Fiber-reinforced composite full-arch prosthetic reconstructions supported by three standard, short or extra-short implants: a two-center retrospective study.
To evaluate the survival of implants and prostheses, and marginal bone level of fiber-reinforced composite implant supported fixed complete prostheses supported by 3 implants. Patients with fiber-reinforced composite fixed prostheses supported by 3 standard-length, short or extra-short implants were included in this retrospective cohort study. Kaplan-Meier survival was computed for implants and prostheses. Univariate and multivariate Cox proportional hazard regressions, clustered by patient, were used to analyze bone level differences as a function of different study covariates. Linear regressions were used to investigate the relationship between distal extension lengths and bone levels. Forty-five patients with 138 implants were followed for up to 10 years after prosthesis insertion (mean 52.8; SD 20.5 months). Kaplan-Meier survival analysis showed overall survival rates of 96.5% for implants and of 97.8% for prostheses. The 10-year success rate for prostheses was 90.8%. Extra-short implants survived at similar rates to short and standard implants. Marginal bone levels surrounding implants remained stable over time, even showing slight bone gain on average (mean + 0.1 mm/year; SD ± 0.5 mm/year) Acrylic denture teeth, overdentures on the opposing arch, and implant placement in the posterior maxilla were correlated with bone gain. Screw retention, opposed to telescopic retention, was correlated with bone loss. Longer distal extensions were correlated with bone gain on the implants closest to the distal extensions. Fiber-reinforced composite fixed prostheses supported by only 3 implants, most of which were extra-short, presented high survival rates with stable bone levels. An encouraging prognosis can be expected for restoration of atrophic maxillary and mandibular arches, when restored with fixed fiber-reinforced composite frameworks with long distal extensions and supported on only 3 short implants.


Comparison of approaches for the rigid fixation of sub-condylar fractures.
The objective of this study was to compare the rate of complications encountered on using different incisions to access the fracture site for the open reduction and internal fixation of isolated subcondylar fractures. The parameters evaluated are: the occurrence of salivary fistula, infection, and injuries to the seventh facial nerve. An assessment of the surgical scar was also undertaken. 20 patients who met the previous criteria and were willing to participate in the study were placed (five each) into the pre-auricular, submandibular, retromandibular transparotid or retromandibular transmassetric group based on the incision scar they selected after a description of the operation and being explained about the possible complications. Comparison of the complications could not ascertain the superiority of any approach over the other since the outcomes were not statistically significant. However, judging by operator and assistants' subjective assessment, the retromandibular approaches seem to provide a more direct visual field and an almost straight line access for the fixation of the fracture. The transmassetric approach seems to be a safer approach since the nerves encountered can be visualized and avoided.


Optimization of the storage conditions for coagulation screening tests.
To determine the optimum storage temperature and time for prothrombin time and activated partial thromboplastin time at various intervals at both room temperature and refrigerator. Experimental study. Advanced Medical and Dental Institute (AMDI), Laboratory at University Sains Malaysia (USM), from August 2009 to June 2010. After obtaining the consent, 33 blood samples were collected from AMDI staffs and students. Prothrombin time (PT) was measured at 0, 4, 8 and 24 hours (h). Partial thromboplastin time (APTT) was measured at 0, 2, 6 and 8 h both at room temperature (RT) and refrigerator. Thirty three subjects (14 males and 19 females, aged from 20 to 40 years) were involved. PT showed no significant differences at RT at 4 h, while significant differences after 8 h and 24 h at RT and after 4 h, 8 h and 24 h at refrigerator were observed. APTT showed no statistically significant differences at 2 h but showed significant differences at 6 h, 8 h at both RT and refrigerator. Samples for PT testing can be accepted only up to 4 h when kept at RT while the samples cannot be accepted when kept at refrigerator for 4 h and above. APTT samples can be accepted up to 2 h only at RT or refrigerator.


Laryngopharyngeal reflux: The microbiota theory.
Laryngopharyngeal reflux (LPR) is a prevalent disease associated with non-specific symptoms and findings. Many gray areas persist in the pathogenesis of LPR, the diagnosis and the treatment. Symptoms are poorly correlated with fiberoptic signs or hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring findings. The therapeutic response remains uncertain with some resistant patients to medical or surgical treatment. The development of LPR-symptoms and findings may be related to the refluxate of a myriad of gastroduodenal enzymes, which may modify the laryngopharyngeal and oral microbiome leading to mucosa maintenance and recovery impairments. The diet of patient is important because it may impact the microbiome composition and some foods are known to increase the number of hypopharyngeal reflux events. The number of hypopharyngeal reflux events may be increased by autonomic nerve dysfunction that may have an important role in the persistence of LPR-symptoms.


[Oocyte vitrification in an ART laboratory].
Oocyte vitrification has been authorized in France after the modification of French bioethics law in July 2011. This evolution will bring a dramatic change in patients' management since, from 2011, infertile couples, oocyte donation and fertility preservation programs will benefit this technique in France. We have introduced oocyte vitrification in our ART laboratory through a validation of the method using Evidence-Based Medicine model: open system Cryotop, Ethylène-glycol 15% and DMSO 15%. Based on our 1-year experience, oocyte vitrification upgrades our daily practice while also minimizing embryo cryoconservation as recommended by the law.


Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models.
Oxidative stress is associated with some forms of both male and female infertility. However, there is insufficient knowledge of the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. There are a number of animal models for understanding age-dependent decrease of reproductive ability and diabetic embryopathy, especially abnormal spermatogenesis, oogenesis and embryogenesis with mitochondrial dysfunctions. Several important processes occur in mitochondria, including ATP synthesis, calcium ion storage, induction of apoptosis and production of reactive oxygen species (ROS). These events have different effects on the several aspects of reproductive function. Tet-mev-1 conditional transgenic mice, developed after studies with the mev-1 mutant of the nematode C. elegans, offer the ability to carefully regulate expression of doxycycline-induced mutated SDHC(V69E) levels and hence modulate endogenous oxidative stress. The mev-1 models have served to illuminate the effects of complex II deficiency-dependent mitochondrial ROS production, although interestingly they maintain normal mitochondrial and intracellular ATP levels. In this review, the reproductive dysfunctions are presented focusing on fertility potentials in each gamete, early embryogenesis, maternal conditions with placental function and neonatal development.


Dual-site ligation-assisted loop-mediated isothermal amplification (dLig-LAMP) for colorimetric and point-of-care determination of real SARS-CoV-2.
A probing system has been developed based on dual-site ligation-assisted loop-mediated isothermal amplification (dLig-LAMP) for the selective colorimetric detection of SARS-CoV-2. This approach can induce false-positive and -negative detection in real clinical samples; dLig-LAMP operates with improved selectivity. Unlike RT-LAMP, the selectivity of dLig-LAMP is determined in both the ligation and primer binding steps, not in the reverse transcription step. With this selective system in hand, we developed a colorimetric signaling system for point-of-care detection. We also developed a colorimetric probe for sensing pyrophosphate, which arises as a side product during the LAMP DNA amplification. Thus, dLig-LAMP appears to be an alternative method for improving the selectivity problems associated with reverse transcription. In addition, combining dLig-LAMP with colorimetric pyrophosphate probing allows point-of-care detection of SARS-CoV-2 within 1 h with high selectivity.


[Prevention of the formation of the infectious process with biologically active thymic factors in the Salmonella typhimurium challenge of mice coincident with macrophage activation].
A single injection of thymostimulin into mice in a dose of 45 micrograms/kg b.w. enhances the functional activity of macrophages, reaching it maximum on day 10, which prevents the formation of an infectious process in mice challenged with S. typhimurium (LD50). The irradiation of the animals in a sublethal dose leads to the complete abolition of the stimulating effect of thymostimulin on macrophages. The presence of an inducer mechanism of the activation of macrophages by thymostimulin, realized in the production of lymphokines, is suggested.


Whole-Exome Sequencing Identifies a Variant in Phosphatidylethanolamine N-Methyltransferase Gene to be Associated With Lean-Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases with simple steatosis on one end and hepatocellular carcinoma on the other. Although obesity is a known risk factor for NAFLD, individuals with normal body mass index (BMI) also have hepatic fatty infiltration, now termed "lean-NAFLD". It represents a distinct entity with a strong underlying genetic component. The present study aimed to sequence the complete exonic regions of individuals with lean-NAFLD to identify germline causative variants associated with disrupted hepatic fatty acid metabolism, thereby conferring susceptibility to NAFLD. Whole blood was collected from patients with lean-NAFLD (n = 6; BMI < 23.0 kg/m2) and matched lean controls (n = 2; discovery set). Liver fat was assessed using acoustic radiation force impulse (ARFI) imaging. Patients with ultrasound-detected NAFLD (n = 191) and controls (n = 105) were part of validation set. DNA was isolated, and whole-exome sequencing (WES) was performed in the discovery cohort (Ion Proton™; Ion AmpliSeq™ Exome RDY Kit). Data were analyzed (Ion Reporter software; Life Technologies), and variants identified. Validation of variants was carried out (Taqman probes; Real time-PCR). Student's t test and Fisher's exact test were used to analyze the statistical significance. Although WES identified ∼74,000 variants in individual samples, using various pipelines. variants in genes namely phosphatidylethanolamine N-methyltransferase (PEMT) and oxysterol-binding protein-related protein10 (OSBPL10) that have roles in dietary choline intake and regulation of cholesterol homeostasis, respectively, were identified (discovery set). Furthermore, significant differences were noted in BMI (p = 0.006), waist/hip circumference (p > 0.001), waist/hip ratio (p > 0.001), aspartate aminotransferase (p > 0.001), alanine aminotransferase (p > 0.001), and triglycerides (p = 0.002) between patients and controls. Validation of variants (rs7946-PEMT and rs2290532-OSBPL10) revealed that variant in PEMT but not OSBPL10 gene was associated (p = 0.04) with threefold increased risk of NAFLD in lean individuals. Our results demonstrate the association of rs7946 with lean-NAFLD. WES may be an effective strategy to identify causative variants underlying lean-NAFLD.


