Preparation and in vivo evaluation of parenteral metoclopramide-loaded poly(alkylcyanoacrylate) nanospheres in rats.
Metoclopramide-loaded poly(alkylcyanoacrylate) (PACA) nanospheres were prepared by emulsifier-free polymerization in aqueous media at ambient conditions. The optimum polymerization conditions for metoclopramide sorption on PACA nanospheres in the presence of dextran (DEX) or hydroxypropyl-beta-cyclodextran (HPCD) in the polymerization medium were studied and the feasibility of either poly(isobutylcyanoacrylate) (PIBCA) or poly(ethylcyanoacrylate) (PECA) nanospheres as parenteral prolonged release drug delivery system of metaclopramide in rats was also investigated. The optimum time for the addition of metaclopramide after initiating the polymerization was 1 h, which results in 14.8 +/- 0.4 and 9.2 +/- 0.5% of drug loading for PIBCA and PECA, respectively. The HPCD in the polymerization medium of PECA nanospheres improved the drug adsorption compared to DEX at all times, but the difference was only significant (p < 0.05) when metoclopramide was added at 0 and 30 min. Wistar rats were given subcutaneous (s.c.) injections of metoclopramide solution (5 mg/kg) and three different metoclopramide nanospheres suspensions (10 mg/kg) on two phases. The drug solution is rapidly absorbed, distributed, and eliminated. The maximum drug concentration was observed after 30 min of s.c. administration of all the tested nanosphere formulations. PECA-HPCD showed the highest concentration (3.16 +/- 0.66 mg/L) followed by PIBCA-DEX (1.95 +/- 0.37 mg/L) and PECA-DEX (1.68 +/- 0.28 mg/L). The AUCs of PECA-DEX, PECA-HPCD and PIBCA-DEX were 4.8, 1.88 and 2.43 times higher than that of the solution form, respectively. Following PECA-DEX the maximum drug concentration, 1.68 +/- 0.28 mg/L, rapidly decreased to 0.54 +/- 0.05 mg/L. The drug was successfully maintained around this serum drug concentration up to 12 h in rats and the mean drug concentration was reduced to 0.2 +/- 0.02 mg/L, 63% reduction, after 24 h of nanosphere administration. The developed aqueous parenteral prolonged release preparation (PECA-DEX) could be used as a promising intermittent formula for metoclopramide or other drugs when the oral route is not accessible, especially during managing chronic nausea in patients with advanced cancer.


Small bowel obstruction due to an internal herniation through a defect of the broad ligament.
We report on a case of internal hernia through a defect of the broad ligament of the uterus. Early diagnostic may be possible with multidetector CT and lead to early treatment. MDCT can help achieving early preoperative diagnostic and allows early laparoscopic treatment with prompt recovery.


Impact of Co-Delivery of EGCG and Tuna Oil within a Broccoli Matrix on Human Gut Microbiota, Phenolic Metabolites and Short Chain Fatty Acids In Vitro.
(-)-Epigallocatechin gallate (EGCG) and tuna oil (TO) are beneficial bioactive compounds. EGCG, TO or a combination of, delivered by broccoli by-products (BBP), were added to an in vitro anaerobic fermentation system containing human fecal inocula to examine their ability to generate short-chain fatty acids (SCFA), metabolize EGCG and change the gut microbiota population (assessed by 16 S gene sequencing). Following 24 h fermentation, EGCG was hydrolyzed to (-)-epigallocatechin and gallic acid. EGCG significantly inhibited the production of SCFA (p < 0.05). Total SCFA in facal slurries with BBP or TO-BBP (48-49 µmol/mL) were significantly higher (p < 0.05) than the negative control with cellulose (21 µmol/mL). EGCG-BBP and TO-EGCG-BBP treatment increased the relative abundance of Gluconacetobacter, Klebsiella and Trabulsiella. BBP and TO-BBP showed the greatest potential for improving gut health with the growth promotion of high butyrate producers, including Collinsella aerofaciens, Bacillus coagulans and Lactobacillus reuteri.


Place of death and its determinants for patients with cancer in Singapore: an analysis of data from the Singapore Cancer Registry, 2000-2009.
To describe the place of death for patients with cancer in Singapore from 2000 to 2009, and determinants of death at home and in in-patient hospice compared to death in hospital. Cross-sectional analysis of all patients registered with the Singapore Cancer Registry who had died in the study period (N=52120). Places of death were grouped as homes, in-patient hospices, hospitals and others. For determinants of death at home and in in-patient hospice, covariates adjusted for in logistic regression analyses were age group, gender, ethnic group, primary tumour site, stage at diagnosis, duration and cause of death. In the 10-year period, 52.9% of patients with cancer had died in the hospital, 30.3% died at home and 10.7% in in-patient hospice. Determinants of death at home were older age, female (odds ratio OR 1.23, 95% confidence interval, CI 1.17-1.29), Malay (OR 2.28, 95% CI 2.13-2.44), cancers of the colo-rectum, liver, stomach, pancreas and nasopharynx (compared to lung cancer), duration of illness of 1-5 years (OR 1.40, 95% CI 1.34-1.48), primary cause of death being 'neoplasms' (OR 2.97, 95% CI 2.79-3.17). Determinants of death in in-patient hospice were older age, distant metastasis (OR 1.35, 95% CI 1.21-1.50) and primary cause of death being 'neoplasms' (OR 20.07, 95% CI 16.05-25.09). Knowledge about place of death and its determinants will facilitate the planning of healthcare services to enable patients with terminal cancer to die at home and in in-patient hospices, thereby avoiding inappropriate hospitalization at the end of life.


Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia.
We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1. Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured. Pravastatin up-regulated eNOS expression in the aorta of sFlt-1 mice by nearly 2-fold (P = .005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups. Pravastatin prevents vascular dysfunction in part by up-regulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention.


Transcriptional Expression of the ompA, cpaf, tarp, and tox Genes of Chlamydia trachomatis Clinical Isolates at Different Stages of the Developmental Cycle.
The transcriptional gene expression patterns of Chlamydia trachomatis have mainly been studied using reference strains propagated in cultured cells. Here, using five low-passage-number C. trachomatis clinical isolates that originated from asymptomatic or symptomatic female patients, the in vitro expression of the ompA, cpaf, tarp, and tox genes was studied with reverse transcriptase real-time PCR during the chlamydial developmental cycle. We observed dissimilarities in the gene expression patterns between the low-passage-number clinical isolates and the reference strains. The expression of ompA and the peak of the tox expression were observed earlier in the reference strains than in most of the clinical isolates. The expression of cpaf was high in the reference strains compared with the clinical isolates at the mid-phase (6-24 hours post infection) of the developmental cycle. All of the strains had a rather similar tarp expression profile. Four out of five clinical isolates exhibited slower growth kinetics compared with the reference strains. The use of low-passage-number C. trachomatis clinical isolates instead of reference strains in the studies might better reflect the situation in human infection.


Photosynthetic and metabolic acclimation to repeated drought events play key roles in drought tolerance in coffee.
Over the last decades, most information on the mechanisms underlying tolerance to drought has been gained by considering this stress as a single event that happens just once in the life of a plant, in contrast to what occurs under natural conditions where recurrent drought episodes are the rule. Here we explored mechanisms of drought tolerance in coffee (Coffea canephora) plants from a broader perspective, integrating key aspects of plant physiology and biochemistry. We show that plants exposed to multiple drought events displayed higher photosynthetic rates, which were largely accounted for by biochemical rather than diffusive or hydraulic factors, than those submitted to drought for the first time. Indeed, these plants displayed higher activities of RuBisCO and other enzymes associated with carbon and antioxidant metabolism. Acclimation to multiple drought events involved the expression of trainable genes related to drought tolerance and was also associated with a deep metabolite reprogramming with concordant alterations in central metabolic processes such as respiration and photorespiration. Our results demonstrate that plants exposed to multiple drought cycles can develop a differential acclimation that potentiates their defence mechanisms, allowing them to be kept in an 'alert state' to successfully cope with further drought events.


Efficient Oxidative Dearomatisations of Substituted Phenols Using Hypervalent Iodine (III) Reagents and Antiprotozoal Evaluation of the Resulting Cyclohexadienones against T. b. rhodesiense and P. falciparum Strain NF54.
Quinones and quinols are secondary metabolites of higher plants that are associated with many biological activities. The oxidative dearomatization of phenols induced by hypervalent iodine(III) reagents has proven to be a very useful synthetic approach for the preparation of these compounds, which are also widely used in organic synthesis and medicinal chemistry. Starting from several substituted phenols and naphthols, a series of cyclohexadienone and naphthoquinone derivatives were synthesized using different hypervalent iodine(III) reagents and evaluated for their in vitro antiprotozoal activity. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. Cytotoxicity of all compounds towards L6 cells was evaluated and the respective selectivity indices (SI) were calculated. We found that benzyl naphthoquinone 5c was the most active and selective molecule against T. brucei rhodesiense (IC50 = 0.08 μM, SI = 275). Furthermore, the antiprotozoal assays revealed no specific effects. In addition, some key physicochemical parameters of the synthesised compounds were calculated.


Left ventricular diastolic function in hemodialysis patients: role of preload increase maneuver on tissue Doppler imaging evaluation.
Tissue Doppler imaging (TDI) has recently been proposed as a relatively preload-independent method to evaluate left ventricular diastolic function. We sought to investigate the higher-accuracy of TDI to assess diastolic function in end-stage renal disease (ESRD) patients on hemodialysis (HD) associated with a preload increase maneuver. Thirty-two consecutiveESRD patients (16 female, ages 48.8 +/- 17.5 years, 14 <or=45 and 18 >45 years old) were evaluated. Measurements of E, A velocities and the E/A ratio from transmitral inflow pulsed wave Doppler, and E', A' velocities and the E'/A' ratio from TDI were obtained 1 h before and 1 h after HD at baseline and with a preload increase maneuver. The E/A ratio changed significantly in all patients aged >45 before and after HD with the preload increase maneuver. The E'/A' ratio increased in all subjects with the preload increase maneuver before HD but did not change with the maneuver after HD in the euvolemic state in all patients. In ESRD patients on routine HD, TDI evaluation associated with a preload increase maneuver proved to be a more accurate method to identify diastolic dysfunction when the evaluation is performed in euvolemic patients after HD.


