Preparation and Characterization of Porous Core-Shell Fibers for Slow Release of Tea Polyphenols.
This study focused on the fabrication, characterization, and release properties of electrospun tea polyphenol (TPP) loaded porous core-shell structured fibers. The morphology, structure and properties of the electrospun TPP loaded porous core-shell fibers were investigated by a combination of Fourier transformation infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle (CA) measurements, transmission electron microscopy (TEM), etc. In addition, the cumulative drug release rate of TPP loaded porous core-shell fibers was determined by ultraviolet (UV) spectrophotometer, and the release mechanism was investigated using Fickian diffusion equation, which would provide the theoretical basis for future study. The results showed TPP loaded porous core-shell structured fibers were successfully prepared by coaxial electrospinning, and the porous structure of the core-shell fibers could further enlarge the specific surface area, enhance the hydrophobic properties, and improve the drug release properties.


Choledochoduodenostomy as the biliary-enteric bypass of choice for benign and malignant distal common bile duct strictures.
Choledochoduodenostomy (including hepaticoduodenostomy) for common bile duct (CBD) strictures has been underused because of concerns regarding postoperative duodenal fistula and cholangitis attending the so-called "sump syndrome." An institutional retrospective review of 55 consecutive choledochoduodenostomy procedures for CBD strictures from 1995 to 2011 was performed to examine its suitability as the biliary-enteric bypass procedure of choice. There were 30 male (55%) and 25 female (45%) patients with a mean age of 49 years (range, 13 to 73 years). Thirty-seven (67%) patients had benign CBD strictures and 18 (33%) had unresectable periampullary adenocarcinomas. Forty-nine (89%) underwent choledochoduodenostomy and six (11%) underwent hepaticoduodenostomy. There were no 30-day postoperative deaths, anastomotic leaks, or intra-abdominal abscesses. Five patients (9%) sustained Clavien Grade III or IV complications. Over a mean long-term follow-up of 29 months (range, 1 to 162 months), there was one anastomotic stricture successfully managed by endoscopic dilation and temporary stenting. Liver function tests in all other patients returned to and remained within normal limits. We conclude that choledochoduodenostomy is the preferred biliary-enteric bypass for both benign and malignant distal CBD strictures because of its ease, safety, and durability. Persistent fears of duodenal fistula and the "sump syndrome" are not warranted by the empiric data and should be abandoned.


Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women.
To test the hypothesis that increasing the intake of isoflavones by dietary supplementation may produce a therapeutic effect in reducing the incidence and severity of hot flushes in menopausal women. Fifty-one postmenopausal women were randomized to placebo and active (one tablet per day of a 40-mg isoflavone supplement) groups in a cross-over design trial. After a 1-week run-in period, subjects were commenced on a 12-week period of treatment (active or placebo), followed by a 1-month placebo wash-out period, then crossed over to the alternative treatment regimen for a further 14 weeks. Symptom diaries were maintained throughout the trial and at the start and end of treatment. Plasma sex hormone binding globulin (SHBG) assay, full blood count, biochemical profiles, vaginal swabs and vaginal ultrasound scans were performed and isoflavones determined in 24-h urine collections by high-pressure liquid chromatography (HPLC) analysis. There was no significant difference between active and placebo groups in the reduction in hot flushes between start and finish time-points. Analysis performed on interim data time-points revealed a substantially greater reduction in flushing in the active group than placebo at 4 and 8 weeks after commencement of treatment, but this was not statistically significant. There were no significant differences between groups for Greene scores or in SHBG levels, hematological or biochemical parameters and vaginal swab or ultrasound findings. The combined values for all subjects, regardless of treatment group, revealed a strong negative correlation between the level of urinary isoflavone excretion and the incidence of hot flushes. These data do not indicate a therapeutic benefit from dietary supplementation with isoflavones in women experiencing menopausal symptoms, but do indicate that the apparent placebo effect in many studies of menopausal symptoms may be attributable to dietary sources of isoflavones. The study also demonstrates that 3 months of isoflavone supplementation did not cause adverse events or endometrial changes.


The mitochondria-independent cytotoxic effect of nelfinavir on leukemia cells can be enhanced by sorafenib-mediated mcl-1 downregulation and mitochondrial membrane destabilization.
Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIV-infected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells. By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed. At a concentration of 9 microg/ml, nelfinavir induced death of 90% of HL60, IM9, and Jurkat cells. At the same concentration and treatment conditions, less than 10% of aspirated human bone marrow cells showed nelfinavir-induced cell damage. Nelfinavir-induced death of leukemia cells was accompanied by activation of caspases 3, 7, and 8. Despite caspase activation, the upregulation of the anti-apoptotic bcl-2 family member protein mcl-1 that resulted from nelfinavir treatment stabilized the mitochondrial membrane potential, resulting in primarily mitochondria-independent cell death. Pharmacological downregulation of mcl-1 expression by treatment with sorafenib (2 microg/ml) significantly enhanced nelfinavir-induced apoptosis even at lower nelfinavir concentrations (5 microg/ml), but did not have additional detrimental effects on non-malignant bone marrow cells. The ability of nelfinavir to induce apoptosis in leukemia cells as a single agent in a mitochondria-independent manner might suggest it could be used as a second or third line of treatment for leukemia patients for whom standard mitochondria-directed treatment strategies have failed. Combination treatment with nelfinavir and sorafenib might further enhance the efficacy of nelfinavir even on chemo-resistant leukemia cells.


Caries experience in rural Victorian adolescents.
An oral health status survey was conducted on 818 adolescents aged 12 to 16 years in a non-fluoridated area in rural Victoria. The prevalence and severity of dental caries experience was found to increase with age. The occlusal surface was the predominant surface affected by dental caries for all age groups. Filled surfaces represented the largest component of the DMFS index and were responsible for the increasing dental caries experience with age. Fewer fissure sealants were present with increasing age and second molars were sealed less often than the first molars. Although no difference was evident in the total caries experience between those with and without access to public dental services, a statistical difference was found to exist in unmet need between these two groups. Untreated caries levels were significantly higher in health card holders. The provision of preventive and dental treatment services to this group should be a priority in the future.


Comparative transcriptomics analysis of testicular miRNA from indicine and taurine cattle.
Numerous studies have shown that several microRNAs (miRNAs) are specifically expressed in testis, play an essential role in regulating testicular spermatogenesis. Hainan and Mongolian cattle are two representative Chinese native cattle breeds representing Bos indicus (indicine cattle) and Bos taurus (taurine cattle), respectively, which are distributed in hot Hainan and cold Inner Mongolia province. To study the functional differences of miRNA in spermatogenesis between indicine and taurine cattle, six mature testes samples from indicine cattle (n = 3) and taurine cattle (n = 3) were collected, respectively. We detected miRNA expression using small RNA sequencing technology following bioinformatic analysis. A total of 578 known miRNAs and 132 novel miRNAs were detected in the six libraries. Among the 710 miRNAs, 564 miRNAs were expressed in both indicine and taurine cattle, 73 miRNAs were found solely in indicine cattle and 73 miRNAs were found solely in taurine cattle. After further analysis, among the miRNAs were identified in both indicine and taurine cattle, 184 miRNAs were differentially expressed (|log2 fold change| ≥ 1 and corrected p-value <0.05). Among the miRNAs that were only expressed in indicine cattle, 10 miRNAs were differentially expressed, whereas, among the miRNAs that were only expressed in taurine cattle, six miRNAs were differentially expressed. The enrichment analysis result showed that predicted target genes of a total of 200 differentially expressed miRNAs were enriched on some testicular spermatogenesis-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, especially mitogen-activated protein kinase (MAPK) signaling pathway. These findings identify miRNAs as key factors to regulate spermatogenesis in both indicine and taurine cattle, which may also be helpful for improving cattle reproductive performance in future studies.


Targeted Temperature Management: A Program Evaluation.
In the United States, more than 350 000 cardiac arrests occur annually. The survival rate after an out-of-hospital cardiac arrest remains low. The majority of patients who have return of spontaneous circulation will die of complications of hypoxic-ischemic brain injury. Targeted temperature management is the only recommended neuroprotective measure for those who do not regain consciousness after return of spontaneous circulation. Despite current practices, a review of the literature revealed that evidence on the ideal time to achieve target temperature after return of spontaneous circulation remains equivocal. A program evaluation of a targeted temperature management program at an academic center was performed; the focus was on timing components of targeted temperature management. The program evaluation revealed that nurse-driven, evidence-based protocols can lead to optimal patient outcomes in this low-frequency, high-impact therapy.


[Spectrum of antibodies to HCV antigens in patients with different clinical patterns of chronic HCV infection].
Correlations between the spectra of antibodies to HCV proteins represented by various antigenic determinants and clinical variants of chronic HCV infection were studied. Synthetic peptides core-16, NS4-20, and NS5-23 simulating the immunodominant regions of the core, NS4 and NS5 proteins and recombinant proteins core-114 and NS4-86 were used as antigens. The results indicate that if the serum of an HCV patients contains no IgG to both antigenic determinants of NS4 or to NS5 in combination with any core antigenic determinant, a clinical and biochemical remission is highly probable. Chronic hepatitis C is characterized by the presence of IgG in high titers to both antigenic determinants of NS4 protein, particularly in combination with anti-NS5 IgG in low titers or none at all, or high titers of anti-core-16 IgG in combination with high titers of anti-NS4-20 IgG.


