Prevalence and risk factors for asymptomatic Clostridium difficile carriage.
Clostridium difficile infection (CDI) incidence has increased dramatically over the last decade. Recent studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We sought to identify the prevalence and risk factors for asymptomatic C. difficile carriage on admission to the hospital. Patients admitted to Barnes-Jewish Hospital without diarrhea were enrolled from June 2010 through October 2011. Demographic information and healthcare and medication exposures 90 days prior to admission were collected. Stool specimens or rectal swabs were collected within 48 hours of admission and stored at -30°C until cultured. Clostridium difficile isolates were typed and compared with isolates from patients with CDI. A stool/swab specimen was obtained for 259 enrolled subjects on admission. Two hundred four (79%) were not colonized, 40 (15%) had toxigenic C. difficile (TCD), and 15 (6%) had nontoxigenic C. difficile. There were no differences between TCD-colonized and -uncolonized subjects for age (mean, 56 vs 58 years; P = .46), comorbidities, admission from another healthcare facility (33% vs 24%; P = .23), or recent hospitalization (50% vs 50%; P = .43). There were no differences in antimicrobial exposures in the 90 days prior to admission (55% vs 56%; P = .91). Asymptomatic carriers were colonized with strains similar to strains from patients with CDI, but the relative proportions were different. There was a high prevalence of TCD colonization on admission. In contrast to past studies, TCD colonization was not associated with recent antimicrobial or healthcare exposures. Additional investigation is needed to determine the role of asymptomatic TCD carriers on hospital-onset CDI incidence.


Positional cloning of the murine flavivirus resistance gene.
Inbred mouse strains exhibit significant differences in their susceptibility to viruses in the genus Flavivirus, which includes human pathogens such as yellow fever, Dengue, and West Nile virus. A single gene, designated Flv, confers this differential susceptibility and was mapped previously to a region of mouse chromosome 5. A positional cloning strategy was used to identify 22 genes from the Flv gene interval including 10 members of the 2'-5'-oligoadenylate synthetase gene family. One 2'-5'-oligoadenylate synthetase gene, Oas1b, was identified as Flv by correlation between genotype and phenotype in nine mouse strains. Susceptible mouse strains produce a protein lacking 30% of the C-terminal sequence as compared with the resistant counterpart because of the presence of a premature stop codon. The Oas1b gene differs from all the other murine Oas genes by a unique four-amino acid deletion in the P-loop located within the conserved RNA binding domain. Expression of the resistant allele of Oas1b in susceptible embryo fibroblasts resulted in partial inhibition of the replication of a flavivirus but not of an alpha togavirus.


Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block.
In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-induced neuromuscular blockade, this advantage has not been confirmed in clinical settings when no neuromuscular monitoring is used. In this multicenter observational study, we sought to determine whether sugammadex reduces the incidence of postoperative residual weakness compared with neostigmine when the administration of rocuronium and its antagonists is not guided by neuromuscular monitoring. This study was conducted in two 5-month periods that preceded and followed the introduction of sugammadex into clinical practice in Japan. Five university-affiliated teaching hospitals participated in this study. Neostigmine was used to antagonize rocuronium-induced neuromuscular blockade in the first phase, and sugammadex was used in the second phase. The timing and doses of rocuronium, neostigmine, and sugammadex were determined by the attending anesthesiologists without the use of neuromuscular function monitoring devices. To ascertain the incidence of postoperative residual neuromuscular weakness, the train-of-four ratio (TOFR) was determined acceleromyographically after tracheal extubation. Since our practice also does not usually involve calibration and normalization of accelerographic responses, both TOFR <0.9 and TOFR <1.0 were used as the criteria for defining postoperative residual weakness. In the first phase, 109 patients received neostigmine (average dose 33 µg/kg) and 23 patients were considered (by clinical criteria) to have adequate recovery and did not receive neostigmine (spontaneous recovery group). In the second phase, 117 patients received sugammadex (average dose 2.7 mg/kg) for antagonism of rocuronium-induced blockade. The incidence (95% confidence interval) of TOFR <0.9 under spontaneous recovery, after neostigmine, and after sugammadex, was 13.0% (2.8%-33.6%), 23.9% (16.2%-33.0%), and 4.3% (1.7%-9.4%), respectively. The incidence (95% confidence interval) of TOFR <1.0 in these groups was 69.6% (47.1%-86.6%), 67.0% (57.3%-75.7%), and 46.2% (36.9%-55.6%), respectively. The use of sevoflurane in the neostigmine group and the short interval between the administration of the last doses of rocuronium and sugammadex were associated with a higher incidence of postoperative residual weakness. This study demonstrated that the risk of TOFR <0.9 after tracheal extubation after sugammadex remains as high as 9.4% in a clinical setting in which neuromuscular monitoring (objective or subjective) was not used. Our finding underscores the importance of neuromuscular monitoring even when sugammadex is used for antagonism of rocuronium-induced neuromuscular block.


Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex.
The class III receptor tyrosine kinase (RTKIII) Fms-like tyrosine kinase receptor 3 (Flt3) and its cytokine ligand (FL) play central roles in hematopoiesis and the immune system, by establishing signaling cascades crucial for the development and homeostasis of hematopoietic progenitors and antigen-presenting dendritic cells. However, Flt3 is also one of the most frequently mutated receptors in hematologic malignancies and is currently a major prognostic factor and clinical target for acute myeloid leukemia. Here, we report the structural basis for the Flt3 ligand-receptor complex and unveil an unanticipated extracellular assembly unlike any other RTKIII/V complex characterized to date. FL induces dimerization of Flt3 via a remarkably compact binding epitope localized at the tip of extracellular domain 3 of Flt3, and it invokes a ternary complex devoid of homotypic receptor interactions. Comparisons of Flt3 with homologous receptors and available mutagenesis data for FL have allowed us to rationalize the unique features of the Flt3 extracellular assembly. Furthermore, thermodynamic dissection of complex formation points to a pronounced enthalpically driven binding event coupled to an entropic penalty. Together, our data suggest that the high-affinity Flt3:FL complex is driven in part by a single preformed binding epitope on FL reminiscent of a "lock-and-key" binding mode, thereby setting the stage for antagonist design.


Sign language vocabulary development practices and internet use among educational interpreters.
Sign language interpreters working in schools often face isolation in terms of their sign language vocabulary development opportunities. The purposes of this study were to determine the key demographic characteristics of educational interpreters in British Columbia, to identify the resources they use to learn new vocabulary, and to shed light on their Internet use and access levels, with a view to exploring the viability of this resource as a tool for vocabulary development for interpreters working in educational settings. Key demographics associated with interpreters' access to time and materials in advance of a lesson were job title and graduation from an interpreter training program. Interpreters with job titles that reflected their status as interpreters had more preparatory time each week than interpreters who had job titles focused on their roles as educational assistants. Interpreters overwhelmingly expressed the need for continuing professional development with respect to vocabulary development. In terms of the resources currently used, human resources (colleagues, deaf adults) were used significantly more often than nonhuman (books, videotapes, Internet). The resource use results showed that convenience was more important than quality. Books were used more often than videotapes, CD-ROMs, and the Internet, although the latter three had higher percentages of very satisfied users than did books. The design and content of online vocabulary resources and limited interpreter preparation time were identified as current issues keeping the Internet from reaching its potential as an easily accessible visual resource. Recommendations aimed at enhancing the viability of the Internet as a vocabulary development tool for educational interpreters are discussed.


Evolution of heterophil/lymphocyte ratios in response to ecological and life-history traits: A comparative analysis across the avian tree of life.
Lymphocytes and heterophils are the two most abundant leucocyte types, which play a major role in adaptive and innate immune defence, respectively. The ratio of heterophils to lymphocytes (H/L ratio) may reflect a readiness to cope with infection through injury (via heterophils) rather than with a communicable disease (via lymphocytes). Since elevated H/L ratio constitutes a corticosterone-mediated response to external stressors, this trait is generally acknowledged as the robust measure of physiological stress in vertebrates. Here, I hypothesized that baseline H/L ratios of birds (as measured under normal physiological function) could be an important evolutionary trait shaped by species' ecology and life history. I predicted that H/L ratios should be determined by traits related to pathogen exposure (migratoriness, sociality, breeding latitude) and trade-offs between investment in reproduction (clutch size) and self-maintenance (longevity). I compiled published data on leucocyte profiles for nearly 250 bird species representing over half of all extant avian orders and nearly 30% of all extant avian families. Phylogenetically informed comparative methods were used to assess evolutionary associations of H/L ratios with ecological and life-history traits across the avian tree of life. Relatively strong phylogenetic signal and phylogenetic autocorrelation in avian H/L ratios indicated that most diversification in this trait occurred relatively early in bird radiation. Fluctuating selection and drift were identified as the major forces responsible for the evolution of H/L ratios in birds, while low H/L ratios were identified as an ancestral state in birds. Finally, phylogenetically informed Bayesian models showed that H/L ratios correlated negatively with longevity and positively with sociality and breeding latitude. This study was the first to describe the patterns of avian H/L ratio evolution in a broad phylogenetic framework. The results indicate that H/L ratios should not be merely recognized as a proxy for the intraspecific variation in physiological stress, but also as an important evolutionary trait, which probably have adaptive significance visible in a wider phylogenetic perspective.


Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium.
The differential polarized distribution of the reduced- folate transporter (RFT-1) and folate receptor alpha (FRalpha), the two proteins involved in the transport of folate, has been characterized in normal mouse retinal pigment epithelium (RPE) and in cultured human RPE cells. RPE cells mediate the vectorial transfer of nutrients from choroidal blood to neural retina. Whereas FRalpha is known to be present in many cell types of the neural retina, in situ hybridization analysis in the present study demonstrated that RFT-1 is present only in RPE. Laser-scanning confocal microscopy using antibodies specific for RFT-1 demonstrated an apical distribution of this protein in cultured human and intact mouse RPE, which contrasts with the basolateral distribution of FRalpha in these cells. The expression of RFT-1 in the RPE cell apical membrane was confirmed by functional studies with purified apical membrane vesicles from bovine RPE. These studies, done with N(5)-methyltetrahydrofolate (the predominant folate derivative in blood) and folate as substrates, have shown that RFT-1 functions in a Na(+)- and C1(-)-independent manner. The transporter is specific for folate and its analogs. A transmembrane H(+) gradient influences the transport function of this protein markedly; the transport mechanism is likely to be either folate/H(+) co-transport or folate/OH(-) exchange. Based on the differential polarization of FRalpha and RFT-1 in RPE, we suggest that these two proteins work in a concerted manner to bring about the vectorial transfer of folate across the RPE cell layer from the choroidal blood to the neural retina. This constitutes the first report of the differential polarization of the two folate transport proteins in any polarized epithelium.


The Arabidopsis IspH homolog is involved in the plastid nonmevalonate pathway of isoprenoid biosynthesis.
Plant isoprenoids are synthesized via two independent pathways, the cytosolic mevalonate (MVA) pathway and the plastid nonmevalonate pathway. The Escherichia coli IspH (LytB) protein is involved in the last step of the nonmevalonate pathway. We have isolated an Arabidopsis (Arabidopsis thaliana) ispH null mutant that has an albino phenotype and have generated Arabidopsis transgenic lines showing various albino patterns caused by IspH transgene-induced gene silencing. The initiation of albino phenotypes rendered by IspH gene silencing can arise independently from multiple sites of the same plant. After a spontaneous initiation, the albino phenotype is systemically spread toward younger tissues along the source-to-sink flow relative to the initiation site. The development of chloroplasts is severely impaired in the IspH-deficient albino tissues. Instead of thylakoids, mutant chloroplasts are filled with vesicles. Immunoblot analysis reveals that Arabidopsis IspH is a chloroplast stromal protein. Expression of Arabidopsis IspH complements the lethal phenotype of an E. coli ispH mutant. In 2-week-old Arabidopsis seedlings, the expression of 1-deoxy-d-xylulose 5-phosphate synthase (DXS), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), IspD, IspE, IspF, and IspG genes is induced by light, whereas the expression of the IspH gene is constitutive. The addition of 3% sucrose in the media slightly increased levels of DXS, DXR, IspD, IspE, and IspF mRNA in the dark. In a 16-h-light/8-h-dark photoperiod, the accumulation of the IspH transcript oscillates with the highest levels detected in the early light period (2-6 h) and the late dark period (4-6 h). The expression patterns of DXS and IspG are similar to that of IspH, indicating that these genes are coordinately regulated in Arabidopsis when grown in a 16-h-light/8-h-dark photoperiod.


Anti-tuberculosis treatment strategies and drug development: challenges and priorities.
Despite two decades of intensified research to understand and cure tuberculosis disease, biological uncertainties remain and hamper progress. However, owing to collaborative initiatives including academia, the pharmaceutical industry and non-for-profit organizations, the drug candidate pipeline is promising. This exceptional success comes with the inherent challenge of prioritizing multidrug regimens for clinical trials and revamping trial designs to accelerate regimen development and capitalize on drug discovery breakthroughs. Most wanted are markers of progression from latent infection to active pulmonary disease, markers of drug response and predictors of relapse, in vitro tools to uncover synergies that translate clinically and animal models to reliably assess the treatment shortening potential of new regimens. In this Review, we highlight the benefits and challenges of 'one-size-fits-all' regimens and treatment duration versus individualized therapy based on disease severity and host and pathogen characteristics, considering scientific and operational perspectives.


[Discriminant analysis of patients with primary open-angle glaucoma by color Doppler exam and visual field].
To determine if variables from color Doppler and visual field exam could discriminate normal from glaucomatous eyes. Prospectively, 36 patients with primary open-angle glaucoma (glaucoma group) and 20 normal volunteers (control group) were studied. Gender, age, central corneal thickness, intraocular pressure, Octopus automated perimetry global indices (mean defect and loss variance) and several parameters of the color Doppler (peak systolic velocity and resistivity index) were compared between groups. There was no statistically significant difference in age, central corneal thickness and intraocular pressure. Discriminant analysis showed that the variables: resistivity index (RI) in the short posterior ciliary artery (SPCA), mean defect (MD) and loss variance (LV) had presented significant influence for the positive diagnosis of glaucoma. The gotten discriminant function was: -3.637 + 0.109 x MD + 0.028 x LV + 4.325 x RI SPCA. Considering score -1.61, the probability of positive diagnosis of glaucoma was 90%. Through discriminant analysis it was possible to identify which of the color Doppler variables that associated to the visual field variables allowed differentiate normal from glaucomatous patients. These variables were: resistivity index in the short posterior ciliary artery, and the visual field variables, mean defect and loss variance.


Moist exposed burn ointment for treating pressure ulcers: A multicenter randomized controlled trial.
Pressure ulcers often seriously affect the quality of life of patients. Moist Exposed Burn Ointment (MEBO) has been developed to treat patients with pressure ulcers. The present study aimed to evaluate the efficacy and safety of MEBO in the treatment of pressure ulcers in Chinese patients. Seventy-two patients with pressure ulcers were randomly assigned to 2 groups who received a placebo or MEBO for 2 months. The primary outcomes included the wound surface area (WSA) and pressure ulcer scale for healing (PUSH) tool. The secondary outcomes included a visual analog scale (VAS), questionnaire of ulcer status, and adverse effects. Sixty-seven patients completed the study. After 2 months of treatment, the difference of mean change from the baseline was greater for MEBO (vs placebo) for WSA mean (SD) -6.0 (-8.8, -3.3), PUSH Tool -2.6 (-4.7, -1.5), and VAS score -2.9 (-4.4, -1.7). On the basis of the questionnaire, the pressure ulcers were "completely healed" (50.0% vs 16.7%) (P < .05) in patients after 2 months of treatment with MEBO versus placebo. No major adverse effects were found in the 2 groups. We showed that MEBO is effective and well tolerated for improving wound healing in Chinese patients with pressure ulcers.


The effect of a mobile integrated health program on health care cost and utilization.
To measure the effect of a mobile integrated health community paramedicine (MIH-CP) transitional care program on hospital utilization, emergency department visits, and charges. Retrospective secondary data from the electronic health record and regional health information exchange were used to analyze patients discharged from a large academic medical center and an affiliated community hospital in Baltimore, Maryland, May 2018-October 2019. We performed an observational study comparing patients enrolled in an MIH-CP program to propensity-matched controls. Propensity scores were calculated using measures of demographics, clinical characteristics, social determinants of health, and prior health care utilization. The primary outcome is inpatient readmission within 30 days of discharge. Secondary outcomes include excess days in acute care 30 days after discharge and emergency department visits, observation hospitalizations, and total health care charges within 30 and 60 days of discharge. Included patients were over 18 years old, discharged to home from internal/family medicine services, and live in eligible ZIP codes. The intervention group was enrolled in the MIH-CP program; controls met inclusion criteria but were not enrolled during the study period. The adjusted model showed no difference in 30-day inpatient readmission between 464 enrolled patients and propensity-matched controls (adjusted incidence rate ratio = 1.19, 95% confidence interval [CI] [0.89, 1.60]). There was a higher rate of observation hospitalizations within 30 days of index discharge for MIH-CP patients (adjusted incidence rate ratio = 1.78, 95% CI = [1.01, 3.14]). This difference did not persist at 60 days, and there were no differences in other secondary outcomes. We found no significant difference in short-term health care utilization or charges between patients enrolled in an MIH-CP transitional care program and propensity-matched controls. This highlights the importance of well-controlled, robust evaluations of effectiveness in novel care-delivery systems.


Invasive examinations in patients with suspected lung cancer: more may be too many.
The recent article entitled "Principles of biopsy in suspected lung cancer: priority still based on invasion in the era of targeted therapy?" published in Journal of Thoracic Disease by Chen et al., concluded the principles of biopsy in suspected lung cancer should be prioritized in sequence based on weight in clinical management, acquisition of tissue, invasion, efficiency and cost. We reported a patient with a 30-year history of pulmonary silicosis, had been found no evidence of tumor after receiving a series of invasive examinations. We conclude that invasive examinations should be limited in patients with suspected lung cancer who had a defined history of underlying disease. Minimal invasion with careful acquisition of the appropriate quantity and quality of tissue should be adequate.


O2-sensitive K+ current in undifferentiated and NGF-treated PC12 cell variants.
It has been reported that cultured PC12 cells can be used as a model for studying mechanisms of O2 sensitivity, previously examined in peripheral chemoreceptors and some neurons. This study compared the hypoxic depression of K+ currents in two PC12 variants, before and after differentiation into neurone-like cells induced by nerve growth factor (NGF). The results show that interaction of O2 and K+ channels is strongly-voltage dependent in the PC12/TM but not the PC12/ES subline. In PC12/TM cells an effect of hypoxia on the K+ current was appreciable only at moderately depolarized voltages, with a loss of sensitivity at +40 to +50 mV. NGF-induced transformation did not affect the responses seen in undifferentiated cells. These results emphasize the importance of screening PC12 cells before selecting a variant for studying O2 sensitivity. In view of evidence cited in the literature that hypoxia may effect membrane channels directly, further molecular and biophysical studies of the differences among PC12 variants are required.


Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.
The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage. To examine the possible mechanism of the "topical" phase of damage in the small intestine. Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg). The effect of conventional and non-acidic NSAIDs on rat liver mitochondrial respiration was measured in vitro in a Clarke-type oxygen electrode. The subcellular organelle marker enzymes showed mitochondrial and brush border involvement within an hour of indomethacin administration. Electron microscopy showed dose dependent mitochondrial changes following indomethacin administration consistent with uncoupling of oxidative phosphorylation (or inhibition of electron transport) which were indistinguishable from those seen with the uncoupler dinitrophenol. Parenteral indomethacin caused similar changes, but not in rats with ligated bile ducts. A range of NSAIDs, but not paracetamol or non-acidic NSAIDs which have a favourable gastrointestinal tolerability profile, uncoupled oxidative phosphorylation in vitro at micromolar concentrations and inhibited respiration at higher concentrations. In vivo studies with nabumetone and aspirin further suggested that uncoupling or inhibition of electron transport underlies the "topical" phase of NSAID induced damage. Collectively, these studies suggest that NSAID induced changes in mitochondrial energy production may be an important component of the "topical" phase of damage induction.


Proportional classifications of COPD phenotypes.
Chronic obstructive pulmonary disease (COPD) encompasses a group of disorders characterised by the presence of incompletely reversible airflow obstruction with overlapping subsets of different phenotypes including chronic bronchitis, emphysema or asthma. The aim of this study was to determine the proportion of adult subjects aged >50 years within each phenotypic subgroup of COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) <0.7, in accordance with current international guidelines. Adults aged >50 years derived from a random population-based survey undertook detailed questionnaires, pulmonary function tests and chest CT scans. The proportion of subjects in each of 16 distinct phenotypes was determined based on combinations of chronic bronchitis, emphysema and asthma, with and without incompletely reversible airflow obstruction defined by a post-bronchodilator FEV(1)/FVC ratio of 0.7. A total of 469 subjects completed the investigative modules, 96 of whom (20.5%) had COPD. Diagrams were constructed to demonstrate the relative proportions of the phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%). When COPD was defined as a post-bronchodilator FEV(1)/FVC less than the lower limit of normal, there were one-third fewer subjects with COPD and a smaller proportion without a defined emphysema, chronic bronchitis or asthma phenotype. This study provides proportional classifications of the phenotypic subgroups of COPD which can be used as the basis for further research into the pathogenesis and treatment of this heterogeneous disorder.


[Delayed sternal closure after open heart surgery in neonates and early infants].
Between November 1992 and February 1996, 84 patients (less than 3 months of age) underwent open heart surgery. Among 76 patients except 8 who required mechanical circulatory support, the sternum was left open. The indication of open sternotomy was hypoplastic left heart syndrome in 14 patients and unstable hemodynamics in 4 patients. Three patients died before delayed sternal closure. Delayed sternal closure was carried out in 15 patients with a mean of 4.7 days postoperatively. By the time of sternal closure, blood pressure, left atrial pressure and respiratory parameters improved and inotropics were reduced with the minus fluid balance. One patient died of sepsis 4 days after delayed sternal closure. Delayed sternal closure was effective modality to neonates or early infants after complex open heart surgery.


[Using Kirlian photography method for risk assessment of the thyroid gland pathology development in adults].
The article considers possibilities of the use of the express method based on the Kirlian-effect to detect prenosological signs of pathology of the thyroid gland. Type of Kirlian emission form fingers was compared with the form of disease, its pathogenesis, clinical peculiarities and ultrasonic data. Obtained data were used to form criteria for different group of the risk development of thyroid gland pathology.


NMR solution structure of a Chymotrypsin inhibitor from the Taiwan cobra Naja naja atra.
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14-Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14-Cys38 disulfide bond.


Decoding moral judgments from neural representations of intentions.
Intentional harms are typically judged to be morally worse than accidental harms. Distinguishing between intentional harms and accidents depends on the capacity for mental state reasoning (i.e., reasoning about beliefs and intentions), which is supported by a group of brain regions including the right temporo-parietal junction (RTPJ). Prior research has found that interfering with activity in RTPJ can impair mental state reasoning for moral judgment and that high-functioning individuals with autism spectrum disorders make moral judgments based less on intent information than neurotypical participants. Three experiments, using multivoxel pattern analysis, find that (i) in neurotypical adults, the RTPJ shows reliable and distinct spatial patterns of responses across voxels for intentional vs. accidental harms, and (ii) individual differences in this neural pattern predict differences in participants' moral judgments. These effects are specific to RTPJ. By contrast, (iii) this distinction was absent in adults with autism spectrum disorders. We conclude that multivoxel pattern analysis can detect features of mental state representations (e.g., intent), and that the corresponding neural patterns are behaviorally and clinically relevant.


Gain-of-function mutation of FGFR3 results in impaired fracture healing due to inhibition of chondrocyte differentiation.
Fracture healing is a complicated regeneration process which to some extent recapitulates bone development. Fibroblast growth factor receptor 3 (FGFR3) has a negative regulatory effect on endochondral ossification, and FGFR3 is also expressed in prehypertrophic and hypertrophic chondrocytes during fracture healing. However, the actual role of FGFR3 during bone regeneration is not fully understood. Therefore we investigated the role of FGFR3 in fracture repair using a non-stabilized fracture model. Fracture repair in gain-of-function mutation of FGFR3 (Fgfr3(G369C/+)) mice was delayed, with more cartilage callus on day 14 and residue of cartilage in the callus on day 21. Histologic, in-situ hybridization and qRT-PCR analysis showed that differentiation of mesenchymal cells into chondrocytes and hypertrophic differentiation was delayed in Fgfr3(G369C/+) mice during fracture healing. These results indicated that activating mutation of FGFR3 could lead to impaired bone repair due to inhibition of chondrocyte differentiation.


[Study on nurse performance evaluation: theoretical approach - Part I].
This first part of the study presents the literature on the evolution of personnel administration and discussess the organization/individual interaction from the mechanistic up to the systemic focusing. The systemic approach is based on the organization sociologic concept. The performance evaluation is studied as an integral part of human resources administration which in the health area, is considered a subsystem of the health system. The objectives of evaluation area analysed as well as the methods and techniques used, the training of the individuals participating in the evaluation process, the periodicity of the evaluation process and the feelings of both the evaluator and the evaluated person. As far as nursing is concerned it is underlined what has been done on nurse performance evaluation in other countries. The lack of studies on this subject in Brasil is stressed.


Surgical interventions for the early management of Bell's palsy.
Bell's palsy is an acute unilateral facial paralysis of unknown aetiology and should only be used as a diagnosis in the absence of any other pathology. As the proposed pathophysiology is swelling and entrapment of the nerve, some surgeons suggest surgical decompression of the nerve as a possible management option; this is ideally performed as soon as possible after onset. This is an update of a review first published in 2011, and last updated in 2013. This update includes evidence from one newly identified study. To assess the effects of surgery in the early management of Bell's palsy. On 20 March 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP. We handsearched selected conference abstracts for the original version of the review. We included all randomised controlled trials (RCTs) or quasi-RCTs involving any surgical intervention for Bell's palsy. Trials compared surgical interventions to no treatment, later treatment (beyond three months), sham treatment, other surgical treatments or medical treatment. Three review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. We used standard methodological procedures expected by Cochrane. The primary outcome was complete recovery of facial palsy at 12 months. Secondary outcomes were complete recovery at three and six months, synkinesis and contracture at 12 months, psychosocial outcomes at 12 months, and side effects and complications of treatment. Two trials with 65 participants met the inclusion criteria; one was newly identified at this update. The first study randomised 25 participants into surgical or non-surgical (no treatment) groups using statistical charts. One participant declined surgery, leaving 24 evaluable participants. The second study quasi-randomised 53 participants; however, only 41 were evaluable as 12 declined the intervention they were allocated. These 41 participants were then divided into early surgery, late surgery or non-surgical (no treatment) groups using alternation. There was no mention on how alternation was decided. Neither study mentioned if there was any attempt to conceal allocation. Neither participants nor outcome assessors were blinded to the interventions in either study. There were no losses to follow-up in the first study. The second study lost three participants to follow-up, and 17 did not contribute to the assessment of secondary outcomes. Both studies were at high risk of bias. Surgeons in both studies used a retro-auricular/transmastoid approach to decompress the facial nerve. For the outcome recovery of facial palsy at 12 months, the evidence was uncertain. The first study reported no differences between the surgical and no treatment groups. The second study fully reported numerical data, but included no statistical comparisons between groups for complete recovery. There was no evidence of a difference for the early surgery versus no treatment comparison (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.05 to 11.11; P = 0.84; 33 participants; very low-certainty evidence) and for the early surgery versus late surgery comparison (RR 0.47, 95% CI 0.03 to 6.60; P = 0.58; 26 participants; very low-certainty evidence). We considered the effects of surgery on facial nerve function at 12 months very uncertain (2 RCTs, 65 participants; very low-certainty evidence). Furthermore, the second study reported adverse effects with a statistically significant decrease in lacrimal control in the surgical group within two to three months of denervation. Four participants in the second study had 35 dB to 50 dB of sensorineural hearing loss at 4000 Hz, and three had tinnitus. Because of the small numbers and trial design we also considered the adverse effects evidence very uncertain (2 RCTs, 65 participants; very low-certainty evidence). There is very low-certainty evidence from RCTs or quasi-RCTs on surgery for the early management of Bell's palsy, and this is insufficient to decide whether surgical intervention is beneficial or harmful. Further research into the role of surgical intervention is unlikely to be performed because spontaneous or medically supported recovery occurs in most cases.


