was examined by SDS-PAGE, and growth factors and cytokines by ELISA, multiplexed Luminex assay and cytokine array. Anti-inflammatory activity was evaluated in RAW 264.7 mouse macrophages treated for 24 h with the blood fractions followed by 24 h of stimulation with 500 ng/ml lipopolysaccharides (LPS). Inflammatory marker nitric oxide (NO) was determined by colorimetry, tumour necrosis factor (TNF)-α by ELISA and inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 by Western blotting. RESULTS: Proteins, growth factors and cytokines composition differed among preparations. Blood fractions alone did not stimulate inflammatory markers expression. Following LPS stimulus, NO and iNOS expressions were significantly inhibited (P < 0.001) by all blood fractions, but inhibition was more pronounced with SDPL. In addition, only SDPL inhibited TNF-α (P < 0.001) and COX-2 expressions. CONCLUSIONS: All the plasma and platelet fractions evaluated in this study exert an anti-inflammatory effect on macrophages, suggesting that both the plasma and platelet proteomes contribute to anti-inflammation. However, the extent and nature of the anti-inflammatory action vary among products. Further studies are needed to better understand the functionality of platelet biomaterials and optimize their clinical use.

Identification of a hidden outbreak due to the spread of a VIM-3-producing, extensive drug-resistant Pseudomonas aeruginosa (XDRPA) clone at a regional hospital in Taiwan.

A review of the annual prevalence of Pseudomonas aeruginosa at a regional hospital in Taiwan revealed a significant increase in the incidence of extensive drug-resistant P. aeruginosa (XDRPA) from 2∙1% in 2003 to 5∙8% in 2007. The first XDRPA isolate was recovered in 2001 from the emergency ward. The widespread dissemination of XDRPA isolates to more than 10 other wards was discovered the following year. Six pulsotypes of 67 XDRPA isolates from 2006 onwards were identified and 91% were a single strain, suggesting the existence of a hidden outbreak. Prior to the recognition of the outbreak, the majority of cases were not considered to be healthcare-associated infections until molecular evidence was provided. A cohort measure was launched by the infection control practitioners that effectively controlled the outbreak. Patients with XDRPA were mostly referred from neighbouring long-term care facilities, which may have been the reservoir of the XDRPA clone.

School participation, supports and barriers of students with and without disabilities.

BACKGROUND: We compared school participation patterns of students ages 5-17 with and without disabilities and examined whether features of the school environment were perceived to help or hinder their participation. METHODS: Parents (n = 576) residing in the USA and Canada completed the Participation and Environment Measure for Children and Youth (PEM-CY) via the internet. RESULTS: Parents of students with disabilities reported that their children participated less frequently in school clubs and organizations and getting together with peers outside the classroom and that they were less involved in all school activities. Parents of students with disabilities also were significantly more likely to report that features of the environment hindered school participation and that resources needed to support their child's participation were not adequate. CONCLUSIONS: Parents of students with disabilities report that their children are participating less in important school-related activities. Barriers limiting school participation include features of the physical and social environment as well as limited resources.

Preoperative ultra-hypofractionation radiotherapy in extremity/trunk wall soft tissue sarcoma - A meta-analysis of prospective studies.

PURPOSE: The neoadjuvant radiotherapy is now standard treatment in soft tissue sarcoma. Using ultra-hypofractionation radiotherapy shorten the treatment time. In the era of COVID pandemic, using less fraction to treat patient is an urgent need. Thus, we aim to use meta-analysis to investigate the clinical efficacy of preoperative stereotactic body radiotherapy. MATERIAL AND METHODS: PRISMA guideline was used in this study. PubMed, Cochrane and Embase were used. We include only prospective study. The main endpoint was set as wound complication rate. Other endpoints include R0 resection rate, overall survival, local control, and distant metastasis free survival. RESULTS: Seven studies were included. The pooled wound complication rate is 0.30 (95% CI=0.26-0.35). The pooled R0 resection rate is 0.87(95%CI: 0.74-0.94). The pooled 2-year overall survival is 0.86 (95%CI: 0.72-0.94). The pooled 2-year local control rate is 0.96(95%CI: 0.89-0.99). The pooled 2-year distant metastasis free survival is 0.60 (95%CI=0.50-0.70). CONCLUSION: Neoadjuvant ultra-hypofractionation radiotherapy in soft tissue sarcoma is a feasible and well tolerable treatment.

Biochemical characterization of the cell-biomaterial interface by quantitative proteomics.

