Diminished benefit from resection of cancer of the head of the pancreas in patients of advanced age.
The incidence of pancreatic cancer is increasing, and an increasing proportion of these patients is older than 65 years. The benefits of resection in the geriatric population, in whom major comorbidity is more likely, are poorly defined. The authors sought to determine the relative benefits of resection of cancer of the head of the pancreas in different age groups, with particular emphasis on the geriatric population. Between 1983 and 1995, 273 patients presented to the University of Miami for evaluation of noncystic epithelial cancer of the head of the pancreas. Resection was performed in 104 patients, and these patients are the subject of this retrospective review. Mean length of follow-up for surviving patients was 37 +/- 24 months. Outcomes were compared in patients < 65 years old (group 1, n = 38), 65-74 years old (group 2, n = 47), and > 74 years old (group 3, n = 19). Total pancreatectomy was performed in 12 patients and pancreaticoduodenectomy was performed in 92 patients. The overall complication rate was similar in all groups, but major morbidity was highest in group 3 (P = 0.05). Median survival for patients in group 2 was 25.1 months. Survival was significantly shorter in patients from groups 1 and 3 (median survivals 12.4 months and 11.4 months, respectively; P = 0.02). Following control for Hispanic ethnicity, which was also a significant prognostic factor on univariate analysis, only the oldest age group had a significantly shorter survival than the other two groups. Age > 74 years and Hispanic ethnicity remained significant after multivariate analysis. Long-term survival after resection is truncated in older patients. This finding and the observation that the major complication rate is higher in the older subgroup emphasize the need to evaluate critically whether older patients should be submitted to radical resection.


The Impact of Monosodium Glutamate on 68Ga-PSMA-11 Biodistribution in Men with Prostate Cancer: A Prospective Randomized, Controlled Imaging Study.
The prostate-specific membrane antigen (PSMA) has been targeted for PET imaging and radioligand therapy (RLT) in patients with prostate cancer. Xerostomia is a common side effect of RLT because of the high salivary gland uptake of PSMA radioligands. Here, we aimed to determine the impact of monosodium glutamate (MSG) administration on PSMA-radioligand biodistribution within healthy organs and tumor lesions by using 68Ga-PSMA-11 PET imaging. Methods: Sixteen men with prostate cancer were randomized (1:1) into oral ingestion and oral topical application ("swishing") arms. Each subject underwent 2 68Ga-PSMA-11 PET/CT scans within 14 d under baseline and MSG conditions. The salivary glands and whole-body tumor lesions were segmented using qPSMA software. We quantified tracer uptake via SUVmean and SUVmax and compared parameters within each patient. Results: For the oral ingestion arm, salivary gland SUVmean and SUVmax decreased on average from the control scan to the MSG scan by 45% ± 15% (P = 0.004) and 53% ± 11% (P < 0.001), respectively. Tumor lesion SUVmean and SUVmax also decreased by 38% (interquartile range, -67% to -33%) and -52% (interquartile range, -70% to -49%), respectively (P = 0.018). Swishing had no significant effect on 68Ga-PSMA-11 accumulation in normal organs or tumor lesions. Conclusion: Oral ingestion but not topical application of MSG reduced 68Ga-PSMA-11 uptake in salivary glands. Tumor uptake also declined; therefore, the clinical application of MSG is unlikely to be useful in the framework of RLT.


Establishing regiocontrol of disulfide bond isomers of alpha-conotoxin ImI via the synthesis of N-to-C cyclic analogs.
alpha-Conotoxins are multiple disulfide bond containing peptides that are isolated from venomous marine cone snails. They display remarkable selectivity for different subtypes of nicotinic acetylcholine receptors (nAChRs). While alpha-conotoxins display poor resistance to in vivo degradation by proteases, which limits their use as drug leads, N-to-C cyclization via an oligopeptide spacer unit has been previously shown to improve stability. However, the effect of N-to-C cyclization on the formation of the disulfide bond framework is not fully understood. Four N-to-C cyclic analogs of alpha-conotoxin ImI; cImI-A, cImI-betaA, cImI-AG, and cImI-AGG were synthesized to evaluate the effect of oligopeptide spacer length on disulfide bond selectivity and stability to proteolysis. Different ratios of disulfide bond isomers were obtained for each analog using a nonselective random disulfide bond forming strategy, which was dependent on the length of the spacer. To identify each isomer obtained using the random strategy, and to gain access to disulfide bond isomers otherwise unattainable using the random strategy, both the native (globular) and ribbon isomers were synthesized in good yield and purity using a selective orthogonal cysteine protecting group strategy. As such, a random oxidation strategy showed a clear preference for the ribbon isomer in cImI-A. The cyclic globular isomers showed a high resistance to enzymatic degradation compared to the ribbon isomers, with the cImI-A and cImI-AG globular isomers demonstrating the highest stability. These results suggest that cyclization can improve the biochemical stability of conotoxins with potential applications in the development of drugs.


Flow cytometry-detected changes in megaloblastic anemia secondary to cobalamin deficiency.
Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis. To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia. Were included patients attended at the Regional Hospital of Concepción with bone marrow samples sent for the study of cytopenia by flow cytometry whose final diagnosis was megaloblastic anemia. The immunophenotype was performed with CD45, CD34, CD117, HLA-DR, markers of neutrophil (CD13, CD11b, CD10, CD16) and/or erythroblast (CD105, CD71, CD36) maturation. From the flow cytometry laboratory database, 8 patients with megaloblastic anemia were identified, and myelodysplastic syndromes (n=9) and normal or reactive bone marrow (n=10) were used as controls. 44% were men, with a median age of 58 years. Megaloblastic anemia was associated with a higher proportion of size and complexity of erythroid and myeloid progenitors compared to lymphocytes compared to controls. The total percentage of erythroblasts and the proportion of CD34+ myeloid cells associated with erythroid lineage was higher in megaloblastic anemia, associated with a maturation arrest in the CD105+ precursor stage (69% vs 19% and 23%, p<0.001). The heterogeneity of CD36 and CD71 in megaloblastic anemia was similar to myelodysplastic syndromes. Megaloblastic anemia produces a heterogeneous involvement of hematopoiesis, characterized by a greater size and cellular complexity of precursors of the neutrophil and erythroid series and a maturation arrest of the erythroblasts.


Prognostic indicators of outcome for patients with skeletal metastases from carcinoma of the prostate.
The purpose of this study was to identify prognostic indicators of outcome at presentation to the orthopaedic surgeon, in patients with metastatic prostate cancer. Our aim was to use this information in a pragmatic, clinic-based approach so that surgical decision making could be optimized to benefit the patient in their remaining lifetime. A cohort analysis was undertaken of all patients with metastatic disease of the prostate who presented to a regional orthopaedic centre in the United Kingdom between 2003 and 2016. Biochemical data were collected in addition to disease and demographic data. These included: prostate-specific antigen (PSA) at orthopaedic presentation; haemoglobin (Hb); platelets (plt); alkaline phosphatase (ALP); albumin (Alb); and corrected calcium (CaC). Statistical analysis included Kaplan-Meier survival analysis, and a Cox proportional hazards model was fitted to the data. From the departmental database, 137 episodes were identified in 136 patients with a median age at presentation of 72 years (interquartile range (IQR) 66 to 78). Most patients had stage IV disease (n = 98, 72%), and most did not undergo surgical intervention. At one-year follow-up, 50% of patients had died. Biomarkers found to be independently associated with poor survival were: low Hb, low Alb, relatively low PSA (< 30 mmol/l), and a raised ALP. Patients who needed surgical intervention had a poorer survival rate than patients who were managed nonoperatively. The study findings are important for orthopaedic clinical practice in the management of patients with metastatic prostate cancer. The interpretation of routine blood tests can help to predict survival in patients who present with orthopaedic manifestations of prostate cancer. A lower PSA is not necessarily a good prognostic sign. We believe that simple blood testing should be carried out routinely when assessing a patient, guiding potential surgical management and palliative care in the future.


Literature based species occurrence data of birds of northeast India.
The northeast region of India is one of the world's most significant biodiversity hotspots. One of the richest bird areas in India, it is an important route for migratory birds and home to many endemic bird species. This paper describes a literature-based dataset of species occurrences of birds of northeast India. The occurrence records documented in the dataset are distributed across eleven states of India, viz.: Arunachal Pradesh, Assam, Bihar, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, Tripura, Uttar Pradesh and West Bengal. The geospatial scope of the dataset represents 24 to 29 degree North latitude and 78 to 94 degree East longitude, and it comprises over 2400 occurrence records. These records have been collated from scholarly literature published between1915 and 2008, especially from the Journal of the Bombay Natural History Society (JBNHS). The temporal scale of the dataset represents bird observations recorded between 1909 and 2007. The dataset has been developed by employing MS Excel. The key elements in the database are scientific name, taxonomic classification, temporal and geospatial details including geo-coordinate precision, data collector, basis of record and primary source of the data record. The temporal and geospatial quality of more than 50% of the data records has been enhanced retrospectively. Where possible, data records are annotated with geospatial coordinate precision to the nearest minute. This dataset is being constantly updated with the addition of new data records, and quality enhancement of documented occurrences. The dataset can be used in species distribution and niche modeling studies. It is planned to expand the scope of the dataset to collate bird species occurrences across the Indian peninsula.