Continuous Butadiyne Addition to Propargyl: A Radical-Efficient Pathway for Polycyclic Aromatic Hydrocarbons.
Polycyclic aromatic hydrocarbons (PAHs) play a crucial role in soot inception, interstellar evolution, and nanomaterial synthesis. Although several mechanisms, such as hydrogen-abstraction acetylene/vinylacetylene addition, have previously been proposed, PAH formation and growth are not yet fully understood. We propose an alternate PAH growth mechanism wherein propargyl radical reacts with butadiyne to form larger radicals containing newly fused aromatic rings. Butadiyne is an important intermediate in hydrocarbon oxidation and carbon rich stars, while propargyl is one of the most important resonantly stabilized radicals that persists for long times. Our proposed mechanism is validated by quantum chemical calculations, elementary reaction experiments, laminar flame analysis, and kinetic modeling. Our findings challenge the conventional wisdom that radical site regeneration, being central to PAH growth, requires sequential hydrogen elimination and/or abstraction. In our proposed mechanism, PAH growth does not depend on abundant free radical consumption, and could, therefore, help explain carbonaceous nanoparticle coalescence in radical-deficient reaction environments.


[Construction of a healthcare-related information technology education praxis for graduate school].
This paper presents an overview of an information technology education practice for healthcare practitioners in graduate school. Based on hands-on experience of the Information Technology Applied to Healthcare classes at the Jequié Campus of the Southeast Bahia State University (UESB) for the Nursing and Physiotherapy courses, an experience is reported that stresses the importance of teaching information technology by establishing links between Information and Communications Technologies and the praxis of the healthcare practitioners, enhancing the educational process and allowing students to 'visualize' how such technologies could be used for producing and qualifying impacts on their professional activities.


Sex steroids and schizophrenia.
The peak in incidence for schizophrenia is during late adolescence for both sexes, but within this time frame the peak is both earlier and steeper for males. Additionally, women have a second peak in incidence following menopause. Two meta-analyses have reported that men have an overall ∼40% greater chance of developing schizophrenia than do women (Aleman et al., 2003; McGrath et al., 2004). These and other findings have led to the suggestion that ovarian hormones may be protective against schizophrenia. Less explored is the potential role of testosterone in schizophrenia, although disruptions in steroid levels have also been reported in men with the illness. The relationship between increased gonadal hormone release per se and peri-adolescent vulnerability for psychiatric illness is difficult to tease apart from other potentially contributory factors in clinical studies, as adolescence is a turbulent period characterized by many social and biological changes. Despite the obvious opportunity provided by animal research, surprisingly little basic science effort has been devoted to this important issue. On the other hand, the animal work offers an understanding of the many ways in which gonadal steroids exert a powerful impact on the brain, both shaping its development and modifying its function during adulthood. Recently, investigators using preclinical models have described a greater male vulnerability to neurodevelopmental insults that are associated with schizophrenia; such studies may provide clinically relevant insights into the role of gonadal steroids in psychiatric illness.


TPHA test. Experience at the Clinic of Dermatology, University of Milan.
The results of serological investigations with the treponemal haemagglutination (TPHA) test are reported in a large number of luetic and non-luetic patients. From these the following conclusions can be drawn: (1) The sensitivity of the TPHA test is decreased if the test is carried out with micromethods; however, in our opinion, the same degree of sensitivity can be obtained either with the macromethod at dilution 1/80-1/60 or with micromethods at 1/20-1/40. (2) The sensitivity of this test is high, being similar to that of the fluorescent treponemal antibody absorption (FTA-ABS) test in primary and secondary syphilis and even higher than that of the FTA-ABS test in treated subjects. (3) The specificity of the reaction is high, as demonstrated by examining sera in patients with a negative history and clinical examination together with negative results to Treponema pallidum immobilisation (TPI) and FTA-ABS tests, and by studying biological false positive sera. (4) For the serological screening, it may be sufficient to perform the TPHA test with the 1/20-1/40 micromethod together with the Venereal Disease Research Laboratory (VDRL) test. In patients with suspected syphilis, it is advisable to perform the TPHA test by the macromethod, in combination with the FTA-ABS test.


Positive end-expiratory pressure lung recruitment: comparison between lower inflection point and ultrasound assessment.
Maintenance of the open lung alveoli in the expiration on mechanical ventilation in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains challenging despite advances in lung imaging. The inspiratory lower inflection point (LIP) on the ventilator pressure-volume (P-V) curve estimates the required end-expiratory pressure for recruitment of alveolar consolidation. Alternatively, the end-expiratory pressure for recruitment of crater-like subpleural alveolar consolidation could be simply followed with ultrasound. These two methods for setting the ventilators positive end-expiratory pressure (PEEP) were compared. The observational study in surgical/neurosurgical intensive care between October 2009 and November 2011 included 17 deeply sedated or relaxed patients. LIP was measured with continuous low-flow method, as a pressure in cmH(2)O. Expiratory levelling between lower border of subpleural consolidation and adjacent pleural line, which means lung recruitment, was followed with linear ultrasound probe. PEEP in cmH(2)O at which the levelling occurs was compared with LIP pressure. LIP pressure never exceeds the PEEP for recruitment of subpleural consolidations followed with ultrasound. A significant correlation (r = 0.839; p < 0.05) was found between two methods. In this study, positive end-expiratory pressures for recruitment of subpleural consolidations followed by ultrasound always exceed the pressures measured with LIP. Respecting this, ultrasound method could be the guide for PEEP lung recruitment.


Multimodality Imaging for Selecting Candidates for CRT: Do We Have a Single Alley to Increase Responders?
Cardiac resynchronization therapy has evolved in recent years to provide a reduction of morbidity and mortality for many patients with heart failure. Its application and optimization is an evolving field and its use requires a multidisciplinary approach for patient and device selection, technical preprocedural planning, and optimization. While echocardiography has always been considered the first line for the evaluation of patients, additional imaging techniques have gained increasing evidence in recent years. Today different details about heart anatomy, function, dissynchrony can be investigated by magnetic resonance, cardiac computed tomography, nuclear imaging, and more, with the aim of obtaining clues to reach a maximal response from the electrical therapy. The purpose of this review is to provide a practical analysis of the single and combined use of different imaging techniques in the preoperative and perioperative phases of cardiac resynchronization therapy, underlining their main advantages, limitations, and information provided.


Vezf1 regulates genomic DNA methylation through its effects on expression of DNA methyltransferase Dnmt3b.
The zinc finger protein vascular endothelial zinc finger 1 (Vezf1) has been implicated in the development of the blood vascular and lymphatic system in mice, and has been characterized as a transcriptional activator in some systems. The chicken homolog, BGP1, has binding sites in the beta-globin locus, including the upstream insulator element. We report that in a mouse embryonic stem cell line deletion of both copies of Vezf1 results in loss of DNA methylation at widespread sites in the genome, including Line1 elements and minor satellite repeats, some imprinted genes, and several CpG islands. Loss of methylation appears to arise from a substantial decrease in the abundance of the de novo DNA methyltransferase, Dnmt3b. These results suggest that naturally occurring mutations in Vezf1/BGP1 might have widespread effects on DNA methylation patterns and therefore on epigenetic regulation of gene expression.


Case studies of the use of biomarkers to assess exposures.
Because many environmental toxicants are ubiquitous, humans are continuously exposed to them. At other times, certain populations may be more highly exposed to these toxicants from point sources. The evaluation of the degree of the exposure to either a population or an individual is frequently based on indirect surrogates of exposure, such as questionnaire data on time-activities and/or concentrations measured in environmental media. We prefer to assess the degree of the exposure to a given toxicant by measuring the concentration of the toxicant, its metabolite(s), or reaction product(s) in human specimens. Then by applying pharmacokinetic information for that toxicant, we can best reconstruct the exposure scenario. These data are then compared to reference range levels of these toxicants in the preferred biologic specimen. The development and uses of the reference range data are exemplified by case studies including potential exposure to dioxin and solvents.


IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.


Bacterial ligases reveal fundamental principles of polyubiquitin specificity.
Homologous to E6AP C terminus (HECT) E3 ubiquitin (Ub) ligases direct substrates toward distinct cellular fates dictated by the specific form of monomeric or polymeric Ub (polyUb) signal attached. How polyUb specificity is achieved has been a long-standing mystery, despite extensive study in various hosts, ranging from yeast to human. The bacterial pathogens enterohemorrhagic Escherichia coli and Salmonella Typhimurium encode outlying examples of "HECT-like" (bHECT) E3 ligases, but commonalities to eukaryotic HECT (eHECT) mechanism and specificity had not been explored. We expanded the bHECT family with examples in human and plant pathogens. Three bHECT structures in primed, Ub-loaded states resolved key details of the entire Ub ligation process. One structure provided a rare glimpse into the act of ligating polyUb, yielding a means to rewire polyUb specificity of both bHECT and eHECT ligases. Studying this evolutionarily distinct bHECT family has revealed insight into the function of key bacterial virulence factors as well as fundamental principles underlying HECT-type Ub ligation.