End-systolic elastance as an evaluation of myocardial function in shock.
The response of the heart during sepsis has been studied in human and animal models with disparate results. Because sepsis induces marked peripheral vascular changes, to accurately determine the cardiac response, one must use indices of cardiac performance that are independent of loading conditions and heart rate. The slope of the end-systolic pressure-diameter relationship (ESPDR) has been proposed to have these properties. Pigs were equipped with transducers to measure left ventricular pressure, internal short axis diameter (D), and pulmonary and coronary artery blood flows. After 7-10 days of basal observations, an endotoxin-loaded osmotic pump delivering endotoxin at 10 micrograms/kg/hr was implanted into each pig. Fourteen pigs were so treated, and 4 expired before 24 hr of endotoxin challenge. In the surviving pigs, cardiac output, heart rate, dP/dtmax, and peak systolic pressures were elevated. However, both ESPDR and % D shortening were both significantly depressed. These data suggest that the cardiac response to chronic endotoxin challenge includes a loss of inotropic state as indicated by the load-insensitive indicator, ESPDR, and confirmed by depressed % D shortening. One possible mechanism for reduced inotropic state during endotoxin challenge could be the loss of coronary perfusion. The surviving endotoxin-challenged pigs demonstrated a significant increase in coronary perfusion while stroke work remained unchanged, suggesting that depressed cardiac inotropic state during endotoxin challenge was not caused by reduced coronary blood flow. Rather, the myocardium was relatively overperfused. Another possible mechanism for the loss of cardiac inotropism during endotoxin challenge may be endotoxin-induced generation of reactive oxygen free radicals. This possibility was tested by measuring total cardiac gluthathione, a cellular component depleted by oxidant stress. Endotoxemia reduced these levels 50%. These results suggest that cardiac injury may be mediated by the generation of reactive oxygen free radicals. Further study will determine if this mechanism participates in the loss of cardiac inotropism during endotoxin challenge.


Watch the GAP: Emerging Roles for IQ Motif-Containing GTPase-Activating Proteins IQGAPs in Hepatocellular Carcinoma.
IQ motif-containing GTPase-activating proteins IQGAP1 and IQGAP2 are highly homologous multidomain scaffolding proteins. Their major function consists of integration of Rho GTPase and Ca(2+)/calmodulin signals with cell adhesive and cytoskeletal reorganizational events. Recent studies showed that they play an important role in carcinogenesis. There is growing evidence that IQGAP2 is a novel tumor suppressor counteracting the effects of IQGAP1, an oncogene, in several cancers, especially in hepatocellular carcinoma (HCC). While HCC is highly prevalent and one of the deadliest cancers worldwide, the signaling pathways involved are not fully understood and treatment of advanced disease still represents an area of high unmet medical need. This paper compiles various findings from studies in mouse models, cell lines, and patient samples that support future development of IQGAPs into new therapeutic targets. It also discusses distinct features of IQGAP2 in an attempt to provide insight into the mechanism of the seemingly paradoxical opposing roles of the two very similar IQGAP proteins in carcinogenesis.


Systemic manifestations of traumatic brain injury.
Traumatic brain injury (TBI) affects functioning of various organ systems in the absence of concomitant non-neurologic organ injury or systemic infection. The systemic manifestations of TBI can be mild or severe and can present in the acute phase or during the recovery phase. Non-neurologic organ dysfunction can manifest following mild TBI or severe TBI. The pathophysiology of systemic manifestations following TBI is multifactorial and involves an effect on the autonomic nervous system, involvement of the hypothalamic-pituitary axis, release of inflammatory mediators, and treatment modalities used for TBI. Endocrine dysfunction, electrolyte imbalance, and respiratory manifestations are common following TBI. The influence of TBI on systemic immune response, coagulation cascade, cardiovascular system, gastrointestinal system, and other systems is becoming more evident through animal studies and clinical trials. Systemic manifestations can independently act as risk factors for mortality and morbidity following TBI. Some conditions like neurogenic pulmonary edema and disseminated intravascular coagulation can adversely affect the outcome. Early recognition and treatment of systemic manifestations may improve the clinical outcome following TBI. Further studies are required especially in the field of neuroimmunology to establish the role of various biochemical cascades, not only in the pathophysiology of TBI but also in its systemic manifestations and outcome.


Rationalizing lead optimization by associating quantitative relevance with molecular structure modification.
Historically, one of the characteristic activities of the medicinal chemist has been the iterative improvement of lead compounds until a suitable therapeutic entity is achieved. Often referred to as lead optimization, this process typically takes the form of minor structural modifications to an existing lead in an attempt to ameliorate deleterious attributes while simultaneously trying to maintain or improve desirable properties. The cumulative effect of this exercise performed over the course of several decades of pharmaceutical research by thousands of trained researchers has resulted in large collections of pharmaceutically relevant chemical structures. As far as the authors are aware, this work represents the first attempt to use that data to define a framework to quantifiably catalogue and summate this information into a medicinal chemistry expert system. A method is proposed that first comprehensively mines a compendium of chemical structures compiling the structural modifications, abridges them to rectify artificially inflated support levels, and then performs an association rule mining experiment to ascribe relative confidences to each transformation. The result is a catalogue of statistically relevant structural modifications that can potentially be used in a number of pharmaceutical applications.


Tuberculosis: a challenge to the general practitioner.
Of 157 patients dying of tuberculosis in Ontario (1960) 132 (87.4%) suffered from the pulmonary form of the disease (incidence 2.6 per 100,000). In the same year, 1632 of 1847, or 88.3%, active new cases reported had the pulmonary type and 183 additional cases were reported without details as to type of disease. Thus, in 1960, a total of 2030 new cases of tuberculosis were reported in Ontario.Of 1367 patients with pulmonary tuberculosis (reinfection type), 357 (26.1%) had "far advanced" disease and 613 (44.8%) had "moderately advanced" disease.This high percentage of patients with "moderately advanced" to "far advanced" disease at the time of diagnosis constitutes the real challenge to physicians in private practice, who made the diagnosis in 45% of cases.Emergence of resistant strains of bacteria increases the urgency of prompt diagnosis and treatment. The most vulnerable population segment is the 15-30 year age-group, many of whom are negative intracutaneous reactors. A high index of suspicion is necessary, particularly in certain segments of the population with a high incidence of infection, combined with a careful history, meticulous physical examination, intracutaneous tests, chest and other radiographs, and appropriate bacteriological studies.


Device-based measurement of physical activity in pre-schoolers: Comparison of machine learning and cut point methods.
Machine learning (ML) accelerometer data processing methods have potential to improve the accuracy of device-based assessments of physical activity (PA) in young children. Yet the uptake of ML methods by health researchers has been minimal and the use of cut-points (CP) continues to be the norm, despite evidence of significant misclassification error. The lack of studies demonstrating a relative advantage for ML approaches over CP methods maybe a key contributing factor. The current study compared the accuracy of PA intensity predictions provided by ML classification models and previously published CPs for preschool-aged children. In a free-living study, 31 preschool-aged children (mean age = 4.0 ± 0.9 y) wore wrist and hip ActiGraph GT3X+ accelerometers while completing a video recorded 20-minute free play session. Ground truth PA intensity was coded continuously using the Children's Activity Rating Scale (CARS). Accelerometer data was classified as sedentary (SED), light intensity (LPA), or moderate-to-vigorous intensity (MVPA) using ML random forest PA classifiers and published CPs for preschool-aged children. Performance differences were evaluated in a hold-out sample by comparing weighted kappa statistics, classification accuracy for each intensity band, and equivalence testing. ML classification models (hip: κ = 0.76; wrist: κ = 0.72) exhibited significantly higher agreement with ground truth PA intensity than CP methods (hip: κ = 0.38-0.49; wrist: κ = 0.31-0.44). For the ML models, classification accuracy for SED and LPA ranged from 83% - 88%, while classification accuracy for MVPA ranged from 68% - 78%. For the CP's, classification accuracy ranged from 50% - 94% for SED, 19% - 75% for LPA, and 44% - 76.1% for MVPA. ML classification models showed equivalence (within ± 0.5 SD) with directly observed time in SED, LPA, and MVPA. None of the CP's exhibited evidence of equivalence. Under free living conditions, ML classification models for hip or wrist accelerometer data provide more accurate assessments of PA intensity in young children than CP methods. The results demonstrate the relative advantage of ML methods over threshold-based approaches and adds to a growing evidence base supporting the feasibility and accuracy of ML accelerometer data processing methods.


Unrestricted somatic stem cells: interaction with CD34+ cells in vitro and in vivo, expression of homing genes and exclusion of tumorigenic potential.
Transplantation of allogeneic hematopoietic stem cells (HSC) within the framework of hematologic oncology or inherited diseases may be associated with complications such as engraftment failure and long-term pancytopenia. HSC engraftment can be improved, for example by co-transplantation with mesenchymal stem cells (MSC). Recently, a new multipotent MSC line from umbilical cord blood, unrestricted somatic stem cells (USSC), has been described. It was demonstrated that USSC significantly support proliferation of HSC in an in vitro feeder layer assay. A NOD/SCID mouse model was used to assess the effect of USSC on co-transplanted CD34(+) cells and look for the fate of transplanted USSC. The migration potential of USSC was studied in a Boyden chamber migration assay and in vivo. Quantitative real-time polymerase chain reaction (qRT-PCR) for CXCR4, CD44, LFA1, CD62L, VLA4, RAC2, VLA5A and RAC1 were performed. NMR1 nu/nu mice were used for a tumorigenicity test. After 4 weeks, homing of human cells (CD45(+)) to the bone marrow of NOD/SCID mice was significantly increased in mice co-transplanted with CD34(+) cells and USSC (median 30.9%, range 7-50%) compared with the CD34(+) cell-only control group (median 5.9%, range 3-10%; P = 0.004). Homing of USSC could not be shown in the bone marrow. A cell-cell contact was not required for the graft enhancing effect of USSC. An in vivo tumorigenicity assay showed no tumorigenic potential of USSC. This pre-clinical study clearly shows that USSC have an enhancing effect on engraftment of human CD34(+) cells. USSC are a safe graft adjunct.


Controlled comparison of buspirone and clomipramine in obsessive-compulsive disorder.
Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.