[Use of the IntelliVent-ASV mode for maintaining the target EtCO2 range in patients with severe TBI].
the study purpose was to evaluate the efficacy of the IntelliVent-ASV mode in maintaining the target range of PaCO2 in patients with severe TBI. The study included 12 severe TBI patients with the wakefulness level scored 4-9 (GCS). This was a crossover design study. Two ventilation modes were consecutively used: IntelliVent-ASV and P-CMV, for 12 h each. When using the P-CMV mode, the ventilation parameters were set to maintain PaCO2 in a range of 35-38 mm Hg. The IntelliVent-ASV mode involved the Brain Injury ventilation algorithm. The target range of EtCO2 was set in accordance with the delta PaCO2-EtCO2 to maintain PaCO2 in a range of 35-38. At the beginning of each ventilation period and every 3 hours, the arterial blood gas composition was analyzed. When PaCO2 occurred out of the 35-38 range, appropriate adjustments were made to the ventilation parameters. In the P-CMV mode, the Pinsp and RR parameters were adjusted to achieve the target PaCO2 range. In IntelliVent mode, a shift of the target EtCO2 range was adjusted in accordance with a changed PaCO2-EtCO2 difference. In all patients, ICP, blood pressure, and EtCO2 were monitored; the arterial blood gas composition was analyzed every 3 h; the frequency of manual settings of ventilation parameters was recorded. The EtCO2 and PaCO2 parameters were found not to be significantly different in the P-CMV and IntelliVent modes, but the spread in these parameters was significantly lower in the IntelliVent ventilation mode. The PaCO2 parameter occurred out of the target range significantly less often in the IntelliVent mode than in the P-CMV mode. The mean frequency of manual respirator settings needed to maintain the target EtCO2 range was significantly lower in the IntelliVent-ASV mode than in the P-CMV mode. The IntelliVent-ASV mode provides more efficient maintenance of PaCO2 in the target range compared to traditional artificial ventilation using fewer manual settings of the ventilation parameters.


[Progressive systemic scleroderma. Clinical spectrum and prognostic parameters in 131 patients].
The course of progressive systemic scleroderma was analysed from data collected on 131 patients. Classification was according to the extent of cutaneous involvement, type I (28%): sclerosis as far as the wrist-joint; type II (65%): sclerosis beyond the wrist-joint; type III (7%): sclerosis beginning to affect the trunk. In addition, they were subdivided into those with or without signs of systemic inflammation. The sex ratio was 3.5 females to 1 male. In half of the patients the disease manifested itself between the age of 30 and 50 years, with a clear peak about the 40th year. Serological evidence of inflammatory and immunological phenomena was present in nearly 50%, predominantly in those with type II or III. Oesophageal involvement was present in 84%, of the lung in 56% of all patients. ECG and echocardiographic changes were demonstrated in 34% of patients, while liver, intestines and kidneys were only rarely affected. The degree of organ involvement increased from type I to type III. Signs of systemic inflammation were predominantly associated with a clinically severe course.


[20th anniversary of the Gerontological Society of the Russian Academy of Sciences].
The overview on the establishment, main activities and results of The Gerontological Society of The Russian Academy of Sciences since March 1994.


Gut Microbiota and Host Thermoregulation in Response to Ambient Temperature Fluctuations.
Ambient temperature (Ta ) is an important factor in shaping phenotypic plasticity. Plasticity is generally beneficial for animals in adapting to their environments. Gut microbiota are crucial in regulating host physiological and behavioral processes. However, whether the gut microbiota play a role in regulating host phenotypic plasticity under the conditions of repeated fluctuations in environmental factors has rarely been examined. We used intermittent Ta acclimations to test the hypothesis that the plasticity of gut microbiota confers on the host a metabolic adaptation to Ta fluctuations. Mongolian gerbils (Meriones unguiculatus) were acclimated to intermittent 5°C to 23°C, 37°C to 23°C or 23°C to 23°C conditions for 3 cycles (totally 3 months). Intermittent Ta acclimations induced variations in resting metabolic rate (RMR), serum thyroid hormones, and core body temperature (Tb ). We further identified that the β-diversity of the microbial community varied with Ta and showed diverse responses during the 3 cycles. Some specific bacteria were more sensitive to Ta and were associated with host dynamic metabolic plasticity during Ta acclimations. In addition, depletion of gut microbiota in antibiotic-treated gerbils impaired metabolic plasticity, particularly at low Ta , whereas supplementation with propionate as an energy resource improved the inhibited thermogenic capacity and increased the survival rate in the cold. These findings demonstrate that both gut microbiota and their host were more adaptive after repeated acclimations, and dynamic gut microbiota and their metabolites may confer host plasticity in thermoregulation in response to Ta fluctuations. It also implies that low Ta is a crucial cue in driving symbiosis between mammals and their gut microbiota during evolution.IMPORTANCE Whether gut microbiota play a role in regulating host phenotypic plasticity in small mammals living in seasonal environments has rarely been examined. The present study, through an intermittent temperature acclimation model, indicates that both gut microbiota and their host were more adaptive after repeated acclimations. It also demonstrates that dynamic gut microbiota confer host plasticity in thermoregulation in response to intermittent temperature fluctuations. Furthermore, low temperature seems to be a crucial cue in driving the symbiosis between mammals and their gut microbiota during evolution.


Perfusion-Phase [18F]THK5351 Tau-PET Imaging as a Surrogate Marker for Neurodegeneration.
We aimed to test if early, perfusion phase tau-PET imaging with [18F]THK5351 might substitute for [18F]FDG PET information on neurodegeneration, as has been previously shown for amyloid-tracers. A patient with cognitive impairment and positive amyloid-PET was examined by [18F]THK5351 tau-PET and [18F]FDG PET. The pattern of early phase of [18F]THK5351 uptake was compared to [18F]FDG visually and by the dice similarity coefficient. Visual inspection of axial slices and stereotactic-surface projection indicated a striking agreement between combined 0-2 min p.i. perfusion images of [18F]THK5351 and standard [18F]FDG 30-60 min p.i. A two-phase protocol of [18F]THK5351 PET might give information on neurodegeneration and tau pathology in a single session.


Yeast Cox11, a protein essential for cytochrome c oxidase assembly, is a Cu(I)-binding protein.
Cox11 is a protein essential for respiratory growth and has been implicated in the assembly of the Cu(B) site of cytochrome c oxidase. In the present study, we demonstrate that Cox11 is a copper-binding protein. The soluble C-terminal domain of Cox11 forms a dimer that coordinates one Cu(I) per monomer via three thiolate ligands. The two Cu(I) ions in the dimer exist in a binuclear cluster and appear to be ligated by three conserved Cys residues. Mutation of any of these Cys residues reduces Cu(I) binding and confers respiratory incompetence. Cytochrome c oxidase activity is reduced in these mutants. Thus, the residues important for Cu(I) binding correlate with in vivo function, suggesting that Cu(I) binding is important in Cox11 function.


Comparison of Movement of the Upper Dentition According to Anchorage Method: Orthodontic Mini-Implant versus Conventional Anchorage Reinforcement in Class I Malocclusion.
Objective. To compare the amounts of anchorage loss in the upper first molar (U6) and of retraction of the upper central incisor (U1) in cases with Class I malocclusion between orthodontic mini-implants (OMIs) and conventional anchorage reinforcements (CARs). Methods. The subjects were 40 female adult patients with Class I malocclusion who were treated with extraction of the first premolars and sliding mechanics. The subjects were divided into Groups 1 (N = 20, CAR) and 2 (N = 20, OMI) according to anchorage method. Lateral cephalograms were taken before (T0) and after treatment (T1). Seven skeletal and dental variables and ten anchorage variables were measured. Mann-Whitney test was used for statistical analysis. Results. Group 2 showed significantly larger retraction of U1 (U1E-sag, 9.5 mm : 7.1 mm, P < .05) and less anchorage loss of U6 (U6M-sag, 0.2 mm : 2.2 mm, P < .05; U6A-sag, 0.3 mm versus 2.4 mm, P < .01) than Group 1. There was opposite vertical movement in U1 and U6 between Groups 1 and 2 (U1E-ver, 0.9 mm intrusion : 0.7 mm extrusion; U6F-ver, 1.0 mm intrusion : 0.9 mm extrusion, P < .05). Conclusion. Although OMI could not reduce the treatment duration, it could provide better maximum anchorage of U6, greater retraction of U1, intrusion of U1 and U6 than CAR.


Treatment of a unicameral bone cyst of calcaneus with endoscopic curettage and percutaneous filling with corticocancellous allograft.
The surgical procedures for unicameral solitary calcaneal bone cysts have ranged from simple curettage and grafting to subperiosteal resection with internal fixation and grafting. In this article, an endoscopically assisted technique is proposed for the curettage of a simple calcaneal cyst that takes advantage of direct visualization of the cyst wall and contents and permits accurate assessment of the extent of the lesion. After curettage, percutaneous filling of the defect with corticocancellous allograft makes the technique a complete, minimally invasive surgical approach for this condition. The technique uses 2 lateral portals, one for viewing and the other for manipulation, both of which are created under fluoroscopic control. Once the cyst has been located, the 30 degrees arthroscope is used to evacuate fluid, after which more solid cyst contents are fragmented and removed. Thereafter, curettage of the inner surface of the cavernous cyst wall is performed. Finally, complete packing of the previously cystic cavity with crushed corticocancellous allograft is performed under endoscopic visualization and confirmed radiographically.


Growth hormone replacement in healthy older men improves body composition but not functional ability.
To determine whether growth hormone replacement in older men improves functional ability. Randomized, controlled, double-blind trial. General community. 52 healthy men older than 69 years of age with well-preserved functional ability but low baseline insulin-like growth factor 1 levels. Growth hormone (0.03 mg/kg of body weight) or placebo given three times a week for 6 months. Body composition, knee and hand grip muscle strength, systemic endurance, and cognitive function. The participants' mean age was 75.0 years (range, 70 to 85 years). At 6 months, lean mass had increased on average by 4.3% in the growth hormone group and had decreased by 0.1% in the placebo group, a difference of 4.4 percentage points (95% CI, 2.1 to 6.8 percentage points). Fat mass decreased by an average of 13.1% in the growth hormone group and by 0.3% in the placebo group, a difference of 12.8 percentage points (CI, 8.6 to 17.0 percentage points). No statistically or clinically significant differences were seen between the groups in knee or hand grip strength or in systemic endurance. The mean Trails B score in the growth hormone group improved by 8.5 seconds, whereas scores in the placebo group deteriorated by 5.0 seconds, a difference of 13.5 seconds (CI, 3.1 seconds to 23.9 seconds; P = 0.01). However, the growth hormone group's score on the Mini-Mental Status Examination deteriorated by 0.4, whereas the placebo group's score improved by 0.2, a difference of 0.6 (P = 0.11). The two treatment groups had almost identical scores on the Digit Symbol Substitution Test (P > 0.2). Twenty-six men in the growth hormone group had 48 incidents of side effects, and 26 placebo recipients had 14 incidents of side effects (P = 0.002). Dose reduction was required in 26% of the growth hormone recipients and in none of the placebo recipients (P < 0.001). Physiologic doses of growth hormone given for 6 months to healthy older men with well-preserved functional abilities increased lean tissue mass and decreased fat mass. Although body composition improved with growth hormone use, functional ability did not improve. Side effects occurred frequently.