Surface topography and texture of cell culture substrata can affect the differentiation and growth of adherent cells. The biochemical basis of the transduction of the physical and mechanical signals to cellular responses is not well understood. The lack of a systematic characterization of cell-biomaterial interaction is the major bottleneck. This study demonstrated the use of a novel subcellular fractionation method combined with quantitative MS-based proteomics to enable the robust and high-throughput analysis of proteins at the adherence interface of Madin-Darby canine kidney cells. This method revealed the enrichment of extracellular matrix proteins and membrane and stress fibers proteins at the adherence surface, whereas it shows depletion of extracellular matrix belonging to the cytoplasmic, nucleus, and lateral and apical membranes. The asymmetric distribution of proteins between apical and adherence sides was also profiled. Apart from classical proteins with clear involvement in cell-material interactions, proteins previously not known to be involved in cell attachment were also discovered.

Evaluation and management of osteochondral lesions of the knee.

Osteochondral lesions of the knee is a common disorder in adolescents, although it may present in children and adults. Despite the fact that the disorder was discovered more than a century ago, no specific causes have been identified, although relationships with ischemia, irregular ossification of epiphyseal cartilage, genetic influences, trauma, and endocrine disorders have been postulated. Taking a thorough history and performing a thorough physical examination will facilitate diagnosis of this condition. Radiographic and magnetic resonance imaging are useful diagnostic tools that aid in the evaluation. A comprehensive knowledge of the relevant anatomy and clinical progression of osteochondral lesions allows for a better understanding of the classification systems and, ultimately management of this disorder. The size, location, and stability of the lesion, as well as the patient's age, are crucial in determining optimal treatment. The spectrum of injury ranges from small, stable lesions, which can be treated nonoperatively, to unstable or displaced lesions, which may require surgical management. Surgical options include drilling of subchondral bone, curettage and microfracture, refixation of detached lesions, autologous osteochondral autograft procedures (eg, mosaicplasty, osteochondral autograft transfer system), autologous chondrocyte implantation, and osteochondral allograft resurfacing. This article provides a basic approach to the evaluation and management of osteochondral lesions, as well as indications for surgery.

Using social media for smoking cessation interventions: a systematic review.

BACKGROUND: Previous studies have shown that smoking tobacco significantly increases both incidence and mortality rates for many diseases. Social media has become one of the most influential platforms for various smoking cessation interventions. However, results from smoking cessation interventions have differed from study to study. Limited studies have summarised cessation outcomes from social media-based interventions. Therefore, the objective of this review is to explore the effectiveness of using social media for smoking cessation. METHODS: We searched PubMed, MEDLINE, PsycINFO, and CINAHL for articles between June 2008 and June 2018, and also assessed the references of selected articles. We included studies that used social media as intervention platforms, provided a baseline assessment before the intervention, and provided smoking cessation outcomes after the intervention. RESULTS: We identified 13 original studies that enrolled between 16 and 1698 participants; 7-day Point Prevalence Abstinence (PPA) rate was the most frequently used measure of abstinence, with a range of 7%-75%, regardless of the measurement time, study design, and analysis methods. Social media-based smoking cessation interventions were effective, because (1) smokers reported higher 7-day PPA rates after intervention compared to baseline and (2) smokers reported higher 7-day PPA rates in intervention groups than in control groups. Moreover, at each time point, approximately half of all smokers in studies reporting abstinence were found to be biochemically abstinent. There were no significant differences in the effectiveness of smoking cessation outcomes between those that used existing popular social networking platforms (e.g. Pechmann et al's studies) and those that used individually designed interactive platforms (e.g. MyLastDip, iQuit system, Quitxt system). CONCLUSIONS: This review highlights the effectiveness of social media-based smoking cessation intervention studies. Due to the widespread use of social media, as well as its low cost, we suggest embedding smoking cessation interventions within existing popular social media platforms.

Cerebral columnar organization of the first nociceptive component induced by CO2 laser on the tail of the rat.

The somatotopic map of the first nociceptive component in the primary somatosensory cortex (S1) is still unclear. In this study, a CO(2) laser was applied to the tail of the rat to induce nociception without the interference from large myelinated (A(beta)) fibers. Thus, only noxious fibers could be activated. Two-dimensional current-source-density analysis was used to analyze the evoked field potentials. Using this method, the nociceptive responses of A(delta)-fibers in S1 were verified, and the somatotopic map of the first nociceptive component in S1 was identified. We found that whether light touch or laser-induced nociception was applied to the tail of the rat, the responsive topography in S1 was consistent. Discrimination of these two modalities was achieved vertically in the same column; the deeper layer represented the nociceptive response while the superficial layer encoded the response to light touch. This is quite different from that of a primate brain.

Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator-activated receptors.