[Final results of an initiative aiming to improve the referrals from primary care to a Department of Urology].
To test two interventions aiming at improving the compliance of primary health care physicians with an agreed-on protocol of referrals to a urology department. Joint formative meetings (every six months) were celebrated throughout a 24-month period. Also a counseling telephone line was implemented. 18.088 referrals were analyzed. The effect of both expositions was tested comparing basal data (T0) with the performance at 6, 12, 18 and 24 months later (T1, T2, T3 and T4, respectively). An additional comparison was conducted to approach the results 1 year after the study ended (T5). 61.7% of the referrals at baseline complied with the protocol. A significant improvement was detected at T1 (compliance 73.4%, RR with respect to T0 1.19, 95% CI 1.14- 1.23). At T2, 73.7% of referrals were adequate (RR with respect to T0 1.19, 95% CI 1.15-1.24). The percent of adequate referrals at T3 remained stable (73.4%, RR with respect to T0 1.18, 95% CI 1.15-1.23). Nevertheless, adequacy of referrals by the end of the second year (T4) significantly decreased (67.3%, RR with respect to T0, 1.09, 95% CI 1.05-1.12). Adequacy at T5 was almost identical to the basal (64.4%, RR with respect to T0, 1.04 95% CI 1.04-1.07). Learning activities can be effective in improving the quality of referrals from primary care to one urology department. Stopping the activities entails an immediate return to the basal standards.


Transcriptome profiling revealed diverse gene expression patterns in poplar (Populus × euramericana) under different planting densities.
Certain plant genotypes can achieve optimal growth under appropriate environmental conditions. Under high planting density conditions, plants undergo competition for uptake and utilization of light and nutrients. However, the relationship between whole-genome expression patterns and the planting density in perennial woody plants remains unknown. In this study, whole-genome RNA sequencing of poplar (Populus × euramericana) was carried out at three different sampling heights to determine gene expression patterns under high (HD) and low (LD) planting densities. As a result, 4,004 differentially expressed genes (DEGs) were detected between HD and LD, of which 2,300, 701, and 1,003 were detected at the three positions, upper, middle and bottom, respectively. Function annotation results further revealed that a large number of the DEGs were involved in distinct biological functions. There were significant changes in the expression of metabolism-related and stimulus-related genes in response to planting density. There were 37 DEGs that were found at all three positions and were subsequently screened. Several DEGs related to plant light responses and photosynthesis were observed at different positions. Meanwhile, numbers of genes related to auxin/indole-3-acetic acid, and carbon and nitrogen metabolism were also revealed, displaying overall trends of upregulation under HD. These findings provide a basis for identifying candidate genes related to planting density and could increase our molecular understanding of the effect of planting density on gene expression.


Detection of β-Lactamase Resistance and Biofilm Genes in Pseudomonas Species Isolated from Chickens.
Bacteria of the genus Pseudomonas are pathogens in both humans and animals. The most prevalent nosocomial pathogen is P. aeruginosa, particularly strains with elevated antibiotic resistance. In this study, a total of eighteen previously identified Pseudomonas species strains, were isolated from chicken. These strains were screened for biofilm formation and antibiotic resistance. In addition, we evaluated clove oil's effectiveness against Pseudomonas isolates as an antibiofilm agent. The results showed that Pseudomonas species isolates were resistant to most antibiotics tested, particularly those from the β-lactamase family. A significant correlation (p < 0.05) between the development of multidrug-resistant isolates and biofilms is too informal. After amplifying the AmpC-plasmid-mediated genes (blaCMY, blaMIR, DHA, and FOX) and biofilm-related genes (psld, rhlA, and pelA) in most of our isolates, PCR confirmed this relationship. Clove oil has a potent antibiofilm effect against Pseudomonas isolates, and may provide a treatment for bacteria that form biofilms and are resistant to antimicrobials.


Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity.
Protein misfolding is a central mechanism for the development of neurodegenerative diseases and type 2 diabetes mellitus. The accumulation of misfolded alpha-synuclein protein inclusions in the Lewy bodies of Parkinson's disease is thought to play a key role in pathogenesis and disease progression. Similarly, the misfolding of the beta-cell hormone human islet amyloid polypeptide (h-IAPP) into toxic oligomers plays a central role in the induction of beta-cell apoptosis in the context of type 2 diabetes. In this study, we show that annexin A5 plays a role in interacting with and reducing the toxicity of the amyloidogenic proteins, h-IAPP and alpha-synuclein. We find that annexin A5 is coexpressed in human beta-cells and that exogenous annexin A5 reduces the level of h-IAPP-induced apoptosis in human islets by approximately 50% and in rodent beta-cells by approximately 90%. Experiments with transgenic expression of alpha-synuclein in Caenorhabditis elegans show that annexin A5 reduces alpha-synuclein inclusions in vivo. Using thioflavin T fluorescence, electron microscopy, and electron paramagnetic resonance, we provide evidence that substoichiometric amounts of annexin A5 inhibit h-IAPP and alpha-synuclein misfolding and fibril formation. We conclude that annexin A5 might act as a molecular safeguard against the formation of toxic amyloid aggregates.


Preterm Assessment at Birth and Its Association With the Development of Retinopathy of Prematurity (ROP): A Tertiary Care Center Experience.
Prematurity is a leading cause of neonatal morbidity and mortality and is associated with insufficient development of multiple body structures, including neurovascular and retinal tissues. Retinopathy of prematurity (ROP) is an abnormal vaso proliferation of the neonatal retina that results from an arrest in the normal development of the retinal nerve and blood supply. Incidence has been increasing due to advancements in intensive care and survival of preterm neonates, as well as improvements in screening methods for ROP. The objective is to assess the initial clinical and laboratory characteristics of preterm infants at the time of birth to identify population-specific risk factors for the development of ROP in a tertiary care center in western Saudi Arabia. This was a retrospective record review conducted at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. The study included 37 patients diagnosed with ROP. Their ROP staging, complete blood count, appearance, pulse, grimace, activity and respiration (APGAR) score, and birth characteristics were all analyzed. Thirty-seven neonates diagnosed with ROP and who met the study inclusion criteria were included. our results showed a female predominance of 51.4%, the mean age of the pregnancy was 27.18 ± 2.29 weeks, the mean birth weight was 0.8 ± 0.26, and 66.7% of our sample was delivered by the cesarean section. A significant association was found between the birth weight and the development of ROP in the right eye (p = 0.026); another significance was found between gestational age and the development of ROP in the same eye (p = 0.016). A low birth weight and gestational age show a significant association with the development of ROP. Early identification and treatment of ROP are important to preserve a neonate's eyesight.


Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral.
Pores regulate access between ferric-oxy biomineral inside and reductants/chelators outside the ferritin protein nanocage to control iron demineralization rates. The pore helix/loop/helix motifs that are contributed by three subunits unfold independently of the protein cage, as observed by crystallography, Fe removal rates, and CD spectroscopy. Pore unfolding is induced in wild type ferritin by increased temperature or urea (1-10 mM), a physiological urea range, 0.1 mM guanidine, or mutation of conserved pore amino acids. A peptide selected for ferritin pore binding from a combinatorial, heptapeptide library increased the rate of Fe demineralization 3-fold (p<0.001), similarly to a mutation that unfolded the pores. Conjugating the peptide to Desferal (desferrioxamine B mesylate), a chelator in therapeutic use, increased the rates to 8-fold (p<0.001). A second pore binding peptide had the opposite effect and decreased the rate of Fe demineralization 60% (p<0.001). The peptides could have pharmacological uses and may model regulators of ferritin demineralization rates in vivo or peptide regulators of gated pores in membranes. The results emphasize that small peptides can exploit the structural plasticity of protein pores to modulate function.


Hollow spherical gold nanoparticle superstructures with tunable diameters and visible to near-infrared extinction.
Hollow spherical gold nanoparticle superstructures with tunable diameters (∼40 nm, ∼70 nm and ∼150 nm) and visible to near-infrared surface plasmon resonances (545 nm, 670 nm, and 740 nm) are prepared using a single peptide conjugate, C6-AA-PEPAu, as the structure-directing agent. Computational models are developed to understand their optical properties.


Osteo-modulatory dietary proteins and peptides: A concise review.
The integrity of the bone is dependent on the strict balance between osteoclastogenesis and osteoblastogenesis, and any imbalance results in bone diseases. Dietary proteins (DP) have been shown to promote osteogenesis while inhibiting bone resorption in cultured osteoblasts, and in animal models of bone diseases such as ovariectomy, 1α,25-dihydroxy-vitamin D3 (VD3), and prostaglandin E2 (PGE2)-induced bone resorption. Hydrolysis of some of these DPs with osteo-modulatory properties has been shown to generate hydrolysates with bioactive peptides that exhibit higher osteo-modulatory properties in comparison to intact (parent) proteins. The higher bioactivity of the isolated peptides and protein hydrolysates compared to intact proteins indicates that the osteo-modulatory properties are dependent on the degree of exposure of the functional groups of amino acid residues involved in target interaction. This review provides an overview of the preparation of DP and select peptides with osteo-modulatory properties, and summarizes the potential underlying mechanisms of action through which the bioactive peptides help maintain bone health. PRACTICAL APPLICATIONS: Bone diseases such as osteoporosis (OP), osteoarthritis (OA), bone cancer (BC), and others have negative impacts on the quality of life, especially in older women after menopause. Current drugs used in treating many bone diseases such as bisphosphonates, anabolic steroids, and selective estrogen receptor modulators have been limited by worrisome adverse effects such as organ toxicity, increased risk of cancer, and cardiovascular abnormalities, and gastrointestinal discomfort. There is growing scientific evidence that certain multifunctional dietary proteins and bioactive peptides may positively modulate bone health by modifying risk factors for bone diseases including inflammation, oxidative stress, hyperlipidemia, and hyperglycemia.


Prevalence and associations for use of a traditional medicine provider in the SAMINOR 1 Survey: a population-based study on Health and Living Conditions in Regions with Sami and Norwegian Populations.
In Northern Norway, traditional medicine (TM) is shaped by both Christianity and traditional Sami nature worship. The healing rituals may include prayer and the use of tools such as moss, water, stones, wool and soil. Examples of TM modalities offered is cupping, blood-stemming, laying on of hands, healing prayers, and rituals. The purpose of this study was to investigate the prevalence of the use of TM in areas with predominantly Sami and Norwegian populations, and the influence of ethnicity, geography, gender, age, education, household income, religiosity and self-reported health on such use. The study is based on data collected in the first SAMINOR Survey (SAMINOR 1) conducted in 2003/2004, including three self-administered questionnaires, clinical measures, and blood analyses. Data was collected in 24 municipalities in Norway known to have a substantial population of Sami. All residents aged 30 and 36-78/79 years in the predefined regions were invited regardless of ethnic background (N = 27,987). Of these, 16,865 (60.3%) accepted to participate and gave their consent to medical research. Of the 16,544 people responding to the question about TM use, 2276 (13.8%) reported to have used TM once or more during their lifetime. The most outstanding characteristic of the TM users was the affiliation to the Laestadian church, where 34.3% (n = 273) reported such use, followed by an inner Finnmark residence (31.1%, n = 481) and a Sami ethnicity (25.7%, n = 1014). Women were slightly more likely to use TM compared to men (15.9% and 11.5% accordingly, p < 0.001), and the TM users were slightly younger than the non-TM users (mean age 52.3 versus 54.3 years, p < 0.001). The TM users also had lower income (p < 0.001) than the non-TM users. We found no significant differences between the TM users and the non-TM users concerning years of education, and whether the participants were living with a spouse/partner or not. Further studies are necessary to examine the development of TM use in Norway over time, and use in areas with mainly Norwegian inhabitants. There is also a lack of studies quantifying TM use among Sami people in Sweden, Finland and Russia.