Transient pulmonary infiltrates possibly induced by quinine sulfate.
Quinine sulfate, which has been available for many years, has not been implicated definitively in the development of pulmonary toxicity. A variety of adverse effects, however, have been reported with quinine administration. A 45-year-old woman with longstanding rheumatoid arthritis experienced wheezing, severe anxiety, breathlessness, cough, orthopnea, mild fever, chills, and pleuritic chest discomfort after taking a single dose of quinine for nocturnal leg cramps. Radiographic imaging demonstrated diffuse, bilateral pulmonary infiltrates suggestive of pulmonary edema. No cause other than acute quinine ingestion could be identified despite thorough cardiac and infectious disease evaluations. Clinicians should be aware of a possible association between quinine sulfate and pulmonary toxicity.


Designability of protein structures: a lattice-model study using the Miyazawa-Jernigan matrix.
We study the designability of all compact 3 x 3 x 3 and 6 x 6 lattice-protein structures using the Miyazawa-Jernigan (MJ) matrix. The designability of a structure is the number of sequences that design the structure, i.e., sequences that have that structure as their unique lowest-energy state. Previous studies of hydrophobic-polar (HP) models showed a wide distribution of structure designabilities. Recently, questions were raised concerning the use of a two-letter (HP) code in such studies. Here, we calculate designabilities using all 20 amino acids, with empirically determined interaction potentials (MJ matrix) and compare with HP model results. We find good qualitative agreement between the two models. In particular, highly designable structures in the HP model are also highly designable in the MJ model-and vice versa-with the associated sequences having enhanced thermodynamic stability.


[Alloplastic hydroxyapatite implants in treatment of periodontitis].
The authors estimated the porous hydroxyapatite alloplasts in the treatment of periodontitis in a clinical and radiological way. The material has been used in 30 patients who had bone pockets deeper than 6 mm. Together, 46 bone pockets were filled. We obtained reduction of the depths of the pockets of 3.02 mm, decrease of the degree of the teeth mobility and the improvement of Engelberger, Marthaler and Raitetschak's radiological indicator by 13%. The results were compared with other works describing the usage of this material in stomatology. Basing on the literature the authors also presented the histological changes in periodontium tissues after the usage of tricalcium phosphate and compact and porous alloplastic hydroxyapatite ceramics.


Antisocial personality disorder: diagnostic, ethical and treatment issues.
Antisocial personality disorder (ASPD) is a complex disorder that creates a diagnostic, ethical, and treatment dilemma for mental health professionals. Psychosocial, biological, and cultural influences play a role in the development of ASPD. People with ASPD often had harsh early childhoods that impaired their ability to trust in adulthood. Research supports intriguing biological links, but it remains unclear if biological differences are the cause or the effect of ASPD. Individualism, patriarchy, and widespread media violence create the cultural context for the development of ASPD. ASPD is difficult to clinically diagnose and treat, and there is controversy concerning whether ASPD is a psychiatric or a legal-ethical problem. However, the management of ASPD often falls to mental health services. This article addresses treatment and primary prevention of ASPD in a way that is relevant to mental health practice.


Nd:YVO4 laser groove treatment can improve the shear bond strength between dental PEEK and adhesive resin cement with an adhesive system.
The purpose of this study was to investigate the effect of various surface treatments on the shear bond strength between dental polyetheretherketone (PEEK) and adhesive resin cement. Two hundred and forty specimens were randomly classified into four groups: no treatment, sandblasted, sulfuric-acid-etched, and laser-grooved treatment. Each group was classified into two adhesive resin cement subgroups. Surface roughness, water contact angle, shear bond strength, and failure mode were measured; SEM and XPS results were obtained. The data were statistically analyzed using one-way or two-way analysis of variance and Tukey's honest significant difference test (α=0.05). Laser-grooved PEEK surface showed regular grooves and carbonization by thermal degradation; the surface roughness as well as water contact angle of were the highest in all groups. Shear bond strength values were significantly higher in the laser-groove-treated and sulfuric-acid-etched groups. Laser-groove-treated specimens showed cohesive failure. Laser-grooved treatment can improve shear bond strength between PEEK and adhesive resin cement.


In vitro effects of pentoxifylline on smooth muscle cell migration and blood monocyte production of chemotactic activity for smooth muscle cells: potential therapeutic benefit in the adult respiratory distress syndrome.
The adult respiratory distress syndrome (ARDS) is a severe lung condition characterized by an acute lung injury leading to a massive intra-alveolar fibrosis with rapid lung failure. ARDS intra-alveolar fibrosis results from the migration of mesenchymal cells (mainly smooth muscle cells [SMC]) into the alveoli through alveolar epithelial basement membrane gaps resulting from the injury. SMC migration is followed by their replication and production of extracellular matrix, which leads to fibrosis. Thus, any pharmacologic agent able to prevent SMC migration should prevent, at least in part, intra-alveolar fibrosis. SMC migration is thought to be due to the presence, in the alveolar spaces, of chemotactic factors for mesenchymal cells, such as fibronectin and platelet-derived growth factor (PDGF). The local presence of these chemotactic factors can be due to plasmatic leakage, platelet degranulation, and mononuclear phagocyte activation. Pentoxifylline is a methylxanthine interacting with the biology of several types of cells, including red blood cells, neutrophils, blood monocytes, and endothelial cells. Pentoxifylline prescription has been suggested in ARDS with respect to its activity on neutrophils, its inhibition of tumor necrosis factor-alpha (TNF) release by mononuclear phagocytes, and its prevention of TNF-induced lung injury. Since pentoxifylline can modulate the migration of several cell types, we hypothesized that it could interfere with mesenchymal cell migration. SMC migratory response was measured in vitro with modified Boyden chemotactic chambers in the presence of PDGF, fibronectin, "platelet extract," and activated blood monocyte supernatants. Pentoxifylline, at therapeutic levels, significantly reduced SMC migration in response to the presence of these chemotactic activities.(ABSTRACT TRUNCATED AT 250 WORDS)


The global prevalence of female genital mutilation/cutting: A systematic review and meta-analysis of national, regional, facility, and school-based studies.
Female genital mutilation/cutting (FGM/C) is a nonmedical procedure entailing the modification of the external female genitalia. A description of the prevalence and distribution of FGM/C allows the tracking of progress toward ending FGM/C by 2030 (Sustainable Development Goal (SDG): target 5.3). This systematic review aimed to examine FGM/C prevalence and types, by World Health Organization (WHO) region and country. A systematic search using Medical Subject Headings (MeSH) and keywords from 2009 to March 24, 2022 was undertaken in MEDLINE, PubMED, PsycINFO, Web of Science, and Embase to identify studies presenting FGM/C prevalence. Abstract and full-text screening, quality assessment, and data extraction were undertaken by 2 reviewers. Only nationally representative studies were included in the meta-analysis. Pooled FGM/C prevalence was estimated by random-effects meta-analysis using generalized linear mixed models (GLMMs). FGM/C prevalence with 95% confidence intervals (CIs), prediction intervals (PIs), and FGM/C type were presented separately by women aged 15 to 49 years and girls aged 0 to 14 years. A total of 163 studies met the inclusion criteria and 30 were included in the meta-analysis, of which 23 were from the WHO African Region (AFR), 6 from the Eastern Mediterranean Region (EMR), and 1 from the South East Asian Region (SEAR). These studies included data from 406,068 women across 30 countries and 296,267 girls across 25 countries; the pooled prevalence estimate of FGM/C among women aged 15 to 49 years was 36.9% (95% CI: 19.6% to 58.3%; PI: 0.4% to 99.0%), and 8.27% (95% CI: 3.7% to 17.3%; PI: 0.1% to 89.3%) among girls aged 0 to 14 years. Among included countries, this gave a total estimated prevalence of 84,650,032 women (95% CI: 45,009,041 to 133,834,224) and 13,734,845 girls with FGM/C (95% CI: 6,211,405 to 28,731,901). Somalia had the highest FGM/C prevalence among women (99.2%), and Mali had the highest among girls (72.7%). The most common type of FGM/C among women was "flesh removed" (Type I or II) in 19 countries. Among girls, "not sewn closed" (Type I, II, or IV) and "flesh removed" (Type I or II) were the most common types in 8 countries, respectively. Among repeated nationally representative studies, FGM/C decreased for both women and girls in 26 countries. The main limitation of the study methodology is that estimates were based on available published data, which may not reflect the actual global prevalence of FGM/C. In this study, we observed large variation in FGM/C prevalence between countries, and the prevalence appears to be declining in many countries, which is encouraging as it minimizes physical and physiological harm for a future generation of women. This prevalence estimate is lower than the actual global prevalence of FGM/C due to data gaps, noncomparable denominators, and unavailable surveys. Yet, considerable policy and community-level interventions are required in many countries to meet the SDG target 5.3. Registration: CRD42020186937.


On the misperception of variability.
It has long been claimed that people perceive the world as less variable and more regular than it actually is. Such misperception, if shown to exist, could explain some perplexing behaviors. However, evidence supporting the claim is indirect, and there is no explanation of its cause. As a possible cause, the authors suggest that people use sample variability as an estimate of population variability. This is so because the sampling distribution of sample variance is downward attenuated, the attenuation being substantial for sample sizes that people consider. Results of 5 experiments show that people use sample variability, uncorrected for sample size, in tasks in which a correction is normatively called for, and indeed perceive variability as smaller than it is.