[Spanish version of the new World Health Organization Disability Assessment Schedule II (WHO-DAS-II): initial phase of development and pilot study. Cantabria disability work group].
The aim of the present paper is to present the initial phases of the development of the Spanish version of the "World Health Organization Disablement Assessment Schedule II" WHO-DAS-II and also to describe the quantitative and qualitative methodological strategies used in the elaboration process of an instrument: i) compatible with the new International Classification of Functioning and Disability -ICIDH-2- of the World Health Organisation; ii) with criteria of cross-cultural applicability and; iii) to allow us to assess the disability in all its dimensions.


Reconstitution of recombinant interleukin-2 (rIL-2): a comparative study of various rIL-2 muteins.
In a previous clinical study using a continuous infusion schedule of recombinant interleukin-2 (rIL-2) we noted a nearly complete loss of activity of EuroCetus rIL-2 when dissolved in 10 ml saline and infused at a very low rate through a plastic infusion device. In the present study, we demonstrated that the loss resulted from a concentration-dependent precipitation of rIL-2 in saline and adherence of the protein to the tubing material. These phenomena were not noted for four other rIL-2 muteins tested [Glaxo, Hoffmann-LaRoche, Amgen (2 muteins)]. EuroCetus rIL-2 was found to be completely soluble in water and 5% glucose.


Chromosomal localization and heterochromatin association of ribosomal RNA gene loci and silver-stained nucleolar organizer regions in salmonid fishes.
Ribosomal RNA gene (rDNA) loci, including those of nucleolus-forming 18S, 5.8S and 28S (major) and non-nucleolus-forming 5S (minor) rDNA, were assigned using fluorescence in situ hybridization (FISH) to the embryonic chromosomes of rainbow trout (Oncorhynchus mykiss), masu salmon (O. masou), brook trout (Salvelinus fontinalis) and Japanese huchen (Hucho perryi). In these species, the minor rDNA loci were located basically on 2-4 chromosome pairs, whereas the major rDNA loci were found essentially on one chromosome pair, except for the brook trout. Its major rDNA loci were dispersed on about half of the chromosome complement, showing a considerable interindividual variation in the number and location. The major and minor rDNA loci were separated onto different chromosomes in the examined species, except for the rainbow trout, in which one chromosome pair had tandemly aligned minor and major rDNA loci. Chromosome regions containing both kinds of rDNA loci in each species were found to be stained with C-banding, showing an association of these loci with heterochromatin. Comparison of the assigned major rDNA loci and sequentially detected silver (Ag)-stained nucleolar organizer regions (AgNORs) in all the species revealed a considerable polymorphism in the number and size of AgNORs among or within those loci, suggesting a possible inter- or intralocus inactivation of the major rDNAs.


Fast accurate stereoradiographic 3D-reconstruction of the spine using a combined geometric and statistic model.
To describe and evaluate a fast accurate stereoradiographic 3D-reconstruction method of the spine. Stereoradiographic methods based on anatomical landmarks identification are the only ones providing information on 3D-deformities of the spine in a standing position, but require 2-4 h for the whole spine, making the method inadequate for clinical routine. The proposed semi-automated method is based on (1) vertebral body volume reconstruction, (2) definition of a local referential associated to this volume, (3) reliable a priori knowledge of the vertebral shape using eight morphologic descriptors of the vertebral body to estimate, from a multiple linear regression, 21 3D-point coordinates per vertebra, (4) kriging of a 2000 points model with regard to the 21 points. The method was evaluated for vertebral orientation and shape accuracy. 3D models of the whole spine are obtained within 15 min. Manual vs. semi-automated reconstruction comparison yield similar accuracy regarding the CT-scan references. For vertebrae orientation, results were slightly different from the manual reconstruction method (however an absolute reference is lacking). The stereoradiographic 3D-reconstruction method allows for a significant reduction of the whole reconstruction time, with regard to previously described methods. Moreover, the accuracy was evaluated and was found to be comparable to the accuracy of previous methods. The results of this study show that stereoradiography could now be employed in routine clinical environment. 3D spine reconstruction from biplanar radiographs in standing position can be obtained using a fast and accurate method.


Social media for early characterization of pandemic symptoms: A qualitative analysis of patient-reported COVID-19 experiences.
Patients use social media forums to discuss their medical history and healthcare experiences, providing early insight into real-world patient experiences. We analyzed COVID-19 patient experiences from Reddit social media posts. We extracted Reddit Application Programming Interface data for the subreddit/COVID-19 positive from March to August 2020 and selected users tagged as "Tested Positive" or "Tested Positive- Me" flair and who posted at least thirty times in any calendar month, excluding users who explicitly stated location outside of the U.S. For tested-positive patients (users), we created and reviewed individual case profiles summarizing their COVID-19 symptoms, testing, and medications or treatments. Data were imported to Nvivo qualitative analysis software and qualitative coding was conducted. There were 31 759 posts and comments from 720 users in March to May 2020 (Q1) and 40 446 posts and comments from 1649 users from June to August 2020 (Q2). Final count of "Tested Positive" was 1296 users (280 in Q1 and 1016 in Q2). Across both quarters, frequently reported symptoms included sore throat, headaches, fevers, or chills. Loss of sense of smell or taste were reported by users in early March, prior to the inclusion of this symptom to the CDC list in April and GI-related symptoms and fatigue were reported in the March to May data, before they were added as a COVID-19 associated symptom in July 2020. Users also reported in-depth descriptions of their symptoms, motivations for testing, and long-term impacts such as post-viral fatigue. Social media data can potentially serve as an early surveillance data source in a pandemic and offer preliminary insights into patient disease experiences.


Prediction equations for digestible and metabolizable energy concentrations in feed ingredients and diets for pigs based on chemical composition.
The objectives were to develop prediction equations for digestible energy (DE) and metabolizable energy (ME) of feed ingredients and diets for pigs based on chemical composition and to evaluate the accuracy of the equations using in vivo data. A total of 734 data points from 81 experiments were employed to develop prediction equations for DE and ME in feed ingredients and diets. The CORR procedure of SAS was used to determine correlation coefficients between chemical components and energy concentrations and the REG procedure was used to generate prediction equations. Developed equations were tested for the accuracy according to the regression analysis using in vivo data. The DE and ME in feed ingredients and diets were most negatively correlated with acid detergent fiber or neutral detergent fiber (NDF; r = -0.46 to r = -0.67; p<0.05). Three prediction equations for feed ingredients reflected in vivo data well as follows: DE = 728+0.76×gross energy (GE)-25.18×NDF (R2 = 0.64); ME = 965+0.66×GE-24.62×NDF (R2 = 0.60); ME = 1,133+0.65×GE-29.05×ash-23.17×NDF (R2 = 0.67). In conclusion, the equations suggested in the current study would predict energy concentration in feed ingredients and diets.


Brain natriuretic peptide is not reno-protective during renal ischemia-reperfusion injury in the rat.
Acute kidney injury (AKI) occurs in 30% of patients undergoing complex cardiovascular surgery, and renal ischemia-reperfusion (I/R) injury is often a contributing factor. A recent meta-analysis observed that perioperative natriuretic peptide administration was associated with a reduction in AKI requiring dialysis in cardiovascular surgery patients. This study was designed to further clarify the potential reno-protective effect of brain natriuretic peptide (BNP) using an established rat model of renal I/R injury. The study comprised three groups (n = 10 kidneys each): (1) control (no injury); (2) I/R injury (45 min of bilateral renal ischemia followed by 3 h of reperfusion); and (3) BNP (I/R injury plus rat-BNP pretreatment at 0.01 μg/kg/min). Glomerular filtration rate (GFR) and a biomarker of AKI, urinary neutrophil gelatinase-associated lipocalin (uNGAL), were measured at baseline and at 30 minute intervals post-ischemia. Groups were compared using two-way repeated measures analysis of variance (mean ± SD, significance P < 0.05). Baseline GFR measurements for control, I/R, and BNP groups were 1.07 ± 0.55, 0.88 ± 0.51, and 1.03 ± 0.59 mL/min (P = 0.90), respectively. Post-ischemia, GFR was significantly lower in I/R and BNP compared with controls at 30 min, 1.29 ± 0.97, 0.08 ± 0.04, and 0.06 ± 0.05 mL/min (P < 0.01), and remained lower through 3 h, 1.79 ± 0.44, 0.30 ± 0.17, and 0.32 ± 0.12 mL/min (P < 0.01). Comparing I/R to BNP groups, GFR did not differ significantly at any time point. There was no significant difference in uNGAL levels at 1 h (552 ± 358 versus 516 ± 259 ng/mL, P = 0.87) or 2 h (1073 ± 589 versus 989 ± 218 ng/mL, P = 0.79) between I/R and BNP. BNP does not reduce the renal injury biomarker, urinary NGAL, or preserve GFR in acute renal ischemia-reperfusion injury.