Effect of berberine on p53 expression by TPA in breast cancer cells.
Berberine (BBR), an isoquinoline derivative alkaloid compound, has been reported to have anti-oxidant and anti-carcinogenic effects. A loss of functional p53 is involved with an increased risk of cancer proliferation and metastasis. Here, we investigated the effect of BBR on the transcriptional activity and the protein expression of p53 in p53-positive (wild- type, MCF7 cells) and p53-negative (mutant, MDA-MB231 cells) human breast cancer cells. Our results showed that the basal level of p53 mRNA and protein expression was increased by BBR treatment. However, tumor promoter, TPA, decreased the level of p53 mRNA and protein expression in MCF7 cells with wild-type p53. In addition, TPA-induced down-regulation of p53 mRNA and protein expression was increased by UO126, but not by SP600125 and SB203580. To verify the regulatory mechanism of p53 protein expression, we investigated the effects of proteasomal inhibitors (ALLN and MG132) or a lysosomal inhibitor (chloroquine) on TPA-induced down-regulation of p53. We observed that TPA-induced down-regulation of p53 protein was prevented by ALLN and MG132, but not by chloroquine. Further, we investigated the effect of BBR on TPA-induced down-regulation of p53 mRNA and protein levels. Interestingly, the levels of TPA-induced down-regulation of p53 mRNA and protein were prevented by BBR, but MDA-MB231 cells with mutated p53 were not affected. In addition, TPA-induced down-regulation of p53 mRNA was also prevented by BBR. Taken together, we suggest that BBR may be used as an effective ingredient for anticancer products, which trigger the transcriptional activity and the inhibition of the degradation of p53, a tumor suppressor gene, in human breast cancer.


Job strain and risk of breast cancer.
Cohort studies investigating the association between stress and breast cancer have shown highly inconsistent results. The Women's Lifestyle and Health Cohort Study included 36,332 Swedish women age 30-50 years who were employed at baseline (1991-1992). Participants were followed through December 2004 using linkages to national registries. A total of 767 women were diagnosed with breast cancer during follow-up. Among women working full-time, low job control and high job demands were weakly associated with breast cancer risk (hazard ratios of 1.2; 95% CI = 1.0-1.5). Women with both low job control and high job demands ("job strain") had higher risk of breast cancer than women with high job control and low demands ("low strain") (1.2; 0.9-1.6). Multivariate adjustment slightly strengthened the association between breast cancer and job strain (1.4; 1.1-1.9), whereas the associations with control and demands were unchanged. Work characteristics were unrelated to breast cancer risk among women working part-time. There was a small increased risk of breast cancer among women in full-time employment who experienced job strain, but not among part-time workers.


"It's like a guessing game all the time": parent insights on barriers, supports, and priorities for children with cortical visual impairment and complex communication needs.
Parents of children with both cortical visual impairment (CVI) and complex communication needs offer unique perspectives on their children's journeys to receiving proper diagnoses, supports, and interventions, such as augmentative and alternative communication (AAC). This study explored the lived experiences, supports, and barriers identified by parents through a qualitative phenomenological approach. Nine parents of children with both CVI and complex communication needs were interviewed virtually. Results indicated five themes descriptive of the parents' experiences: Challenges Piecing Together a CVI Diagnosis; Dealing with Low Expectations of Others; Parents Empowered to Take Action; Guessing Game to Determine Appropriate AAC to Accommodate CVI; and Aligning Professional Practice with Parent Priorities. Whereas some of these themes echoed the experiences of parents of children with complex communication needs (such as those with cerebral palsy) who were not specifically diagnosed with CVI, other themes were unique to this set of parents including the uncertainty of AAC design and intervention given the challenges of CVI and the necessity of more than one way for children to communicate given their visual challenges. This study highlighted the dire need for continued investigation to determine effective AAC interventions for individuals with CVI.


Role of Veratryl Alcohol in Regulating Ligninase Activity in Phanerochaete chrysosporium.
Ligninase activity in Phanerochaete chrysosporium is stimulated by incubating cultures with various substrates for the enzyme, including veratryl (3,4-dimethoxybenzyl) alcohol, which is a secondary metabolite of this fungus. This study was designed to provide insight into the mechanism involved in this stimulation. Ligninase activity increased 2 to 4 h after the addition of exogenous veratryl alcohol to ligninolytic cultures. This increase was prevented by inhibitors of protein synthesis. Analysis of the extracellular proteins by high-performance anion-exchange liquid chromatography revealed increases in the amounts of some, but not all, ligninase species. The normal rapid decrease in ligninase activity in aging cultures was not prevented or retarded by veratryl alcohol, indicating that veratryl alcohol does not increase ligninase activity by protecting extant enzyme. We conclude that veratryl alcohol probably functions via an induction type of mechanism, affecting only certain ligninase species. Results with an isolated lignin indicate that lignin (or its biodegradation products) functions in the same way that veratryl alcohol does.


Exact-mass library for pesticides using a molecular-feature database.
An automated molecular-feature database (MFD) consisting of the exact monoisotopic mass of 100 compounds, at least one exact mass product ion for each compound, and chromatographic retention time were used to identify pesticides in food and water samples. The MFD software compiles a list of accurate mass ions, excludes noise, and compares them with the monoisotopic exact masses in the database. The screening criteria consisted of +/-5 ppm accurate mass window, +/-0.2 min retention time window, and a minimum 1000 counts (signal-to-noise (S/N) ratio of approximately 10:1). The limit of detection for 100 tested compounds varied from <0.01 mg/kg for 72% of the compounds to <0.1 mg/kg for 95% of the compounds. The MFD search was useful for rapid screening and identification of pesticides in food and water, as shown in actual samples. The combined use of accurate mass and chromatographic retention time eliminated false positives in the automated analysis. The major weakness of the MFD is matrix interferences and loss of mass accuracy. Strengths of the MFD include rapid screening of 100 compounds at sensitive levels compared with a manual approach and the ease of use of the library for any accurate mass spectrometer instrumentation capable of routine sub-5-ppm mass accuracy.


[Removal of biventricular thrombi for dilated cardiomyopathy in a patient with acute heart failure].
We report a rare case of a 49-year-old man with biventricular thrombi associated with idiopathic dilated cardiomyopathy (DCM). The patient was admitted with congestive heart failure and pneumonia. Echocardiography revealed mobile "ball-like" biventricular thrombi associated with significantly impaired left ventricular function and severe mitral/tricuspid valve regurgitation. The biventricular thrombi were removed and subsequently, a mitral annuloplasty, as well as papillary muscle approximation and tricuspid annuloplasty were performed. The postoperative course has been uneventful over a period of 2 years and neither thromboembolic events nor recurrence of congestive heart failure has been observed.


An operation for evangelization: Friar Francisco González Laguna, the cesarean section, and fetal baptism in late colonial Peru.
By publishing a medical-theological treatise in 1781, Friar Francisco González Laguna of Lima initiated a campaign to train Andean priests to perform postmortem cesarean sections for the purpose of baptizing the fetus. Linking González Laguna's text to European works on cesarean sections and Peruvian decrees ordering priests to train in surgery, this paper argues the friar saw the operation's utility as extending beyond saving unborn souls. Writing in the aftermath of indigenous and peasant uprisings, he argued the procedure constituted a tool for defeating the devil's presence in the Andes and carrying out evangelization, teaching parishioners by pious example.


The pathophysiology of hyperuricemia in essential hypertension: a pilot study.
We have examined whether hyperuricemia in essential hypertension may be related to an increased insulin secretion thereby enhancing the tubular reabsorption of sodium and thus uric acid. Insulin hypersecretion, as elicited by the oral glucose tolerance test (OGTT), increased a mean of 5-fold in 12 essential hypertensive patients. Urinary uric acid to creatinine ratio significantly diminished by a mean of 62% after the OGTT. Simultaneously, urinary sodium to creatinine ratio decreased by a mean of 54%. These results suggest that insulin may mediate uric acid underexcretion due to its tubular sodium retaining effect in essential hypertensive patients.


Intracranial pressure-volume response in dog subjected to repeated infusion tests: an experimental study.
Several experimental studies have been made in the past to try to understand the nature of the fluid-induced changes in the intracranial pressures of the animals by infusing fluid into their craniospinal complex. The objective of the present investigation was to study the changes in the characteristics of the ventricular and epidural pressure-volume curves when a dog was subjected to repeated fluid infusion tests. The animals were subjected to three cycles of infusion tests with a time interval of either 10 min or 2 h between any two successive tests. An infusion test repeated 10 min after the preceding test exhibited a significant change in the characteristics of the ventricular fluid pressure (VFP) response but not in the epidural pressure (EDP) response. However, in the case of an infusion test which was repeated 2 h after the preceding test, it was observed that both the VFP and EDP responses remained the same as those found in the first infusion test.