All-optical switching with 1-ps response time in a DDMEBT enabled silicon grating coupler/resonator hybrid device.
An amorphous film of the third-order nonlinear optical material DDMEBT was spun onto silicon chips for the first time, filling 80 nm lithographic features. A 710 μm² device was designed, fabricated, and tested that acts both as a nonlinear resonator switch and as an input/output grating coupler to a perfectly vertical single mode fiber. Autocorrelation and spectral measurements indicate the device has <1 ps response time, 4 nm of switching bandwidth, and 4 dB of on/off contrast. With sufficient power, this all-optical device can potentially modulate a single optical carrier frequency in excess of 1 THz.


The stigma of AIDS: fear of disease and prejudice toward gay men.
Three hundred college students were presented with vignettes describing an ill person; the vignettes were identical except the illness was identified as either AIDS or leukemia and the individual was described as either homosexual or heterosexual. After reading one vignette, each subject completed a set of measures sensitive to interpersonal evaluation, prejudicial attitudes, and willingness to interact casually with the portrayed individual. The findings indicate the presence of highly stigmatizing attitudes towards AIDS patients and suggest that the public views AIDS patients and gay persons with similar attitudinal prejudice. The need for greater attention to AIDS by social and behavioral researchers is discussed.


The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex.
Protein C activation on the surface of the endothelium is critical to the negative regulation of blood coagulation. We now demonstrate that monoclonal antibodies that block protein C binding to the endothelial cell protein C receptor (EPCR) reduce protein C activation rates by the thrombin-thrombomodulin complex on endothelium, but that antibodies that bind to EPCR without blocking protein C binding have no effect. The kinetic result of blocking the EPCR-protein C interaction is an increased apparent Km for the activation without altering the affinity of thrombin for thrombomodulin. Activation rates of the protein C derivative lacking the gamma-carboxyglutamic acid domain, which is required for binding to EPCR, are not altered by the anti-EPCR antibodies. These data indicate that the protein C activation complex involves protein C, thrombin, thrombomodulin, and EPCR. These observations open new questions about the control of coagulation reactions on vascular endothelium.


Implementing a Web-based information resource at an inner-city community church: lessons learned.
The objective of this project was to develop and implement electronic access to HIV/AIDS information resources at Glide Memorial Church in San Francisco, CA. This involved developing tailored Web-based access to the relevant information for the Glide Clinic patients. In addition, the project deployed workstations in 2 clinic areas and provided support to clinic patients as they learned to access the information resources. This article describes the experience with information retrieval in a clinic setting for underserved patients, including lessons learned, effective strategies, and anecdotes of effect on patients. Required nursing informatics competencies in this particular area are also addressed.


Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.
The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.


Similia similibus: pairing of homologous chromosomes driven by the physicochemical properties of DNA.
Genetic recombination in eukaryotes requires the pairing of homologous chromosomes to allow precise molecular exchanges between chromosome pairs at intertwined structures called Holliday junctions, the formation of which requires the action of the RecA protein. The mechanism behind the precise pairing of structures as long as chromosomes remains mysterious. In yeast, during the initial phases of meiosis, chromosomes are paired at approximately 65 kilobase intervals via paranemic interactions that do not involve strand breakage nor the intervention of analogs of the RecA protein. It has been proposed that these paranemic interactions could occur between G-rich chromosomal regions, but putting in register stretches of homologous sequences hundreds of kb long remains challenging. Recent developments on the theory of the physicochemical properties of DNA in aqueous solutions, in presence of di- or multivalent counterions, leads to the prediction that molecules with the same sequence tend to pair spontaneously by paranemic interactions depending on the electrostatic properties of DNA. Experimental support for this prediction has now been provided in vitro with naked DNA. This newly discovered property of DNA duplexes may thus provide a clue to solve the puzzle of the premeiotic pairing.


Technetium-99m-MIBI myocardial SPECT: supine versus right lateral imaging and comparison with coronary arteriography.
Myocardial perfusion SPECT using the prone position improves inferior wall counts and decreases motion problems as compared with the usual supine position. Nonetheless, it is not suitable for women. In addition, it is associated with artifactual anteroseptal defects and hot spots. The right lateral (RL) position was evaluated instead of the prone position in 72 patients (26 women). RL imaging was performed immediately after the supine imaging during a routine 2-day 99mTc-sestamibi exercise protocol. The SPECT images were scored semiquantitatively by three physicians. Moreover, regional myocardial counts, as well as extent and severity of defects, were assessed by quantitative polar map analysis. All patients tolerated the RL position well and there was no significant patient movement in either position. Higher inferior myocardial counts per pixel were observed in the RL than in supine images. Inferior wall defects (especially mild ones) were more common in the supine than the RL images, whereas defects in other regions were not different. Quantitative analysis confirmed these findings. Analysis of 34 patients with recent coronary arteriography revealed an overall coronary artery disease (CAD) supine- and RL-imaging specificity of 50% and 75%, respectively, and the sensitivities of both were 93%. Right CAD sensitivity, specificity and normalcy rates for the supine position were 100%, 44% and 55%, whereas those of the RL position were 94%, 75% and 90%, respectively. The RL position improves CAD diagnostic accuracy, particularly right CAD, without significant artifacts in other myocardial regions. Unlike the prone position, the RL position is well tolerated by both women and men.


Combination of video-assisted thoracoscopic surgery and hand-assisted laparoscopic surgery for early cancer of the thoracic esophagus.
From June 1997 to July 2002, we enrolled 10 patients with T1 esophageal squamous cell carcinoma according to the findings of chest computerized tomography scans and transesophageal ultrasound. There were nine men and one woman. The average age was 57.1 years (range, 43-70 years). We performed a combination of video-assisted thoracoscopic surgery including endoscopic esophageal mobilization and mediastinal lymph nodes dissection for early thoracic esophageal carcinoma as well as hand-assisted laparoscopic gastric mobilization as an esophageal substitute under double-lumen intubated anesthesia. The average operative time was 330 minutes (range, 290-425 minutes). The average hospital stay was 11.2 days (range, 9-17 days). There was no surgical mortality or severe complication except one mild leakage of cervical esophagogastrostomy. All patients have tolerated solid food well and are still alive, without evidence of tumor recurrence, after a mean of 37.2 months of follow-up (range, 9-62 months). In conclusion, we suggest that a combination of video-assisted thoracoscopic esophageal mobilization and mediastinal lymph nodes dissection and hand-assisted laparoscopic mobilization of stomach via a hand-port device for esophageal reconstruction is a safe and feasible operation for patients with T1 thoracic esophageal carcinoma.


Preparation of a conjugate of 2',5'-triadenylate 5'-triphosphate and biotinylated firefly luciferase and its use for sensitive bioluminescent enzyme immunoassay.
A bioluminescent enzyme immunoassay (BLEIA) for 2',5'-oligoadenylate 5'-triphosphate (pppA2'p5'A2'Ap5'A, 2-5A) was developed using a conjugate of 2-5A and firefly luciferase as a probe. The conjugate was prepared from a 2-5A derivative bearing a thiol group at the 2'(or 3') end, and streptavidin (SA) bearing maleimide via a linker-arm and biotinylated luciferase. The thiol group of the 2-5A derivative was relatively stable under aerobic conditions and remained 100% and 56% intact at 25 degrees C after 1 and 96 h, respectively, without dimerization by aerobic oxidation. The thiol-modified 2-5A was coupled with the SA-maleimide conjugate, followed by complex formation with biotinylated firefly luciferase. BLEIA using this conjugate allowed for the direct analysis of 2-5A in a range of 5-500 fmol (0.1-10 nM in a 50 microL sample) and in a reaction time of 15 min. The measurement of microquantities of 2-5 A from various sources is easy to perform by this BLEIA, because no radioisotope labeled 2-5A was required as a probe.


Dimensional effects in Rayleigh-Taylor mixing.
We study the effects of dimensional confinement on the evolution of incompressible Rayleigh-Taylor mixing both in a bulk flow and in porous media by means of numerical simulations of the transport equations. In both cases, the confinement to two-dimensional flow accelerates the mixing process and increases the speed of the mixing layer. Dimensional confinement also produces stronger correlations between the density and the velocity fields affecting the efficiency of the mass transfer, quantified by the dependence of the Nusselt number on the Rayleigh number. This article is part of the theme issue 'Scaling the turbulence edifice (part 2)'.


Weight Loss Following Roux-en-Y Gastric Bypass Causally Implicated with Serum Levels of IL-22: A Mendelian Randomization and Phenome-Wide Association Study.
Laparoscopic Roux-en-Y gastric bypass (RYGB) modulates the low-grade inflammatory state associated with severe obesity. This study sought to investigate whether weight loss is causally implicated with changes in serum levels of inflammatory molecules. Using the largest genome-wide association study (n = 1,020 individuals), this study curated five genetic variants associated with weight loss following RYGB. Phenome-wide association studies (PheWAS) were performed to identify other phenotypes associated with these variants. Subsequently, two-sample Mendelian randomization was used to study the causal effects of weight loss on the serum levels of 382 inflammatory proteins (measured in 3,033 individuals). This is the first systematic quasi-experimental investigation of weight loss following RYGB and serum markers of inflammation. The PheWAS analysis revealed that four of the five variants are associated with phenotypes relating to metabolism and inflammation, including insulin response and levels of C-reactive protein. Two-sample Mendelian randomization of the 382 serum inflammatory markers revealed that weight loss following RYGB increases serum levels of interleukin 22 (IL-22) (beta = 0.021, P < 10-3 ; 95% CI: 0.010-0.031). Sensitivity analyses further supported the results and the causal direction. Weight loss following RYGB may cause an increase in IL-22 serum levels, suggesting that weight loss directly contributes to immune modulation following bypass. These results demonstrate the utility of genetic studies to disentangling molecular cause and effect following bariatric surgery.