Estrogen receptor alpha, but not beta, is required for optimal dendritic cell differentiation and [corrected] CD40-induced cytokine production.
Dendritic cells (DC) are critical actors in the initiation of primary immune responses and regulation of self-tolerance. The steroid sex hormone 17beta-estradiol (E(2)) has been shown to promote the differentiation of DCs from bone marrow (BM) precursors in vitro. However, the estrogen receptor (ER) involved in this effect has not yet been characterized. Using recently generated ERalpha- or ERbeta-deficient mice, we investigated the role of ER isotypes in DC differentiation and acquisition of effector functions. We report that estrogen-dependent activation of ERalpha, but not ERbeta, is required for normal DC development from BM precursors cultured with GM-CSF. We show that reduced numbers of DCs were generated in the absence of ERalpha activation and provide evidence for a cell-autonomous function of ERalpha signaling in DC differentiation. ERalpha-deficient DCs were phenotypically and functionally distinct from wild-type DCs generated in the presence of estrogens. In response to microbial components, ERalpha-deficient DCs failed to up-regulate MHC class II and CD86 molecules, which could account for their reduced capacity to prime naive CD4(+) T lymphocytes. Although they retained the ability to express CD40 and to produce proinflammatory cytokines (e.g., IL-12, IL-6) upon TLR engagement, ERalpha-deficient DCs were defective in their ability to secrete such cytokines in response to CD40-CD40L interactions. Taken together, these results provide the first genetic evidence that ERalpha is the main receptor regulating estrogen-dependent DC differentiation in vitro and acquisition of their effector functions.


Hearing and vision impairment and the 5-year incidence of falls in older adults.
concurrent vision and hearing loss are common in older adults; however, epidemiological data on their relationship with the incidence of falls are lacking. we assessed the association between dual sensory impairment (DSI) and incidence of falls. We examined the influence of self-perceived hearing handicap and hearing aid use and risk of falls. a population-based, cohort study of participants followed over 5 years. Blue Mountains, west of Sydney, Australia. one thousand four hundred and seventy-eight participants aged 55 and older at baseline were included in longitudinal analyses. visual impairment was defined as presenting or best-corrected visual acuity less than 20/40 (better eye), and hearing impairment as average pure-tone air conduction threshold >25 dB HL (500-4,000 Hz, better ear). The shortened version of the hearing handicap inventory for the elderly was administered. Incident falls were assessed over the 12 months before each visit. Cognitive impairment was determined using the Mini-Mental State Examination. five-year incidence of falls was 10.4%. Participants with severe self-perceived hearing handicap versus no hearing handicap had increased risk of incident falls, multivariable-adjusted OR 1.93 (95% confidence intervals, CI, 1.02-3.64). Hearing aid users versus non-users had 75% increased likelihood of incident falls. Participants with co-existing best-corrected visual impairment and mild hearing loss (>25 to ≤40 dB HL) had higher odds of incident falls, OR 2.19 (95% CI 1.03-4.67). After excluding persons with cognitive impairment, this association did not persist. these epidemiological data show that DSI in older adults could significantly increase their risk of falling.


Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up.
To characterize the impact of intermittent use of triple drug antiretroviral therapy on survival. Population-based analysis of 1282 antiretroviral therapy naive HIV-positive individuals aged 18 years and older in British Columbia who started triple-combination therapy between August 1996 and December 1999. Therapy use was estimated by dividing the number of months of medications dispensed by the number of months of follow-up. Intermittent therapy was defined as the participant having obtained less than 75% of their medication in the first 12 months. Cumulative all-cause mortality rates from the start of triple drug antiretroviral therapy to 30 September 2000. As of 30 September 2000, 106 subjects had died. Cumulative mortality was 3.9% (+/- 0.5%) at 12 months. In a multivariate model, after controlling for other variables that were significant in the univariate analyses each 100 cell decrement in baseline CD4 cell count and the intermittent use of antiretroviral drugs were associated with increased mortality with risk ratios of 1.31 [95% confidence interval (CI), 1.16-1.49; P < 0.001] and 2.90 (95% CI, 1.93-4.36; P < 0.001), respectively. In order to control for downward drift, intermittent use of therapy was measured over the first year whereas other factors were measured at the end of year 1. After adjusting for all other factors, those participants who used antiretroviral drugs intermittently were 2.97 times (95% CI, 1.33-6.62; P = 0.008) more likely to die. Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.


Long-term Follow-up of Intravesical Onabotulinum Toxin-A Injections in Male Patients with Idiopathic Overactive Bladder: Comparing Surgery-naïve Patients and Patients After Prostate Surgery.
Evidence regarding long-term results in male idiopathic overactive bladder (iOAB) patients is limited and rarely focuses on the effects of prior prostatic surgery. This study aims to identify the long-term treatment persistency and occurrence of adverse events of intravesical onabotulinum toxin-A (BoNT-A) injections in male iOAB patients after prostatic surgery (ie, transurethral resection of the prostate [TURP] or radical prostatectomy [RP]) compared with surgery-naïve patients. In this retrospective, single-centre study, data from 477 patients treated with intravesical BoNT-A injections were collected. Outcome data of 120 male patients with iOAB, with collectively 207 BoNT-A injections, were analysed and presented in this study. At the last point of follow-up, 35 patients (29.2%) were still on active treatment. Twenty patients (16.7%) required de novo clean intermittent self-catheterisation (CISC). Three groups were identified: 56 patients without prostate surgery, 40 patients with TURP, and 24 patients with RP prior to treatment. Discontinuation rates and patient-reported outcomes of BoNT-A treatment (none, insufficient, or satisfactory) were similar, but a significant difference was seen in de novo CISC (p=0.004): 28.6% in the group without prior surgery, 7.5% in the TURP subgroup, and 4.2% in the RP subgroup. Odds of de novo CISC was significantly higher for the group without prior surgery than for both the TURP subgroup (odds ratio [OR] 4.9; 95% confidence interval [CI]: 1.33-18.31; p=0.017) and the RP subgroup (OR 9.2; 95% CI: 1.14-73.96; p= 0.037). The data of this retrospective, single-centre cohort suggest that BoNT-A treatment leads to lower CISC rates in male patients after prior desobstructive surgery than in surgery-naïve patients. This study describes the results of onabotulinum toxin-A (BoNT-A) injections in the bladder of male patients with idiopathic overactive bladder after initial prostate surgery compared with surgery-naïve patients. The results showed that BoNT-A treatment leads to lower catheterisation rates in patients after prior prostate surgery than in men without prior prostate surgery.


Size and distribution of the iron oxide nanoparticles in SBA-15 nanoporous silica via SANS study.
Structural characteristics of nanocomposite series consisting of iron oxide nanoparticles (NPs) embedded in the regular pores of amorphous silica matrix (SBA-15) were investigated by means of small angle neutron scattering (SANS). By virtue of unique neutron properties, insight into the inner structure and matter organization of this kind of systems was facilitated for the first time. Based on rigorous experimental support, fundamental model describing the neutron scattering intensity distribution was proposed by assuming general composite structural features. Model application to SANS data confirmed the presence of iron oxide NPs in the body of examined matrices, providing additional information on their shape, concentration and size distribution. Scattering superposition principle employed in the model conception allows for tailoring its fundamental characteristics, and renders it a potent and versatile tool for a wide range of applications.


Cardiac Point-of-Care Ultrasound in Pediatric Neurocritical Care: A Case Series.
Pediatric brain injury is accompanied by hemodynamic perturbations complicating the optimization of cerebral physiology. Point-of-care ultrasound (POCUS) uses dynamic real-time imaging to complement the physical examination and identify hemodynamic abnormalities in preload, contractility, and afterload conditions, but the contribution of cardiac POCUS in the context of pediatric brain injury is unclear. We reviewed cardiac POCUS images integrated in clinical care to examine those with neurological injury and hemodynamic abnormalities. We discuss three children with acute brain injury and myocardial dysfunction identified using cardiac POCUS by bedside clinicians. Cardiac POCUS may have an important role in caring for children with neurologic injury. These patients received personalized care informed by POCUS data in attempts to stabilize hemodynamics and optimize clinical outcomes.


Bis-(3-allyl-4-hydroxyphenyl) sulfone decreases embryonic viability and alters hepatic mRNA expression at two distinct developmental stages in chicken embryos exposed via egg injection.
Concerns surrounding the toxicological effects and environmental prevalence of bisphenol A (BPA) have increased efforts to identify suitable safer replacement alternatives. Bis-(3-allyl-4-hydroxyphenyl) sulfone (TGSH) represents a potential BPA alternative; however, exposure and ecotoxicological data are scarce. To determine effects on embryonic viability, development, and hepatic mRNA expression at 2 distinct developmental periods (midincubation [day 11] and pipping [days 20-21]), TGSH was injected into the air cell of unincubated, fertilized chicken embryos at 4 concentrations ranging from 0 to 180 μg/g egg. Concentrations of TGSH increased in a dose-dependent manner in whole-embryo homogenates, and the estimated median lethal dose (LD50) based on embryonic viability at midincubation was 66 µg/g (95% confidence interval = 31-142 µg/g), which is similar to the BPA LD50 (∼ 67 μg/g) reported in a previous study. Modulation of hepatic gene targets from a chicken ToxChip polymerase chain reaction (PCR) array was observed at both developmental stages. At midincubation, 21/43 genes on the PCR array were significantly altered (by >1.5-fold) in the 180 μg/g dose group, whereas 9 and 6/43 were altered at pipping in the 9.2 and 48 μg/g groups, respectively. Predominant toxicity pathways included xenobiotic metabolism, lipid homeostasis, bile acid synthesis, and cell cycle regulation. The estrogen-responsive gene apolipoprotein II was significantly up-regulated in liver tissue of midincubation embryos at 180 μg/g; however, neither apolipoprotein II nor vitellogenin II were altered at the other concentrations or developmental time points. Given the importance of identifying suitable BPA replacement alternatives, the present study provides novel, whole-animal toxicological data for a BPA replacement alternative that has an effect on embryonic viability similar to that of the compound it could replace. Environ Toxicol Chem 2018;37:530-537. © 2017 SETAC.