[Determination of hepatitis B virus genotypes in chronic hepatitis B patients in Mersin province, Turkey].
Currently, ten genotypes (A-J) of hepatitis B virus (HBV) are identified based on the nucleic acid sequence heterogeneity, and these genotypes have been shown to have distinct geographic distribution. Reports of previous studies indicated that the genotype D is the predominant type among hepatitis B patients in different regions of Turkey, however there is no data for HBV genotypes to date from Mersin region. The aim of this study was to investigate the HBV genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in chronic hepatitis B patients in Mersin province (located in the Mediterranean region of Turkey). A total of 54 serum samples were obtained from the chronic hepatitis B patients (33 male, 21 female; mean age: 40.05 years) followed-up at Gastroenterology Clinic of Mersin University Hospital. Patients had detectable HBV-DNA levels in their serum samples, and they were under antiviral therapy for at least one year. Genotyping of HBV was performed by RFLP analysis with the use of AvaII and MboI restriction enzymes after amplification of pre-S gene region by PCR. Confirmation of selected 18 cases was carried out with direct DNA sequencing. The genotypes were determined by phylogenetic comparison with 43 reference NCBI (National Center for Biotechnology Information) HBV sequences. Genotype determination was not successful in seven cases; since three of them were negative in preS-PCR, three of them yielded non-specific bands, and one of them exhibited a deleted PCR product, at the 300 bp level that was shorter than expected. Four different restriction patterns were determined in PCR-RFLP analysis of the remaining 47 samples. One of these patterns which was AvaII [-]/MboI [306/89/51], was clearly discriminated in 72.3% (34/47) of the samples as genotype D. Genotype discrimination of three patterns could not be done properly and these patterns were AvaII [- ]/MboI [357/306/89/51] (7/47, 14.9%), AvaII [300/146]/MboI [306/89/51] (5/47, 10.7%), and AvaII [- ]/MboI [357/89/---] (1/47, 2.1%). Phylogenetic comparison of HBV sequences demonstrated that all patterns in our cases were clustered in NCBI genotype D sequences. Patterns of AvaII [300/146]/MboI [306/89/51] and AvaII [-]/ MboI [357/89/---] and deleted sample were recognized as pre-S gene variants of HBV isolates. Our data indicated that the predominant HBV type was genotype D as commonly seen in Turkey and other Mediterranean countries. The results of this study also showed that the genotype uniformity and pre-S gene variants within the HBV isolates could be crucial in terms of understanding the molecular epidemiology of HBV circulating in the Mediterranean region of Turkey.


Three-dimensional reconstruction of the angioarchitecture of the ciliary body of the West Indian manatee (Trichechus manatus).
To examine the angioarchitecture of the ciliary body in the West Indian manatee (Trichechus manatus), through the use of three-dimensional reconstruction. Specimens from West Indian manatee were preserved in 10% buffered formalin, embedded in paraffin, serial sectioned and stained by Masson trichrome for light microscopic three-dimensional reconstruction and evaluation. The network of blood vessels in the ciliary processes of the West Indian manatee is fed by the major arterial circle that lies mostly near the base of the iris. The branching arterioles give rise to a capillary-sinusoidal bed that extends internally along each process, emptying into two sets of veins, one being elevated. The elevated and nonelevated veins join posteriorly before emptying into the choroidal venous system. The angioarchitecture of the ciliary body of the West Indian manatee is clearly unique when compared to those previously examined in land mammals. Three-dimensional reconstruction of paraffin sections is an effective means to evaluate vascular patterns in ocular specimens, especially those unavailable for corrosion casting.


Diketopyrrolopyrrole-Based Metallated Polymer for Bulk-Heterojunction Solar Cells and Organic Field-Effect Transistors.
We report the synthesis and optoelectronic properties of novel platinum-based polymers (p-Pt-DPP) incorporating 3,6-di-2-thienyl-2,5-dihydro-2,5-diethylhexylpyrrolo[3,4-c]pyrrole-1,4-dione. The synthesized amorphous metallated polymer exhibited long wavelength absorption in the range of 500–684 nm and a band-gap as low as 1.75 eV. Organic field-effect transistors (OFETs) fabricated from p-Pt-DPP showed hole mobility of 1.6 × 10⁻³ cm² · V⁻¹s⁻¹ and an on/off ratio of 5 × 10⁴. In addition, polymer solar cells (PSCs) based on p-Pt-DPP and PC₇₁BM exhibited a photovoltaic efficiency of 1.22% under AM 1.5 G conditions with an illumination of 100 mW·cm−2 without any annealing process.


Administration of Bovine Milk Oligosaccharide to Weaning Gnotobiotic Mice Inoculated with a Simplified Infant Type Microbiota.
Bovine milk oligosaccharides (BMO) share structural similarity to selected human milk oligosaccharides, which are natural prebiotics for infants. Thus, there is a potential in including BMOs as a prebiotic in infant formula. To examine the in vivo effect of BMO-supplementation on the infant gut microbiota, a BMO-rich diet (2% w/w) was fed to gnotobiotic mice (n = 11) inoculated with an infant type co-culture and compared with gnotobiotic mice receiving a control diet (n = 9). Nuclear magnetic resonance metabolomics in combination with high-throughput 16S rRNA gene amplicon sequencing was used to compare metabolic activity and microbiota composition in different compartments of the lower gastrointestinal tract. BMO components were detected in cecum and colon contents, revealing that BMO was available for the gut bacteria. The gut microbiota was dominated by Enterobacteriaceae and minor abundance of Lactobacilliaceae, while colonization of Bifidobacteriaceae did not succeed. Apart from a lower E. coli population in cecum content and lower formate (in colon) and succinate (in colon and cecum) concentrations, BMO supplementation did not result in significant changes in microbiota composition nor metabolic activity. The present study corroborates the importance of the presence of bifidobacteria for obtaining microbial-derived effects of milk oligosaccharides in the gastrointestinal tract.


Tuning oxygen reduction reaction activity via controllable dealloying: a model study of ordered Cu3Pt/C intermetallic nanocatalysts.
A promising electrocatalyst prototype of low Pt mole fraction, intermetallic nanoparticles of Cu(3)Pt, has been prepared using a simple impregnation-reduction method, followed by a post heat-treatment. Two dealloying methods (electrochemical and chemical) were implemented to control the atomic-level morphology and improve performance for the oxygen reduction reaction (ORR). The morphology and elemental composition of the dealloyed nanoparticles were characterized at angstrom resolution using an aberration-corrected scanning transmission electron microscope equipped with an electron energy loss spectrometer. We found that the electrochemical dealloying method led to the formation of a thin Pt skin of ca. 1 nm in thickness with an ordered Cu(3)Pt core structure, while chemical leaching gave rise to a "spongy" structure with no ordered structure being preserved. A three-dimensional tomographic reconstruction indicated that numerous voids were formed in the chemically dealloyed nanoparticles. Both dealloying methods yielded enhanced specific and mass activities toward the ORR and higher stability relative to Pt/C. The spongy nanoparticles exhibited better mass activity with a slightly lower specific activity than the electrochemically dealloyed nanoparticles after 50 potential cycles. In both cases, the mass activity was still enhanced after 5000 potential cycles.


An "attenuator domain" is sandwiched by two distinct transactivation domains in the transcription factor C/EBP.
C/EBP is a rat liver DNA-binding protein which can act as a transcription factor. Its N-terminal portion contains three distinct domains. The first domain (amino acids 1 to 107) appears to be a highly potent transactivator. The second domain (amino acids 107 to 170) does not appear to exhibit either activation or repression activity. This domain is defined as an "attenuator domain" because its presence under four different sequence contexts reproducibly decreases the effect of transactivation of C/EBP. The third domain (amino acids 171 to 245) is a relatively weaker transactivator with a striking proline-rich motif. Deletional analysis of this third domain has shown that a 45-amino-acid region is sufficient for transactivation. This region (amino acids 171 to 215) contains 12 proline, 6 histidine, and mainly hydrophobic or noncharged amino acids. Further mutational analysis of a highly conserved proline-octamer region within this domain indicates that a specific proline content is not crucial for transactivation.


[Clinical results of needle Dao for the treatment of subacromial impingement syndrome].
To study the clinical results of needle Dao for the treatment of subacromial impingement syndrome. From September 2013 to August 2014, 90 patients with subacromial impingement syndrome were treated, including 61 females and 29 males, with the average age of (55.21±8.30) years old(ranged, 45 to 65 years old), and mean course of disease (3.49±2.98) months (ranged, 4 weeks to 7 months). Twenty-six patients had pains in left shoulder, and 64 patients had pains in right shoulder. Under local anesthesia, needle Dao was performed to release the pain point at the lower edge of the acromion and the subacromial adhesion. By observing the abduction of shoulder joint, anterior flexion and lifting, internal rotation and external rotation, shoulder pain score, the number of cases cured, markedly effective, effective and ineffective after treatment were counted, and the curative effect of needle Dao for the treatment of subacromial impingement syndrome was evaluated. All the patients completed the treatment successfully without obvious adverse reactions. All the patients were followed up for more than 12 months. The visual analogue scale(VAS) decreased from preoperative 7.72±5.42 to postoperative 1.35±0.78(t=15.89, P<0.01). The Constant score at the 12th month after operation increased from preoperative 58.89±15.63 to 83.17±19.11(t=28.48, P<0.01). Overall efficacy evaluation was that, 46 cases were cured, 33 cases were markedly effective, 11 cases were effective, and 0 cases were invalid. The advantage of needle Dao in the treatment of subacromial impingement syndrome is the minimally invasive treatment of the underlying lesions. The disadvantage is that it can not deal with the impact caused by bone abnormalities.


Production of docosahexaenoic acid (DHA) enriched bacon.
North American consumers interested in improving their health through diet perceive red meat as a source of too much saturated and unhealthy fat in the diet. The purpose of this trial was to produce bacon enriched with the long-chain omega-3 fatty acid, docosahexaenoic acid (DHA). In this 25 day study, pigs were fed a standard finisher diet of canola, pea, corn, and barley, mixed with DHA, added in the form of alga biomass. Bacon content of DHA was increased to 97 mg/100 g when 1 g of DHA was added to a kilogram of feed. The pigs fed the highest diet level of alga biomass, containing 0.29% DHA, produced bacon with approximately 3.4 mg of DHA/g and 1.2% of the fat as omega-3 fatty acids. Feed to gain was significantly improved, and carcass quality was unaffected. However, problems of off-odors and off-flavors were reported in the bacon from the taste panel survey. Polyunsaturated fat and potential unsaturated fat oxidation as indicated by malonaldehyde levels were significantly higher in the pigs fed the higher concentrations of DHA.