Suppression of interleukin-1 beta-induced nitric oxide production in RINm5F cells by inhibition of glucose-6-phosphate dehydrogenase.
In rat pancreatic islets and insulin-producing cell lines, IL-1beta induces expression of inducible nitric oxide synthase and NO production leading to impairment of glucose-stimulated insulin release and decreased cell survival. NADPH is an obligatory cosubstrate for iNOS synthesis of NO. We hypothesized that IL-1beta stimulates an increase in activity of NADPH-producing enzyme(s) prior to NO production and that this increase is necessary for NO production. Using rat insulin-secreting RINm5F cells, we found that (1) IL-1beta caused a biphasic change in the NADPH level (increased by 6 h and decreased after prolonged incubation in the presence of 2 ng/mL IL-1beta); (2) IL-1beta stimulated increased activity of glucose-6-phosphate dehydrogenase (G6PD) in a time- and dose-dependent manner, and G6PD expression was increased by about 80% after exposure to 2 ng/mL IL-1beta for 18 h: (3) IL-1beta-stimulated NO production was positively correlated with increased G6PD activity; (4) IL-1beta did not cause any significant change in enzyme activity of another NADPH-producing enzyme, malic enzyme; (5) IL-1beta-induced NO production was significantly reduced either by inhibiting G6PD activity using an inhibitor of G6PD (dehydroepiandrosterone) or by inhibiting G6PD expression using an antisense oligonucleotide to G6PD mRNA; and (6) IL-1beta stimulated a decrease in the cAMP level. 8-Bromo-cAMP caused decreased G6PD activity, and the protein kinase A inhibitor H89 led to a increase in G6PD activity in RINm5F cells. In conclusion, our data show that IL-1beta stimulated G6PD activity and expression level, providing NADPH that is required by iNOS for NO production in RINm5F cells. Also, inhibition of the cAMP-dependent PKA signal pathway is involved in an IL-1beta-stimulated increase in G6PD activity.


[Posterior sternoclavicular dislocation: diagnosis initially easy to miss].
Posterior sternoclavicular (SC) dislocation is a rare diagnosis, which tends to be missed initially. Here we report two cases of a dislocated SC joint: one left and one right. The first case describes a 25-year-old male who sustained a direct injury caused by his seatbelt during a car accident. The diagnosis was made 3 months after the initial trauma following performance of a CT scan. His left SC joint was stabilized using a hamstring tendon allograft. The second patient, a 55-year-old female, sustained an indirect injury following a fall onto her right shoulder. The diagnosis was made 6 weeks after the trauma had occurred. Her SC joint was also stabilized using a tendon allograft reconstruction. The clinical outcome of both cases was very satisfactory. Better diagnostics - more attention for subtle symptoms during physical examination, the right choice of imaging (CT scan) and meticulous following of Advanced Trauma Life Support (ATLS) protocols - could diminish the number of delayed diagnoses in this rare but potentially dangerous injury.


Geospatial Analysis of Food Deserts and Their Impact on Health Outcomes in Children with Cystic Fibrosis.
Food insecurity (FI) is defined as "the limited or uncertain access to adequate food." One root cause of FI is living in a food desert. FI rates among people with cystic fibrosis (CF) are higher than the general United States (US) population. There is limited data on the association between food deserts and CF health outcomes. We conducted a retrospective review of people with CF under 18 years of age at a single pediatric CF center from January to December 2019 using demographic information and CF health parameters. Using a Geographic Information System, we conducted a spatial overlay analysis at the census tract level using the 2015 Food Access Research Atlas to assess the association between food deserts and CF health outcomes. We used multivariate logistic regression analysis and adjusted for clinical covariates and demographic covariates, using the Child Opportunity Index (COI) to calculate odds ratios (OR) with confidence intervals (CI) for each health outcome. People with CF living in food deserts and the surrounding regions had lower body mass index/weight-for-length (OR 3.18, 95% CI: 1.01, 9.40, p ≤ 0.05 (food desert); OR 4.41, 95% CI: 1.60, 12.14, p ≤ 0.05 (600 ft buffer zone); OR 2.83, 95% CI: 1.18, 6.76, p ≤ 0.05 (1200 ft buffer zone)). Food deserts and their surrounding regions impact pediatric CF outcomes independent of COI. Providers should routinely screen for FI and proximity to food deserts. Interventions are essential to increase access to healthy and affordable food.


Endoscopic third ventriculostomy in the management of Chiari I malformation and syringomyelia associated with hydrocephalus.
Chiari malformation with syringomyelia is conventionally managed with foramen magnum decompression and duroplasty. In presence of hydrocephalus, a ventriculoperitoneal shunt insertion has been the initial preferred mode of treatment. Two patients of Chiari I malformation with syringomyelia who had associated hydrocephalus were initially treated with endoscopic third ventriculostomy (ETV). At follow up, both the patients symptomatically improved. Repeat MRI studies revealed collapse of the syrinx cavity and reduction of the Chiari malformation. Chiari malformation and syrinx associated with hydrocephalus may be effectively managed with endoscopic third ventriculostomy.


Evaluation of the prognostic values of solute carrier (SLC) family 39 genes for patients with lung adenocarcinoma.
Lung cancer is the first fatality rate of cancer-related death worldwide. This study aimed to evaluate the solute carrier family 39 (SLC39A) genes as biological markers associated with the prognosis of lung adenocarcinoma (LUAD). MRNA expression of SLC39A genes in non-small cell lung cancer (NSCLC) was analyzed using UCSC database. We investigated the overall survival (OS) of SLC39A genes in patients with NSCLC as the only prognostic indicator using the Kaplan-Meier plotter. CERES score obtained from the Project Achilles was used to perform the survival analysis. Crystal violet-glutaraldehyde solution staining and CCK-8 assay were used to determine colony formation and cell viability, respectively. For patients with lung squamous cell carcinoma, only high expression of SLC39A3, SLC39A4 and SLC39A7 have significant affections to the prognosis. But for patients with LUAD, 11 out of 14 SLC39A genes were significantly associated with prognostic values. Additional analysis indicated that SLC39A7 played an essential role for cell survival of LUAD. Furthermore, SLC39A7 high expression in LUAD was associated with current smoking. Our findings indicated that SLC39A groups were significantly associated with prognosis of LUAD. The SLC39A7 gene was significantly linked with survival and growth of LUAD cells.


A never before reported variant of the sacrum.
Several important steps occur in order for the sacrum to develop properly. Embryological derailment can result in several different anatomical variants. Herein, we report, to our knowledge, the first case of a duplicated sacrum in the sagittal plane. Clinicians and radiologists should be aware of such a finding if found during imaging. We would hypothesize that such a variant occurred near the 29th day of development and probably arose from an error in the HOX gene. To our knowledge, this represents the first reported case.


Pediatric Cranioplasty Using Hydroxyapatite Cement: A Retrospective Review and Preliminary Computational Model.
Cranioplasty is a standard technique for skull defect repair. Restoration of cranial defects is imperative for brain protection and allowing for homeostasis of cerebral spinal fluid within the cranial vault. Calcium phosphate hydroxyapatite (HA) is a synthetic-organic material that is commonly used in cranioplasty. We evaluate a patient series undergoing HA cement cranioplasty with underlying bioresorbable mesh for various cranial defects and propose a preliminary computational model for understanding skull osteointegration. A retrospective review was performed at the institution for all pediatric patients who underwent HA cement cranioplasty. Seventeen patients were identified, and success of cranioplasty was determined based on clinical and radiographic follow-up. A preliminary computational model was developed using bone growth and scaffold decay equations from previously published literature. The model was dependent on defect size and shape. Patient data were used to optimize the computational model. Seventeen patients were identified with an average age of 6 ± 5.6 years. Average defect size was 11.7 ± 16.8 cm2. Average time to last follow-up computer tomography scan was 10 ± 6 months. Three patients had failure of cranioplasty, all with a defect size above 15 cm2. The computational model developed shows a constant decay rate of the scaffold, regardless of size or shape. The bone growth rate was dependent on the shape and number of edges within the defect. Thus, a star-shaped defect obtained a higher rate of growth than a circular defect because of faster growth rates at the edges. The computational simulations suggest that shape and size of defects may alter success of osteointegration. Pediatric cranioplasty is a necessary procedure for cranial defects with a relatively higher rate of failure than adults. Here, we use HA cement to perform the procedure while creating a preliminary computational model to understand osteointegration. Based on the findings, cranioplasty shape may alter the rate of integration and lead to higher success rates.


Treatment with one-alpha-hydroxycholecalciferol in middle-aged men with impaired glucose tolerance--a prospective randomized double-blind study.
Experimental evidence suggests a specific role for the active metabolite of vitamin D (1,25(OH)2D3) in insulin secretion. In order to evaluate the possible clinical significance, 65 middle-aged men with impaired glucose tolerance, and normal serum levels of vitamin D metabolites, were enrolled in a three-month study where they were given either 0.75 micrograms alpha-calcidol (1 alpha(OH)D3) daily or placebo. Indices of glucose and lipid metabolism were evaluated before and after treatment. There were no significant changes during the trial neither for fasting blood glucose, hemoglobin A1c or for the intravenous glucose tolerance between the treatment and the placebo groups, nor were there any consistent changes in insulin values during the glucose tolerance test. Subjects treated with alpha-calcidol displayed a significant reduction in body weight with an average of 1.1 kg, while those receiving placebo lost no weight. Treatment did not affect the serum lipoprotein values. Thus, a modest dose of active vitamin D, which did not cause elevation of serum calcium, did not provide general improvement of glucose tolerance or of insulin secretion when given to patients with impaired glucose tolerance, but without vitamin D deficiency, over a three-month period.


The Substrate Specificity of Sirtuins.
Sirtuins are NAD(+)-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early studies showed that sirtuins deacetylated lysines in a reaction that consumes NAD(+), more recent studies have revealed that these enzymes can remove a variety of acyl-lysine modifications. The specificities for varied acyl modifications may thus underlie the distinct roles of the different sirtuins within a given organism. This review summarizes the structure, chemistry, and substrate specificity of sirtuins with a focus on how different sirtuins recognize distinct substrates and thus carry out specific functions.