Gender Differences: A Lifetime Analysis of the Economic Burden of Alzheimer's Disease.
Gender is one of the best-established differences in risk for Alzheimer's disease (AD) and other forms of dementia, with women being at greater risk. However, the financial implications are unknown. This study aims at understanding the economic burden of AD by gender. This study takes a life-time perspective to investigate the burden of AD over the course of the disease. Nationally representative Medicare Current Beneficiary Survey data were used to estimate the course of illness of AD from age 65 to death and the incremental costs of AD on Medicare and Medicaid. Published data on the use and costs of assisted living facilities, home health care, and informal care were imputed into the course of illness to calculate the lifetime costs of these services. Females and males have distinctively different patterns of course of illness of AD. Women face higher risks of having AD (15.5% vs. 13.1%) and of serving as informal caregivers for AD patients (6.8% vs. 4.0%) before death. Medicare and Medicaid account for major payers of AD care for both genders, but the greatest economic challenge of AD to women is the cost of the informal care they deliver, resulting in women bearing six times the cost of men. Public policy interventions that aim at curing or slowing the progress of AD will greatly benefit the welfare and economic status of women.


A novel nuclear FGF Receptor-1 partnership with retinoid and Nur receptors during developmental gene programming of embryonic stem cells.
FGF Receptor-1 (FGFR1), a membrane-targeted protein, is also involved in independent direct nuclear signaling. We show that nuclear accumulation of FGFR1 is a common response to retinoic acid (RA) in pluripotent embryonic stem cells (ESC) and neural progenitors and is both necessary and sufficient for neuronal-like differentiation and accompanying neuritic outgrowth. Dominant negative nuclear FGFR1, which lacks the tyrosine kinase domain, prevents RA-induced differentiation while full-length nuclear FGFR1 elicits differentiation in the absence of RA. Immunoprecipitation and GST assays demonstrate that FGFR1 interacts with RXR, RAR and their Nur77 and Nurr1 partners. Conditions that promote these interactions decrease the mobility of nuclear FGFR1 and RXR in live cells. RXR and FGFR1 co-associate with 5'-Fluorouridine-labeled transcription sites and with RA Responsive Elements (RARE). RA activation of neuronal (tyrosine hydroxylase) and neurogenic (fgf-2 and fgfr1) genes is accompanied by increased FGFR1, Nur, and histone H3.3 binding to their regulatory sequences. Reporter-gene assays show synergistic activations of RARE, NBRE, and NurRE by FGFR1, RAR/RXR, and Nurs. As shown for mESC differentiation, FGFR1 mediates gene activation by RA and augments transcription in the absence of RA. Cooperation of FGFR1 with RXR/RAR and Nurs at targeted genomic sequences offers a new mechanism in developmental gene regulation.


Heavy metals in food crops, soil, and water in the Lihe River Watershed of the Taihu Region and their potential health risks when ingested.
Environmental pollution by heavy metals resulting from rapid economic development is a major concern. Soil, water, wheat, and rice samples were collected from the Lihe River Watershed in the Taihu Region (east China). In this study area, many types of industrial plants, including ceramics factories, plants working with refractory materials, and chemical plants are densely distributed and cause serious heavy metal pollution. In addition, well-developed transportation and agricultural activities are also important sources of heavy metals. Thus, the concentrations of selected heavy metals including cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn) in the samples were analyzed to evaluate their potential integral risk (IR) to the health of the local population. Accordingly, the spatial distribution pattern of the IR values was determined in the study. The soil in the study area showed heavy Cd pollution, whereas the pollution by other elements was relatively slight. When the proportions of grain samples in which the concentrations exceeded the tolerance limits were examined, the grains were primarily contaminated with Pb, Ni, Cd, and Zn; and less contaminated with Cu and Cr. The drinking water of the local inhabitants was safe. The average IR value was 3.53 for adults and 3.91 for children, indicating that both adults and children may experience adverse health effects. The spatial distribution pattern of the IR values among the exposed populations in the study area showed high values in the eastern and middle parts, with maximum values >5, and low values in the western part, with minimum values <2. This is consistent with the distributions of the industries and the population. The study may provide a basis for comparison to other regions both in China and worldwide.


Carbon budgets for a phytoplanktivorous fish fed three different unialgal populations.
The filter feeding blue tilapia, Tilapia aurea, was fed three different algae. Blue tilapia ingestion of two green algae, Chlamydomonas sp. and Ankistrodesmus falcatus and the filamentous blue-green alga, Anabaena flos-aquae, ranged from 21%-89% of the available cells. There were significant differences in the assimilation of algal carbon by the fish depending on the alga fed; A. flos-aquae was the easiest to assimilate (83%). The fish respired significantly less of the Chlamydomonas sp. ingested carbon (15%). The gross growth efficiency of fishes fed either green alga was not significantly different (22%-24%), but these efficiencies were significantly less than the gross growth efficiency of fish fed A. flos-aquae (46%). The carbon budgets for fish feeding on the green algae were similar to that constructed from the literature for a congener fed a mixed algae diet. However, the assimilation component of the budget for blue tilapia fed A. flos-aquae was 2 times greater than that of the literature budget.


Biofilm formation by Enterococcus faecalis on intraocular lens material.
To compare biofilm formation by Enterococcus faecalis on different intraocular lens (IOL) materials. E. faecalis biofilms were cultivated on disks of IOL material (silicone, PMMA [polymethylmethacrylate], or acrylic). Biofilms were stained with crystal violet (CV), which served as an index of biofilm formation. The bacterial population was enumerated after biofilm homogenization. Biofilms were also examined by confocal microscopy. At 24 hr, there was no significant difference in biofilm formation, or the population within biofilms, among the three materials tested. However, after 48 and 72 hr, it was observed that silicone supported the least amount of biofilm formation (p < 0.05); biomass on PMMA and acrylic IOLs continued to increase, with acrylic demonstrating the greatest amount of stainable biofilm (p < 0.0005). The population on PMMA was significantly greater than the other IOL materials (p < 0.005). Confocal microscopy confirmed the lack of biomass on silicone. Among three IOL materials, E. faecalis biofilms formed more readily on PMMA and acrylic compared to silicone.


Determinants of under-five mortality in Ethiopia using the recent 2019 Ethiopian demographic and health survey data: nested shared frailty survival analysis.
Worldwide, there is remarkable progress in child survival in the past three decades. Ethiopia is off-track on sustainable development targets in under-five mortality since 2020. Therefore, this study aimed to investigate time to death and its associated factors among under-five children in Ethiopia. Nationally representative demographic and health survey data were used for this study. A total of 5772 under-five children were included. Data were analyzed using R software. Semi-parametric nested shared frailty survival analysis was employed to identify factors affecting under-five mortality. Adjusted hazard ratio (AHR) with 95% Confidence interval (CI) was reported and log-likelihood was used for model comparison. Statistical significance was declared at P-value < 0.05. The weighted incidence of under-five death before celebrating the first fifth year was 5.76% (95% CI: 5.17 - 6.40). Female sex and under-five children living in urban areas were high probability of survival than their counterparts. After controlling cluster and region level frailty, multiple births (AHR = 7.03, 95% CI: 4.40-11.24), breastfed within one hour after birth (AHR = 0.41, 95% CI: 0.28-0.61), preceding birth interval 18-23 months (AHR = 1.62, 95% CI: 1.12 -2.36), and under-five children younger than 18 months (AHR = 2.73, 95% CI: 1.93 -3.86), and teenage pregnancy (AHR = 1.70, 95% CI: 1.01-2.87) were statistically significant factors for time to under-five death. Even though Ethiopia has a significant decline under-five death, still a significant number of under-five children were dying. Early initiation of breastfeeding, preceding birth interval and teenage pregnancy were the preventable factors of under-five mortality. To curve and achieve the SDG targets regarding under-five mortality in Ethiopia, policymakers and health planners should give prior attention to preventable factors for under-five mortality.


The effect of hemin and of allyl isopropyl acetamide on protein synthesis in rat hepatocytes.
Protein synthesis was measured in incubated hepatocytes. While hemin brings about a slight stimulation, allyl isopropyl acetamide (a compound that destroys the heme bound to cytochrome P450) inhibits protein synthesis by a mechanism that appears to result exclusively from depletion of cytoplasmic heme. Indications that in hepatocytes, as in reticulocytes, protein synthesis may be in part regulated by heme at the level of initiation are: i) that inhibition is accompanied by polysome breakdown; ii) that the protein synthesis inhibitor already isolated from rat liver, is hemin reversible iii) that hepatocyte extracts contain a Mr 38,000 phosphoprotein which comigrates with the Mr 38,000 subunit of rabbit initiation factor 2 and iv) that the phosphorylation of both of these subunits is inhibited by hemin.


Abscisic acid-deficient sit tomato mutant responses to cadmium-induced stress.
There is a very effective cross-talk between signals triggered by reactive oxygen species and hormonal responses in plants, activating proteins/enzymes likely to be involved in stress tolerance. Abscisic acid (ABA) is known as a stress hormone that takes part in the integration of signals. This work aimed to characterize the biochemical response and ultrastructural changes induced by cadmium (Cd) in the Micro-Tom (MT) sitiens ABA-deficient mutant (sit) and its wild-type (MT) counterpart. MT and sit plants were grown over a 96-h period in the presence of Cd (0, 10, and 100 μM CdCl2). The overall results indicated increases in lipid peroxidation, hydrogen peroxide content and in the activities of the key antioxidant enzymes such as catalase, glutathione reductase, and ascorbate peroxidase in both genotypes. On the other hand, no alteration was observed in chlorophyll content, while the activity of another antioxidant enzyme, superoxide dismutase, remained constant or even decreased in the presence of Cd. Roots and shoots of the sit mutant and MT were analyzed by light and transmission electron microscopy in order to characterize the structural changes caused by the exposure to this metal. Cd caused a decrease in intercellular spaces in shoots and a decrease in cell size in roots of both genotypes. In leaves, Cd affected organelle shape and internal organization of the thylakoid membranes, whereas noticeable increase in the number of mitochondria and vacuoles in MT and sit roots were observed. These results add new information that should help unravel the relative importance of ABA in regulating the cell responses to stressful conditions induced by Cd apart from providing the first characterization of this mutant to oxidative stress.