Computationally efficient algorithm for photoplethysmography-based atrial fibrillation detection using smartphones.
Atrial fibrillation (AF) is one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity and the most common type of arrhythmia. Its diagnosis and the initiation of treatment, however, currently requires electrocardiogram (ECG)-based heart rhythm monitoring. The photoplethysmogram (PPG) offers an alternative method, which is convenient in terms of its recording and allows for self-monitoring, thus relieving clinical staff and enabling early AF diagnosis. We introduce a PPG-based AF detection algorithm using smartphones that has a low computational cost and low memory requirements. In particular, we propose a modified PPG signal acquisition, explore new statistical discriminating features and propose simple classification equations by using sequential forward selection (SFS) and support vector machines (SVM). The algorithm is applied to clinical data and evaluated in terms of receiver operating characteristic (ROC) curve and statistical measures. The combination of Shannon entropy and the median of the peak rise height achieves perfect detection of AF on the recorded data, highlighting the potential of PPG for reliable AF detection.


Bilateral Central Retinal Vein Occlusion as a First Presentation of Multiple Myeloma: A Case Report.
Acute presentation of multiple myeloma in the emergency department (ED) is an uncommon yet life-threatening clinical entity. A 42-year-old male presented to the ED with severe generalized fatigue and vision changes most notable in his left eye. Bilateral central retinal vein occlusion (CRVO) was diagnosed on dilated fundus exam in the ED. The most common cause of CRVO in adults over age 50 is vascular disease, but in younger adults, conditions of systemic inflammation or hyperviscosity must be considered. Diagnosis of CRVO requires emergent ophthalmology consultation and further treatment with phototherapy, steroids, and potentially anti-vascular endothelial growth factor. Ultimately, patients require hematology/oncology and ongoing management of acute hyperviscosity syndrome. We present this case to increase awareness surrounding this diagnosis among emergency physicians. Multiple myeloma should be considered in young patients who present to the ED with bilateral CRVO, acute renal failure, and symptomatic anemia.


The octamer binding transcription factor Oct-1 is a stress sensor.
The POU-domain transcription factor Oct-1 is widely expressed in adult tissues and has been proposed to regulate a large group of target genes. Microarray expression profiling was used to evaluate gene expression changes in Oct-1-deficient mouse fibroblasts. A number of genes associated with cellular stress exhibited altered expression. Consistent with this finding, Oct-1-deficient fibroblasts were hypersensitive to gamma radiation, doxorubicin, and hydrogen peroxide and harbored elevated reactive oxygen species. Expression profiling identified a second group of genes dysregulated in Oct-1-deficient fibroblasts following irradiation, including many associated with oxidative and metabolic stress. A number of these genes contain octamer sequences in their immediate 5' regulatory regions, some of which are conserved in human. These results indicate that Oct-1 modulates the activity of genes important for the cellular response to stress.


Feasibility and acceptability of a structured quality by design approach to enhancing the rigor of clinical studies at an academic health center.
Clinical trials are a critical step in the meaningful translation of biomedical discoveries into effective diagnostic and therapeutic interventions. Quality by design (QbD) is a framework for embedding quality into the design, conduct, and monitoring of clinical trials. Here we report the feasibility and acceptability of a process for implementing QbD in clinical research at an academic health center via multidisciplinary design studios aimed at identifying and prioritizing critical to quality (CTQ) factors. The Clinical Trial Transformation Initiative's Principles Document served as a guide to identify and categorize key CTQ factors, defined as elements of a clinical trial that are critical to patient safety and data integrity. Individual trials were reviewed in CTQ design studios (CTQ-DS) and the feasibility and acceptability of this intervention was examined through post-meeting interviews and surveys. Eight clinical research protocols underwent the QbD evaluation process. The protocols ranged from multicenter randomized clinical trials to nonrandomized investigator-initiated studies. A developmental evaluation informed the iterative refinement of the CTQ-DS process, and post-meeting surveys revealed that CTQ-DS were highly valued by principal investigators (PIs) and resulted in multiple protocol changes. The present study demonstrated that QbD principles can be implemented to inform the design and conduct of clinical research at an academic health center using multidisciplinary design studios aimed at identifying and prioritizing CTQ elements. This approach was well received by the participants including study PIs. Future research will need to evaluate the effectiveness of this approach in improving the quality of clinical research.


Cloning and Expression Analysis of a Novel Gene, UBAP1, Possibly Involved in Ubiquitin Pathway.
The 9p21-22 region shows loss of heterozygosity in up to 60% of human nasopharyngeal carcinomas (NPC), indicating the presence of a tumor suppressor gene in this region. We have identified a novel minimal common deletion region at 9p21-22. Twenty-two epithelial-derived expressed sequence tags (ESTs) in this critical region were systematically screened by differential RT-PCR to investigate the expression patterns in NPC cell line HNE1 and primary cultures of normal nasopharyngeal epithelial cells. One of these ESTs was found down-expressed in HNE1, whose differential expression was confirmed by Northern blot. Subsequently the corresponding gene sequence for this EST was established by cDNA cloning and RACE procedures (GenBank Accession No.AF222043). Furthermore, a mouse homologueof this gene was identified (GenBank Accession No.AF275549). This gene is 2.7 kb long and contains two UBA domains. It is a new member of UBA domain protein family, encoding a putative protein of 502 amino acids with a theoretical molecular mass of 55 kD, so we have named this gene UBAP1 for ubiquitin associated protein 1 (HUGO Gene Nomenclature Committee-approved symbol). Northern blot and RT-PCR analysis demonstrated a ubiquitous pattern of gene expression in human and mouse tissues. Direct sequencing analysis of the coding region of hUBAP1 following RT-PCR failed to reveal any mutations in a preliminary screening of NPC cell line HNE1 and primary nasopharyngeal carcinomas samples. However, more detailed analysis is to be performed to reveal if fine mutations of this gene are present in NPC.


Rhizomicrobium electricum sp. nov., a facultatively anaerobic, fermentative, prosthecate bacterium isolated from a cellulose-fed microbial fuel cell.
A facultatively anaerobic, prosthecate bacterium, strain Mfc52(T), was isolated from a microbial fuel cell inoculated with soil and fed with cellulose as the sole fuel. Cells were Gram-negative, non-spore-forming, straight or slightly curved rods, and some of them had one or two polar prosthecae (stalks). Cells reproduced by binary fission or by budding from mother cells having prosthecae. Strain Mfc52(T) fermented various sugars and produced lactate, acetate and fumarate. Ferric iron, nitrate, oxygen and fumarate served as electron acceptors, while sulfate and malate did not. Nitrate was reduced to nitrite. The DNA G+C content was 64.7 mol%. On the basis of 16S rRNA gene sequence phylogeny, strain Mfc52(T) was affiliated with the genus Rhizomicrobium in the class Alphaproteobacteria and most closely related to Rhizomicrobium palustre with a sequence similarity of 97 %. Based on these physiological and phylogenetic characteristics, the name Rhizomicrobium electricum sp. nov. is proposed; the type strain is Mfc52(T) ( = JCM 15089(T) = KCTC 5806(T)).


Cellular mechanisms of aminoglycoside ototoxicity.
To summarize advances in the study of the interaction between sensory hair cells and aminoglycoside antibiotics. Aminoglycosides enter hair cells through mechanotransduction channels and initiate an active signaling pathway that leads to cell death. Early expression of heat shock proteins can protect hair cells from aminoglycosides, although signaling from surrounding supporting cells appears to promote hair cell death. Studies of certain human deafness mutations have revealed new insights into the role of mitochondria in aminoglycoside ototoxicity. The cellular mechanisms of aminoglycoside ototoxicity continue to be an active topic of research and newly developed animal models offer great promise for future advances. Nevertheless, proven clinical methods for the prevention of ototoxic injury are not yet available.


MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification.
In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.


Development of the Canadian Eating Practices Screener to assess eating practices based on 2019 Canada's Food Guide recommendations.
In 2019, Health Canada released a new iteration of Canada's Food Guide (2019-CFG), which, for the first time, highlighted recommendations regarding eating practices, i.e., guidance on where, when, why, and how to eat. The objective of this study was to develop a brief self-administered screener to assess eating practices recommended in the 2019-CFG among adults aged 18-65 years. Development of the screener items was informed by a review of existing tools and mapping of items onto 2019-CFG recommendations. Face and content validity were assessed with experts in public health nutrition and/or dietary assessment (n = 16) and individuals from Government of Canada (n = 14). Cognitive interviews were conducted with English-speaking (n = 16) and French-speaking (n = 16) adults living in Canada to assess face validity and understanding of the screener items. While some modifications were identified to improve relevance or clarity, overall, the screener items were found to be relevant, well-constructed, and clearly worded. This comprehensive process resulted in the Canadian Eating Practices Screener/Questionnaire court canadien sur les pratiques alimentaires, which includes 21 items that assess eating practices recommended in the 2019-CFG. This screener can facilitate monitoring and surveillance efforts of the 2019-CFG eating practices as well as research exploring how these practices are associated with various health outcomes.


The role of antiresorptive therapies in improving patient care in early and metastatic breast cancer.
Breast cancer is the second most common cancer among American women and has a high rate of metastasis to bone. Patients regularly undergo adjuvant therapy (chemotherapy or hormonal therapy) following surgical resection of the tumor. In addition to potential direct effects on bone cells, both chemotherapy and hormonal therapy induce ovarian dysfunction and dramatically decrease estrogen levels in both pre- and postmenopausal women. This leads to decreased bone mineral density and increased fracture risk. Antiresorptive therapies (e.g, zoledronic acid and denosumab) have demonstrated efficacy in preventing cancer therapy-induced bone loss in patients with breast cancer and are approved for the prevention of skeletal-related events in patients with bone metastases from breast cancer. This review will focus on the evolving role of these antiresorptive therapies in the care of women with early or metastatic breast cancer.