Effects of Acclimation to Diluted Seawater on Metabolic and Growth Parameters of Underyearling Masu Salmon (Oncorhynchus masou).
We examined the effects of environmental salinity and feeding status on the growth and metabolic parameters of underyearling masu salmon. Fish were first acclimated to salinities of 0 (< 0.1), 11, or 22 psu for 10 days, after which time 50% of the fish in each group were fasted for 5 days followed by refeeding for 5 days. No effects on body length/weight were observed over the 20 days from the beginning of the experiment. Gill Na+, K+-ATPase (NKA) activity increased 20 and 10 days after transfer to water at 11 and 22 psu, respectively. Serum Na+ and Cl- levels were high in fish at 22 psu on day 20 but much lower than those in the environmental water, suggesting that fish at this salinity were able to hypo-osmoregulate. However, acclimation to 22 psu resulted in a reduction in feeding rate on day 20. Serum insulin-like growth factor (IGF)-I levels and liver glycogen content were reduced by fasting and restored after 5 days of refeeding, except in the fish at 22 psu. Intensities of serum IGFBP-1a and -1b bands were increased at higher salinities, whereas fasting/refeeding affected only IGFBP-1b. The present study suggests that acclimating masu salmon parr to 11 psu had no effect on metabolic and growth parameters, while 22 psu presumably suppressed their growth potential due to the possible energy cost or stress for osmoregulation. The disparate responses of circulating IGFBP-1a and -1b to higher salinity and fasting highlight their utility as indices of various catabolic statuses.


Persistent hyperplastic tunica vasculosa lentis and persistent hyaloid artery in a 2-year-old basset hound.
A 2-year-old Basset hound with unilateral persistent hyperplastic tunica vasculosa lentis and primary vitreous is described. There was leukokoria in the left eye, caused by bluish-white polar densities and haemorrhagic discoloration in the nucleus of the lens. Ultrasonographic examination of the eye revealed a small hyperechoic lens and a hyperechoic linear soft-tissue strand extending from the posterior pole of the lens through the optic disc. Power Doppler imaging revealed blood flow in this persistent hyaloid artery, but 5 months later, immediately prior to surgery, there was no flow in this artery. Ultrasonography, including Power Doppler imaging, was useful to confirm the diagnosis and to estimate the complications of surgery, especially the risk of vitreal haemorrhage after cutting of the persistent hyaloid artery. Comparison of the ultrasonographic images with those obtained by computed tomography suggested that the resolution of computed tomography is inadequate for identifying structures as fine as a persistent hyaloid artery.


Coronary hemodynamic and ventricular responses to angiotensin type 1 receptor inhibition in SHR: interaction with angiotensin type 2 receptors.
This study was designed to determine the effects of angiotensin II type 1 (AT(1)) receptor inhibition on coronary hemodynamics and ventricular mass and hydroxyproline content and the additive effects of angiotensin II type 2 (AT(2)) receptor inhibition in spontaneously hypertensive rats (SHR). The selective AT(1) receptor antagonist candesartan (10 mg/kg per day) was administered alone or in combination with the AT(2) receptor antagonist PD 123319 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the same period. Left and right ventricular coronary blood flow, blood flow reserve, and minimal coronary vascular resistance were determined by using radiomicrospheres in male 35-week-old rats. Mean arterial pressure; total peripheral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of AT(1) receptor inhibition and reversed the effect on myocardial hydroxyproline concentration. These data suggest that AT(2) receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic improvement or reduced left ventricular mass of AT(1) receptor inhibition in these adult SHR.


Europium-Containing Mesoporous Bioactive Glass Scaffolds for Stimulating in Vitro and in Vivo Osteogenesis.
Bone tissue engineering offers a possible strategy for regenerating large bone defects, in which how to design beneficial scaffolds for accelerating bone formation remains significantly challenging. Europium, as an important rare earth element, has been used as a solid-state lighting material. However, there are few reports on whether Eu can be used for labeling bone tissue engineering scaffolds, and its biological effect on bone cells and bone tissue regeneration is unknown. In this study, we incorporated Eu into mesoporous bioactive glass (Eu-MBG) scaffolds by an in situ cotemplate method to achieve a bifunctional biomaterial with biolabeling and bone regeneration. The prepared Eu-MBG scaffolds have highly interconnective large pores (300-500 μm), a high specific surface area (140-290 m(2)/g), and well-ordered mesopores (5 nm) as well as uniformly distributed Eu. The incorporation of 2-5 mol % Eu into MBG scaffolds gives them a luminescent property. The in vitro degradation of Eu-MBG scaffolds has a functional effect on the change of the luminescence intensity. In addition, Eu-MBG can be used for labeling bone marrow stromal cells (BMSCs) in vitro and still presents a distinct luminescence signal in deep bone tissues in vivo to label new bone tissue via release of Eu ions. Furthermore, the incorporation of different contents of Eu (1, 2, and 5 mol %) into MBG scaffolds significantly enhances the osteogenic gene expression of BMSCs in the scaffolds. The Eu- and Si-containing ionic products released from Eu-MBG scaffolds distinctly promote the osteogenic differentiation of BMSCs. Critically sized femur defects in ovariectomized (OVX) rats are created to simulate an osteoporotic phenotype. The results show that Eu-MBG scaffolds significantly stimulate new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone and Eu may be involved in the acceleration of bone regeneration in OVX rats. Our study for the first time reports that the incorporation of the rare earth element Eu into bioscaffolds has the ability to accelerate bone regeneration in vivo, and thus, the prepared Eu-MBG scaffolds possess bifunctional properties with biolabeling and bone regeneration.


The Truth of Toxicity Caused by Yttrium Oxide Nanoparticles to Yeast Cells.
Yttrium oxide (Y₂O₃) nanoparticles have widespread applications; however, toxicity due to these nanoparticles has also been reported. In this study, we evaluated the in vitro toxicity of Y₂O₃ nanoparticles according to the technical specifications published by the International Standard Organization (ISO/TS 19337:2016). We used Saccharomyces cerevisiae as a model microorganism represented the environment. We carried out catch ball analysis of yttrium oxide and yttrium ion toxicities. The result showed that Y₂O₃ nanoparticles (20 mg/5 ml) and YCl₃ (5 mg/5 ml) treatment caused oxidative stress in yeast cells. Based on transcriptome analysis, fluorescent spectroscopy, and solubility analysis of Y₂O₃ nanoparticles, we conclude that the toxicity is due to yttrium ions derived from the nanoparticles. The ions induce oxidative stress and cause protein denaturation, which in turn induces proteasome formation to eliminate denatured proteins. Yttrium nanoparticles induce oxidative stress, which has associated with heavy metal ions. Thus, the use of yttrium nanoparticles or yttrium ions must be controlled like heavy metals.


Does Anteromedial Portal Drilling Improve Footprint Placement in Anterior Cruciate Ligament Reconstruction?
Considerable debate remains over which anterior cruciate ligament (ACL) reconstruction technique can best restore knee stability. Traditionally, femoral tunnel drilling has been done through a previously drilled tibial tunnel; however, potential nonanatomic tunnel placement can produce a vertical graft, which although it would restore sagittal stability, it would not control rotational stability. To address this, some suggest that the femoral tunnel be created independently of the tibial tunnel through the use of an anteromedial (AM) portal, but whether this results in a more anatomic footprint or in stability comparable to that of the intact contralateral knee still remains controversial. (1) Does the AM technique achieve footprints closer to anatomic than the transtibial (TT) technique? (2) Does the AM technique result in stability equivalent to that of the intact contralateral knee? (3) Are there differences in patient-reported outcomes between the two techniques? Twenty male patients who underwent a bone-patellar tendon-bone autograft were recruited for this study, 10 in the TT group and 10 in the AM group. Patients in each group were randomly selected from four surgeons at our institution with both groups demonstrating similar demographics. The type of procedure chosen for each patient was based on the preferred technique of the surgeon. Some surgeons exclusively used the TT technique, whereas other surgeons specifically used the AM technique. Surgeons had no input on which patients were chosen to participate in this study. Mean postoperative time was 13 ± 2.8 and 15 ± 3.2 months for the TT and AM groups, respectively. Patients were identified retrospectively as having either the TT or AM Technique from our institutional database. At followup, clinical outcome scores were gathered as well as the footprint placement and knee stability assessed. To assess the footprint placement and knee stability, three-dimensional surface models of the femur, tibia, and ACL were created from MRI scans. The femoral and tibial footprints of the ACL reconstruction as compared with the intact contralateral ACL were determined. In addition, the AP displacement and rotational displacement of the femur were determined. Lastly, as a secondary measurement of stability, KT-1000 measurements were obtained at the followup visit. An a priori sample size calculation indicated that with 2n = 20 patients, we could detect a difference of 1 mm with 80% power at p < 0.05. A Welch two-sample t-test (p < 0.05) was performed to determine differences in the footprint measurements, AP displacement, rotational displacement, and KT-1000 measurements between the TT and AM groups. We further used the confidence interval approach with 90% confidence intervals on the pairwise mean group differences using a Games-Howell post hoc test to assess equivalence between the TT and AM groups for the previously mentioned measures. The AM and TT techniques were the same in terms of footprint except in the distal-proximal location of the femur. The TT for the femoral footprint (DP%D) was 9% ± 6%, whereas the AM was -1% ± 13% (p = 0.04). The TT technique resulted in a more proximal footprint and therefore a more vertical graft compared with intact ACL. The AP displacement and rotation between groups were the same and clinical outcomes did not demonstrate a difference. Although the AM portal drilling may place the femoral footprint in a more anatomic position, clinical stability and outcomes may be similar as long as attempts are made at creating an anatomic position of the graft. Level III, therapeutic study.


Narrative in Exergames: Thoughts on Procedure, Mechanism, and Others.
Narratives are stories with a beginning, middle, and end that provide information about the characters and plot. Exergames are videogames that require players to move or exercise. Narratives and exergames have seldom been examined together. Based on my review of the literature, there are five potential opportunities narratives could bring to exergames: Enhanced engagement with characters and with the plot, increased motivation, repeated play sessions, and better behavioral consequence. However, the rewards offered by these possibilities may be offset by the challenges they pose. These challenges include the difficulty in fully integrating narratives into the gameplay, the players' limited information processing capacity, difficulty in measurement, the lack of full understanding of the player-character identification process, and the narrative saturation effects. Innovative research is needed to bridge the two potentially important domains.