(E)-2-(4-tert-But-ylphen-yl)-2-cyano-1-(3-methyl-1-vinyl-1H-pyrazol-5-yl)vinyl 2,2-dimethyl-propano-ate.
In the title compound, C(24)H(29)N(3)O(2), the dihedral angle between the benzene and pyrazole rings is 80.55 (7)°. The mol-ecule contains an acrylonitrile moiety and exists in an E conformation. Bioassay tests showed that the title compound exhibited higher acaricidal activity than its Z isomer.


Pelvic ramus fractures in the elderly: 50 patients studied with MRI.
Whilst it is well known that fractures of the pelvic rami in the elderly are frequently associated with posterior ring injuries, the extent of this second injury is less well known. We evaluated this question by MRI scanning a group of elderly patients presenting at our unit with pelvic rami fractures. We investigated 50 consecutive elderly patients (45 women) with fractures of the pelvic rami using an MRI scan of the pelvis in order to assess the competency of the pelvic ring. On MRI, 45 (95% CI 42-48) patients had a sacral fracture. At 5-month follow-up, 39 (of 41 reviewed) still complained of posterior sacral tenderness. Pelvic rami fractures in the elderly are nearly always associated with posterior ring injuries. This probably explains why these patients take longer to rehabilitate than might be expected if only the anterior injury is considered, and it also explains why they experience long-term back pain.


Serum CA-125 levels do not depend on ovarian steroidogenesis.
To investigate the relationship between CA-125 production and ovarian steroidogenesis, serum CA-125 levels were evaluated in patients with normal pelvis in different ovarian endocrine situations: (1) during the menstrual cycle, (2) during stimulatory treatment with gonadotropin for the induction of ovulation, and (3) during suppression treatment with gonadotropin-releasing hormone agonists. In spite of the spontaneous or the markedly induced variations of estradiol (E2) or ovarian volume, CA-125 levels remained unvaried in all patients. Moreover, CA-125 serum levels did not correlate with the increasing values of the plasma E2 or ovarian volume. In conclusion, steroidogenetic activity of the ovary is unlikely to affect CA-125 production.


Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.
Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.


Interaction between FIP5 and SNX18 regulates epithelial lumen formation.
During the morphogenesis of the epithelial lumen, apical proteins are thought to be transported via endocytic compartments to the site of the forming lumen, although the machinery mediating this transport remains to be elucidated. Rab11 GTPase and its binding protein, FIP5, are important regulators of polarized endocytic transport. In this study, we identify sorting nexin 18 as a novel FIP5-interacting protein and characterize the role of FIP5 and SNX18 in epithelial lumen morphogenesis. We show that FIP5 mediates the transport of apical proteins from apical endosomes to the apical plasma membrane and, along with SNX18, is required for the early stages of apical lumen formation. Furthermore, both proteins bind lipids, and FIP5 promotes the capacity of SNX18 to tubulate membranes, which implies a role for FIP5 and SNX18 in endocytic carrier formation and/or scission. In summary, the present findings support the hypothesis that this FIP5-SNX18 complex plays a pivotal role in the polarized transport of apical proteins during apical lumen initiation in epithelial cells.


Patient-Centered Intimate Partner Violence Screening, Brief Intervention, and Referral to Treatment.
To increase rates of screening for intimate partner violence (IPV), education, and follow-up of women being seen at a private obstetrics and gynecology clinic to 52% in 90 days. Quality improvement project. IPV screening was not the standard of care at a private suburban obstetric and gynecologic practice. This project used an evidence-backed model for improvement that incorporated plan-do-study-act cycles to implement four core interventions. The Hurt, Insult, Threaten, Scream (HITS) screening tool, the investigator-developed Duluth model tool, a case management log, and a team engagement plan were implemented. Implementation of the HITS screening tool was associated with an increase in IPV screening to 94.7% from a baseline of 2.5%. In addition, the IPV disclosure rate increased 7.5% over the course of the initiative. The majority of staff (64%) participated in IPV educational offerings, and an increase in IPV knowledge was noted in team surveys, on which scores increased from 68% to 76.9%. The combined use of the HITS screening tool and the Duluth model tool were associated with increased rates of IPV screening. Women who screened positive for IPV were referred to appropriate resources. These findings can be used as a guide for clinics to implement IPV screening into practice.


PD-1 in Tregs predicts the survival in sepsis patients using sepsis-3 criteria: A prospective, two-stage study.
The expression of Tregs co-signaling molecules serves as the marker of immune dysfunction. The present study aimed to verify their predictive role in the 28-day mortality of sepsis patients. A prospective, observational, two-stage cohort study was conducted. The patients who fulfilled the sepsis-3 criteria were enrolled, and peripheral blood samples were collected within 24 h post-enrollment. The expression of the four co-signaling molecules of Tregs, namely, PD-1, CD28, PD-L1 and CD86, was measured, and sequential organ failure assessment (SOFA) scores were recorded on day 1 of inclusion. Patients were followed up for 28 days or, otherwise, deceased. Multivariate regression analysis was used to assess the independent risk factors for 28-day mortality, and a prognostic prediction model was established, which was verified in the validation set. A total of 292 patients were recruited in the study, of which 120 patients were finally included in the analysis, that is 58 patients in stage I (test set) and 62 patients in stage II (validation set). In stage I, 14 (24.1%), patients died during 28 days, and the expression of PD-1 in Tregs (OR:1.037;95%CI:1.003-1.071) and SOFA scores(OR:1.262;95%CI:1.046-1.524) were independent risk factors for 28-day mortality. The ability of Tregs PD-1 in predicting 28-day mortality was validated in stage II (AUC = 0.792). PD-1 overexpression in Tregs was associated with poor outcomes, and PD-1 in Tregs is considered to be a valuable tool for the prediction of prognosis in septic patients using sepsis-3.0 criteria.


Maintenance of multicopy plasmid Clo DF13 III. Role of plasmid size and copy number in partitioning.
To elucidate the mechanisms that operate in plasmid maintenance, we analysed the stability of different combinations of Clo DF13 derivatives present in the same bacterial cell. From the data described in this paper we conclude: (i) each Clo DF13 plasmid molecule has an equal chance of colonizing daughter cells upon cell division, (ii) the Clo DF13 minimal replicon harbours functions involved in plasmid segregation and incompatibility, (iii) in the case of cells harbouring plasmid replicons which differ in size, the smaller plasmid is gradually lost from the cell population, (iv) in the case of cells habouring plasmid replicons which differ in copy number, the lower copy number plasmid is always lost from the cell population. The effect of plasmid copy number is dominant over the effect of plasmid size.


Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation.
Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX). The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF) and mortality after HTX. Five hundred and thirty patients (age ≥18 years) receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year) were compared to those without long-term use (none or <1 year of amiodarone). Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan-Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival. Of the 530 patients, 74 (14.0%) received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff-Parkinson-White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105). Further, Kaplan-Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this group (P=0.0123). There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596), 2-year (P=0.8620), 5-year (P=0.2737), or overall follow-up mortality after HTX (P=0.1049). Moreover, Kaplan-Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786). Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX.


Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches.
Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.


Neointimal proliferation within carotid stents is more pronounced in diabetic patients with initial poor glycaemic state.
We studied the influence of initial hyperglycaemia on neointimal proliferation within carotid Wallstents. A total of 112 patients were followed by duplex sonography after carotid stenting for 24 months. Patients were assigned to three groups: non-diabetic subjects (group A) and diabetic patients, who were assigned according to their baseline HbA(1)c values, to group B1(HbA(1)c<or=6.5%) or group B2 (HbA(1)c>6.5%). At baseline the groups did not differ with respect to other vascular risk factors and residual stenosis on angiograms. The maximal thickness of the layer between the stent and the perfused lumen was measured at the duplex follow-ups. At 3 months the typical ultrasonic structure of the neointima was clearly discernible. From this point on, group B2 differed significantly ( p<0.001) compared with B1 and A with respect to the maximal thickness of neointima and the time course of its ingrowth: group A vs B1 vs B2 was 0.51+/-0.39 vs 0.52+/-0.33 vs 0.56+/-0.35 at 3 months, 0.91+/-0.27 vs 0.90+/-0.38 vs 1.14+/-0.48 at 6 months, 1.02+/-0.24 vs 0.97+/-0.34 vs 1.21+/-0.44 at 12 months and 1.09+/-0.23 vs 1.10+/-0.31 vs 1.23+/-0.37 at 24 months. Initial hyperglycaemia seems to be a predictor of more pronounced neointimal proliferation after carotid stenting independent of diabetes. As intimal hyperplasia is known to be responsible for stent restenosis, strict optimisation of the hyperglycaemic state should be aimed at before elective carotid artery stenting.


Myelopathy: a report of two cases.
To present diagnostic imaging findings of two cases of cervical myelopathy, with different etiologies, presenting to a chiropractic office. The patient with acute transverse myelitis had neck and upper back pain and nonspecific headaches for 40 years. The patient with posttraumatic syringomyelia experienced intermittent left arm pain starting in the anterolateral shoulder and radiating down the arm into the third, fourth, and fifth digits. Neither of these patients presented with typical myelopathic symptoms. Chiropractic spinal manipulative therapy using high-velocity low-amplitude thrusts and concomitant medical management were used for the patient with posttraumatic syringomyelia. The patient with acute transverse myelitis was not treated. Practitioners should be aware of the etiology, pathophysiology, clinical features, laboratory, diagnostic imaging findings, and treatment options pertaining to patients with cervical myelopathy.


Tubelight Adrenals in Diabetic Ketoacidosis.
We report a patient with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis associated with computed tomography hypoperfusion complex and adrenal hyperdensity on abdominal imaging - an association not previously reported in diabetic ketoacidosis. Presence of computed tomography hypoperfusion complex with hyperdense 'Tubelight adrenals' in a patient with diabetic ketoacidosis is associated with poor prognosis and thus serves to guide clinicians towards early and aggressive management.


Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing ICAM-1 expression.
Eosinophil chemotactic factor-L (ECF-L) is a novel stimulator of osteoclast (OCL) formation that acts at the differentiation/fusion stage of OCL formation, and is a cofactor for RANK ligand (RANKL). We examined the effects of ECF-L on the intracellular signaling pathways utilized by RANKL, and on the expression of ICAM-1/LFA-1 to determine its mechanism of action. RAW 264.7 and bone marrow cells were treated with RANKL and/or ECF-L Fc protein to determine their effect on NF-kappaB and AP-1 activity. ECF-L by itself only modestly increased NF-kappaB binding and JNK activity in RAW 264.7 cells, which were further enhanced by RANKL. In contrast, ECF-L Fc increased LFA-1alpha and ICAM-1 mRNA levels 1.8-fold in mouse marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation induced by 10(-10) M 1,25-(OH)2D3, and ECF-L Fc. Furthermore, ECF-L Fc did not enhance OCL formation by ICAM-1 knockout (KO) cells. Increased expression of ICAM-1 by ECF-L appears to be critical for its effects on OCL formation.


Outcomes After Endovascular Treatment of Direct Carotid Cavernous Fistulas: Systematic Review and Meta-Analysis.
Direct carotid cavernous fistulas (dCCF) involve pathologic shunting from the internal carotid artery into the cavernous sinus. We systematically reviewed the methods and outcomes of endovascular therapy for dCCF. PubMed, Scopus, and EMBASE were used to identify studies that reported outcomes for patients undergoing embolization of dCCF. Outcomes included rates of occlusion, complications, symptom improvement, and recurrence. Pooled rates for each outcome were obtained with random effects models. The influence of embolization method on outcomes was assessed with meta-regressions. There were 16 studies comprising 270 patients. The mean age was 39.6 years, there were 36.3% females, and the mean follow-up was 19.7 months. Coils were the most common method of embolization (69.3%), followed by Onyx (31.1%), covered stent (22.2%), N-butyl cyanoacrylate (6.7%), and flow diversion (4.8%). The pooled overall occlusion rate was 92.1% (95% confidence interval [CI], 86.3-95.6; I2 = 29.2%). The pooled complication rate was 10.9% (95% CI, 7.3-16; I2 = 0%). Use of coils were associated with a slightly lower odds of overall complications (odds ratio, 0.98; 95% CI, 0.97-0.99) and cranial nerve palsy (odds ratio, 0.98; 95% CI, 0.97-0.99). The pooled fistula recurrence rate was 8.3% (95% CI, 4.3-15.4; I2 = 30.9%). Endovascular therapy for dCCF is associated with high occlusion and low complication rates. Recurrence is not uncommon, highlighting the need for close follow-up.


Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine.
The aim of this study was to examine the inflammation induced by saturated acyl lysophosphatidylcholine (LPC) in vivo and to investigate whether it could be attenuated by the action of polyunsaturated acyl lysophosphatidylcholines (LPCs), which are known as anti-inflammatory lipid mediators. First, saturated acyl LPC was administered intraperitoneally (i.p.) to mice and the inflammatory profile was extensively characterized. Subsequently, the preventive effect of polyunsaturated acyl LPCs, i.p. administered 30 min after saturated acyl LPC, was evaluated by measuring indices of inflammation such as leukocyte migration, plasma leakage, and eicosanoid or cytokine formation by light microscopy, Evans blue dye as indicator, and enzyme-linked immunosorbent assay, respectively. Saturated acyl LPCs as LPC16:0 (100 mg/kg, i.p.) proved to be an effective inflammation inducer which causes a significant increase in plasma leakage, leukocyte migration into peritoneum and elevation of pro-inflammatory mediators. Interestingly, LPC20:4 and LPC22:6 (50 and 150 μg/kg) significantly nullified LPC16:0-induced inflammation. The anti-inflammatory effects of LPC20:4 and LPC22:6 were related to down-regulation of leukocyte extravasation, plasma leakage, and formation of pro-inflammatory mediators (IL-5, IL-6, NO, 12-HETE and PGE(2)) stimulated by LPC16:0, and up-regulation of anti-inflammatory mediators (IL-4 and IL-10). These results indicated that the pro-inflammatory activity of saturated acyl LPCs could be antagonized by the actions of polyunsaturated acyl LPCs, anti-inflammatory lipid mediators.


The behaviors of seeking a second opinion from other health-care professionals and the utilization of complementary and alternative medicine in gynecologic cancer patients.
The aim of the study is to determine the predictors for seeking a second opinion and the utilization of complementary and alternative medicine (CAM) among gynecologic cancer patients. Patients attending a gynecologic cancer clinic of a tertiary referral center were recruited over a period of 1 year. A survey was conducted for all the participants in a one-on-one basis. One hundred ninety-one patients were recruited. Eighty patients (41.9%) had consulted other health-care professionals (HCP) for a second opinion after they were diagnosed to have cancer and 89 (46.6%) had utilized CAM. In multivariate analysis, late-stage disease (OR=2.65, 95% CI 1.26-5.58), treatment with radiotherapy (OR=2.27, 95% CI 1.19-4.33) and tertiary education (OR=11.28, 95% CI 3.06-41.54) were independent predictors for seeking a second opinion from other HCP and utilization of CAM. Patients who sought a second opinion from other HCP were more likely to utilize CAM (OR=6.12, 95% CI 3.24-11.54). Eighty percent of the patients did not inform their usual caregiver their utilization of CAM. Seeking a second opinion from other HCP is common in gynecologic cancer patients. Patients who seek a second opinion are more likely to utilize CAM.


Impact on the Raman spectra of liquids when a polarized light source is used.
The polarization state of the excitation light used in two Raman systems was controlled to study its effect in the unpolarized Raman spectra of unstructured samples. Both systems work in different regions of the electromagnetic spectrum (NIR and visible). Four polarization states (linear, linear at 45° and 90°, and circular) were used to excite liquid samples (ethanol, acetone, and their mixture). The results show that the Raman peaks intensities' ratio varies according to the polarization state of the excitation light. Peaks related to functional groups and C-H stretching modes increase their intensity when circular polarization (CP) is applied. The latter may help to study liquid mixtures with low concentrations. Different polarizing light states give a more detailed spectroscopic analysis since it gathers more structural information of the samples tested in this work with an undefined structure.


[Breech Presentation: CNGOF Guidelines for Clinical Practice - Short Text].
To determine the optimal management of singleton breech presentation. The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. In France, 5% of women have breech deliveries (Level of Evidence [LE3]). One third of them have a planned vaginal delivery (LE3) of whom 70% deliver vaginally (LE3). External cephalic version (ECV) is associated with a reduced rate of breech presentation at birth (LE2), and with a lower rate of cesarean section (LE3) without increases in severe maternal (LE3) and perinatal morbidity (LE3). It is therefore recommended to inform women with a breech presentation at term that ECV could be attempted from 36 weeks of gestation (Professional consensus). In case of breech presentation, planned vaginal compared with planned cesarean delivery might be associated with an increased risk of composite perinatal mortality or serious neonatal morbidity (LE2). No difference has been found between planned vaginal and planned cesarean delivery for neurodevelopmental outcomes at two years (LE2), cognitive and psychomotor outcomes between 5 and 8 years (LE3), and adult intellectual performances (LE4). Short and long term maternal complications appear similar in case of planned vaginal compared with planned cesarean delivery in the absence of subsequent pregnancies. A previous cesarean delivery results for subsequent pregnancies in higher risks of uterine rupture, placenta accreta spectrum and hysterectomy (LE2). It is recommended to offer women who wish a planned vaginal delivery a pelvimetry at term (Grade C) and to check the absence of hyperextension of the fetal head by ultrasonography (Professional consensus) to plan their mode of delivery. Complete breech presentation, previous cesarean, nulliparity, term prelabor rupture of membranes do not contraindicate planned vaginal delivery (Professionnal consensus). Term breech presentation is not a contraindication to labor induction when the criteria for acceptance of vaginal delivery are met (Grade C). In case of breech presentation at term, the risks of severe morbidity for the child and the mother are low after both planned vaginal and planned cesarean delivery. For the French College of Obstetricians and Gynecologists (CNGOF), planned vaginal delivery is a reasonable option in most cases (Professional consensus). The choice of the planned route of delivery should be shared by the woman and her caregiver, respecting the right to woman's autonomy.


A new psychometric test of attention-related behavior in rats; its validity in the aging process.
The ability to distinguish relevance from irrelevance has been attributed to an attention-related mechanism and may be supposed to be disturbed in aging. The reaction to low electrical stimuli which causes neither pain nor escape behavior was investigated by means of a newly developed test in adult and aged rats. The animals' reaction was classified into two different responses depending on the intensity of the electrical stimuli. The first reaction related to sensitivity, the second reaction contained two components, an orienting response and a cognition-controlled type of discriminative behavior. There was no significant difference between the amperage values of the two reactions in adult rats. With respect to aged rats, the amperage values of both reactions are significantly increased as compared with the adult rats. The sensitivity reaction and the attention-related behaviors diverged considerably. These findings show very precisely that certain behavioral reactions may decline differently or even independently with age indicating different age-related changes in the underlying neuroanatomical systems of attention. The results demonstrate the sensitivity of the test used as a model for studying some types of attention-related mechanisms in the aging process. The use of a relatively simple test of animals' reactivity to sensory stimuli may reveal changes that are critical to understanding not only of the aging brain, but of different types of brain lesions and disorders, as well as of drug treatments.