Effect of feeding system and grain source on lactation characteristics and milk components in dairy cattle.
The objective of this study was to examine the effect of feeding systems [component and total mixed rations (TMR)] and dietary grain sources (barley, commercial concentrate, corn grain, and high-moisture corn) on lactation characteristics and milk composition. A total of 852,242 test-day records, information on animal characteristics, feed composition, and feeding systems from 104,129 Holstein cows in 4,319 herds covering a period of 5 yr were obtained from Quebec's Dairy Herd Improvement Association (Valacta). We performed descriptive statistics and graphical representations of the data for each type of feeding system and grain source by parity (1 to 3). The milk records were binned in 15-d in milk blocks. Mixed models using a combination of forward and backward stepwise selections were developed to predict milk and milk component yields. The TMR-fed cows had greater yield of milk, fat, protein, and lactose and lower milk urea N (MUN) concentration than component-fed cows at all parities. Cows fed a TMR had higher peak milk yields and greater persistency after peak lactation compared with component-fed cows. In addition, greater yields of milk fat and protein from peak to mid-lactation were found in TMR- versus component-fed cows. In general, greater milk fat and protein yields as well as lower MUN concentration were observed in cows fed corn grain or high-moisture corn compared with barley or commercial concentrate, but parity influenced these relationships. The feeding system by day in milk blocks interaction was significant in models of milk and components yields for all parities, but only for second-lactation cows for MUN concentration. This means that effect of TMR and component feeding differs with stage of lactation. In conclusion, feeding TMR and corn-based diets are associated with greater yield of milk and milk components under commercial conditions.


Specific immunoglobulin E in patients with immediate persulfate hypersensitivity.
Persulfate salts may cause contact urticaria, allergic and irritant contact dermatitis, rhinitis and asthma. The mechanism of the immediate reactions has been unclear. Positive prick test, skin application and nasal and bronchial provocations identify immediate allergy. There is only 1 previous report of specific binding of immunoglobulin E (IgE) to ammonium persulfate demonstrated by radioallergosorbent test (RAST). In the present study, fresh 2% ammonium and potassium persulfate solutions were used for prick testing. Patients with positive prick tests were further evaluated with open skin application, immunospot and RAST. Prick testing with persulfate salts was performed in a total of 138 patients. 7 patients had a positive reaction to at least 1 persulfate salt. 6 of the patients had had skin symptoms, urticaria, eczema or angioedema, because of contact with hair bleaches. Open application on healthy skin was performed in 4 patients, and 3 out of them had urticarial reactions. The sera of 5 patients were investigated with immunospot and RAST. On immunospot, specific binding of IgE to human serum albumin (HSA)-conjugated ammonium and potassium persulfate was found in 2 patients. 1 immunospot-positive patient also had a positive RAST to ammonium persulfate-HSA conjugate. The mechanism of immediate hypersensitivity to persulfates thus seems to be IgE-mediated at least in some patients.


Plasma Free Hemoglobin Generation Using the EOS PMP™ Oxygenator and the CentriMag® Blood Pump.
Hemolysis is a known consequence of extracorporeal membrane oxygenation (ECMO) resulting from shear force within the different components of the extracorporeal circuit. The primary aim of this study was to evaluate the EOS PMP™ oxygenator for generation of plasma free hemoglobin (PfHg) over 24 hours at nominal operating range flow rates. The EOS ECMO™ (LivaNova, Inc.; formerly Sorin, Arvada, CO) is equipped with a plasma tight polymethylpentene (PMP) hollow fiber oxygenator. We hypothesized that PfHg generation would be elevated in circuits with higher flow rates, because of the significant pressure drop across the oxygenator according to manufacturer provided flow charts. Generated PfHg concentrations were compared with PfHg concentrations from blood not exposed to an ECMO circuit. The secondary aim was to evaluate circuit flow-rate-induced changes in platelet count and platelet function over 24 hours. Circuits contained a CentriMag® (St. Jude Medical, St. Paul, MN) blood pump and an EOS ECMO PMP™ oxygenator. Circuits in triplicate were run continuously for 24 hours at three flow rates [1, 3, and 5 liters per minute {LPM}]. PfHg was analyzed at baseline, 6, 12, 18, and 24 hours. Platelet count and function were measured at baseline and 24 hours. Concentrations of PfHg at baseline for circuits operating at 1, 3, and 5 LPM were 24.4 ± 4.0, 38.4 ± 28.6, and 26.7 ± 6.9 mg/dL, respectively. PfHg concentrations after 24 hours were statistically compared for the three flow rates using analysis of variance; PfHg concentrations at 1 LPM (181.4 ± 29.1 mg/dL), 3 LPM (145.9 ± 8.7 mg/dL), and 5 LPM (100.1 ± 111.3 mg/dL) circuits. The F-test was not statistically significant (p = .632), indicating that PfHg generation at 24 hours was similar among the three flow rates. Excessive hemolysis using PfHg levels in the EOS PMP™ membrane oxygenator was not observed.


Vascularized Pedicled Fibula for Pediatric Tibia Reconstruction.
This video reviews the technique of a vascularized fibula flap for pediatric tibia reconstruction. A 4-year-old boy with a history of a left tibial infected nonunion status after multiple debridements presented with segmental bone loss and difficulty with ambulation. An ipsilateral vascularized fibula flap was used for reconstruction. The patient proceeded to union and was independently ambulatory with bracing.


Lofepramine--a safe anti-depressant in acute hepatic porphyria?
The acute porphyrias are a group of neuropsychiatric disorders in which a life-threatening crisis can be precipitated by a variety of drugs, including antidepressants. Because of the need to find an antidepressant that is safe for porphyria patients, we have studied the effects of lofepramine on porphyria in laboratory rats and porphyria patients. The rats did not exhibit a significant rise in hepatic δ-aminolaevulinic acid synthase activity (a marker of drug porphyrinogenicity) when given the drug compared with its solvent alone. Four porphyria patients exhibited no clinical evidence of disease activation after exposure to the drug. The biochemical activity of their disease was assessed by measurement of the 24-h urinary excretion of δ- aminolaevulinic acid and porphobilinogen (haem precursors formed prior to the metabolic block). No patient exhibited a sustained rise compared to pre-treatment levels, or between low dose and high dose lofepramine. We suggest that lofepramine is probably safe in acute porphyria, but should be used with caution.


[Copper treatment alters the barrier functions of human intestinal Caco-2 cells].
To investigate the effects of copper on permeability and P-glycoprotein (P-gp) of Caco-2 cell monolayers. The differentiated Caco-2 cell model was used in this study. Permeability of cell monolayers was reflected by monitoring transepithelial electrical resistance (TEER); distribution of tight junctional protein ZO-1 was measured by immunofluorescent staining; F actin was measured by fluorescence staining; and Activity of P-gp was reflected by changes of transcellular transport and accumulation of Rho-123 in Caco-2 cells. Apical treatment with copper (30 - 100 micromol/L, Hanks' buffered salt solution, up to 3 hours) induced a time- and concentration-dependent increase in permeability reflected by progressive decrease of TEER of Caco-2 cell monolayers, accompanied by deorganization of F actin, but without significant effects on tight junctional protein ZO-1; at a dose without any adverse effects on viability and permeability of Caco-2 monolayers, copper treatment (300 micromol/L, complete medium, 24 hours) decreased Papp(BL-->AP) from 7.37 +/- 0.20 x 10(-6) cm/s (controls) to (6.43 +/- 0.27) x 10(-6) cm/s, the increased Papp(AP-->BL) from (1.23 +/- 0.05) x 10(-7) cm/s (controls) to (3.41 +/- 0.08) x 10(-7) cm/s, and enhanced the intracellular Rho-123 from (0.31 +/- 0.01) nmol/filter (controls) to (0.50 +/- 0.03) nmol/filter. Copper might alter the barrier functions of Caco-2 cells through increasing the permeability and inhibiting P-gp of Caco-2 cells.


Effect of SiC Abrasive Blasting Parameters on the Quality of the Ceramic and Ni-Cr Dental Alloy Joint.
The SiC abrasive blasting parameters are vital in ensuring a suitable bond between dental ceramics and the Ni-Cr alloy. The purpose of this in vitro test was to examine the strength of the joint between the Ni-Cr alloy and fused dental ceramics for SiC abrasive blasting at a specific pressure (400, 600 kPa) and particle size (50, 110, 250 µm) in order to determine the optimal treatment parameters. The test also accounted for thermal loads (5000 cycles, 5-55 °C) to which the metal-ceramic joint is subjected during use. One hundred and forty-four Ni-Cr cylinders were divided into six groups (n = 12) and subjected to the airborne-particle abrasion with SiC with various pressure and grit size parameters. After treatment, the specimens were rinsed, dried, fused to dental ceramics, and examined for their shear strength using the Zwick/Roell Z020 machine. The results were statistically analysed using the ANOVA analysis of variance (α = 0.05). The highest metal-ceramic joint strength was obtained for abrasive blasting with 110 and 250 µm SiC grit at a pressure of 400 kPa. This relationship was also observed after the joint was subjected to thermal loads (5000 thermocycles). Additionally, thermal loads did not significantly reduce the joint's strength compared with non-loaded joints. For small SiC abrasive grit sizes (50 µm) under pressure 400 kPa, the treatment pressure had a significant effect on the strength of the joint (p < 0.05). For larger particle sizes, the pressure had no effect. After abrasive blasting using SiC, the Ni-Cr metal-ceramic joint retained its properties, even under thermal load, ensuring the joint properties' stability during use.


[Comparison between the results of ICSI with fresh and with frozen-thawed sperm obtained by PESA to treat azoospermia].
Retrospective study of the results of ICSI (intracytoplasmic sperm insemination) with frozen sperm obtained by PESA (percutaneous epididymal sperm aspiration) was performed in 27 patients. With conventional freezing method, sperm from diagnosing PESA and the remaining motile sperm after treating cycle were frozen. After frozen-thawed and ICSI process, fertilization rate, implantation rate, clinical pregnancy rate were compared and other outcomes including pregnant combinations and parameters of newborns of experimental group (which used frozen-thawed sperm) and control group (which used fresh PESA sperm) were analyzed respectively. One hundred and sixty three and 1 157 oocytes of stage M II were injected respectively in the experimental group (15 cycles) and control group (100 cycles), and fertilization rate of experimental group was prominently higher than that of control group (84.05% vs 73.29%, P < 0.05), while implantation rate and clinical pregnancy rate were of no difference from the control, respectively (23.07% vs 15.73%; 53.33% vs 37.00%, P > 0.05). The differences in newborn's weights between two groups were of no statistical significance (P > 0.05). In the experimental group, eight clinical pregnancies were achieved including 5 live deliveries and 3 ongoing pregnancies, 37 clinical pregnancies including 30 deliveries with only 1 fetal death, 3 ongoing pregnancies and 4 abortions in the control group. Neither vital pregnant combinations nor neonate malformations were found in both groups. ICSI using frozen-thawed sperm obtained by PESA is an economic effective and safe method to treat azoospermia. Recovering rates of frozen sperm form PESA should be further increased.