Torsades de pointes induced by transesophageal atrial stimulation after administration of almokalant.
This case-report describes a patient who developed a torsades de pointes tachycardia after infusion of almokalant, a selective class III antiarrhythmic agent. The patient was studied with transesophageal atrial stimulation because of Wolff-Parkinson-White syndrome. After a base-line procedure during which an orthodromic tachycardia was induced and pace-terminated, almokalant was given intravenously. The corrected QT interval was markedly prolonged despite similar plasma concentration compared to the rest of the studied patients. During the continued pacing protocol several episodes of non-sustained ventricular tachycardia was observed after pacing induced pauses. A sustained orthodromic tachycardia with left bundle branch morphology was induced, and another almokalant infusion was given. At a plasma concentration of approximately 252 nmol/l the corrected QT interval was further prolonged to 680 ms and the patient developed a torsades de pointes tachycardia after a pacing induced pause. The tachycardia degenerated into ventricular fibrillation that required immediate defibrillation. One week later the patient underwent ablation of the accessory pathway. The QT interval was in the absence of preexcitation normal, and programmed electrical stimulation did not reveal any ventricular arrhythmias. Further studies will have to be performed to clarify whether an early and marked QT interval prolongation, such as observed in this patient, will be useful in identifying patients prone for proarrhythmias in relation to therapy with selective class III drugs.


Hemorheological parameters and aging.
There is increasing evidence that impaired hemorheological parameters are associated with increased risk of cardio- and cerebrovascular events. The aim of our present study was to examine the relationship of these parameters to the advancing age. The data of 6236 cardio- and cerebrovascular patients (3774 males, mean age 59.8 +/- 13.2 years and 2462 females, mean age 60.9 +/- 12.8 years) were included into this analysis. Males and females were divided into three groups, A < 45 years of age (young), B 45-65 years (middle-aged), C > 65 years (old). To exclude the effect of risk profile, previous diseases and medication, 623 patients (397 males, mean age 60.2 +/- 12.7 yrs and 226 females, mean age 60.5 +/- 12.4 yrs) were selected from the examined group with matching parameters. Blood was collected after an overnight fasting. Hematocrit, fibrinogen, red blood cell aggregation, plasma and whole blood viscosity were determined. All the measured parameters correlated significantly with advancing age in the whole population (p < 0.01), however the values of the correlation coefficients were very low. On the other hand, examining the different age-groups we found that these parameters did not consequently correlate with age, in fact hematocrit, red blood cell aggregation and whole blood viscosity values were negatively correlated with age in old males (p < 0.05). In the selected population these parameters did not correlate with advancing age. In the whole population the correlation of hemorheological parameters and advancing age may be just of statistical, but not clinical significance because of the high number of subjects. In the selected population these parameters did not correlate with advancing age. Our results suggest that these parameters are mostly independent of aging, increased values are not associated with older age but the more frequently occurring diseases.


Risk factors for medication non-adherence among psychiatric patients with substance misuse histories.
Medication non-adherence among psychiatric patients is known to be associated with poorer treatment outcomes. The study examined a comprehensive set of modifiable risk factors for non-adherence in a theoretical framework among a diverse, high risk sample of psychiatric patients with substance misuse histories (N=299). Medication side effects and excessive alcohol use were related to lower medication adherence and higher motivation for mental health treatment and recovery support were related to greater adherence. The results suggest that a multifaceted model for intervention to increase psychiatric medication adherence should be developed and tested.


Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient.
Evidence is accumulating in favour of a link between erectile dysfunction (ED) and coronary artery disease (CAD). This review attempts to identify which patients, among those with ED and no cardiovascular (CV) disease, should be screened for early, subclinical CAD, which coronary targets should be investigated, and which tests should be used. A comprehensive evaluation of available published data included analysis of published full-length papers that were identified with Medline and Cancerlit from January 1988 to January 2006. Initial screening of patients with ED may adopt risk assessment office-based approaches to score patients into low, intermediate, or high risk of future cardiovascular events. Attention should be drawn to patients at intermediate risk. Targets for the assessment of subclinical CAD in this subset of patients should include both obstructive (flow-limiting) and nonobstructive (non-flow-limiting) CAD. Some tests address obstructive atherosclerosis by directly assessing coronary flow reserve (i.e., standard exercise stress test, rest/stress myocardial scintigraphy or echocardiography). Other tests are general measures of atherosclerosis burden (not necessarily obstructive) either in the coronary circulation (i.e., coronary calcium score by electron-beam computed tomography), or in extracoronary vessels (i.e., ankle brachial index, carotid intima-media thickness by B-mode ultrasound) as surrogate markers of CAD. Although a systematic use of these measures of nonobstructive atherosclerosis burden has not yet been recommended in the guidelines for coronary risk assessment, their use is progressively being extended from the research area to clinical practice. ED is definitely a vascular disorder and all men with ED should be considered at risk of CV disease until proven otherwise. Available risk assessment charts should be used to stratify (low, intermediate, and high) the coronary risk score in each patient with ED.


Automated atlas-based clustering of white matter fiber tracts from DTMRI.
A new framework is presented for clustering fiber tracts into anatomically known bundles. This work is motivated by medical applications in which variation analysis of known bundles of fiber tracts in the human brain is desired. To include the anatomical knowledge in the clustering, we invoke an atlas of fiber tracts, labeled by the number of bundles of interest. In this work, we construct such an atlas and use it to cluster all fiber tracts in the white matter. To build the atlas, we start with a set of labeled ROIs specified by an expert and extract the fiber tracts initiating from each ROI. Affine registration is used to project the extracted fiber tracts of each subject to the atlas, whereas their B-spline representation is used to efficiently compare them to the fiber tracts in the atlas and assign cluster labels. Expert visual inspection of the result confirms that the proposed method is very promising and efficient in clustering of the known bundles of fiber tracts.


Expression of MHC Class II and B7-1 and B7-2 costimulatory molecules accompanies tumor rejection and reduces the metastatic potential of tumor cells.
Mouse tumor cells transfected with syngeneic MHC class II genes are highly immunogenic in the autologous host, and induce a potent tumor-specific immunity against wild type tumor. Previous studies with sarcoma tumor cells expressing transfected class II gene products with truncated cytoplasmic domains suggested that during the process of tumor rejection costimulatory molecules are induced on the tumor cells, contributing to the cells' ability to stimulate immunity. In the present study we directly demonstrate that tumor cells containing full-length class II heterodimers are induced to express B7-1 and B7-2 costimulatory molecules during the rejection process. In contrast, tumor cells expressing class II heterodimers truncated for their cytoplasmic tails are not induced to express B7-1 and/or B7-2. Blocking the interaction of the induced costimulatory molecules with their corresponding receptors on T cells prevents tumor rejection. These results support the hypothesis that the cytoplasmic domain of the MHC class II molecule is involved in induction of costimulatory molecule expression, perhaps via intracellular signalling pathways. Because class II, B7 transfected tumor cells are such effective immunogens against ascites and solid tumors, they have also been tested in metastatic disease. K1735 and B16BL6 mouse melanomas, when transfected with syngeneic MHC class II and B7-1 genes, are significantly less metastatic than parental cells, and immunization with the transfectants protects against subsequent challenge with wild type tumor.


Improvement of wastewater sludge dewatering using ferric chloride, aluminum sulfate, and calcium oxide (experimental investigation and descriptive statistical analysis).
In this research, application of chemical conditioners for the conditioning of sludge and their effects on the improvement of sludge thickening of the wastewater treatment plant in the city of Bojnourd (Iran) is investigated. The concentration of chemical conditioners, pH and coagulation and flocculation time is from among the parameters studied in this research work. The results obtained indicate that sludge volume reduction for the chemical conditioners used, including Ferric Chloride (FeCl3 ), Aluminum Sulfate (Al2 (SO4 )3 ), and Calcium Oxide (CaO) are 41, 17, and 33 percent, respectively. The optimal concentration for FeCl3 , Al2 (SO4 )3, and CaO are 550, 1100, and 292 mg/L, respectively, and the optimal values of pH are 9, 7.5, and 10, respectively. The time to filtration (TTF) and reduction in sludge moisture content (SMC) for Ferric Chloride, Aluminum Sulfate, and Calcium Oxide are 45 s and 6.2%, 135 s and 3.3%, 190 s and 2.4% respectively. PRACTITIONER POINTS: Investigating the sludge conditioning by Ferric Chloride, Aluminum Sulfate, and Calcium Oxide. Determining the optimal concentration, pH, and coagulation/flocculation time. Calculating the time to filtration (TTF) and reduction in sludge moisture content (SMC). Predicting the settled sludge volume using descriptive statistical analysis.


Bilateral deficit of voluntary quadriceps muscle activation after unilateral ACL tear.
The inability to fully activate the quadriceps femoris muscle voluntarily is known to accompany several different knee-joint pathologies. The extent of a voluntary-activation deficit in patients after isolated rupture of the anterior cruciate ligament (ACL), however, has been reported to be small or nonexistent, making it questionable if a voluntary-activation deficit is a relevant factor for these patients at all. In this study the ability to voluntarily activate the quadriceps femoris muscles was quantified in 22 male patients with arthroscopically-proven isolated ACL ruptures using an established highly sensitive twitch-interpolation technique. Furthermore, the maximal voluntary contraction force of the quadriceps muscle was obtained by isometric knee-joint torque measurements. The results were compared with an age-, gender-, and activity-matched control group. There was a moderate but significant mean reduction in maximal voluntary activation (VA) in both the injured (VA: 83.9 +/- 2.3%, mean +/- SEM) and uninjured side (VA: 84.7 +/- 2.2%) in comparison with controls (VA: 91.1 +/- 0.8%). However, of the patients the 23% who presented a considerably reduced voluntary-activation of less than 80% were mainly responsible for the significant mean deficit. The deficit of isometric muscle strength on the injured side compared with that of controls was explained by the voluntary-activation deficit and a true muscle weakness. On the other hand, the diminished muscle strength of the uninjured side was explained sufficiently by the voluntary-activation deficit alone. Considering the bilateral voluntary-activation deficit, functional muscle tests might not be valid when the uninjured extremity serves as reference.