[The Multilayer Flow Modulator Stent (MFM) for the treatment of arterial aneurysms].
Arterial Aneurysms are traditionally treated surgically but the operative risks remain high. More and more interventional procedures are proposed: - For Visceral and Peripheral aneurysms covered stents, endografts, coils can be used, but these techniques have a lot of disadvantages, drawbacks. Aneurysms with collateral branches cannot be treated with covered stents. The stent can occlude these collaterals leading to severe complications. - For Aortic Aneurysms (AAA, TAAA) hybrid techniques, endografts have been used to reduce morbidity/mortality rates encountered with surgical procedures. Recently new techniques have been developed: branched grafts, fenestrated grafts, chimney techniques. The technical success of these techniques is high but the complications rate is always high despite experienced, skilled operators: high morbidity/mortality rates, endoleaks, renal impairment, neurological complications with paraplegiadue to spinal cord ischemia. For these reasons we used a new concept of stent, the Multilayer Flow Modulator Stent (MFM) to treat any aneurysm. This MFM is a 3 Dimensional braided tube made of several interconnected layers without any covering. Our earliest tests, through studies as theoritical simulation, computerized Fluid dynamics, Molecular Modelization and through in vitro and in vivo tests demonstrate that this MFM reduces the velocity in the aneurysmal sac up to 90% by modifying the hemodynamic conditions. A saccular aneurysm without collateral branch will thrombose quickly. If a collateral branch is present the flow is directed towards this branch leading to progressive shrinkage of the aneurysm. In a Fusiform Aneurysm (AAA, TAAA) the MFM eliminates the damaging flow vortex pressure, laminates and redirects its flow along the wall, directs and increases the flow in the collateral branches which remain patent. As demonstrated in animal and human studies this MFM preserves the collateral branches allowing the possibility to cover any artery without compromising the flow (renal, digestive arteries, supra aortic vessel). We will report our experience with the new device, summarize the main literature data and compare the results obtained with this stent, with the most recent techniques such as fenestrated, branched grafts, chimney technique. If we respect hard endpoints, important guidelines, technical points of stent implantation, the results are very promising and the MFM seems to be a breakthrough to treat any aneurysm.


Drosophila Patj plays a supporting role in apical-basal polarity but is essential for viability.
Patj has been characterized as one of the so-called polarity proteins that play essential and conserved roles in regulating cell polarity in many different cell types. Studies of Drosophila and mammalian cells suggest that Patj is required for the apical polarity protein complex Crumbs-Stardust (Pals1 or Mpp5 in mammalian cells) to establish apical-basal polarity. However, owing to the lack of suitable genetic mutants, the exact in vivo function of Patj in regulating apical-basal polarity and development remains to be elucidated. Here, we generated molecularly defined null mutants of Drosophila Patj (dPatj). Our data show conclusively that dPatj only plays supporting and non-essential roles in regulating apical-basal polarity, although such a supporting role may become crucial in cells such as photoreceptors that undergo complex cellular morphogenesis. In addition, our results confirm that dPatj possesses an as yet unidentified function that is essential for pupal development.


Proteasome subunits, low-molecular-mass polypeptides 2 and 7 are hyperexpressed by target cells in autoimmune thyroid disease but not in insulin-dependent diabetes mellitus: implications for autoimmunity.
Autoimmune thyroid diseases (AITD) and insulin-dependent diabetes mellitus (IDDM) are two autoimmune syndromes of unknown etiology with common immune features. One is that the target cells, thyrocytes and pancreatic islet beta cells respectively, hyperexpress several proteins encoded in the HLA region: HLA class I, HLA class II and transporter associated with antigen processing (TAP-1): the clinical course and many aspects of the immunopathology are, however, quite different. Low-molecular-mass polypeptides 2 and 7 (LMP2 and LMP7) are proteasome subunits that increase the efficiency of endogenous antigen processing and are encoded in close vicinity to the TAP genes. We investigated whether LMP2 and LMP7 are hyperexpressed in thyrocytes and islet cells in AITD and IDDM. Thyroid tissue from Graves' disease patients (GD, n = 8) and Hashimoto thyroiditis (HT, n = 1) and pancreatic tissue from IDDM patients (n = 4) as well as control tissues were examined by the two-color indirect immunofluorescence technique. The results demonstrate that, in normal glands, thyrocytes and pancreatic islet cells express comparable moderate to low levels of LMP2 and LMP7. In AITD and IDDM, expression of LMP2/7 in the endocrine cells was disparate: while in AITD glands there was hyperexpression of LMP2 and 7 parallel to that of HLA class I and TAP-1, in the islet cells of recent onset diabetic pancreases (n = 2) the level of LMP2 and 7 expression was totally normal, including islets that were infiltrated by lymphocytes and hyperexpressed HLA class I and TAP-1. These observations suggest different mechanisms of endogenous peptides generation at the target cells in AITD from IDDM. Since this is a key step for the maintenance of peripheral tolerance, it may help to understand some of the different clinical features of the two autoimmune diseases.


Is there one measure-of-fit that fits all? A taxonomy and review of measures-of-fit for risk-equalization models.
This study provides a taxonomy of measures-of-fit that have been used for evaluating risk-equalization models since 2000 and discusses important properties of these measures, including variations in analytic method. It is important to consider the properties of measures-of-fit and variations in analytic method, because they influence the outcomes of evaluations that eventually serve as a basis for policymaking. Analysis of 81 eligible studies resulted in the identification of 71 unique measures that were divided into 3 categories based on treatment of the prediction error: measured based on squared errors, untransformed errors, and absolute errors. We conclude that no single measure-of-fit is best across situations. The choice of a measure depends on preferences about the treatment of the prediction error and the analytic method. If the objective is measuring financial incentives for risk selection, the only adequate evaluation method is to assess the predictive performance for non-random groups.


Renal outcome of type 2 diabetes in South Africa--a 12-year follow-up study.
Previous studies of type 2 diabetes mellitus have indicated a benign renal outcome after long-term follow-up. The aim of this study was to determine how often renal failure due to diabetic nephropathy was a cause of death in patients with type 2 diabetes. Prospective observational study of 59 South African patients with type 2 diabetes over a 12-year period. During the study repeated clinical evaluations were accompanied by measurements of serum creatinine, serum cholesterol, random blood sugar, and urine protein/creatinine ratios. The mean duration of diabetes at the end of the study was 17.8 years. There was a wide variation in the time from clinical diagnosis of diabetes to macroproteinuria (mean 9.7 years, SD 5.9, range 0 - 21) and the rate of deterioration of renal function. This rate correlated with poor control of blood pressure, a glucose level of > 14 mmol/l, heavy proteinuria, a high retinopathy score, a body mass index of < 28 and the number of pack years of smoking. At the end of the study 47 patients (79.7%) had died. Of these deaths 17 (28.8%) were due to chronic renal failure. In contrast to other studies we have shown that in a developing country renal failure in type 2 diabetic patients is a major cause of death. Determining the prognosis for an individual patient is difficult as there are wide ranges in the time of onset of proteinuria, the rise in serum creatinine and the time to ultimate progression to end-stage renal failure.


Teleconferencing model for forensic consultation, court testimony, and continuing education.
A medical center-based forensic clinic that provides the necessary comprehensive consultation, continuing education, court testimony, and clinical services through an applied model of teleconferencing applications is addressed. Telemedicine technology and services have gained the attention of both legal and clinical practitioners, examining trends and models of health care for underserved populations, and identifying where consultation with a team of professionals may benefit service providers in rural communities. The contribution offered herein provides an understanding of the history of the development of the clinic, a theoretical model that has been applied to a clinical forensic program that employs telepsychiatry services, and the ethical and malpractice liability issues confronted in using teleconferencing services. This model is examined through a child and adolescent forensic evaluation clinic. The goals of this model are offered, as are a number of applications within the broad spectrum of services utilizing telemedicine. Finally, changing patterns are addressed in clinically based health-care delivery for criminal justice, social services, and forensic mental health.


Prediction of noisy chaotic time series using an optimal radial basis function neural network.
This paper considers the problem of optimum prediction of noisy chaotic time series using a basis function neural network, in particular, the radial basis function (RBF) network. In the noiseless environment, predicting a chaotic time series is equivalent to approximating a nonlinear function. The optimal generalization is achieved when the number of hidden units of a RBF predictor approaches infinity. When noise exists, it is shown that an optimal RBF predictor should use a finite number of hidden units. To determine the structure of an optimal RBF predictor, we propose a new technique called the cross-validated subspace method to estimate the optimum number of hidden units. While the subspace technique is used to identify a suitable number of hidden units by detecting the dimension of the subspace spanned by the signal eigenvectors, the cross validation method is applied to prevent the problem of overfitting. The effectiveness of this new method is evaluated using simulated noisy chaotic time series as well as real-life oceanic radar signals. Results show that the proposed method can find the correct number of hidden units of an RBF network for an optimal prediction.


Application of CAD-CAM for Fabrication of Metal-Free Band and Loop Space Maintainer.
An ideal occlusion with proper tooth alignment and fully functional teeth is the ultimate goal of all dental treatments. Premature extraction of deciduous teeth is a common sequeale of untreated dental caries in teeth in which the damage is far beyond repair. Premature extraction might lead to loss of space for the successor tooth, drifting of teeth and loss of arch integrity leading to malocclusion in the permanent teeth. To prevent the space loss, space maintainers are designed and delivered at the time of extraction to allow for development of proper functional occlusion in children till the eruption of the succedaneous permanent tooth. A six-year-old female patient with chronic intra-radicular abscess in upper right first primary molar was treated with extraction followed by the placement of BruxZir zirconia space maintainer. Clinical and radiographic examinations were performed at one and six months. At the end of six months, the patient was completely asymptomatic and there were no visible signs of gingival inflammation and tissue irritation at the site of the space maintainer.


Cutaneous metastases from carcinoma of the cervix.
Metastases to the skin from internal malignant neoplasms are an uncommon and often preterminal event. Cutaneous metastases from a carcinoma of the uterine cervix, however, have rarely been reported, even in the advanced stages of the disease. A patient was initially seen with cutaneous metastases and was found to have an extensive tumor in the pelvis, which proved to be a squamous cell carcinoma arising in the cervix.