Post-COVID mucormycosis osteomyelitis and its imaging manifestations in the North of Iran: case series.
Mucormycosis is an invasive fungal infection that usually affects patients with immunocompromised conditions. In the context of the COVID-19 pandemic and the following corticosteroid therapy, mucormycosis prevalence has increased. The situation may be more complicated with some underlying diseases such as diabetes mellitus. In addition, due to the vicinity of maxillary bone to the nasal cavity and paranasal sinuses, which are the main routes for the infection to spread, dentists, maxillofacial radiologists, and surgeons may be the first to encounter these patients. Post-COVID mucormycosis osteomyelitis is one of the complications of this infection Bone destruction and the erosion or breach of cortical boundaries of the maxilla and the bone structures in the vicinity of paranasal sinuses are the most critical radiographic findings of post-covid osteomyelitis. Herein, there are some cases of post-covid mucormycosis osteomyelitis involving the maxillary and other facial bones.


Cold restraint stress-induced gastric mucosal dysfunction. Role of nitric oxide.
The objectives of this study were to determine the cold restraint stress-induced changes in gastric mucosal permeability and to assess whether nitric oxide synthesis inhibition affects gastric mucosal integrity after cold-restraint administration. Cold-restraint stress caused multiple gastric lesions in 90% of animals. The lesion index was found to be 3.87 +/- 0.97 mm. Gastric mucosal permeability to the [51CR]EDTA molecule was significantly elevated in the cold-restraint group compared to control. In order to evaluate the role of nitric oxide in cold restraint stress-induced gastropathy, L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) was given as a bolus (10 mg/kg, intravenously) and infused at a rate of 2 mg/ml/hr for 2 hr after cold-restraint administration. L-NAME greatly exacerbated gastric mucosal dysfunction associated with cold-restraint stress. D-NAME, the biologically inactive enantiomer, did not enhance mucosal dysfunction, whereas L-arginine, the substrate for nitric oxide, reversed the effect of L-NAME. In an additional group of experiments, effects of cold-restraint stress and L-NAME on net transmucosal fluid flux as well as tissue myeloperoxidase activity (MPO) were assessed. Cold-restraint stress administration significantly reduced the absorptive capacity of stomach, whereas L-NAME treatment did not affect the stress-induced alterations on net fluid absorption. Furthermore, L-NAME treatment did not affect the cold restraint stress-induced changes in tissue MPO activity. Our results suggest that gastric barrier function is altered after cold-restraint stress and nitric oxide production is important in minimizing mucosal barrier dysfunction associated with cold-restraint stress administration. Our results also indicate that L-NAME-induced alterations on mucosal permeability are not related to net transmucosal fluid flux and tissue neutrophils.


[Clinical application progress of bioresorbable vascular scaffolds in lower extremities arteriosclerotic obliterans].
Endovascular technology has become the first choice for the treatment of lower extremities arteriosclerotic obliterans. Bioresorbable vascular scaffolds have attracted more and more attention as a choice of endovascular technology. In the last decade, poly(L-lactic acid) bioresorbable scaffolds with or without drug coating have shown acceptable medium and long-term safety and efficacy in lower extremities arteriosclerotic obliterans, but the lesions of the subjects were relatively simple. Magnesium alloy bioresorbable scaffolds are safe but less effective in the treatment of lower extremities arteriosclerotic obliterans. Both iron and zinc alloy bioresorbable scaffolds have shown considerable results in animal experiments. In particular, the success of implantation of drug-coated iron alloy bioresorbable scaffolds in below-the-knee artery indicated that the iron alloy bioresorbable scaffolds have officially entered the clinical trial stage. Through the comprehensive summation of the previous clinical and experimental data of bioresorbable vascular scaffolds and the pathological characteristics of lower extremities arteriosclerotic obliterans, it is shown that the drug-coated poly(L-lactic acid) bioresorbable scaffolds and iron alloy bioresorbable scaffolds will have greater development potential in the treatment of lower extremities arteriosclerotic obliterans.


Diabetes mellitus influences the degree of colocalization of calcitonin gene-related peptide with insulin and somatostatin in the rat pancreas.
Although calcitonin-gene related peptide (CGRP) (C162H262N50O50S2) has been shown to be present in pancreatic islet cells, no data have been reported on the pattern of its distribution in the islets of Langerhans of diabetic rats. The present study used immunohistochemical and immunofluorescence techniques to examine the pattern of distribution of CGRP-like immunoreactive (CGRP-LIR) cells and nerves in the pancreata of rats with streptozotocin-induced diabetes. The effect of CGRP on insulin secretion from rat pancreatic tissue fragments was also investigated using a radioimmunoassay technique. Numerous CGRP-LIR cells were observed in both the peripheral and central regions of the islets of Langerhans of normal pancreata where they colocalized with large and small subsets of insulin-LIR and somatostatin-LIR cells, respectively. By contrast, the islets of diabetic rat pancreata contained significantly (P < 0.0001) fewer CGRP-LIR cells compared with normal rats. In diabetic rat pancreata, CGRP was colocalized with larger and smaller subsets of somatostatin-LIR and insulin-LIR cells, respectively. CGRP-LIR nerve fibers were discerned in the perivascular and periacinar regions of the pancreata of both normal and diabetic rats. CGRP (10 M) induced a significant (P < 0.02) increase in insulin secretion from the pancreas of normal rat. CGRP is colocalized with insulin and somatostatin in the pancreata of normal and diabetic rats and may play an important role in the humoral and neural regulation of the endocrine pancreas.


Human recombinant migration inhibitory factor activates human macrophages to kill Leishmania donovani.
A recombinant form of the first lymphokine to be discovered, migration inhibitory factor (rMIF) was obtained from COS-1 cells transfected with a cDNA library from a human T cell hybridoma (6). rMIF has an amino acid sequence unrelated to that of any known protein. To learn more about the biology of MIF, we tested its ability to effect the survival of Leishmania donovani in macrophages. We found that rMIF activates blood monocyte-derived macrophages in vitro to suppress the growth of and kill these intracellular parasites. The anti-leishmanial effect (ranging from 50 to 77% reduction of parasites) is maximal when macrophages have been incubated with rMIF 48 to 72 h before infection and is similar to that seen with macrophages activated by IFN-gamma. Of interest, whereas the activation of human macrophages by IFN-gamma is inhibited by IL-4 and not enhanced by LPS, the activation by rMIF is enhanced by LPS but is not inhibited by IL-4. The data presented here demonstrate that rMIF is a potent activator of macrophages and is likely to be critical in cell-mediated immune host defenses.


Are patients' initial experiences at the diagnosis of type 2 diabetes associated with attitudes and self-management over time?
Objective The purpose of this study was to investigate patients' experiences when diagnosed with type 2 diabetes and diabetes-related distress and self-management years later. Method One hundred seventy-nine adults with type 2 diabetes, 1 to 5 years after diagnosis, completed a questionnaire assessing what they were told and what was recommended at diagnosis as well as current diet, physical activity, and diabetes distress. Most patients (60%) expressed confidence in their health care provider (HCP) at diagnosis, but 30% reported that a clear action plan was not communicated. Current diabetes distress was significantly lower among those who reported being reassured at diagnosis that diabetes could be managed successfully and had developed a clearer action plan with their HCP. Patients' current dietary behaviors were significantly better among those receiving a clearer action plan at diagnosis. Patients' retrospective reports of reassuring HCP messages when diagnosed, along with the presentation of a clear action plan, are associated with less diabetes distress and better self-management at 1 to 5 years after diagnosis. Practical implications Findings suggest a long-lasting impact on patients' attitudes and behaviors when the diagnosis of type 2 diabetes is delivered clearly, a sense of hope is provided, and a specific care plan is put forward.


Geometric interpretation for coupled-cluster theory. A comparison of accuracy with the corresponding configuration interaction model.
Although coupled-cluster theory is well-known for its accuracy, the geometry associated with the manifold of wave functions reached by the coupled-cluster Ansatz has not been deeply explored. In this article, we look for an interpretation for the high accuracy of coupled-cluster theory based on how the manifold of coupled-cluster wave functions is embedded within the space of n-electron wave functions. We define the coupled-cluster and configuration interaction manifolds and measure the distances from the full-configuration interaction (FCI) wave function to these manifolds. We clearly observe that the FCI wave function is closer to the coupled-cluster manifold that is curved than to the configuration interaction manifold that is flat for the selected systems studied in this work. Furthermore, the decomposition of the distances among these manifolds and wave functions into excitation ranks gives insights into the failure of the coupled-cluster approach for multireference systems. The present results show a new interpretation for the quality of the coupled-cluster method, as contrasted to the truncated configuration interaction approach, besides the well-established argument based on size extensivity. Furthermore, we show how a geometric description of wave function methods can be used in electronic structure theory.


Salmonella paratyphi A infection presenting as breast abscess.
Salmonella in a breast abscess is uncommon, and Salmonella paratyphi A causing breast abscess is a rare entity. It has been reported post immunosuppression. We report here a 35-year-old woman with breast abscess caused by S. paratyphi A without obvious enteric fever-like symptoms. The case was managed with combined surgical and medical approach to treat the aetiology and focal infection.


Simultaneous quantification of carbamazepine crystal forms in ternary mixtures (I, III, and IV) by diffuse reflectance FTIR spectroscopy (DRIFTS) and multivariate calibration.
Diffuse reflectance FTIR spectroscopy (DRIFTS) coupled with modern multivariate calibration methods, namely artificial neural networks (ANNs) in two versions (ANN-raw and ANN-pca), support vector machines (SVMs), lazy learning (LL) and partial least squares (PLS) regression, is used in this study for the quantification of carbamazepine crystal forms in ternary powder mixtures (I, III, and IV). Two spectral regions (675-1180 and 3400-3600/cm) were selected and the data were partitioned into training and test subsets applying the Kennard-Stone design. It was found that all the selected algorithms perform better than the PLS regression (root mean squared error of prediction (RMSEP) from 3.0% to 8.2%). ANN-raw, trained on uncompressed spectral data, shows best predictive performance (RMSEP < 2.25%) but longest computation (up to 10 min). Principal component analysis (PCA) compression of the input spectral data accelerates significantly the computation (<16 s) at a relatively low cost in precision (RMSEP < 3.24%). The LL algorithm shows excellent performance in the 3400-3600/cm range (RMSEP < 1.6%), but in the 675-1180/cm range it shows strong dependence on data set structure (RMSEP between 1.6% and 8.9%). SVMs perform comparably well with ANNs (RMSEP < 3.1%), not showing the long computation time of ANNs (<1 s) and therefore may provide an attractive alternative to ANNs.