Outcome of Latissimus Dorsi Flap Chest Wall Reconstruction In Rajavithi Hospital.
Latissimus Dorsi flap (LD flap) has been used since the eighteenth century to cover large chest wall defects after total mastectomy and is thought to be superior to split thickness skin graft in terms of both cosmetic results and functionality. The outcomes and complications resulting from the use of LD flap reconstruction for large breast cancer are not well documented in Thailand. To describe a technique using the Latissimus Dorsi musculocutaneous flap for breast reconstruction. The outcomes, complications and length of stay after operation were also reported. Between 2009 and 2014, fifty-five patients with large breast cancer with skin involvement were selected. Of these, forty-four cases had modified radical mastectomy (MRM) alone, and eleven cases underwent total mastectomy with immediate LD flap chest wall reconstruction. The age of the patients ranged from 33 to 81 years. The flaprelated complications and donor site morbidity were evaluated. This retrospective study was reviewed and approved by the ethics committee, Rajavithi Hospital. The eleven patients with LD flap for breast reconstruction had a mean age of 53.82±14.50 years (range 33 to 81). All tumors were T4 lesions, and the mean tumor size was 15 cm. Average body mass index (BMI) was 23.83±4.18 kg/m2, hematocrit (Hct) was 34.90±4.06% and albumin (Alb) was 3.68±1.03 mg/dl. Three patients had diabetes mellitus and two had hypertension. Six of these LD flap patients had the following postoperative complications: wound infections (36.36%); wound dehiscence (27.27%); seroma (18.18%); and partial flap loss (27.27%). No patient had total flap loss. Mean drainage durations of chest and axillary were 7.73 day and 8.09 days respectively, and mean length of hospital stay (LOS) was 20.00±16.72 days. The median tumor size in the LD flap group was significantly bigger than that of the MRM group (15 vs. 3.6 cm, p<0.001). There were no significant differences between MRM and LD flap in terms of gender, age, marital status, BMI, Hct, Albor underlying diseases. LD flap is a safe option for autologous breast reconstruction, although donor-site complications are often observed. A larger series to investigate the results and adverse effects of this procedure is needed.


An empirical analysis: Did green supply chain management alleviate the effects of COVID-19?
Supply chain management played a central role during the COVID-19 crisis, as the outbreak of the pandemic disrupted the majority of all global supply chains. This paper tests whether companies that use green supply chain management (GSCM) practices benefited from a buffer effect in the context of COVID-19. Our empirical analysis, conducted on a sample of U.S. companies, shows that GSCM companies experienced less negative abnormal stock returns during the crisis. This result contributes to the literature on financial impact of GSCM, finding that GSCM is perceived as an effective risk management tool and can serve as an effective drug against COVID-19 crisis. Our paper also contributes to the business debate on the role of green supply chains in the post-COVID19 world.


Behavioral Tracking and Neuromast Imaging of Mexican Cavefish.
Cave-dwelling animals have evolved a series of morphological and behavioral traits to adapt to their perpetually dark and food-sparse environments. Among these traits, foraging behavior is one of the useful windows into functional advantages of behavioral trait evolution. Presented herein are updated methods for analyzing vibration attraction behavior (VAB: an adaptive foraging behavior) and imaging of associated mechanosensors of cave-adapted tetra, Astyanax mexicanus. In addition, methods are presented for high-throughput tracking of a series of additional cavefish behaviors including hyperactivity and sleep-loss. Cavefish also show asociality, repetitive behavior and higher anxiety. Therefore, cavefish serve as an animal model for evolved behaviors. These methods use free-software and custom-made scripts that can be applied to other types of behavior. These methods provide practical and cost-effective alternatives to commercially available tracking software.


Application of sonodynamic technology and sonosensitizers in food sterilization: a review of developments, trends and challenges.
Food safety and food waste have always been hot topics of discussion in recent years. However, the infection of human pathogenic bacteria and the waste of food resources caused by microbial-contaminated food remains common. Although traditional sterilization technology has been very mature, it causes changes in food flavor and excessive energy consumption to a certain extent. Moreover, the widespread bacterial resistance has also sounded a warning for researchers and finding a new alternative to antibiotics is urgently needed. The application of sonodynamic sterilization technology in medical treatment has aroused the interest of researchers. It provides ideas for new food sterilization technology. As a new non-thermal sterilization technology, sonodynamic sterilization technology has strong penetration, safety, less residue and by-products, and will less change the quality of the food itself. Therefore, sonodynamic sterilization technology has great potential applied in food sterilization technology. This review describes the concept of sonodynamic sterilization technology, the sterilization mechanism of sonodynamic sterilization and the inactivation mechanism of various pathogens, the classification and application of sonosensitizers, and the ultrasonic technology in sonodynamic sterilization in the application over the recent years. It provides a scientific reference for the application of sonodynamic sterilization technology in the field of food sterilization.


Exploration of Aboriginal and Torres Strait Islander perspectives of Home Medicines Review.
In Australia, Home Medicines Review (HMR) has been found to be an important tool to raise awareness of medication safety, reduce adverse events and improve medication adherence. Aboriginal and Torres Strait Islander people are 'underserviced' by the HMR program and are the most likely of all Australians to miss out on HMRs despite their high burden of chronic disease and high rates of hospitalisation due to medication misadventure. The goal of this study was to explore Aboriginal and Torres Strait Islander perspectives of the Home Medicines Review program and their suggestions for an 'improved' or more readily accessible model of service. Eighteen semi-structured focus groups were conducted with 102 Aboriginal and Torres Strait Islander patients at 11 Aboriginal Health Services (AHSs). Participants who were multiple medication users and understood English were recruited to the study by AHS staff. Seven focus groups were conducted for people who had already used the HMR program (User, n=23) and 11 focus groups were conducted for people who had not had an HMR (Non User, n=79). Focus groups were recorded, de-identified and transcribed. Transcripts were coded and analysed for themes. Focus groups continued and concepts were explored until no new findings were being generated and thus saturation of data occurred. Focus group participants who had not had an HMR had little or no awareness of the HMR program. All the participants felt that lack of awareness and promotion of the HMR program were contributing factors to the low uptake of the HMR program by Aboriginal and Torres Strait Islander people. Most participants felt that an HMR would assist them to better understand their medicines, would empower them to seek information about medicines, would improve relationships with health professionals and would increase the likelihood of medication adherence. Most of the User participants reported that the HMR interview had been very useful for learning more about their medicines. However, many reported that they found the process confusing and confronting. The majority of participants felt HMRs for Aboriginal and Torres Strait Islander patients should be organised by AHS staff, with patients being offered a choice of location for the HMR interview. Participants identified that Aboriginal Health Workers should play a key role in communication, knowledge translation, referral and follow-up. Current HMR rules impede rather than facilitate HMRs for Aboriginal and Torres Strait Islander people. Tailoring and remodelling of the HMR program is needed to increase the awareness, accessibility, acceptability and effectiveness of the HMR program for Aboriginal and Torres Strait Islander people.


Case Report: Invasive Fungal Infection and Daratumumab: A Case Series and Review of Literature.
Life expectancy of multiple myeloma (MM) patients has improved in last years due to the advent of anti-CD38 monoclonal antibodies in combination with immunomodulators and proteasome inhibitors. However, morbidity and mortality related to infections remain high and represent a major concern. This paper describes the "real life" risk of invasive fungal infections (IFI) in patients treated with daratumumab-based therapy and reviews the relevant literature. In a series of 75 patients we only observed three cases of fungal pneumonia. Unfortunately, the early signs and symptoms were not specific for fungal infection. Diagnostic imaging, microbiology and patient history, especially previous therapies, are critical in the decision to start antifungal treatment. Recognising the subgroup of MM patients with high risk of IFI can increase the rate of diagnosis, adequate treatment and MM-treatment recovery.


The effect of programme testimonials on registrations for an online cognitive behaviour therapy intervention: a randomised trial.
Suboptimal visit-to-registration rates limit the reach and potential impact of online health interventions. In this study, we examined whether testimonials presented during a new-user registration process could increase the uptake rates of MoodGYM, an open-access automated intervention designed to reduce the symptoms of depression. We conducted a three-armed parallel randomised controlled trial on the MoodGYM website involving variations of the first page of the registration process. Spontaneous visitors saw either the current pre-registration content, the current content supplemented by a first-person past user testimonial or the current content accompanied by a testimonial from a third-party health professional. The primary outcome measure was the proportion of visitors seeing each version who completed registration. A total of 14,267 visits were recorded across the three conditions. The past user, health professional and control condition registration rates were 45.6%, 45.5% and 45.5% respectively, indicating that there was no effect of registration content on registration rate. (p > 0.05). There may be limited use for testimonials in well-established interventions that have programme benefits clearly stated and presented in other forms. However, we cannot exclude the possibility that testimonial effects might be moderated by positioning or other elements within the registration flow or by visitor source. Further research is required to examine these factors and, more broadly, assess whether modifications to other aspects of the registration process can improve visit-to-registration rates.


Yield of summer maize hybrids with different growth duration determined by light and temperature resource use efficiency from silking to physiological maturity stage.
In order to explore the physiological mechanism of different yield of summer maize (Zea mays L.) hybrids with different growth duration, a field experiment was conducted to study the growth stage, leaf photosynthetic characteristics, dry matter accumulation (DMA), transport and distribution characteristics and yield of the early maturity hybrid Denghai 518 (DH518) and the mid-late maturity hybrid Denghai 605 (DH605) from 2017 to 2021. The results showed that the yield of DH605 was significantly higher than that of DH518. The growth period of DH518 was 7-10 days shorter and the days of the growth stage of the sowing-silking stage (R1) were 5-6 days shorter compared to that of DH605. The contribution to grain dry matter by leaf and stalk dry matter remobilization (DMRC) of DH518 was significantly higher than that of DH605. There was a significant negative correlation between pre-silking growth days and harvest index (HI). The 13C distribution to grains of DH518 was significantly higher than that of DH605, and the HI and the corresponding contribution of HI to yield was also higher than that of DH605. The light and temperature resource use efficiency from silking to physiological maturity stage of DH605 was significantly higher than that of DH518. The yield per GDD of DH605 increased by 7.25% than that of DH518. At post-silking, the duration of higher leaf area index (DLAI) (>56 days) and active photosynthesis duration (APD) (>50 days) of DH605 were longer compared with that of DH518, and the average plant growth rate was 7.15% higher than that of DH518, which significantly increased the DMA of DH605. Therefore, the significant reduction of DH518 yield compared with DH605 was not due to the shortening of the growth stage of sowing-R1, but the lower light and temperature resource use efficiency from silking to physiological maturity stage.