Cardiovascular magnetic resonance in patients with myocardial infarction: current and emerging applications.
In patients with known or suspected myocardial infarction (MI), cardiovascular magnetic resonance (CMR) provides a comprehensive, multifaceted view of the heart. The data, including that from a recent multicenter clinical trial, indicate that delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) is a well-validated, robust technique that can be easily implemented on scanners that are commonly available worldwide, with an effectiveness that clearly rivals the best available imaging techniques for the detection and assessment of acute and chronic MI. When patients present outside the diagnostic window of cardiac troponins, DE-CMR may be especially useful. Moreover, because DE-CMR can uniquely differentiate between ischemic and various nonischemic forms of myocardial injury, it may be helpful in cases of diagnostic uncertainty, such as in patients with classical features of MI in whom coronary angiography does not show a culprit lesion. Even after the diagnosis of MI has been made, CMR provides clinically relevant information by identifying residual viability, microvascular damage, stunning, and right ventricular infarction. In addition, post-MI sequelae, including left ventricular thrombus and pericarditis, are easily identified. Given that quantification of infarct size by DE-CMR is highly reproducible, this technique may provide a useful surrogate end point for clinical trials with appreciable reductions in sample size compared with alternative methods.


Adherence to the Mediterranean diet and serum uric acid: the ATTICA study.
The present study aimed to explore potential associations between adherence to a Mediterranean diet and serum uric acid (UA) levels. The sample consisted of 2380 men and women free of cardiovascular or renal disease who participated in the ATTICA study. Dietary intake was assessed using a food frequency questionnaire (FFQ) and adherence to the Mediterranean diet was evaluated with the MedDietScore. Serum UA was measured and hyperuricaemia was defined as UA concentration > 7.0 mg/dL in men or > 6.0 mg/dL in women. MedDietScore was inversely associated with UA levels (b-coefficient per quartile of the score = -0.07 ± 0.03, p = 0.02) independently of sex, presence of overweight, hypertension, or abnormal glucose metabolism, and alcohol or coffee intake. Those at the fourth quartile of MedDietScore had a 70% lower likelihood of having hyperuricaemia [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.11-0.82] compared to those at the first quartile, after adjustment for several confounders. According to stratified analyses by sex, body mass index (BMI) status, hypertension, abnormal glucose, alcohol and coffee intake, the inverse association between serum UA and MedDietScore remained significant in women (b-coefficient = -0.194 ± 0.055, p < 0.001), overweight subjects (b-coefficient = -0.103 ± 0.047, p = 0.02), in those with normal glucose metabolism (b-coefficient = -0.074 ± 0.037, p = 0.04), and in those abstaining from alcohol (b-coefficient = -0.212 ± 0.073, p = 0.004) and coffee (b-coefficient = -0.221 ± 0.096, p = 0.02). Adherence to the Mediterranean diet is associated with lower serum UA levels and lower likelihood of hyperuricaemia. These findings support a potential role of this dietary pattern in the prevention and treatment of hyperuricaemia and gout.


Skin hydration measurement and the prediction of the early development of pressure ulcers among at risk adults: A systematic review.
This systematic review aimed to examine skin hydration and determine if this biophysical parameter can predict pressure ulcer development in at risk adults. A literature search was conducted in March 2022, using PubMed, CINAHL, SCOPUS, Cochrane, and EMBASE databases. A total of 1727 records were returned, with 9 studies satisfying the inclusion criteria. Data were extracted using a pre-designed extraction tool and a narrative synthesis of the data was undertaken. The methodological quality of the included articles was assessed using the evidence-based librarianship checklist. Included studies were published between 1997 and 2021, with most using a prospective cohort design (88.9%, n = 8). The mean sample size was 74 participants (SD = 38.6; median 71). All studies measured skin hydration objectively, with 55.6% (n = 5) using the Corneometer® CM825 and 33.3% (n = 3) of studies reported a statistically significant association between skin hydration and pressure ulcer development. The mean evidence-based librarianship percentage was 66.6% (SD: 20.7%), however, only 33.3% (n = 3) of studies scored ≥75%, indicating validity. The quality of included studies, methodology variation, and reported results has reduced the homogeneity of outcomes. This review highlights the requirement for future research evidence to ascertain the role of skin hydration in pressure ulcer development.


Evans syndrome in children below 13 years of age - A nationwide population-based cohort study.
Evans syndrome is defined by autoimmune haemolytic anaemia and immune thrombocytopenia occurring in the same patient. Although known to be rare the frequency and prognosis of Evans syndrome in children is unknown, and only few registry-based studies are available. The epidemiology and prognosis of Evans syndrome in patients above 13 years of age has recently been investigated. In this age group both incidence and prevalence of Evans syndrome increased during the study period and median survival was just 7.2 years. Using Danish health registries and the same approach, we identified 21 children below 13 years of age with Evans syndrome during 1981-2015. Patients with Evans syndrome were age-and sex matched with children both from the general population, and with patients with either autoimmune haemolytic anaemia or immune thrombocytopenia. The incidence of Evans syndrome ranged between 0.5 and 1.2/1,000,000 person-years. Prevalence was 6.7 and 19.3/1,000,000 in 1990 and 2015 respectively. Hazard ratio for death was 22 fold higher for children with ES compared to matched children from general population, and was also elevated compared to children with autoimmune haemolytic anaemia or immune thrombocytopenia. We conclude that pediatric ES is very rare and associated with elevated mortality. However, despite the nationwide study and a long and complete follow-up, results are imprecise due to the rarity of this disorder.


Digital quadrature amplitude modulation with optimized non-rectangular constellations for 100 Gb/s transmission by a directly-modulated laser.
We study the performance of novel quadrature amplitude modulation (QAM) constellations for 100 Gb/s transmission by a directly-modulated laser. Due to the strong nonlinearity of a directly-modulated laser, rectangular constellations suffer a large penalty from their regular spacing between symbols. We present a method for synthesizing irregular constellations which position symbols more efficiently. We will demonstrate the improved performance of these novel constellations over the conventional rectangular constellation as well as the superior performance achievable with digital QAM compared to optimally bit-loaded discrete-multitone modulation.


Timing of surgical intervention does not influence return of esophageal peristalsis or outcome for patients with achalasia.
It has been suggested that abnormal function of the lower esophageal sphincter is the primary abnormality in esophageal achalasia, and that the absence of esophageal peristalsis is secondary to the outflow obstruction caused by the lower esophageal sphincter. Furthermore, it has been proposed that early elimination of the resistance at the level of the gastroesophageal junction by surgical intervention could result in return of esophageal peristalsis. This study aimed to assess whether the timing of surgical intervention affects the return of esophageal peristalsis and the clinical outcome for patients with achalasia. Between January 1991 and May 2003, 173 patients underwent a Heller myotomy by minimally invasive surgery for treatment of esophageal achalasia. Of these patients, 41 (24%) had pre- and postoperative esophageal manometry. These patients were divided into three groups based on the duration of symptoms: group A (10 patients; duration of symptoms 12 months group B (19 patients, duration of symptoms 12 to 60 months), and group C (12 patients; duration of symptoms longer than 60 months). The average duration of symptoms (dysphagia was present in all patients) was as follows: group A (8 +/- 4 months), group B, (35 +/- 16 months), and group C, (157 +/- 94 months). Vigorous achalasia was present in 40%, 21%, and 17% of the groups respectively. The differences between the groups were not significant. Postoperatively, improvement in esophageal motility was seen in no patient in group A, 1 patient (5%) in group B, and 1 patient (8%) in group C. Excellent or good results were obtained for 90% of the group A patients, 95% of group B patients, and 92% of the group C patients. Again, the differences were not significant. The results show that: a) the presence of vigorous achalasia is independent of symptoms duration; b) the timing of surgical intervention does not influence the return of peristalsis; and c) the results of a Heller myotomy are independent of symptoms duration.


A Novel Antiserum Against a Predicted Human Peripheral Choline Acetyltransferase (hpChAT) for Labeling Neuronal Structures in Human Colon.
Choline acetyltransferase (ChAT), the enzyme synthesizing acetylcholine (ACh), has an exon-skipping splice variant which is expressed preferentially in the peripheral nervous system (PNS) and thus termed peripheral ChAT (pChAT). A rabbit antiserum previously produced against rat pChAT (rpChAT) has been used for immunohistochemistry (IHC) to study peripheral cholinergic structures in various animals. The present study was undertaken to develop a specific antiserum against a predicted human pChAT (hpChAT) protein. A novel mouse antiserum has been successfully raised against a unique 14-amino acid sequence of hpChAT protein. Our Western blot using this antiserum (termed here anti-hpChAT serum) on human colon extracts revealed only a single band of 47 kDa, matching the deduced size of hpChAT protein. By IHC, the antiserum gave intense staining in many neuronal cells and fibers of human colon but not brain, and such a pattern of staining seemed identical with that reported in colon of various animals using anti-rpChAT serum. In the antibody-absorption test, hpChAT-immunoreactive staining in human colon was completely blocked by using the antiserum pre-absorbed with the antigen peptide. Double immunofluorescence in human colon moreover indicated that structures stained with anti-hpChAT were also stained with anti-rpChAT, and vice versa. hpChAT antiserum allowed the identification of cell types, as Dogiel type cells in intramural plexuses, and fiber innervation of colon muscles and mucosae. The present results demonstrate the specificity and reliability of the hpChAT antiserum as a novel tool for immunohistochemical studies in human colon, opening venues to map cholinergic innervation in other human PNS tissues.