BACKGROUND: Peroxisome proliferator-activated receptors (PPAR) mediate inflammatory processes and alter cardiac function. However, it is not clear whether inflammatory cytokines or PPAR ligands regulate PPARs in the cardiomyocytes to modulate cardiac functions. We investigated the effects of tumour necrosis factor-alpha (TNF-alpha) and PPAR ligands on the expression of PPARs in HL-1 cardiomyocytes. MATERIALS AND METHODS: HL-1 cardiomyocytes were incubated with and without TNF-alpha (1, 10, 25 and 50 ng mL(-1)) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0.1, 1 and 10 microM for 24 h. The cells also received SN-50 (NF-kappaB inhibitor, 50 microg mL(-1)), ascorbic acid (100 microM) and coenzyme Q10 (10 microM) alone or combined with TNF-alpha. RESULTS: Using reverse transcriptase-polymerase chain reaction and Western blot, we found that incubation of TNF-alpha (50 ng mL(-1)) for 24 h decreased PPAR-alpha, but increased PPAR-gamma without altering PPAR-delta. These effects were not changed by co-administration of SN-50. However, co-administration of ascorbic acid prevented the effect of TNF-alpha both on PPAR-alpha and PPAR-gamma. Coenzyme Q10 partially attenuated the effect of TNF-alpha on PPAR-gamma but did not alter its effect on PPAR-alpha. The administration of rosiglitazone (10 microM) and pioglitazone (10 microM) for 24 h increased PPAR-gamma mRNA, but did not alter PPAR-alpha or PPAR-delta. Moreover, fenofibrate (0.1, 1 and 10 microM) increased PPAR-gamma without any effects on PPAR-alpha or PPAR-delta. CONCLUSIONS: Oxidative stress causes the regulations of PPAR-alpha and PPAR-gamma in the TNF-alpha-treated cardiomyocytes. The up-regulation of PPAR-gamma by PPAR ligands may contribute to their anti-inflammation effects.

Small molecule clearance in ultrafiltration/diafiltration in relation to protein interactions:Study of citrate binding to a Fab.

Ultrafiltration/diafiltration (UFDF) is commonly utilized in the purification of recombinant proteins to concentrate and buffer exchange the product. It is often the final step in the purification process, placing the protein in its final formulation and clearing small molecules introduced in upstream purification steps. This article presents a case study of reduced small molecule clearance in ultrafiltration/diafiltration of an antigen-binding fragment of a monoclonal antibody. Citrate, a commonly utilized small molecule in downstream processes, is shown to have reduced clearance due to specific interactions with the protein product. The study presents process solutions and utilizes a simple model to characterize clearance of small molecules which exhibit interactions with product protein.

Serotonin transporter gene promoter polymorphism is associated with body mass index and obesity in non-elderly stroke patients.

BACKGROUND: The serotonergic system is involved in the complex behavioral and physiological process in maintaining energy balance. Genetic factors regulating serotonergic function may have links with the development of obesity. AIM: To investigate whether the 5-HTTLPR polymorphism of the serotonin transporter gene is associated with body mass index (BMI) and obesity in stroke patients. SUBJECTS AND METHODS: The study included 376 patients (65.3+/-11.3 yr; male, 61.7%) with stroke. Associations between the 5-HTTLPR and BMI and obesity (BMI > or = 25 kg/m2) were examined in all subjects. In order to test age-dependent effects of the genetic variant, the association was also examined in the non-elderly subgroup (<65 yr) and the elderly subgroup (> or =65 yr) respectively. RESULTS: For non-elderly subjects, the SS genotype was independently associated with increased BMI level (beta=1.84, p=0.037) and obesity (odds ratio 4.17, 95% CI 1.25-14.0, p=0.021) when the LL genotype was used as the reference. The association was not found for all patients or in the elderly subgroup. The LS genotype was not different from the LL genotype in BMI level or risk of obesity, either for all subjects or with regard to the non-elderly and elderly subgroups. CONCLUSIONS: The SS genotype of 5-HTTLPR is an independent determinant of increased BMI level and obesity in non-elderly stroke patients but not in elderly patients. An age-dependent modification for the effect of the 5-HTTLPR on development of obesity is considered.

Validating the Automatic Independent Component Analysis of DSA.

Time-density curve analysis of DSA provides useful blood flow information. However, manually selecting the ROI is time-consuming. We developed an automatic technique to provide arterial, capillary, and venous vasculatures with corresponding time-density curves. This study retrospectively analyzed the data of 36 patients with unilateral carotid stenosis. We found that the full width at half maximum of the time-density curve for the automatically segmented capillary vasculature is a suitable representation of the cerebral circulation time.

Behavioral and Structural Effects of Single and Repeat Closed-Head Injury.

BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure. MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model (n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively. RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (P < .05). Behavioral deficits (P < .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period. CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression.

Epithelial cell adhesion molecule (Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that Ep-CAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness. Ep-CAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter-reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hypermethylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/metastatic proclivity of tumors.