Biodistribution of two 99mTc-cardiac glycosides with end glucose unit: effect of lipophilicity on their relative myocardial accumulation.
In biodistribution experiments with tritium labelled cardiac glycoside it was observed that compounds of low lipophilicity showed a considerably higher affinity towards myocardium with respect to other tissues and organs. A similar trend was also observed with 99mTc-cardiac glycosides except for one compound with glucose residue, which in spite of its lower lipophilicity exhibited an unexpectedly low heart to non-target concentration ratio, thereby indicating a possible influence of carbohydrate residue on biodistribution. To confirm this, in this article we radiolabelled two glucose containing cardiac glycosides (K-strophanthin-beta and K-strophanthoside) with 99mTc and, in biodistribution experiments, less lipophilic 99mTc-K-strophanthoside showed a much better heart to non-target ratio over 99mTc-K-strophanthin-beta. It is thus concluded that, in addition to lipophilicity, the affinity of the carbohydrate residue for non-target organs is also an important consideration in determining the structure-distribution relationship of 99mTc-cardiac glycosides.


Sleep complaints in older adults: a racial comparison.
Sleep complaints have been reported in epidemiologic studies to be more frequent in late life, among females, among the physically impaired, and among persons experiencing psychiatric disorders. To date, however, no studies have reported a racial difference in sleep complaints among older persons in the United States. The Duke EPESE (Established Populations for Epidemiologic Studies of the Elderly) assessed 3,976 community-dwelling elders age 65+ for sleep complaints and relevant control variables. In bivariate analyses, sleep complaints were associated with female gender, White race, older age, cognitive impairment, lower education, presence of chronic health conditions, poor self-rated health, and higher scores on a self-rated depression scale (the CES-D). In logistic regression analysis, the association of White race and more sleep complaints persisted (p < .001) when the above variables were simultaneously controlled. Fewer reported sleep complaints in community-dwelling Black elders compared to White elders remains unexplained, though it may be secondary to a higher threshold for Black elders reporting complaints.


Weight Change Trajectories After Incident Lower-Limb Amputation.
To characterize weight change after amputation by identifying typical weight trajectories in men with incident lower-limb amputation (LLA) and describing characteristics associated with each trajectory. Retrospective cohort study and analyzed using group-based trajectory modeling. Administrative data. Veterans who were men (N=759), living in the Northwest United States, and who had an incident toe, foot, or leg amputation between 1997 and 2008 and at least 18 months of amputation-free survival thereafter. Not applicable. Postamputation weight and body mass index change. The mean weight at baseline was 91.6±24 kg (202±53 lb), and average follow-up was 2.4 years. We identified 4 trajectory groups for weight change: weight loss (13%), stable weight (47%), slow weight gain (33%), and rapid weight gain (7%). Men with a toe or foot amputation most frequently were assigned to the stable weight group (58%), whereas men with transtibial or transfemoral amputations were most commonly assigned to the slow weight gain group (42% each). Men who died during follow-up were more likely to be assigned to the weight loss group (24%) than men who did not die (11%). We identified distinct weight change trajectories that represent heterogeneity in weight change after LLA. An improved understanding of factors predictive of weight gain or loss in people with LLA may help better target rehabilitation and prosthetic prescription. Additional research is needed to fully understand the relation between weight change and health status after amputation.


Effects of biological and technical factors on brain and muscle cholinesterases in Nile tilapia, Oreochromis niloticus: implications for biomonitoring neurotoxic contaminations.
Influence of body length, body weight, gender, sexual maturity, and tissue storage on brain and muscle cholinesterases (ChE) in Nile tilapia was evaluated considering its potential use in biomonitoring neurotoxic contaminations in tropical environments. Results show that ChE activities in both tissues decreased significantly with increased total length (4-24.5 cm) or body weight (1-186 g) of the fish and the relationships were curvilinear. Comparisons of the slopes and elevations of the regression lines of the logarithmic ChE and body size relationships of males with those of females indicated that gender had no significant effect on the body size-specific ChE activities. Response of the ChE of sexually mature males to chlorpyrifos exposure was similar to that of females. Gonadal maturity stage of this fish does not seem to influence ChE activities. Storage of tissues at -80 degrees C for 28 days had no significant effect on ChE activities in the control fish and the fish exposed to carbofuran. However, a partial reactivation of brain ChE activities was observed in the fish exposed to carbosulfan after 28 days of storage. The results emphasize the importance of consideration of body size of the fish and storage time of the tissues in order to formulate accurate conclusions about the neurotoxic chemical exposure when ChE of the fish is used in biomonitoring programs.


Connexin43-containing gap junctions potentiate extracellular Ca²⁺-induced odontoblastic differentiation of human dental pulp stem cells via Erk1/2.
Extracellular Ca(2+) can promote dentin sialophosphoprotein (DSPP) expression and odontoblastic differentiation of dental pulp stem cells (DPSCs). Gap junctions mediated by connexin43 (Cx43) allow diffusion of small molecules (such as Ca(2+)) among cells to regulate cell-to-cell communications. However, it is unclear whether Cx43 is required for the Ca(2+)-induced cell differentiation. Here, we found that the influx of extracellular Ca(2+) through L-type Ca(2+) channels increases intracellular free Ca(2+) levels to promote DSPP expression. Cx43 overexpression potentiated the extracellular Ca(2+)-induced DSPP expression via Erk1/2. Flow cytometry analyses showed that Cx43 increased the percentage of p-Erk1/2 positive cells in response to Ca(2+), indicating that Cx43 in DPSCs possibly acts as a traditional gap junction channel, which permits the sharing of signals among coupled cells to make more DPSCs respond to Ca(2+). Furthermore, inhibition of Cx43 function and gap junction communication decreased Ca(2+)-induced the expression of DSPP, suggesting that cell-to-cell contacts are required for Cx43 to promote the Ca(2+)-induced cell differentiation. Similarly, the study performed on DPSCs cultured at low-density and high-density revealed that intercellular contacts are required to potentiate Erk1/2 activity and DSPP expression. In total, this study indicates that Cx43 increases Ca(2+)-induced DSPP expression and odontoblastic differentiation of DPSCs via Erk1/2 through gap junction-mediated cell-to-cell contacts.


Antioxidant enzyme immunoreactivity in rat von Ebner gland after nickel treatment.
Our study was designed to clarify the role of antioxidant enzymes in the rat von Ebner gland during acute nickel toxicity. After treatment with nickel acetate, we monitored ultrastructural alterations in acinar and ductal cells, immunohistochemical staining for glutathione peroxidase (GPx) and glutathione S-transferases (GST mu and GST pi), and immunoreactivity for malondialdehyde (MDA). Immunoreactivity for MDA was present only in the acinar cells, and it was enhanced at 3 h after Ni treatment. In contrast, immunoreactivities for GPx and GSTs did not change in acinar cells but significantly increased in ductal cells after Ni treatment. Cytoplasmic vacuoles increased in acinar cells at 3 h after Ni treatment, but they almost completely disappeared at 24 h. No morphological changes were observed in taste bud cells from Ni-treated rats. Because lipid peroxidation, as monitored by immunoreactivity for MDA, was only transiently increased in the acinar cells, the enhanced antioxidant enzyme immunoreactivity in ductal cells of the von Ebner gland plays a crucial role in the self-defense system against nickel toxicity in the rat oral cavity.


Real-time and label-free analysis of binding thermodynamics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a QCM biosensor.
A novel approach to the study of binding thermodynamics and kinetics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a quartz crystal microbalance (QCM) biosensor was developed, in which binding events take place at the cell surface, more closely mimicking a biologically relevant environment. In this study, colon adenocarcinoma cells (KM-12) and ovary adenocarcinoma cells (SKOV-3) grew on the optimized polystyrene-coated biosensor chip without fixation. The association and dissociation between the cell surface carbohydrates and a range of lectins, including WGA, Con A, UEA-I, GS-II, PNA and SBA, were monitored in real time and without label for evaluation of cell surface glycosylation. Furthermore, the thermodynamic and kinetic parameters of the interaction between lectins and cell surface glycan were studied, providing detailed information about the interactions, such as the association rate constant, dissociation rate constant, affinity constant, as well as the changes of entropy, enthalpy and Gibbs free energy. This application provides an insight into the cell surface glycosylation and the complex molecular recognition on the intact cell surface, which may have impacts on disease diagnosis and drug discovery.


Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors.
Natural genetic variation can cause significant differences in gene expression, but little is known about the polymorphisms that affect gene regulation. We analyzed regulatory variation in a cross between laboratory and wild strains of Saccharomyces cerevisiae. Clustering and linkage analysis defined groups of coregulated genes and the loci involved in their regulation. Most expression differences mapped to trans-acting loci. Positional cloning and functional assays showed that polymorphisms in GPA1 and AMN1 affect expression of genes involved in pheromone response and daughter cell separation, respectively. We also asked whether particular classes of genes were more likely to contain trans-regulatory polymorphisms. Notably, transcription factors showed no enrichment, and trans-regulatory variation seems to be broadly dispersed across classes of genes with different molecular functions.


Protein kinases of Dictyostelium discoideum, strain AX-2.
In cell homogenates of Dictyostelium discoideum, strain AX-2, four major soluble protein kinases (ATP:protein phosphotransferase, EC 22.214.171.124) and one membrane-associated protein kinase activity were identified. The enzymes showed high affinity for casein. One of the enzymes was purified by affinity chromatography on casein-coated Sepharose. The soluble high molecular weight enzymes phosphorylated histones, whereas the low molecular weight enzymes did not. The same protein kinase species were present in vegetative and aggregation-competent cells. Their specific activity, however, changed during the development to aggregation competence. None of the enzymes was stimulated by cyclic AMP or cyclic GMP, regardless of their origin from vegetative or aggregation-competent cells.