[Value of reflecting disposable insulation (Thermodrape) in preventing perioperative hypothermia].
The aim of the study was to evaluate the value of reflecting disposable insulation for the prevention of perioperative hypothermia. After approval by the local ethics committee 36 patients undergoing long lasting urological intraabdominal surgery were studied. Anaesthesia was performed using etomidate, fentanyl, midazolam, pancuronium and succinylcholine. Patients were randomly assigned to 4 groups. These groups were treated as follows: Gr. 1: Infusion warmer (Hotline HL-90 with System L-70, Level 1 Technologies Inc., Marshfield, USA) and standard O.R. draping with two layers of cotton drapes. Gr. 2: Infusion warmer and reflecting disposable insulation (Thermadrape, O.R. Concepts Inc., Roanoke, USA) covering the legs, upper body, arms and head. Gr. 3: Infusion warmer and convective air warming with upper body blanket (WarmTouch, Mallinckrodt Medical, Hennef/Sieg, Germany). Gr. 4: Infusion warmer, convective air warming and reflecting disposable insulation. After 2 hours of surgery patients of groups 1 and 2 became hypothermic with core temperatures of 35.1 and 35.6 degrees C respectively. No relevant difference could be found between the two groups. The combination of an infusion warmer and convective air warming was an effective method to prevent hypothermia in groups 3 and 4. After 2 hours of surgery these patients had core temperatures of 36.6 and 36.4 degrees C respectively. Reflecting disposable insulation did not improve the effect of convective air warming. Reflecting disposable insulation was insufficient in the investigated operative setting.


Tales of biographical disintegration: how parents make sense of their sons' suicides.
Suicide research relies heavily on accounts provided by bereaved relatives, using a method known as the psychological autopsy. Psychological autopsy studies are invariably quantitative in design and their findings reinforce the medical model of suicide, emphasising the role of mental illness. They largely ignore the meanings that narrators attach to events, the nature of the sense-making task and the influences bearing upon it. This study drew on psychological autopsy data but used qualitative analytic methods. Fourteen semi-structured interviews with the parents of young men aged 18-30 who had taken their own lives form the basis for this paper. Some parents represent their sons as victims who were cruelly destroyed by external forces, while others portray them as agents of their own destruction. Either way, their narratives are dominated by moral rather than medical categories and by questions of personal accountability. We show how the parents use the interview to perform a complex reconstructive task, striving to piece together both their son's and their own shattered biographies and repair damage to their moral identities. We argue that their stories represent survival tools, enabling them not only to make sense of the past but also to face their own future.


Measuring Liquid-into-Liquid Diffusion Coefficients by Dissolving Microdroplet Electroanalysis.
Diffusion is a fundamental process in various domains, such as pollution control, drug delivery, and isotope separation. Accurately measuring the diffusion coefficients (D) of one liquid into another often encounters challenges stemming from intermolecular interactions, precise observations at the liquid interface, convection, etc. Here, we present an innovative electrochemical methodology for determining the diffusion coefficient of a liquid into another liquid. The method involves precisely tracking the lifetime of a nonaqueous droplet. An organic droplet is placed on an ultramicroelectrode surrounded by an aqueous solution of potassium hexacyanoferrate(II/III). The droplet initially blocks the reduction or oxidation of the redox species. As the droplet dissolves, giving access to the conductive microelectrode surface, a continuously increasing current is observed in voltammetry and the amperometric i-t response. The electrochemical response thus directly reports on the flux of redox species on the electrode surface, allowing us to precisely determine the lifetime of the droplet. D values are directly determined through a combination of electrochemical analysis and the principles of droplet dissolution. We demonstrate the quantification of 1,2-dichloroethane and nitrobenzene into water, yielding diffusion coefficients of (11.3 ± 1.2) × 10-6 cm2/s and (5.2 ± 1.1) × 10-6 cm2/s, respectively. This work establishes a reliable electrochemical approach for quantifying diffusion coefficients based on droplet lifetime analysis.


Ameliorative Effects of Loganin on Arthritis in Chondrocytes and Destabilization of the Medial Meniscus-Induced Animal Model.
Arthritis is a common inflammatory disease that causes pain, stiffness, and joint swelling. Here, we investigated the ameliorative effects of loganin on arthritis in vitro and in vivo. A single bioactive compound was fractionated and isolated from Cornus officinalis (CO) extract to screen for anti-arthritic effects. A single component, loganin, was identified as a candidate. The CO extract and loganin inhibited the expression of factors associated with cartilage degradation, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMP-3), and matrix metalloproteinase 13 (MMP-13), in interukin-1 beta (IL-1β)-induced chondrocyte inflammation. In addition, prostaglandin and collagenase levels were reduced following treatment of IL-1β-induced chondrocytes with loganin. In the destabilization of the medial meniscus (DMM)-induced mouse model, loganin administration attenuated cartilage degeneration by inhibiting COX-2, MMP-3, and MMP-13. Transverse micro-CT images revealed that loganin reduced DMM-induced osteophyte formation. These results indicate that loganin has protective effects in DMM-induced mice.


Characterization and genomic insight of surfactin-producing Bacillus velezensis and its biocontrol potential against pathogenic contamination in lettuce hydroponics.
Due to food borne pathogen, maintaining the viability of fresh fruits and vegetable is a great concern. Several strategies including microbial and plant-based formulations to reduce their infection and maintain quality of the fresh food are in practice. Currently, Bacillus has gained significant traction as a biocontrol agent for regulating diseases affecting a variety of agricultural and horticultural crops. Food-grade citric acid and plant growth-promoting rhizobacteria (PGPR) were used as antimicrobial agent, MIC results showed that PGPR (14.87 mm) and CA (20.25 mm) exhibited notable antimicrobial activity against E. coli. Lettuce treated with PGPR showed reduction in E. coli contamination, E. coli was detected at 3.30, 3.68 in control, and 2.7 log CFU/g in random root injury lettuce inoculated with PGPR KACC 21110 respectively. Random root injury showed a trend toward increasing E. coli internalization. The strains exhibited resistance to multiple antibiotics, including Imipenem, tetracycline, ampicillin, cefotaxime, cefoxitin, and ceftriaxone. Comprehensive data analysis revealed the presence of ten putative bacteriocin or bacteriocin-like gene clusters. The structure of lipopeptide homologs was characterized by using QTOF-MS/MS. The mass ion peaks attributed to surfactin homologs, surfactin A ion at m/z 1008.66, surfactin B, C at m/z 1022.67 and 1036.69. In addition to surfactin, a polyketide oxydifficidin and lipopeptide NO were extracted and detected from the extract of B. velezensis. Both isolates are key biocontrol agents and have significant potential in combating foodborne pathogens and can be utilized to explore novel antibacterial products for preventing pathogens in fresh produce.


Power-Dependent Characteristics of Spin Current Transfer in Metal Bilayer Devices under High-Power Pulse Excitation.
The power-dependent transfer characteristics of spin currents generated at the interface of the permalloy/Pt bilayer device have been investigated over a wide power range from a few tens of milliwatt to 396 W. We built a high-power pulse excitation system for spin pumping, which achieves large electromotive force (EMF) values of 10 mV at 396 W excitation through the inverse spin Hall effect (ISHE) and demonstrates that the EMF generation after pulse excitation is very fast. Under strong pulse microwave excitation more than 80 W, the EMF spectrum exhibits an asymmetrical lineshape, which is well reproduced by simulations that take into account the fold-over effect due to the nonlinear ferromagnetic resonance excitation. The maximum output power at an external load through spin pumping and the ISHE is shown to increase in proportion to the square of the input microwave power (Pin) in the power range below 80 W. This power generation proportional to Pin2 is unique to spin current-mediated power flow. In the strong excitation regime with the fold-over type EMF spectra, the EMF values of the peak magnetic field position are found to increase less linearly due to spectral broadening. This feature can be used for power generation that increases nonlinearly with respect to the input excitation power, where the nonlinearity is adjusted by varying the magnetic field position.


Melanotic neuroectodermal tumour of infancy (progonoma).
A case of Melanotic neuroectodermal tumour of infancy (melanotic progonoma, melanoameloblastoma, retinal anlarge tumour) presenting as tumour of maxilla in a female infant is reported. Clinically a teratoma was suspected but ultrasound shoved it a solid mass. At exploration, characteristic melanotic pigmentation clinched the diagnosis which was later confirmed by histopathological examination.


Epidural hygroma of the posterior fossa. Case report.
A case of posttraumatic epidural hygroma is reported. This child presented with occipital injury. Slowly but progressively he developed bilateral Wallenberg's syndrome and retrocollis. Correct preoperative diagnosis was made with the aid of computerized tomography. The case is discussed with emphasis on the mechanism of formation of an epidural hygroma and its clinical presentation.


Fungal nutrient allocation in common mycorrhizal networks is regulated by the carbon source strength of individual host plants.
Common mycorrhizal networks (CMNs) of arbuscular mycorrhizal (AM) fungi in the soil simultaneously provide multiple host plants with nutrients, but the mechanisms by which the nutrient transport to individual host plants within one CMN is controlled are unknown. Using radioactive and stable isotopes, we followed the transport of phosphorus (P) and nitrogen (N) in the CMNs of two fungal species to plants that differed in their carbon (C) source strength, and correlated the transport to the expression of mycorrhiza-inducible plant P (MtPt4) and ammonium (1723.m00046) transporters in mycorrhizal roots. AM fungi discriminated between host plants that shared a CMN and preferentially allocated nutrients to high-quality (nonshaded) hosts. However, the fungus also supplied low-quality (shaded) hosts with nutrients and maintained a high colonization rate in these plants. Fungal P transport was correlated to the expression of MtPt4. The expression of the putative ammonium transporter 1723.m00046 was dependent on the fungal nutrient supply and was induced when the CMN had access to N. Biological market theory has emerged as a tool with which the strategic investment of competing partners in trading networks can be studied. Our work demonstrates how fungal partners are able to retain bargaining power, despite being obligately dependent on their hosts.