Treatment of pediatric vascular injuries: the experience of a single non-pediatric referral center.
Pediatric peripheral vascular trauma carries significant risk of complications including limb loss and long-term invalidity. Mechanisms and types of morphological lesions are very diverse. The objectives of this study are to present the experience of a single vascular center in the surgical approach to pediatric vascular injuries, and to analyze the main challenges related to this clinical entity. Over a period of 25 years, 17 pediatric peripheral vascular injuries were treated in our institution. Patient's age ranged between one day (newborn) and 15 years (mean: 10.7 years). There were five injuries of upper and 12 injuries of the lower extremity. Preoperative diagnosis was established by clinical examination (N.=4), ultrasonography (N.=1) and angiography (N.=12). Blunt trauma mainly caused arterial thrombosis while penetrating trauma caused arterial laceration or complete transection. Five patients had associated orthopedic injuries (29,4%). There were two posttraumatic pseudoaneurysms and two arterio-venous fistulas. There was no perioperative mortality. Vascular reconstructions included arterial suture (N.=4), thrombectomy + patch angioplasty (N.=1), termino-terminal anastomosis (N.=3), venous anatomic bypass (N.=6), PTFE graft reconstruction (N.=2), and venous extra-anatomic reconstruction (N.=1). Two patients had associated venous injury demanding both arterial and venous reconstruction. In the only case of war trauma treatment ended with limb loss. Other reconstructions presented good early and long-term patency. Pediatric vascular injuries are extremely challenging issues. Treatment includes broad spectrum of different types of vascular reconstructions. It should be performed by vascular surgeon trained in open vascular treatment or pediatric surgeon with significant experience in vascular surgery.


The SOCE Machinery: An Unbalanced Knowledge between Left and Right Ventricular Pathophysiology.
Right ventricular failure (RVF) is the most important prognostic factor for morbidity and mortality in pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) caused by left heart diseases. However, right ventricle (RV) remodeling is understudied and not targeted by specific therapies. This can be partly explained by the lack of basic knowledge of RV remodeling. Since the physiology and hemodynamic function of the RV differ from those of the left ventricle (LV), the mechanisms of LV dysfunction cannot be generalized to that of the RV, albeit a knowledge of these being helpful to understanding RV remodeling and dysfunction. Store-operated Ca2+ entry (SOCE) has recently emerged to participate in the LV cardiomyocyte Ca2+ homeostasis and as a critical player in Ca2+ mishandling in a pathological context. In this paper, we highlight the current knowledge on the SOCE contribution to the LV and RV dysfunctions, as SOCE molecules are present in both compartments. he relative lack of studies on RV dysfunction indicates the necessity of further investigations, a significant challenge over the coming years.


Needling revision of failed filtering blebs after trabeculectomy: a retrospective study.
To determine the efficacy and safety of needling revision of failed filtering blebs. We reviewed retrospectively 26 eyes that had undergone needling revision for a failed trabeculectomy. The needling revisions were performed either with adjunctive use of Mitomycin C, 5-Fluorouracil or without antimetabolites. The procedure was usually performed as a clinic procedure, using a 27-gauge needle. The mean follow-up time was 14.5 +/- 11.3 months (range 6.0-48.0 months). Intraocular pressure (IOP) decreased from 28.8 +/- 6.8 mmHg (range 19.0-40.0 mmHg) to 15.3 +/- 5.2 mmHg (range 7.0-35.0 mmHg). Twelve eyes (46.2%) achieved success, defined as IOP < or = 18 mmHg without medication; 11 eyes (42.3%) achieved qualified success, defined as IOP < or = 18 mmHg with antiglaucomatous medication, and three of 26 eyes (11.5%) were classified as failures. The success rate after the initial needling was 64% at 6 months and the same after 1 year and 2 years. The success rate after one or more needlings was 96% at 6 months and 77% at 1 year and 2 years. Complications developed in six of the 26 eyes (23.1%). These involved transient corneal epithelial defects in three eyes (11.5%), temporary conjunctival wound leak in two eyes (7.7%), and development of bullous keratopathy in one high risk eye (3.8%). Our results are comparable to the results of other studies. Needling revision appears to be a useful tool in the management of glaucoma.


Screening of LRP10 mutations in Parkinson's disease patients from Italy.
Parkinson's disease (PD) belongs to a family of neurodegenerative diseases characterized by alpha-synuclein accumulation in neurons, whose etiopathogenesis remains largely uncovered. Recently, LRP10 has been associated with PD, Parkinson's disease Dementia (PDD) and Dementia with Lewy Bodies (DLB) by linkage analysis and positional cloning in an Italian family with late-onset PD. After the first characterization of a LRP10 pathogenic variant, other eight mutations have been detected in an international series of 660 probands with either a clinical or pathological diagnosis of PD, PDD or DLB. However, the results of following replication studies were inconclusive and the pathogenic role of LRP10 is still debated. The aim of this study is to sequence the LRP10 gene in an Italian cohort of clinically-diagnosed PD patients and to compare the frequency of the identified variants with the ones found in a large cohort of Italian exomes. A cohort of 664 PD patients was analyzed by targeted Next Generation Sequencing approach. Identified LRP10 variants were subsequently confirmed by Sanger sequencing and searched for in an in-house database including 3596 Italian exomes. We identified three PD patients carrying a rare heterozygous, potentially pathogenic variant (p.R296C, p.R549Q, p.R661C). None of them was detected in 3596 Italian exomes. Two of them (p.R296C and p.R661C) have been previously reported in one sporadic PD and one definite Progressive supranuclear palsy patients respectively. All three carriers had late-onset PD responsive to levodopa, characterized by both motor and non-motor features, but no cognitive impairment. We report three rare possibly-pathogenic LRP10 variants in PD patients from Italy. Further investigations are required to definitively establish their role in alpha-synucleinopathies.


Once daily bioadhesive vaginal clotrimazole tablets: design and evaluation.
In this study, a bioadhesive dosage form of clotrimazole was designed using a combination of bioadhesive polymers Carbopol 934P, sodium carboxymethyl cellulose and sodium alginate in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablets from porcine vaginal mucosal membrane. The strong interaction between polymer and mucus lining of the tissue helps increase the contact time and permits localization of activity. Carbopol 934P showed maximum bioadhesion and required maximum force for detachment; the force required for detachment was directly proportional to its content. The formulations were tested for their swelling behavior using the agar gel plate method. The swelling index was a function of the concentration of the hydrophilic polymer and the formulations containing Carbopol 934P and sodium carboxymethyl cellulose were found to swell to a greater extent than those containing Carbopol and sodium alginate. In vitro release studies showed that the batch consisting of 2:1 ratio of Carbopol 934P/sodium alginate (batch C3) released clotrimazole over 24 h. The similarity factor showed that the dissolution profiles of fresh and aged tablets were similar, suggesting good stability of vaginal tablets prepared using a combination of Carbopol 934P and sodium alginate.


Distribution of polysialylated neural cell adhesion molecule in rat septal nuclei and septohippocampal pathway: transient increase of polysialylated interneurons in the subtriangular septal zone during memory consolidation.
During memory consolidation neuroplastic events in the mediotemporal corticohippocampal pathway are accompanied by transient increases in the frequency of neurons expressing polysialylated neural cell adhesion molecule (NCAM PSA), a posttranslational modification associated with morphofunctional change. As a bidirectional pathway between the hippocampus and the septal nuclei also influences memory processing, we have determined the distribution of NCAM PSA within this system before and after learning in the adult Wistar rat. The most intense NCAM PSA immunoreactivity was observed in the medial and triangular septal nuclei, regions that regulate hippocampal theta rhythm during memory consolidation. Within the fimbria, NCAM PSA was expressed only in a subpopulation of fibres, most likely cholinergic projections from the medial septum to the hippocampus. Grey level analysis or direct cell counting revealed no learning-specific change in NCAM PSA expression in these septal subregions after avoidance conditioning or spatial training. A population of discrete polysialylated neurons in the subtriangular septal zone, however, exhibited a transient twofold frequency increase at 12 hr after training in either task. Immunohistochemical analysis revealed these cells to be gamma-aminobutyric acid (GABAergic) interneurons co-expressing vasoactive intestinal peptide. The unique location of these interneurons is proposed to provide a natural plexus by which bidirectional communication between the septum and hippocampus may be modified during memory consolidation.


Herpesvirus sylvilagus infects both B and T lymphocytes in vivo.
Herpesvirus sylvilagus infection of cottontail rabbits (Sylvilagus floridanus) was studied as a model of herpesvirus-induced lymphoproliferative disorders. Leukocytosis, splenomegaly, proliferation of T cells and virus production by lymphocytes characterized this infectious mononucleosis-like disease. Approximately two copies of circular herpesvirus sylvilagus genomes per cell were detected in spleen cells at 2 weeks postinfection, and circular genomes could still be observed after 4 months. Circular viral genomes were found in both B and T lymphocytes. Small amounts of linear viral DNA (0.1 to 0.3 copies per cell) were also detected in both B and T cells. These results indicated that the virus did not replicate in the majority of lymphocytes in vivo. Herpesvirus sylvilagus infection in cottontail rabbits could be useful as a model for studying the complex virus-host relationships of lymphotropic herpesviruses and perhaps as an animal model for Epstein-Barr virus infection in humans.


[Feeding, morbidity, and growth in infants born to a a group of primiparous mothers].
This study describes the feeding pattern, morbidity and the growth of an infant group from birth to six months old. A sample of 14 primiparous mother-infant dyads were selected in three public hospitals of Hermosillo, Sonora, Mexico. The design included the "study case" technique. The planned feeding pattern at 24 hours post-delivery was different from the one practiced at home. Frequency of mixed-feeding was higher in the first three months. Half of the participants weaned gradually before the recommended period, with high consumption of industrialized cereals and pap of natural fruits at the beginning. Incidence and prevalence of gastrointestinal disorders and respiratory illness were high since the first 15 days of life. The weight/length, weight/age and length/age values were within the 50th percentile of the NCHS standard (1977). In spite of the difference in the feeding and morbidity patterns among the infants, their growth patterns were considered normal.