Economic analysis of a pragmatic randomised trial of home visits by a nurse to elderly people with hypertension in Mexico.
To analyse the costs and the effectiveness of an intervention of home visits made by nurses to elderly people versus usual care given by the family medicine units. A sample of 4,777 subjects aged 60 years and over covered by the Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS) were screened. Those with a systolic and/or diastolic blood pressure level higher or equal than 160/90 mm Hg were randomly allocated to the intervention or control groups. The intervention consisted of visits at home by nurses who gave health and lifestyle advice to the participants. The economic evaluation was considered from a health services and patient perspective. Direct and indirect costs were calculated as incremental. Effectiveness was measured in terms of cost per millimetre of mercury reduced. Three hundred and forty five participants were allocated to the intervention group and compared with 338 controls. At the end of the intervention period the difference in the mean change in systolic blood pressure was 3.31 mm Hg (95% CI 6.32, 0.29; p = 0.03) comparing with the control group. In diastolic blood pressure the difference was 3.67 (95% CI 5.22, 2.12; p < 0.001). The total cost of the intervention was 101 901.66 pesos. The intervention cost per patient was 34.61 pesos (US$3.78), (CI 95% 34.44, 35.46). The cost-effectiveness ratios was 10.46 pesos (US$1.14) for systolic (CI 95% 129.31, 5.51) and 9.43 (US$1.03) for diastolic (CI 95% 19.90, 2.49). The reduction in blood pressure obtained may well justify the small incremental cost of the intervention.


Significant non-serotonergic raphe projection to the visual cortex of the rat. An immunohistochemical study combined with retrograde tracing.
The present study investigated the distribution of serotonergic and non-serotonergic raphe neurons with direct projections to the visual cortex. The study employed the WGA-apoHRP-Au retrograde transport technique combined with 5-HT immunohistochemical staining. Retrogradely labeled cells were observed in the dorsal raphe nucleus, the median raphe nucleus, and in the B9 and B6 cell groups. One notable finding was the great number of retrogradely labeled, non-5-HT immunoreactive cells. The average percentages of such cells in the various raphe regions were as follows: DR: 52% (n = 401); MR: 35% (n = 311); B9: 24% (n = 129); B6: 95% (n = 200). The present study demonstrated the presence of a significant proportion of non-serotonergic raphe region neurons projecting to the primary visual cortex in the rat. It is suggested that these neurons may complement the aminergic neurons as part of the ascending system which controls the functions of the visual cortex.


Innovation in immediate neonatal care: development of the Bedside Assessment, Stabilisation and Initial Cardiorespiratory Support (BASICS) trolley.
Babies receive oxygen through their umbilical cord while in the uterus and for a few minutes after birth. Currently, if the baby is not breathing well at birth, the cord is cut so as to transfer the newborn to a resuscitation unit. We sought to develop a mobile resuscitation trolley on which newly born babies can be resuscitated while still receiving oxygenated blood and the 'placental transfusion' through the umbilical cord. This would also prevent separation of the mother and baby in the first minutes after birth. Multidisciplinary iterative product development. Clinical Engineering Department of a University Teaching Hospital. Following an initial design meeting, a series of prototypes were developed. At each stage, the prototype was reviewed by a team of experts in the laboratory and in the hospital delivery suite to determine ease of use and fitness for purpose. A commercial company was identified to collaborate on the trolley's development and secure marking with the Conformité Européenne mark, allowing the trolley to be introduced into clinical practice. The trolley is a small mobile resuscitation unit based on the concept of an overbed hospital table. It can be manoeuvred to within 50 cm of the mother's pelvis so that the umbilical cord can remain intact during resuscitation, irrespective of whether the baby is born naturally, by instrumental delivery or by caesarean section. Warmth for the newborn comes from a heated mattress and the trolley has the facility to provide suction, oxygen and air. This is the first mobile resuscitation device designed specifically to facilitate newborn resuscitation at the bedside and with an intact cord. The next step is to assess its safety, its acceptability to clinicians and parents, and to determine whether it allows resuscitation with an intact cord.


Absolute and relative pitch processing in the human brain: neural and behavioral evidence.
Pitch is a primary perceptual dimension of sounds and is crucial in music and speech perception. When listening to melodies, most humans encode the relations between pitches into memory using an ability called relative pitch (RP). A small subpopulation, almost exclusively musicians, preferentially encode pitches using absolute pitch (AP): the ability to identify the pitch of a sound without an external reference. In this study, we recruited a large sample of musicians with AP (AP musicians) and without AP (RP musicians). The participants performed a pitch-processing task with a Listening and a Labeling condition during functional magnetic resonance imaging. General linear model analysis revealed that while labeling tones, AP musicians showed lower blood oxygenation level-dependent (BOLD) signal in the inferior frontal gyrus and the presupplementary motor area-brain regions associated with working memory, language functions, and auditory imagery. At the same time, AP musicians labeled tones more accurately suggesting that AP might be an example of neural efficiency. In addition, using multivariate pattern analysis, we found that BOLD signal patterns in the inferior frontal gyrus and the presupplementary motor area differentiated between the groups. These clusters were similar, but not identical compared to the general linear model-based clusters. Therefore, information about AP and RP might be present on different spatial scales. While listening to tones, AP musicians showed increased BOLD signal in the right planum temporale which may reflect the matching of pitch information with internal templates and corroborates the importance of the planum temporale in AP processing. Taken together, AP and RP musicians show diverging frontal activations during Labeling and, more subtly, differences in right auditory activation during Listening. The results of this study do not support the previously reported importance of the dorsolateral prefrontal cortex in associating a pitch with its label.


Recurrence Quantification Analysis of Sentence-Level Speech Kinematics.
Current approaches to assessing sentence-level speech variability rely on measures that quantify variability across utterances and use normalization procedures that alter raw trajectory data. The current work tests the feasibility of a less restrictive nonlinear approach-recurrence quantification analysis (RQA)-via a procedural example and subsequent analysis of kinematic data. To test the feasibility of RQA, lip aperture (i.e., the Euclidean distance between lip-tracking sensors) was recorded for 21 typically developing adult speakers during production of a simple utterance. The utterance was produced in isolation and in carrier structures differing just in length or in length and complexity. Four RQA indices were calculated: percent recurrence (%REC), percent determinism (%DET), stability (MAXLINE), and stationarity (TREND). Percent determinism (%DET) decreased only for the most linguistically complex sentence; MAXLINE decreased as a function of linguistic complexity but increased for the longer-only sentence; TREND decreased as a function of both length and linguistic complexity. This research note demonstrates the feasibility of using RQA as a tool to compare speech variability across speakers and groups. RQA offers promise as a technique to assess effects of potential stressors (e.g., linguistic or cognitive factors) on the speech production system.


Two polymorphs of tris(ethylenediamine)cobalt(III) tetrathioantimonate(V).
Details of the structures of two polymorphs of tris(ethylenediamine)cobalt(III) tetrathioantimonate(V), [Co(C₂H₈N₂)₃][SbS₄], are reported. The first polymorph crystallizes in the orthorhombic space group Pna2₁, whereas the second polymorph belongs to the tetragonal space group P4₂bc. Both structures contain octahedral [Co(en)₃]³⁺ cations (en is ethylenediamine) and tetrahedral [SbS₄]³⁻ anions, which are interconnected via various N-H∙∙∙S hydrogen bonds to form two different types of three-dimensional network.


The impact of COVID-19 epidemic on eating disorders: A longitudinal observation of pre versus post psychopathological features in a sample of patients with eating disorders and a group of healthy controls.
the aim of this longitudinal study was to evaluate the impact of COVID-19 epidemic on Eating Disorders (EDs) patients, considering the role of pre-existing vulnerabilities. 74 patients with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) and 97 healthy controls (HCs) were evaluated before lockdown (T1) and during lockdown (T2). Patients were also evaluated at the beginning of treatment (T0). Questionnaires were collected to assess psychopathology, childhood trauma, attachment style, and COVID-19-related post-traumatic symptoms. A different trend between patients and HCs was observed only for pathological eating behaviors. Patients experienced increased compensatory exercise during lockdown; BN patients also exacerbated binge eating. Lockdown interfered with treatment outcomes: the descending trend of ED-specific psychopathology was interrupted during the epidemic in BN patients. Previously remitted patients showed re-exacerbation of binge eating after lockdown. Household arguments and fear for the safety of loved ones predicted increased symptoms during the lockdown. BN patients reported more severe COVID-19-related post-traumatic symptomatology than AN and HCs, and these symptoms were predicted by childhood trauma and insecure attachment. COVID-19 epidemic significantly impacted on EDs, both in terms of post-traumatic symptomatology and interference with the recovery process. Individuals with early trauma or insecure attachment were particularly vulnerable.


Maternal prenatal stress and depression-like behavior associated with hippocampal and cortical neuroinflammation in the offspring: An experimental study.
Prenatal stress can negatively impact neonatal health, growth, and bonding with the mother. However, molecular basis of these modifications is not completely understood. The aim of this experimental study was to test the hypothesis that intrauterine stress exposure may contribute to subsequent depression-like comorbidities associated with neuroinflammation. Wistar Albino nulliparous female rats were divided into two groups (each, n = 6): controls and pregnancy stress (Days 1 through 21). Two live rat pups (one female and one male) from each term delivery were randomly selected, and depression-like behavior tests were performed on Postpartum Days 30-34, followed by euthanasia on Day 35. NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) pathway gene expressions in the hippocampus and immunohistochemical caspase 3 (cas-3), mammalian target of rapamycin (mTOR), and transient receptor potential melastatin (TRPM) staining in the temporal and prefrontal cortices were evaluated. Compared with controls, exposure to prenatal stress was associated with increased depression and anxiety-like behavior, hippocampal NLRP3 inflammasome activation (p = 0.022 and p = 0.035 for female and male pups, respectively), neuronal degeneration and increased cas-3, mTOR, and TRPM immunostaining in the prefrontal and temporal cortices of both female and male offspring (p < 0.05 for all comparisons except p < 0.01 for cas-3 in the male cortex and female temporal cortex). Exposure to antenatal stress can lead to depression-like behavior in the infant, mainly driven by hippocampal NLRP3 inflammasome activation, cortical neuroinflammation, and neurodegeneration. Future perspectives include NLRP3-targeted therapies with anti-inflammatory and anti-apoptotic effects against adverse prenatal effects of maternal stress.