Ginsenoside Rg1 attenuates the inflammation and oxidative stress induced by diabetic nephropathy through regulating the PI3K/AKT/FOXO3 pathway.
Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus. Ginsenoside Rg1 (Rg1) is an important active ingredient extracted from Panax ginseng. This study aimed to investigate the role and molecular mechanism of Rg1 in DN model. The mesangial cell line HBZY-1 was induced by high glucose (HG; 30 mM D-glucose). HG-induced HBZY-1 cells were treated with Rg1 (2.5, 5, 10 µmol/L). Cell viability was measured by the MTT assay. Apoptosis was detected by flow cytometry. Related proteins were measured by western blot. Reactive oxygen species (ROS) production was measured by dichlorodihydrofluorescein diacetate (DCFH-DA). Inflammatory factors and molecules associated with oxidative stress were detected by enzyme-linked immunoassay (ELISA). DN rats model were treated with 50mg/kg/d Rg1 for 8 weeks, the histopathological changes and the expression of relevant markers were analyzed. We found that Rg1 treatment markedly elevated the survival rates of HG-induced HBZY-1 cells and reduced apoptosis induced by HG. Rg1 treatment attenuated the HG-induced inflammatory response by decreasing the high levels of TNF-α, IL-1β, and IL-6. Furthermore, Rg1 treatment alleviated HG-induced oxidative stress by decreasing ROS generation, malondialdehyde (MDA), and lactate dehydrogenase (LDH) accumulation and increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). After Rg1 (50 mg/kg/d) treatment, the severe glomerular thylakoid hyperplasia, glomerular atrophy, tubule dermal cell exfoliation, basement membrane exposure, interstitial edema and inflammatory cell cytoplasmic infiltration were alleviated in DN rats. DN rat model treated with Rg1 (50 mg/kg/d) showed good anti-inflammatory and antioxidant activities. Rg1 treatment also increased the levels of the phosphorylation of PI3K (p-PI3K) and AKT (p-AKT) and promoted the transfer of FOXO3 from the nucleus to the cytoplasm in vitro and in vivo. Rg1 exhibited protective effects on DN-induced inflammatory responses and oxidative stress via regulating the PI3K/AKT/FOXO3 pathway in in vitro and in vivo. The results suggest that Rg1 may be a potential therapeutic agent for DN treatment.


Placement history of foster children: a study of placement history and outcomes in long-term family foster care.
The files of 419 children in family foster care and kinship foster care were used in a retrospective longitudinal design study that examined their placement histories in child welfare. Significant associations were found between the number of placements on one hand, and the prevalence of attachment disorders, severity of behavioral problems, and breakdowns of new foster care placements on the other hand. It appears that a breakdown can be predicted to a certain extent, the implications of which are discussed.


Novel ionically crosslinked casein nanoparticles for flutamide delivery: formulation, characterization, and in vivo pharmacokinetics.
A novel particulate delivery matrix based on ionically crosslinked casein (CAS) nanoparticles was developed for controlled release of the poorly soluble anticancer drug flutamide (FLT). Nanoparticles were fabricated via oil-in-water emulsification then stabilized by ionic crosslinking of the positively charged CAS molecules below their isoelectric point, with the polyanionic crosslinker sodium tripolyphosphate. With the optimal preparation conditions, the drug loading and incorporation efficiency achieved were 8.73% and 64.55%, respectively. The nanoparticles exhibited a spherical shape with a size below 100 nm and a positive zeta potential (+7.54 to +17.3 mV). FLT was molecularly dispersed inside the nanoparticle protein matrix, as revealed by thermal analysis. The biodegradability of CAS nanoparticles in trypsin solution could be easily modulated by varying the sodium tripolyphosphate crosslinking density. A sustained release of FLT from CAS nanoparticles for up to 4 days was observed, depending on the crosslinking density. After intravenous administration of FLT-CAS nanoparticles into rats, CAS nanoparticles exhibited a longer circulation time and a markedly delayed blood clearance of FLT, with the half-life of FLT extended from 0.88 hours to 14.64 hours, compared with drug cosolvent. The results offer a promising method for tailoring biodegradable, drug-loaded CAS nanoparticles as controlled, long-circulating drug delivery systems of hydrophobic anticancer drugs in aqueous vehicles.


Regulation and properties of the glutamine synthetase purified from Photobacterium phosphoreum.
Glutamine synthetase from a marine enterobacterium, Photobacterium phosphoreum, was purified to homogeneity from cells grown in glycerol-yeast extract medium. The purified enzyme had a molecular weight of approximately 670,000 and a subunit size of 56,000, i.e. larger than that of the enzyme from E. coli. Regulation of the glutamine synthetase activity by adenylylation/deadenylylation was demonstrated on snake venom phosphodiesterase treatment. The state of adenylylation appeared to influence both the biosynthetic and gamma-glutamyltransferase activities of P. phosphoreum glutamine synthetase similar to in the case of the E. coli enzyme. The enzyme activity was controlled by adenylylation and possibly in combination with feedback inhibition by alanine, serine, and glycine, metabolites which are especially effective in inhibiting P. phosphoreum glutamine synthetase. When either Mn2+ or Mg2+ was added to the relaxed (divalent cation-free) enzyme, similar UV-difference spectra were obtained for the enzyme, indicating that the conformational states induced by these cations were also similar. The profile of these spectra varied from those published for E. coli, and three peaks were four 1 at 282.5, 288.5, and 298 nm.


Hemodynamic and catecholamine responses to laryngoscopy with vs. without endotracheal intubation.
To study the relationship between the intensity of the stimulus exerted against the base of the tongue during direct laryngoscopy and the magnitude of associated hemodynamic and catecholamine responses, a study was conducted in 40 ASA I or II patients. Laryngoscopy lasting 40 s was performed with a size 3 Macintosh blade connected to a force-displacement transducer. The intensity of the stimulus exerted during laryngoscopy is expressed by the product of its average force (N) and duration (s) and given as impulse in Ns. Highly significant relationships were found between the impulse during laryngoscopy and the maximal hemodynamic and catecholamine responses. Also, when laryngoscopy was followed by orotracheal intubation, significant relationships were found with steeper slopes of the regression lines for systolic blood pressure, heart rate and plasma epinephrine concentrations. A more rapid regression of hemodynamic data was seen in intubated patients, whereas their plasma catecholamine concentrations regressed more slowly. The mechanisms of the responses to laryngoscopy and orotracheal intubation are proposed to be by somato-visceral reflexes. Stimulation of proprioceptors at the base of the tongue during laryngoscopy induces impulse-dependent increases of systemic blood pressure, heart rate and plasma catecholamine concentrations. Subsequent orotracheal intubation recruits additional receptors that elicit augmented hemodynamic and epinephrine responses as well as some vagal inhibition of the heart.


Solubilization and dissolution of tamoxifen-hydroxybutenyl cyclodextrin complexes.
The solubility and dissolution of tamoxifen base and tamoxifen citrate with and without hydroxybutenyl-beta-cyclodextrin (HBenBCD) in aqueous and organic media were examined. The solubility of tamoxifen was greatly enhanced by complexation with HBenBCD; pH of the medium, and choice of buffer significantly impacted the amount of drug that could be solubilized. Different tamoxifen:HBenBCD formulations were prepared, including liquid fill capsule formulations, and their dissolution profiles were obtained. These dissolution studies demonstrated that enhanced solubilization of tamoxifen with HBenBCD was effective across a wide variety of formulation options. By complexation of tamoxifen base with HBenBCD, it was possible to obtain solubility and dissolution profiles for tamoxifen base that were essentially identical to that of tamoxifen citrate.


Strategies to improve adherence and acceptability of hormonal methods of contraception.
Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite their high theoretical effectiveness, typical use results in much lower effectiveness. In large part, this disparity reflects difficulties in adherence to the contraceptive regimen and low rates for long-term continuation. The intent was to determine the effectiveness of ancillary counseling techniques to improve adherence to, and continuation of, hormonal methods of contraception. Through August 2013, we searched computerized databases for randomized controlled trials (RCTs) comparing client-provider interventions with standard family planning counseling. Sources included CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov and ICTRP. Earlier searches also included LILACS, PsycINFO, Dissertation Abstracts, African Index Medicus, and IMEMR. We included RCTs of an intensive counseling technique or other client-provider intervention compared to routine family planning counseling. Interventions included group motivation; structured, peer, or multi-component counseling; and intensive reminders of appointments or next dosing. Outcome measures were discontinuation, reasons for discontinuation, number of missed pills or on-time injections, and pregnancy. One author evaluated the titles and abstracts from the searches to determine eligibility. Two authors extracted data from the included studies. We calculated the Mantel-Haenszel odds ratio (OR) for dichotomous outcomes. For continuous variables, the mean difference (MD) was computed; RevMan uses the inverse variance approach. For all analyses, 95% confidence intervals (CI) were also computed. Since the studies identified differed in both interventions and outcome measures, we did not conduct a meta-analysis. Nine RCTs met our inclusion criteria. Five involved direct counseling; of those, two also provided multiple contacts by telephone. Four other trials provided intensive reminders, two of which also provided health education information. Three trials showed some benefit of the experimental intervention. In a counseling intervention, women who received repeated structured information about the injectable depot medroxyprogesterone acetate (DMPA) were less likely to discontinue the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than women who had routine counseling. The intervention group was also less likely to discontinue due to menstrual disturbances (OR 0.20; 95% CI 0.11 to 0.37). Another trial showed a group with special counseling plus phone calls was more likely than the special-counseling group to report consistent use of oral contraceptives (OC) at 3 months (OR 1.41; 95% CI 1.06 to 1.87), though not at 12 months. The group with only special counseling did not differ significantly from those with standard care for any outcome. The third trial compared daily text-message reminders about OCs plus health information versus standard care. Women in the text-message group were more likely than the standard-care group to continue OC use by six months (OR 1.54; 95% CI 1.14 to 2.10). The text-message group was also more likely to avoid an interruption in OC use longer than seven days (OR 1.53; 95% CI 1.13 to 2.07). Only three trials showed some benefit of strategies to improve adherence and continuation. However, several had small sample sizes and six had high losses to follow up. The overall quality of evidence was considered moderate. The intervention type and intensity varied greatly across the studies. A combination of intensive counseling and multiple contacts and reminders may be needed to improve adherence and acceptability of contraceptive use. High-quality RCTs with adequate power and well-designed interventions could help identify ways to improve adherence to, and continuation of, hormonal contraceptive methods.