Dramatic impact of morbid obesity on child lung development.
To assess the respiratory function and sleep characteristics of obese adults and children. All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m2 for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included. A total of 69 children (mean±SD BMI 36.8±6.7 and mean BMI z-score 4.7±1.0) and 70 adults were included (mean BMI 45.7±6.2). Metabolic syndrome was diagnosed in 13 children (26%) and 40 adults (80%). Reduced lung volumes were observed in 34 children (50.0%) and 16 adults (24.0%) and both the mean functional residual capacity (FRC) and the mean residual volume (RV) were lower in children than in adults (FRC: -1.7±2.1 z-score in children vs. -1.0±1.1 in adults, P=0.026; and RV: -0.8±1.2 z-score in children vs. -0.1±1.1 in adults, P=0.002). The prevalence of severe obstructive sleep apnea syndrome was greater in adults (40.7% vs. 18.8%, P=0.007). Children had a higher average oxygen saturation (median of 96.0% [91.0-98.0] vs. 93.0% [76.0-97.0] in adults, P<0.0001). Obesity has consequences for lung volumes in children; however, a longitudinal study is needed to determine the impact on pulmonary expansion and growth.


Barriers and facilitators to the implementation of clinical practice guidelines: a cross-sectional survey among physicians in Estonia.
In an era when an increasing amount of clinical information is available to health care professionals, the effective implementation of clinical practice guidelines requires the development of strategies to facilitate the use of these guidelines. The objective of this study was to assess attitudes towards clinical practice guidelines, as well as the barriers and facilitators to their use, among Estonian physicians. The study was conducted to inform the revision of the clinical practice guideline development process and can provide inspiration to other countries considering the increasing use of evidence-based medicine. We conducted an online survey of physicians to assess resource, system, and attitudinal barriers. We also asked a set of questions related to improving the use of clinical practice guidelines and collected free-text comments. We hypothesized that attitudes concerning guidelines may differ by gender, years of experience and practice setting. The study population consisted of physicians from the database of the Department of Continuing Medical Education of the University of Tartu. Differences between groups were analyzed using the Kruskal-Wallis non-parametric test. 41% (497/1212) of physicians in the database completed the questionnaire, comprising more than 10% of physicians in the country. Most respondents (79%) used treatment guidelines in their daily clinical practice. Lack of time was the barrier identified by the most physicians (42%), followed by lack of medical resources for implementation (32%). The majority of physicians disagreed with the statement that guidelines were not accessible (73%) or too complicated (70%). Physicians practicing in outpatient settings or for more than 25 years were the most likely to experience difficulties in guideline use. 95% of respondents agreed that an easy-to-find online database of guidelines would facilitate use. Use of updated evidence-based guidelines is a prerequisite for the high-quality management of diseases, and recognizing the factors that affect guideline compliance makes it possible to work towards improving guideline adherence in clinical practice. In our study, physicians with long-term clinical experience and doctors in outpatient settings perceived more barriers, which should be taken into account when planning strategies in improving the use of guidelines. Informed by the results of the survey, leading health authorities are making an effort to develop specially designed interventions to implement clinical practice guidelines, including an easily accessible online database.


How far can States take health reform?
Expectations for state leadership in health reform have never been higher. States are thought to function as "laboratories of democracy," but they do not fulfill this role effectively because insufficient attention is paid to experimentation and knowledge translation. Congressional proposals to encourage state action cover too narrow a span of state health policy, do not provide states with sufficient authority to tackle major health policy challenges, and supply insufficient funding. This paper concludes with a description of a more robust state-federal partnership that would be more likely to yield substantial health reform.


Brief report: accelerated aging influences cardiovascular disease risk in rheumatoid arthritis.
To determine whether the impact of aging on cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) differs from that in the general population (as estimated by the Framingham Risk Score [FRS]). A population-based inception cohort of Olmsted County, Minnesota residents ages≥30 years who fulfilled the American College of Rheumatology 1987 criteria for RA in 1988-2008 was assembled and followed up until death, migration, or July 1, 2012. Data on CVD events were collected by medical records review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk. The study included 563 patients with RA without prior CVD (mean age 55 years, 72% women, and 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean followup of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but the FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the effect of age on CVD risk in seropositive RA was nearly double its effect in the general population, with additional log(age) coefficients of 2.91 for women (P=0.002) and 2.06 for men (P=0.027). Our findings indicate that age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation.


Identification of human gene products containing Pro-Pro-x-Tyr (PY) motifs that enhance glutathione and endocytotic marker uptake in yeast.
In an attempt to identify genes involved in glutathione (GSH) transport, a human mammary gland cDNA library was screened for clones capable of complementing a defect in GSH uptake in yeast cells that lack Hgt1p, the primary yeast GSH uptake transporter. Five genes capable of rescuing growth on sulfur-deficient GSH-containing medium were identified: prostate transmembrane protein, androgen induced 1 (PMEPA1); lysosomal-associated protein transmembrane 4 alpha (LAPTM4alpha); solute carrier family 25, member 1 (SLC25A1); lipopolysaccharide-induced TNF factor (LITAF); and cysteine/tyrosine-rich-1 (CYYR1). All of these genes encode small integral membrane proteins of unknown function, although none appear to encode prototypical GSH transporters. Nevertheless, they all increased both intracellular glutathione levels and [(3)H]GSH uptake rates. [(3)H]GSH uptake was uniformly inhibited by high concentrations of unlabeled GSH, GSSG, and ophthalmic acid. Interestingly, each protein is predicted to contain Pro-Pro-x-Tyr (PY) motifs, which are thought to be important for regulating protein cell surface expression. Uptake of the endocytotic markers lucifer yellow and FM4-64 was also enhanced by each of the five genes. Mutations of the PY motifs in LITAF largely abolished all of its effects. In summary, although the results do not reveal novel GSH transporters, they identify five PY-containing human gene products that may influence plasma membrane transport activity.


Radiological evaluation of inferior alveolar nerve displacement after removal of impacted mandibular third molars prior to sagittal split osteotomy.
We hypothesize that the removal of mandibular third molars (M3) 6 months prior to a bilateral sagittal split osteotomy (BSSO) could allow the displacement of the inferior alveolar nerve (IAN) in a favorable lingual position. This study aimed to radiographically compare the position of IAN before and after M3 removal in patients with Class II malocclusion. The CBCT images of 30 randomly selected patients (mean age 15.5 years, 19 females and 11 males) were segmented regarding the mandibular bone and the IAN canal. Mandibles were then superimposed and compared using 3D slicer (www.slicer.org). An orthonormal system was constructed, and the coordinates of IAN were assessed in the x- (horizontal axis), y- (depth axis), and z- (vertical axis) directions. The mean changes in x- and z-values were 0.37 %, -0.09 % for the right IAN, 0.07 %, and -0.10 % for the left IAN, respectively. Y-axis was the dimension the most impacted by the M3 removal with a mean variation of -11.96 % for the right IAN, and 0.45 % for the left nerve (p1=0.74 and p2=0.04, respectively). Three patients presented a change in the IAN position superior to 1 mm on at least one coordinate axis. We observed a more important change in x-values of the right IAN in male than in female (p = 0.04), and no significant modifications regarding the other dimensions. Finally, there was no correlation between the age of the patients and the changes in IAN position. This study confirms the absence of influence of mandibular third molar removal on the inferior alveolar nerve route prior to BSSO.


Reconstruction of the Cranial Vault Contour Using Tissue Expander and Castor Oil Prosthesis.
Nowadays the reconstruction of craniofacial defects can be performed with different kinds of materials, which include the bone and the so-called biomaterials, which have the advantage of not needing a surgical site donor. Among these materials, great attention is given to polymers. In this large group, current attention is focused on the castor oil polymer, since this polymer is biocompatible, low cost, and has adequate strength for reconstruction of the craniomaxillofacial complex. This study aims to report the use of a prosthetic castor oil polymer for reconstruction of extensive defect, caused by a trauma, in the temporoparietal region.


Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines.
We developed and characterized a canine model of outer retinal degeneration induced by sodium iodate (SI) intravitreal injection after vitrectomy. In the preliminary study, we repeatedly injected SI intravitreally into the eyes of three canines to develop outer retinal degeneration two weeks after vitrectomy. Based on the preliminary study, a single dose of either 1.2 mg or 1.0 mg SI/0.05 mL was also injected (1.2 mg in n = 5 canines, 1.0 mg in n = 2 canines). Spectral domain-optical coherence tomography (OCT), electroretinography (ERG), and histological examinations were performed at baseline and following intravitreal injection. In the preliminary study, after a 0.5-mg SI injection and a 1.0-mg SI injection and after two 0.8-mg SI injections, retinal degeneration with retinal thinning was observed on OCT imaging. In the second study, after a single 1.0- or 1.2-mg SI injection, outer retinal degeneration was induced. All eyes showed diffuse outer retinal degeneration on OCT and a loss of both cone and rod responses in ERG. Histological examination also showed the loss of outer retinal layer. Intravitreally injected SI (1.0-1.2 mg) in a vitrectomized canine model induced outer retinal degeneration effectively, and could be evaluated through in vivo ophthalmic examination.


Tocilizumab for the Treatment of Mevalonate Kinase Deficiency.
Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by recessive mutations in MVK resulting in reduced function of the enzyme mevalonate kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with periodic episodes of severe systemic inflammation, poor quality of life, and life-threatening sequelae if inadequately treated. We report the case of a 12-year-old girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF-α blockade. In view of this, she commenced intravenous tocilizumab (8 mg/kg every 2 weeks), a humanised monoclonal antibody targeting the IL-6 receptor (IL-6R) that binds to membrane and soluble IL-6R, inhibiting IL-6-mediated signaling. She reported immediate cessation of fever and marked improvement in her energy levels following the first infusion; after the fifth dose, she was in complete clinical and serological remission, now sustained for 24 months. This is one of the first reported cases of a child with MKD treated successfully with tocilizumab and adds to the very limited experience of this treatment for MKD. IL-6 blockade could therefore be an important addition to the armamentarium for the treatment of this rare monogenic autoinflammatory disease.