Prognostic significance of argyrophilic nucleolar organizer regions in esophageal carcinoma.
The argyrophilic nucleolar organizer region (AgNOR) of 100 cancer cells from biopsy specimens of esophageal squamous cell carcinomas in 98 surgically treated cases was examined, using a silver colloid staining technique on biopsy specimens. The number of AgNOR per nucleus (AgNOR number) was higher in the more advanced groups with regard to the length of the tumor (P less than 0.01), the depth of penetration (P less than 0.05), and lymph node metastasis (P less than 0.01). The survival of the patients with a high AgNOR number (greater than or equal to 6) was significantly poorer than those with either a medium range AgNOR number (4 less than or equal to-less than 6) (P less than 0.05) or a low AgNOR number (less than 4) (P less than 0.01). In the multivariate analysis including conventional clinicopathological factors, the AgNOR number was found to be one of the independent and significant variables (P less than 0.01). Because the AgNOR method is simple and can be applied to paraffin-embedded sections, the AgNOR number may provide potential benefit in the pretherapeutic assessment of malignant potentiality in esophageal carcinoma.


Locally different role of atrial natriuretic peptide (ANP) in the pericardial fluid.
Pericardial fluid (PF) contains several vasoactive agents in higher concentrations than venous plasma (VP). However, with human atrial natriuretic peptide (ANP) controversial data have been reported in earlier studies performed on a limited number of patients (less than 20). The present study was designed to characterize the ANP levels in human PF and cardiac tissues, and to ascertain whether myocardial ischemic state is a major factor in determining ANP production of the human heart. In a total of 316 consecutive patients undergoing open heart surgery ANP levels in VP, PF, atrial and ventricular tissues were measured by radioimmunoassay and analyzed by high-performance liquid chromatography (HPLC). The data are presented as median and 25th-75th percentiles. Our results showed ANP concentration [ANP] of PF significantly exceeded that of VP and [ANP] in the atrial tissue was significantly higher than in the ventricular tissue (p < 0.001). In patients without myocardial ischemia (valvular heart disease) [ANP] in the PF was 258.3 (189.9-342.5) pg/ml, in the VP 28.4 (11.7-57.6) pg/ml and 151.7 (78.4-447.6) ng/mg in the atrial, 0.4 (0.2-1.6) ng/mg in the ventricular tissue. The corresponding values for patients with coronary artery disease were 208.1 (153.8-318.9) pg/ml in the PF, 19.8 (9.4-27.9) pg/ml in the VP, 129.6 (66.5-455.0) ng/mg in the atrial and 1.0 (0.1-1.8) ng/mg in the ventricular tissue. The ventricular tissue levels correlated to the atrial tissue levels (r = 0.317; p < 0.05). Great difference (p < 0.001) was found in the atrial tissue levels between females [414.6 (119.7-734.4) ng/mg] and males [105.4 (65.3-204.2) ng/mg]. In HPLC analysis the majority of the pericardial fluid and tissue ir-ANP coeluted with human ANP [99-126]. In conclusion, [ANP] in PF of cardiosurgical patients is higher by an order of magnitude than in VP. Intrapericardial ANP may reflect the peptide concentration in the myocardial interstitium and may represent a paracrine regulatory mechanism, which seems independent of ANP-induced putative antiischemic influences.


Lead toxicity: from overt to subclinical to subtle health effects.
Although the toxicity of lead was recognized centuries ago, concern was restricted to overt symptoms: colic, encephalopathy, anemia, or renal disease. Two major reasons for lack of progress in restricting toxicity were that interest was limited to occupational exposures and there was lack of awareness of specific biochemical or metabolic effects. Identification of subclinical effects has been possible the last 15 or 20 years because of the development of sensitive measures to detect cognitive and behavioral changes that are not apparent clinically and because of methods to measure the reduced activity of heme enzymes. This progress was driven by basic and clinical research that resulted in a better understanding of cellular toxicology. The new awareness prompted the lowering of acceptable occupational exposures, as measured by blood lead from 80 to 40 to 60 micrograms/dL range, and the establishment of maximum recommended exposures in children to a blood lead level of 25 micrograms/dL. Lowering the lead content in gasoline has been accomplished by a nearly 50% decrease in average blood levels of persons in the United States (NHANES II data). Current research implicates lead as a contributing etiologic factor in a number of common diseases affecting large portions of the population such as subtle cognitive and neurological deficits, hypertension, congenital malformations, immunotoxicity, and deficits in growth and development. For each of these disorders there may be multiple etiologic factors; the scientific challenge is to develop sensitive methodology to detect the specific role of lead. Other potential subtle health effects include the influence of small amounts of lead on cell proliferation and lead as a cofactor in carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Arabidopsis redox status in response to caterpillar herbivory.
Plant responses to insect herbivory are regulated through complex, hormone-mediated interactions. Some caterpillar species have evolved strategies to manipulate this system by inducing specific pathways that suppress plant defense responses. Effectors in the labial saliva (LS) secretions of Spodoptera exigua caterpillars are believed to induce the salicylic acid (SA) pathway to interfere with the jasmonic acid (JA) defense pathway; however, the mechanism underlying this subversion is unknown. Since noctuid caterpillar LS contains enzymes that may affect cellular redox balance, this study investigated rapid changes in cellular redox metabolites within 45 min after herbivory. Caterpillar LS is involved in suppressing the increase in oxidative stress that was observed in plants fed upon by caterpillars with impaired LS secretions. To further understand the link between cellular redox balance and plant defense responses, marker genes of SA, JA and ethylene (ET) pathways were compared in wildtype, the glutathione-compromised pad2-1 mutant and the tga2/5/6 triple mutant plants. AtPR1 and AtPDF1.2 showed LS-dependent expression that was alleviated in the pad2-1 and tga2/5/6 triple mutants. In comparison, the ET-dependent genes ERF1 expression showed LS-associated changes in both wildtype and pad2-1 mutant plants and the ORA 59 marker AtHEL had increased expression in response to herbivory, but a LS-dependent difference was not noted. These data support the model that there are SA/NPR1-, glutathione-dependent and ET-, glutathione-independent mechanisms leading to LS-associated suppression of plant induced defenses.


Multiple fission in Allogromia sp., strain NF (Foraminiferida): release, dispersal, and ultrastructure of offspring.
The release, dispersal, and ultrastructure of juveniles arising through multiple fission in the benthic foraminiferan Allogromia sp., strain NF (Lee & Pierce, 1963) has been examined by light and electron microscopy. An extensive reticulopodial network participates in the dispersal of fully differentiated young as they emerge from the fragmented parental test. During the earliest stages of release, offspring are of two classes--aroused and unaroused. Unaroused juveniles, which have not extended pseudopods, attach externally to the network and are transported bidirectionally along its surface. Aroused juveniles, which have extended pseudopods and are in protoplasmic continuity with the network, move quickly to the periphery of the network. Within 24 h, juveniles establish a communal "feeding reticulum" in which dispersed individuals are in protoplasmic continuity with neighbors via a common reticulopodial network. At the ultrastructural level, the cell body cytoplasm of unaroused juveniles contains numerous patches of a paracrystalline material, which disappears as their pseudopodia are extended to join the communal feeding reticulum. This paracrystalline material therefore appears to be a temporary reservoir of precursors required for pseudopod construction.


Renal vein thrombosis in Chinese patients with systemic lupus erythematosus.
To evaluate the risk factors associated with renal vein thrombosis (RVT) in Chinese patients with systemic lupus erythematosus (SLE). Data on clinical symptoms, renal biopsy, antiphospholipid antibody syndrome profile, and serological examinations of lupus features were examined retrospectively in six patients with RVT confirmed by angiography from a total of 625 patients with SLE over a 14 year period (1982-1996). The lupus patients with RVT did not have acute symptoms of severe flank pain, haematuria, and oligouria. In contrast, most patients were suspected to have RVT because of peripheral oedema and worsening proteinuria. Roentgenological examinations (including renal sonography, renal computer tomography, or renal Doppler, or all three) were positive only in some patients. Positive antiphospholipid antibody profiles were found in four of six lupus patients. By renal biopsy, only two samples were confirmed as World Health Organisation (WHO) class V lupus membranous glomerulonephritis. The others were class IV in three patients, and class III in the remaining one. No RVT was found in lupus patients without nephrotic syndrome. Peripheral thrombophlebitis was, however, noted in only one patient. Nephrotic syndrome could be a distinct risk factor in the development of RVT in Chinese SLE patients, in contrast with that reported in white populations in whom the peripheral thrombotic events were recognised as a determining factor.


The Discovery of Actinospene, a New Polyene Macrolide with Broad Activity against Plant Fungal Pathogens and Pathogenic Yeasts.
Phytopathogenic fungi infect crops, presenting a worldwide threat to agriculture. Polyene macrolides are one of the most effective antifungal agents applied in human therapy and crop protection. In this study, we found a cryptic polyene biosynthetic gene cluster in Actinokineospora spheciospongiae by genome mining. Then, this gene cluster was activated via varying fermentation conditions, leading to the discovery of new polyene actinospene (1), which was subsequently isolated and its structure determined through spectroscopic techniques including UV, HR-MS, and NMR. The absolute configuration was confirmed by comparing the calculated and experimental electronic circular dichroism (ECD) spectra. Unlike known polyene macrolides, actinospene (1) demonstrated more versatile post-assembling decorations including two epoxide groups and an unusual isobutenyl side chain. In bioassays, actinospene (1) showed a broad spectrum of antifungal activity against several plant fungal pathogens as well as pathogenic yeasts with minimum inhibitory concentrations ranging between 2 and 10 μg/mL.