Evaluation of the potential absorbed doses from patients based on whole-body 131I clearance in thyroid cancer therapy.
The evaluation of the absorbed dose from radioactive patients during the treatment of thyroid disease is an important factor in establishing precautions in these procedures, and the I retention/excretion by patients' bodies provides additional information to medical and radioprotection service. In 94 patients, the measurement of exposure rates was performed over 7 d following NaI administration, and the rates permitted the study of the dynamics of excretion and the potential dose evaluation. The administered activities ranged from 3.7 GBq (100 mCi) to 16.65 GBq (450 mCi), and the results proved that the majority of the activity is excreted by patients in the first 3 d after NaI administration. The average (131)I activity excreted at 24, 48, 72, 96, and 120 h after oral administration was (72 +/- 10), (91 +/- 6), (97 +/- 3), (98.9 +/- 1.5), and (99.6 +/- 0.7)%, respectively. According to the administered activity, the evaluation of the accumulated absorbed dose from patients ranged from 3.0 +/- 0.7 to 8.4 +/- 1.1 mSv at 1 m and 1.2 +/- 0.4 to 3.2 +/- 0.4 mSv at 2 m. The data reported here are important to radioprotection policy and to add to and improve on the guidelines reported in U.S. NRC Regulatory Guide 8.39.


Longitudinal differences of susceptibility to ischaemia in human sensory nerve fibres.
The effect on the median nerve of ischaemia induced by a tourniquet (at a pressure of 250 mm Hg) placed on the upper arm was investigated in 12 young volunteers. In 6 of these 12 persons a second cuff, applying the same pressure as the first, was placed on the mid-forearm. In both groups the decrease in sensory action potentials and in nerve conduction velocity was more rapid in the proximal than in the distal segments. No other difference was detected between the two groups. It is concluded that the pressure induced by the cuff was not responsible for the changes and it is suggested that this phenomenon is due to internodal lengths being greater in the proximal than in the distal segments.


TD-92, a novel erlotinib derivative, depletes tumor-associated macrophages in non-small cell lung cancer via down-regulation of CSF-1R and enhances the anti-tumor effects of anti-PD-1.
Recent advances in immune checkpoint inhibition, which augment T-cell immune responses, have highlighted the potential of exploiting one's immune system to combat cancer. However, only a relatively small number of non-small cell lung cancer (NSCLC) patients benefit from immune checkpoint blockade due to the immunosuppressive tumor microenvironment. Therefore, combination immunotherapies are now being developed to achieve maximal therapeutic benefits. In this study, we assessed whether a novel erlotinib derivative, TD-92, which possesses anti-tumor effects across several cancer cell lines, could enhance anti-PD-1 treatment. Our results demonstrated that the combined treatment of anti-PD-1 and TD-92 resulted in a potent anti-tumor response in a Lewis lung carcinoma cancer model, as evidenced by the reduced tumor growth and increased survival. Analysis of immune cell population counts revealed that TD-92 reduced the number of pro-tumorigenic CD11b+ F4/80+ tumor-associated macrophages, without significantly affecting the total numbers of other major immunocytes. Further experiments showed that TD-92 induced a marked decline in colony stimulating factor 1 receptor (CSF-1R) expression in macrophage cell lines. The results also suggested that c-Cbl-mediated proteasome degradation was involved in TD-92-mediated CSF-1R downregulation. Our data paves the way for the development of additional combination immunotherapies for NSCLC patients.


Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy.
To correlate the North Star Ambulatory Assessment (NSAA) and timed rise from floor (TRF) recorded at age of expected peak with age at loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD). Male children with DMD enrolled in the UK North Start Network database were included according to the following criteria: follow-up longer than 3 years, one NSAA record between 6 years and 7 years 6 months (baseline), at least one visit when older than 8 years. Data about corticosteroid treatment, LOA, genotype, NSAA, and TRF were analysed. Age at LOA among the different groups based on NSAA and TRF was determined by log-rank tests. Cox proportional hazard models were used for multivariable analysis. A total of 293 patients from 13 different centres were included. Mean (SD) age at first and last visit was 5 years 6 months (1 year 2 months) and 12 years 8 months (2 years 11 months) (median follow-up 7 years 4 months). Higher NSAA and lower TRF at baseline were associated with older age at LOA (p<0.001). Patients scoring NSAA 32 to 34 had a probability of 0.61 of being ambulant when older than 13 years compared with 0.34 for those scoring 26 to 31. In multivariable analysis, NSAA, TRF, and corticosteroid daily regimen (vs intermittent) were all independently associated with outcome (p=0.01). Higher functional abilities at peak are associated with older age at LOA in DMD. This information is important for counselling families. These baseline measures should also be considered when designing clinical trials.


Overlay Technique for Transcatheter Left Atrial Appendage Closure.
The Overlay technique is popular in peripheral artery interventions, but not in coronary or cardiac structural procedures. We present an initial experience using three-episode overlays during a transcatheter left atrial appendage closure. The first overlay was applied to facilitate advancement of the delivery sheath into left atrium. The second overlay was used to navigate the advancement of prepped delivery system containing the compressed occluder into its optimal position in the left atrium. The third overlay facilitated the real-time deployment of the closure device. This case report demonstrates the effectiveness of the overlay technique in facilitating each step of the transcatheter left atrial appendage closure.


Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer.
miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT-PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR-133a were negatively correlated with the status of N classification (N0-N1 vs. N2-N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings.


Characterization of bioactive film from pectin incorporated with gamma-aminobutyric acid.
Gamma-aminobutyric acid (GABA) is a nutritious bioactive compound that is also an antioxidant. The effect of GABA contents (5-15%) on pectin film properties were investigated and compared to those obtained by adding 10% glycerol, with pure pectin film as the control. The addition of 5% GABA led to similar film tensile strength and elastic modulus with lower film solubility and water vapor permeability compared with film plasticized with 10% glycerol. Additionally, 5% GABA had higher film flexibility compared with the control film. Moreover, GABA content slightly affected the color and moisture content of pectin films with a high antioxidant activity. Furthermore, thermal properties of film plasticized with GABA supported the changes in mechanical properties of pectin film. Therefore, this small amount of GABA provided a desirable film with functional properties similar to those obtained by using the higher amount of glycerol. Thus, GABA not only acted as an alternative plasticizer but also showed antioxidant activity as a bioactive film.


[Age(ing), ambivalence and mimicry].
This essay aims to show that the concept of ambivalence could prove especially productive for gerontology. It is known that age(ing) is a category that is characterized by difference and at the same time delineates a process. Ambivalence is eminently suitable for capturing this duality as it enables us to take into account the dynamics peculiar to age(ing) and move beyond those conventional rigid distinctions which fail to grasp key nuances. These theoretical considerations will be put to the test by looking at the so-called young-old and their ambivalent positioning as well as their own mimicry of the middle-agers.


Benign prostatic hyperplasia: cost and effectiveness of three alternative surgical treatment methods used in a Turkish hospital.
The purpose of this study was to compare three alternative surgical therapies for Benign prostatic hyperplasia (BPH) in terms of their cost and effectiveness in a general hospital setting in Turkey. BPH is an important potential burden on health care resources in developing countries like Turkey, not only because of the increasing incidence of the disease, but also because of the differences in cost and effectiveness that exist among the various available treatment technologies. In this study, three alternative surgical treatments for BPH, namely open prostatectomy, transurethral resection of the prostate (TURP), and laser prostatectomy were compared in terms of their cost and effectiveness. Effectiveness was measured through the use of the International Prostate Symptom Score (IPSS) before the operation and at 3 months after. Laser prostatectomy was found to be the most costly and least effective way of treating BPH. This conclusion was valid both in terms of cost per prostate symptom score and cost per improvement of quality of life index. This study shows how a rough estimate can be made of the potential burdens that alternative treatment methods would impose on a country's health budget.


Apoptotic mitochondrial pathway in neurones and astrocytes after neonatal hypoxia-ischaemia in the rat brain.
Neuronal apoptosis plays an essential role in early brain development and contributes to secondary neuronal loss after acute ischaemia. Recent studies have provided evidence that caspase-3 is an important downstream event after hypoxia-ischaemia in the immature brain, but a minor event in the adult brain. Our investigations have focused on cell populations that expressed apoptotic effectors in the enzymatic death pathway including cytochrome c, caspase-9 and caspase-3. Expression, activation and cellular localization of these proteins were studied using cleavage of fluorogenic substrate and immunohistochemistry in neonatal rat brain after unilateral focal ischaemia. Caspase-3 enzyme activity was elevated in brain homogenate between 6 and 48 h after reperfusion. This activation was preceded by that of caspase-9, between 3 and 24 h. Apoptotic cell death was finally accomplished by poly-ADP-ribose polymerase cleavage, an endogenous caspase-3 substrate. In addition, immunodetection demonstrated that cytochrome c and activated caspase-9 and caspase-3 were expressed not only in the neurones, the primarily affected cells, but also within the astrocytes, which constituted a dense network delineating the infarct. These results suggested that glial injury may promote the formation of cystic lesions such as those observed clinically in the newborn brain.


Malic acid production from biodiesel derived crude glycerol using morphologically controlled Aspergillus niger in batch fermentation.
In the present investigation, the effects of crude glycerol concentration, spore inoculum concentration, yeast extract concentration and shaking frequency on seed morphology of Aspergillus niger PJR1 on malic acid production were investigated and dispersed fungal mycelium with higher biomass (20.25 ± 0.91 g/L) was obtained when A. niger PJR1 grow on crude glycerol. Dry cell weight under dispersed fermentation was 21.28% higher than usual pellet fermentation. The optimal crude glycerol, nitrogen source and nitrogen source concentration were found to be 160 g/L, yeast extract and 1.5 g/L, respectively. Batch fermentation in a shake flask culture containing 160 g/L crude glycerol resulted in the yield of malic acid 83.23 ± 1.86 g/L, after 192 h at 25 °C. Results revealed that morphological control of A. niger is an efficient method for increased malic acid production when crude glycerol derived from biodiesel production is used as feedstock.