Evolving standards in patient and caregiver support.
It has become increasingly clear that family members and others have enormous potential to contribute positively to the care of the patient suffering from Alzheimer disease (AD). Various methods such as respite services and day care as well as counseling and support groups have been shown to reduce caregiver stress and burnout. Moreover, there are many areas in which the informed, trained caregiver can contribute positively to, and even lead, the interdisciplinary ongoing care of AD patients. For example, the caregiver can help with memory aids, behavioral interventions, the maintenance of exercise and nutrition, healthcare proxies and housing arrangements, decisions about intensity of treatment, and the timely implementation of palliative care approaches. Caregivers skilled in such matters will increase the quality of life of the AD patient and reduce their dependency. Many support services and educational activities are known to help caregivers and their patients, yet their availability is variable, and it is unclear whose responsibility it is to organize and finance them.


Charcoal: from antiquity to artificial kidney.
According to Herodotus, the use of charcoal was introduced in ancient Egypt; however only in 1773 Carl Willhelm Scheele utilized it for adsorbing gases. Finally, Hippocrates Yatzidis in 1963 demonstrated its binding capacity for toxic substances of endogenous or exogenous origin and used it for hemoperfusion systems.


Human granulocytic anaplasmosis: First reported case in Canada.
Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infection of peripheral blood neutrophils caused by Anaplasma phagocytophilum. While this infection is increasingly recognized as endemic throughout much of the United States, no Canadian cases have been previously described, despite the agent being identified in Canadian ticks. Herein we present a case of HGA acquired in an urban Alberta centre. Canadian physicians must be aware of the possibility of tick-borne rickettsial diseases as etiology of fever in individuals presenting with leukopenia/lymphopenia, thrombocytopenia and elevated transaminases during periods of tick activity. Prompt recognition and treatment are important in minimizing resultant morbidity and mortality.


Perception of risk and sexual self-protective behavior: a methodological critique.
Although several theories suggest that perceptions of the risk of transmission of sexually transmitted diseases, including HIV, motivate individuals to adopt or maintain self-protective behaviors, the research literature has generally failed to demonstrate this relationship. Because many HIV prevention interventions are based on the presumption of this relationship and because there is support for the effects of risk perception on self-protective behaviors in other health domains, a closer examination of the research concerning HIV risk perception is warranted. Therefore, a critical review of methodological features of research in this area was conducted. Issues considered were measurement; research design; the distinctive characteristics of HIV risk; the sexual and social nature of HIV transmission; and ecological, construct, and statistical conclusion validity. Methodological and design recommendations were made for testing the effects of HIV risk perception more adequately.


Molecular analysis of blood group Rh transcripts from a rGr variant.
The Rh blood group antigens D, Cc and Ee are encoded by two related genes, RHD and RHCE. The RhG antigen (Rh12) is associated with the expression of RhC and/or RhD, except in rare variant red cells. Here we have determined the molecular basis of G expression in the absence of D and C in the rGr phenotype. Nucleotide sequence analysis revealed that the rG allele resulted either from a segmental DNA exchange between part of exon 2 of the RHce gene and the equivalent region of the RHCE or RHD genes or from a crossing over between positions nt150 and nt178 of the RHce and RHCe genes. The predicted protein encoded by the hybrid rG gene (c-C-e or c-D-e) carries Ile60, Ser68 and Ser103 (as C and D polypeptides); any of these positions appear to be critical in the formation of the G antigen. In addition, Cys16 was found to be important in the phenotypic expression of C.


Cerebellar ataxia with coenzyme Q10 deficiency: diagnosis and follow-up after coenzyme Q10 supplementation.
Our aim was to report a new case with cerebellar ataxia associated with coenzyme Q10 (CoQ) deficiency, the biochemical findings caused by this deficiency and the response to CoQ supplementation. A 12-year-old girl presenting ataxia and cerebellar atrophy. BIOCHEMICAL STUDIES: Coenzyme Q10 in muscle was analysed by HPLC with electrochemical detection and mitochondrial respiratory chain (MRC) enzyme activities by spectrophotometric methods. CoQ biosynthesis in fibroblasts was assayed by studying the incorporation of radiolabeled 4-hydroxy[U 14C] benzoic acid by HPLC with radiometric detection. Mitochondrial respiratory chain enzyme analysis showed a decrease in complex I + III and complex II + III activities. CoQ concentration in muscle was decreased (56 nmol/g of protein: reference values: 157-488 nmol/g protein). A reduced incorporation of radiolabeled 4-hydroxy[U- 14C] benzoic acid was observed in the patient (19% of incorporation respect to the median control values). After 16 months of CoQ supplementation, the patient is now able to walk unaided and cerebellar signs have disappeared. Cerebellar ataxia associated with CoQ deficiency in our case might be allocated in the transprenylation pathway or in the metabolic steps after condensation of 4-hydroxybenzoate and the prenyl side chain of CoQ. Clinical improvement after CoQ supplementation was remarkable, supporting the importance of an early diagnosis of this kind of disorders.


Description and validation of a dynamical systems model of presynaptic serotonin function: genetic variation, brain activation and impulsivity.
Despite more than a decade of empirical work on the role of genetic polymorphisms in the serotonin system on behavior, the details across levels of analysis are not well understood. We describe a mathematical model of the genetic control of presynaptic serotonergic function that is based on control theory, implemented using systems of differential equations, and focused on better characterizing pathways from genes to behavior. We present the results of model validation tests that include the comparison of simulation outcomes with empirical data on genetic effects on brain response to affective stimuli and on impulsivity. Patterns of simulated neural firing were consistent with recent findings of additive effects of serotonin transporter and tryptophan hydroxylase-2 polymorphisms on brain activation. In addition, simulated levels of cerebral spinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) were negatively correlated with Barratt Impulsiveness Scale (Version 11) Total scores in college students (r = -.22, p = .002, N = 187), which is consistent with the well-established negative correlation between CSF 5-HIAA and impulsivity. The results of the validation tests suggest that the model captures important aspects of the genetic control of presynaptic serotonergic function and behavior via brain activation. The proposed model can be: (1) extended to include other system components, neurotransmitter systems, behaviors and environmental influences; (2) used to generate testable hypotheses.


Occipital Interhemispheric Transtentorial Approach for a Pineal Region Meningioma with Pseudobulbar Palsy.
Meningiomas represent 8%-10% of all pineal region (PR) tumors. When they arise from the falx, tentorium, or tentorial incisura, they are not always considered a true PR tumor, as they do not originate from it but instead only grow toward the region. The true meningioma of PR must be originated from the arachnoid envelope of the pineal gland or from the 2 leaflets of the velum interpositum. In both conditions there are no dural attachments.1,2 Occipital interhemispheric transtentorial and supracerebellar infratentorial are the 2 main approaches for tumors within this region. Aside from the surgeon's preference, the position of the venous system and the direction of the tumor growth guide the approach choice. Endoscope assistance can help reach areas unable to be visualized under the microscope.3-5 We report the case of a 37-year-old female with a large PR meningioma (velum interpositum) presenting with intense dysphagia, dysphonia, and bilateral tongue palsy. Given the affected bilateral upper motor tracts associated with bulbar symptoms, a diagnosis of pseudobulbar palsy was considered.6,7 Preoperative imaging also showed compression of the deep venous system. The patient underwent a total resection of the tumor via an occipital interhemispheric transtentorial approach and exhibited a dramatic recovery of neurologic symptoms after the surgery (Video 1). Postoperative venogram showed restoration of the usual deep venous system pattern, which may be associated with significant neurologic improvement. Careful management of the deep veins is mandatory during the resection of PR meningiomas. The venous system improvement after the surgery may be associated with the dramatic recovery seen in this unique case. The patient consented to publication of her images.


Acquisition of competence in colonoscopy: the learning curve of trainees.
Most official training programs in colonoscopy recommend that trainees should carry out a minimum of 100 procedures, but limited data exist on the technical progress of trainees. The aim of our study was to estimate the number of supervised procedures required for obtaining competence in colonoscopy. Between 1990 and 1997 we have prospectively evaluated the performance of eight consecutive trainees in colonoscopy. The extent of intubated colon was recorded after each endoscopic procedure. Regression analysis was used to study the effect on the trainees' success rates on the number of colonoscopies which they had done. Out of 2,255 colonoscopies carried out over an 8-year period 1,408 were suitable for evaluation, fulfilling the training criteria for diagnostic colonoscopy. Senior staff (n=2) did 430 colonoscopies with a success rate of 91%, which was significantly reduced to 79% (344/434 colonoscopies; X2=20.67, df=l, P<0.001), when taking over colonoscopies which trainees had failed to complete. Regression analysis of trainees' data (y=88.97-(2185/x), r=0.74, F1,21=23.43, P<0.001) showed success rates of 67 % (95 % CI, 59 to 75 %) and 77 % (95 % CI, 66 to 88 %), when 100 and 180 procedures, respectively, had been done. These figures had been attained by the end of the second and third year of training in colonoscopy. Our regression analysis model shows the technical progress of trainees over a 3-year period as they learned how to carry out colonoscopy. Depending on individual skill, between 100-180 procedures, done over a 2-3-year period, are required before trainees can be considered competent in colonoscopy.