P311 Facilitates the Angiogenesis and Wound Healing Function of MSCs by Increasing VEGF Production.
As a potential clinical therapeutic cell for injured tissue repair, mesenchymal stem cells (MSCs) have attracted increasing attention. Enhancing the pro-healing function of MSCs has gradually become an essential topic in improving the clinical efficacy of MSCs. Recently, studies have shown that neuronal protein 3.1 (P311) plays a crucial role in promoting skin wound healing, suggesting P311 gene modification may improve the pro-healing function of MSCs. In this study, we demonstrated that increasing the in vivo expression of P311 could significantly enhance the ability of MSCs to lessen the number of inflammatory cells, increase the expression of IL10, reduce the levels of TNF-α and IFN-γ, increase collagen deposition, promote angiogenesis, and ultimately accelerate skin wound closure and improve the quality of wound healing. Importantly, we uncovered that P311 enhanced the pro-angiogenesis function of MSCs by increasing the production of vascular endothelial growth factor (VEGF) in vitro and in vivo. Mechanistically, we revealed that the mTOR signalling pathway was closely related to the regulation of P311 on VEGF production in MSCs. Together, our data displayed that P311 gene modification in MSCs augments their capabilities to promote skin wound closure, which might bring the dawn for its clinical application in the future.


Arabidopsis ovate family proteins, a novel transcriptional repressor family, control multiple aspects of plant growth and development.
The Arabidopsis genome contains 18 genes that are predicted to encode Ovate Family Proteins (AtOFPs), a protein family characterized by a conserved OVATE domain, an approximately 70-amino acid domain that was originally found in tomato OVATE protein. Among AtOFP family members, AtOFP1 has been shown to suppress cell elongation, in part, by suppressing the expression of AtGA20ox1, AtOFP4 has been shown to regulate secondary cell wall formation by interact with KNOTTED1-LIKE HOMEODOMAIN PROTEIN 7 (KNAT7), and AtOFP5 has been shown to regulate the activity of a BEL1-LIKEHOMEODOMAIN 1(BLH1)-KNAT3 complex during early embryo sac development, but little is known about the function of other AtOFPs. We demonstrated here that AtOFP proteins could function as effective transcriptional repressors in the Arabidopsis protoplast transient expression system. The analysis of loss-of-function alleles of AtOFPs suggested AtOFP genes may have overlapping function in regulating plant growth and development, because none of the single mutants identified, including T-DNA insertion mutants in AtOFP1, AtOFP4, AtOFP8, AtOFP10, AtOFP15 and AtOFP16, displayed any apparent morphological defects. Further, Atofp1 Atofp4 and Atofp15 Atofp16 double mutants still did not differ significantly from wild-type. On the other hand, plants overexpressing AtOFP genes displayed a number of abnormal phenotypes, which could be categorized into three distinct classes, suggesting that AtOFP genes may also have diverse functions in regulating plant growth and development. Further analysis suggested that AtOFP1 regulates cotyledon development in a postembryonic manner, and global transcript profiling revealed that it suppress the expression of many other genes. Our results showed that AtOFPs function as transcriptional repressors and they regulate multiple aspects of plant growth and development. These results provided the first overview of a previously unknown transcriptional repressor family, and revealed their possible roles in plant growth and development.


From animal to molecule: aspects of the biology of insulin-like growth factors.
The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)


[A study on the promoting effects of recombinant human epidermal growth factor on skin wound healing in rats].
To observe the effects of recombinant human epidermal growth factor (rhEGF) on skin wound healing. The dorsal trauma model of rats was used. A total of 68 dorsal wounds in 34 rats were created and divided into the rhEGF group and the isotonic saline group according to self-control. The process of wound healing was observed and a mean healing time was calculated. Furthermore, the dynamic analysis was performed at different times on wound OHP contents, ratio of collagen I/III and cell DNA cycle. The wound healing was accelerated obviously in all wounds treated with rhEGF. The mean time of wound healing of the two groups was (17.2 +/- 1.3) days and (20.5 +/- 1.6) days respectively (P < 0.01). In the rhEGF group, the new granulation tissue was more and the re-epithelialization was faster than that of the saline group. External rhEGF increased OHP content, reduced collagen I/II ratio and accelerated cell DNA replication. External rhEGF can shorten wound healing time, increase granulation tissue and OHP contents, reduce collagen I/III ratio and accelerate cell DNA replication, thus obviously promoting skin wound repair.


Anxiety and Depression Comorbidities in Moroccan Patients With Breast Cancer.
Background: Breast cancer is the leading cause of cancer death in women worldwide with more than 1. 7 million new cases annually. Major advances have been made in the therapeutic management of this condition in many countries. However, neuropsychiatric disorders in patients with breast cancer constitute a significant concern due to their negative impact on patient's life and on the success of therapy itself. Methodology: In this study we aimed to evaluate psychological disorders in a population of 212 Moroccan women treated for breast cancer within the Mohammed VI Center for the Treatment of Cancers of Casablanca. A questionnaire was designed to this end on the basis of different validated scales, including the Hospital Anxiety Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI), and the Body Image Scale (BIS). Results: Data analysis has shown that 69.3% of participants had significant sleep disorders; 87% suffer from an anxiety-depressive syndrome (ADS), and 83.0% had significant body image dissatisfaction. A positive correlation was shown between ADS and both patients' national health insurance coverage and patients or husbands' education. Analysis further revealed that anxiety and depression were negatively correlated with different types of treatment. Similarly, both BIS and PSQI scores were positively associated with anxiety and depression disorders. Conclusion: The present investigation highlights the need to generalize and strengthen the psychological approach of patients treated for breast cancer in Morocco. We anticipate that such a strategy will alleviate suffering and promote therapy success in these patients and will diminish or prevent conjugal and familial impacts of the illness.


The relationship between dietary inflammatory index (DII) and muscle mass and strength in Chinese children aged 6-9 years.
The dietary inflammatory index (DII®) is a measure of the overall inflammatory potential of a person's diet. However, there have been no studies looking at the effect of DII on measures of muscle mass and strength. We aimed to examine the association between DII and skeletal muscle mass and strength in Chinese children. A total of 466 children aged 6-9 years completed the study. Total body skeletal muscle mass (TSM), appendicular skeletal mass (ASM) and appendicular lean mass (ALM) were determined using Dual-energy X-ray absorptiometry. TSM/Height², TSM/Weight, ASM/Height² and ASM/Weight were calculated. The residual method was applied to compute ALM index (ALMI) adjusted for height and body fat. Hand grip strength was measured using hand dynamometer. DII scores were calculated from a 79-item food frequency questionnaire. Fully adjusted linear regression models showed a statistically significant negative relationship between DII and ASM, ASM/Height², ASM/Weight, ALMI, TSM, TSM/Height², and TSM/Weight (p: 0.019‒0.014). The analysis of covariance indicated that the percentage differences in the extreme quartiles (Q4 vs Q1) of DII for the above-mentioned measures ranged from -1.04% to -4.36% (p-trend: <0.001‒0.013). When boys and girls were analyzed separately, similar findings were observed for boys but not for girls. No significant associations were detected between DII and hand grip strength. DII score was inversely associated with skeletal muscle mass in boys but not in girls aged 6-9 years old. No significant associations were observed between DII and hand grip strength.


Biomineralization on chemically synthesized collagen containing immobilized poly-γ-glutamic acid.
Chemically synthesized collagen with a triple helix structure similar to that of natural collagen is attractive as a safe biomaterial. Hybrids of chemically synthesized collagen and apatite are proposed for novel bone substitutes. However their apatite-forming ability in simulated body fluid is still quite low. We examined acceleration of apatite formation on collagen by immobilized poly-γ-glutamic acid (PGA), which has excellent apatite-forming ability. Apatite was formed within 3 days when collagen was treated with PGA solutions containing an appropriate amount of CaCl2. A mixture of apatite and calcite was formed at high CaCl2 concentration. The present results indicate the possibility of preparing hybrid materials, with tailored mechanical and biological properties, based on chemically synthesized collagen.


The transcription factor Sox5 modulates Sox10 function during melanocyte development.
The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage.


The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes.
In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels.


Urban Fine Particulate Matter and Elements Associated with Subclinical Atherosclerosis in Adolescents and Young Adults.
The relationships between the elemental constituents of PM2.5 and atherosclerosis remain limited, especially in young populations. This study included 755 subjects aged 12-30 years in the Taipei metropolis. A land use regression model was used to estimate residential annual mean concentrations of PM2.5 and eight elemental constituents. We evaluated the percent differences in carotid intima-media thickness (CIMT) with PM2.5 and elemental constituent exposures by linear regressions. Interquartile range increments for PM2.5 (4.5 μg/m3), sulfur (108.6 ng/m3), manganese (2.0 ng/m3), iron (34.5 ng/m3), copper (3.6 ng/m3), and zinc (20.7 ng/m3) were found to associate with 0.92% (95% confidence interval (CI): 0.17-1.66), 0.51% (0.02-1.00), 0.36% (0.05-0.67), 0.98% (0.15-1.82), 0.74% (0.01-1.48), and 1.20% (0.33-2.08) higher CIMTs, respectively. Factor analysis identified four air pollution source-related factors, and the factors interpreted as traffic and industry sources were associated with higher CIMTs. Stratified analyses showed the estimates were more evident in subjects who were ≥18 years old, females, or who had lower household income. Our study results provide new insight into the impacts of source-specific air pollution, and future research on source-specific air pollution effects in young populations, especially in vulnerable subpopulations, is warranted.


Carbon Dioxide and Water Vapor Exchange in the Crassulacean Acid Metabolism Plant Kalanchoë pinnáta during a Prolonged Light Period: METABOLIC AND STOMATAL CONTROL OF CARBON METABOLISM.
Net CO(2) and water vapor exchange were studied in the Crassulacean acid metabolism plant Kalanchoë pinnáta during a normal 12-hour light/12-hour dark cycle and during a prolonged light period. Leaf temperature and leaf-air vapor pressure difference were kept constant at 20 C and 9 to 10 millibar. There was a 25% increase in the rate of CO(2) fixation during the first 6 hours prolonged light without change in stomatal conductance. This was associated with a decrease in the intracellular partial pressure of CO(2), a decrease in the stimulation of net CO(2) uptake by 2% O(2), and a decrease in the CO(2) compensation point from 45 to 0 microbar. In the normal light period after deacidification, leaves showed a normal light dependence of CO(2) uptake but, in prolonged light, CO(2) uptake was scarcely light-dependent. The increase in titratable acidity in prolonged light was similar to that in the dark.The results suggest a change from C(3) photosynthetic CO(2) fixation in the second part of the 12-hour light period to a mixed metabolism in prolonged light with both ribulose bisphosphate carboxylase and phosphoenolpyruvate carboxylase as primary carboxylating enzymes.


Functional bundle branch block: discordant response of right and left bundle branches to changes in heart rate.
Faster heart rates shorten refractoriness more in some tissues than in others. This study investigates whether faster heart rates shorten relative refractoriness more in the right than left bundle branch in humans. Premature atrial stimulation at 2 or more basic cycle lengths was performed in 314 patients with no evidence of atrioventricular conduction system disease. In 10 patients, both functional right and left bundle branch block (BBB) developed with premature atrial stimulation. Functional right BBB occurred at the longer basic cycle length, and functional left BBB at the shorter cycle length in 8 patients. In 2 patients functional right and functional left BBB were present at the same cycle length, but functional left BBB occurred at a shorter premature atrial coupling interval. For all patients, the mean functional right bundle branch relative refractoriness was 438 ms at a basic cycle length of 847 ms, and functional left bundle branch relative refractoriness was 357 ms at a cycle length of 622 ms (p less than 0.01). The HV interval was 45 +/- 15 ms at control and increased with functional left BBB to 77 +/- 19 ms (p less than 0.01), but not with functional right BBB. Thus, relative refractoriness of the right and left bundle branches are rate-dependent and discordant. At longer cycle lengths, relative refractoriness of the right bundle branch is greater than that of the left bundle branch, and at shorter cycle lengths relative refractoriness of the left bundle branch is greater than that of the right bundle branch. The relative refractory period curves "cross over" and can explain the presence of both functional right and left BBB in the same patient.


Reproducibility of the blood lactate-running speed curve in horses under field conditions.
To examine the reproducibility of blood lactate-running speed curve parameters derived by a curve-fit equation and by linear interpolation from the results of 4-speed tests of sport horses under field conditions. Thoroughbreds completed 10 test pairs with 3 to 11 days between tests and retest. 7 Thoroughbreds. The 4-speed test consisted of 4 runs over a distance of 2,110 m. Exercise intensity was increased by 1 m/s for each run. Blood lactate concentration measured after each run was plotted against running speed to determine the blood lactate-running speed relation. By means of the blood lactate-running speed relation, velocity inducing 2, 2.5, 3, 3.5, or 4 mM blood lactate concentration was calculated by a curve-fit equation and by linear interpolation. The test-retest correlation coefficient of velocity inducing 2, 2.5, 3, 3.5, and 4 mM blood lactate concentration determined by curve-fit equation was 0.67, 0.78, 0.84, 0.86, and 0.86, respectively, and by linear interpolation was 0.42, 0.58, 0.77, 0.87, and 0.78, respectively. But the test-retest regression was equal to the line of identity only for velocity inducing 3.5 and 4 mM blood lactate concentration. The reproducibility of velocity inducing 3.5 and 4 mM blood lactate concentration was sufficient to be used to compare horses and evaluate conditioning effects. This holds both methods of calculation of the parameters derived from the blood lactate-running speed relation.


[Occupation and mortality in the Brazilian Navy].
To describe the distribution of mortality due to digestive tract, genitourinary and nervous system diseases according to occupation among Brazilian Navy servicemen. This was an exploratory study of proportional mortality among male servicemen in the Brazilian Navy who died between 1991 and 1995. The study population comprises the entire contingent of servicemen during this same time period. Data were obtained from death certificates submitted in order to obtain dependents' pensions, and from the corresponding occupational histories of these individuals. Basic causes of death were coded in accordance with the International Classification of Diseases (9th Revision). Servicemen presented increased proportional mortality for liver diseases related to alcohol consumption (age-adjusted proportional mortality ratio, PMRadj=2.03; 95% confidence interval, CI: 1.26-3.00), pancreatitis (PMRadj=2.03; 95% CI: 1.06-3.38), digestive hemorrhage (PMRadj=1.61; 95% CI: 1.10-2.23), chronic kidney diseases (PMRadj=2.82; 95% CI: 1.98-3.84), Parkinson's disease (PMRadj=3.00; 95% CI: 1.27-5.72) and degenerative brain diseases (PMRadj=2.88; 95% CI: 1.14-5.70), in relation to the reference population. A statistically non-significant association was observed between radar operators (PMR=6.50; 95% CI: 1.43-29.56) and nervous system diseases was observed. The results indicate the existence of possible occupational risk factors in the working environment of the Brazilian Navy, and the need for studies using quantitative measurement of such exposure.


Type of plasma preparation used for plasma exchange and clinical outcome of adult patients with acquired idiopathic thrombotic thrombocytopenic purpura: a French retrospective multicenter cohort study.
Plasma exchange (PE) is the first-line therapy of acquired thrombotic thrombocytopenic purpura (TTP). Several plasma preparations have been available; their equivalence in terms of outcome remains uncertain. We performed a retrospective analysis of the cases prospectively reported from 2005 to 2010 to the national registry established by the thrombotic microangiopathies French reference center. We analyzed 108 initial episodes of acquired idiopathic TTP in adults treated with PE, 81 with solvent/detergent (S/D) plasma, and 27 with quarantine fresh-frozen plasma (qFFP). The primary endpoint was the time to platelet (PLT) count recovery. Time to PLT count recovery was not significantly different with S/D plasma versus qFFP (median, 15 days vs. 19 days, respectively; p = 0.126). Complete remission rates, exacerbations, and survival were comparable. By multivariate competitive risk (Fine-Gray) analysis, the only significant association with a shorter time to PLT count recovery was the absence of additional treatment (hazard ratio, 2.06; 95% confidence interval [CI], 1.39-3.05; p < 0.001). There was a significant interaction between type of plasma and age, and for patients less than 40 years old, the use of S/D plasma was associated with a shorter time to PLT count recovery versus qFFP (median, 13 [95% CI, 9-16] days vs. 20 [95% CI, 16-64] days, respectively; p = 0.004). The outcomes of acquired TTP treated with S/D plasma or qFFP seem similar and therefore both preparations can be used safely for PE in this indication. The faster response of S/D plasma observed in younger patients warrants confirmation in prospective studies.


Erythrocyte porphobilinogen deaminase activity in porphyria cutanea tarda.
Porphyria cutanea tarda (PCT) results from a metabolic block in heme synthesis at the level of uroporphyrinogen decarboxylase. We measured the activity of one of the enzymes preceding it in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD; EC 188.8.131.52), in erythrocytes of 47 patients with symptomatic or asymptomatic familial or sporadic PCT. PBGD activity was significantly increased in all four PCT groups, compared with controls. To study the mechanism of this increased PBGD activity, we determined, using polyclonal antibodies, the amount of immuno-detectable PBGD per 100 units of PBGD activity (Ig PBGD/100 U) and the total amount of immuno-detectable PBGD (Ig PBGD) in erythrocytes from all 47 patients and from controls. In both familial and sporadic PCT, Ig PBGD/100 U was decreased compared with that in controls (P less than 0.05). Especially in asymptomatic patients of the familial PCT group there was an inverse correlation between increasing PBGD activity and Ig PBGD/100 U (r = -0.90). In familial PCT, and to a minor degree in sporadic PCT, an increase in PBGD activity was accompanied by an increased Ig PBGD, compared with controls (familial PCT: P less than 0.001, sporadic PCT: P less than 0.05). In familial and sporadic PCT an increase in erythrocyte PBGD activity can, at least partly, be explained by a diminished degradation of PBGD. In familial PCT, in the symptomatic group more than in the asymptomatic group, and to a minor degree in sporadic PCT, there is in addition an increase in the absolute amount of PBGD.


Urban bomb blast injuries: patterns of injury and treatment.
A review of many series reporting injuries following blasts, data allows certain conclusions to be made: 1. Most patients sustain minor injuries, which may be treated on an outpatient basis. 2. Injuries predominantly affect the head and neck and the periphery, which suggests that clothing plays a major role in protection from secondary injuries. 3. Injuries to the chest and abdomen are relatively uncommon but have a high mortality, also associated with head injury. 4. Primary blast injuries are uncommonly seen in a hospital setting, because they usually result in immediate death.


Proteomic analysis of extracellular proteins from Aspergillus oryzae grown under submerged and solid-state culture conditions.
Filamentous fungi are widely used for the production of homologous and heterologous proteins. Recently, there has been increasing interest in Aspergillus oryzae because of its ability to produce heterologous proteins in solid-state culture. To provide an overview of protein secretion by A. oryzae in solid-state culture, we carried out a comparative proteome analysis of extracellular proteins in solid-state and submerged (liquid) cultures. Extracellular proteins prepared from both cultures sequentially from 0 to 40 h were subjected to two-dimensional electrophoresis, and protein spots at 40 h were identified by peptide mass fingerprinting using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. We also attempted to identify cell wall-bound proteins of the submerged culture. We analyzed 85 spots from the solid-state culture and 110 spots from the submerged culture. We identified a total of 29 proteins, which were classified into 4 groups. Group 1 consisted of extracellular proteins specifically produced in the solid-state growth condition, such as glucoamylase B and alanyl dipeptidyl peptidase. Group 2 consisted of extracellular proteins specifically produced in the submerged condition, such as glucoamylase A (GlaA) and xylanase G2 (XynG2). Group 3 consisted of proteins produced in both conditions, such as xylanase G1. Group 4 consisted of proteins that were secreted to the medium in the solid-state growth condition but trapped in the cell wall in the submerged condition, such as alpha-amylase (TAA) and beta-glucosidase (Bgl). A Northern analysis of seven genes from the four groups suggested that the secretion of TAA and Bgl was regulated by trapping these proteins in the cell wall in submerged culture and that secretion of GlaA and XynG2 was regulated at the posttranscriptional level in the solid-state culture.