Puerperal pyrexia: a review. Part I.
Puerperal pyrexia and sepsis are among the leading causes of preventable maternal morbidity and mortality not only in developing countries but in developed countries as well. Most postpartum infections take place after hospital discharge, which is usually 24 hours after delivery. In the absence of postnatal follow-up, as is the case in many developing countries, many cases of puerperal infections can go undiagnosed and unreported. Besides endometritis (endomyometritis or endomyoparametritis), wound infection, mastitis, urinary tract infection, and septic thrombophlebitis are the chief causes of puerperal infections. The predisposing factors leading to the development of sepsis include home birth in unhygienic conditions, low socioeconomic status, poor nutrition, primiparity, anemia, prolonged rupture of membranes, prolonged labor, multiple vaginal examinations in labor, cesarean section, obstetrical maneuvers, retained secundines within the uterus and postpartum hemorrhage. Maternal complications include septicemia, endotoxic shock, peritonitis or abscess formation leading to surgery and compromised future fertility. The transmissions of infecting organisms are typically categorized into nosocomial, exogenous, and endogenous. Nosocomial infections are acquired in hospitals or other health facilities and may come from the hospital environment or from the patient's own flora. Exogenous infections come from external contamination, especially when deliveries take place under unhygienic conditions. Endogenous organisms, consisting of mixed flora colonizing the woman's own genital tract, are also a source of infection in puerperal sepsis. Aseptic precautions, advances in investigative tools and the use of antibiotics have played a major role in reducing the incidence of puerperal infections. Part I of this review provides background information and definitions, discusses the incidence and risk factors, explains the microbiology and pathophysiology of various infections, and delineates the signs and symptoms of major puerperal infection. Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that world wide puerperal sepsis is a leading cause of maternal mortality, state that many of the predisposing factors are preventable, explain that both nosocomial infections as well as exogenous infections are serious factors, and relate that septic techniques and antibiotics can play a major role in reducing the incidence of puerperal infections.


Aging analysis reveals slowed tau turnover and enhanced stress response in a mouse model of tauopathy.
We have extensively analyzed the biochemical and histochemical profiles of the tau protein from the rTg4510 transgenic mouse model in which the animals uniquely develop forebrain tau pathologies similar to those found in human tauopathies. Levels of several soluble phosphorylated tau species were highest at 1 month relative to later time points, suggesting that certain tau hyperphosphorylation events were insufficient to drive tangle formation in young mice. Despite a robust, pre-tangle-like accumulation of phospho-tau in 1-month-old mice, this material was cleared by 3 months, indicating that the young mouse brain either fails to facilitate tau insolubility or possesses an enhanced ability to clear tau relative to the adult. We also found that while heat shock protein expression increased with normal aging, this process was accelerated in rTg4510 mice. Moreover, by exploiting an exon 10 (-) specific antibody, we demonstrated that endogenous mouse tau turnover was slowed in response to human tau over-expression, and that this endogenous tau adopted disease-related properties. These data suggest that a younger brain fails to develop lasting tau pathology despite elevated levels of phosphorylated tau, perhaps because of reduced expression of stress-related proteins. Moreover, we show that the active production of small amounts of abnormal tau protein facilitates dysfunction and accumulation of otherwise normal tau, a significant implication for the pathogenesis of patients with Alzheimer's disease.


Inhibitory effect of progesterone on androgen-induced lordosis in ovariectomized rats.
Androgen has a potency to induce female sexual behavior in ovariectomized rats. This study investigated the inhibitory effect of progesterone (P) on lordosis behavior facilitated by androgen. Ovariectomized female rats were given 100 to 800 micrograms/kg testosterone propionate (TP) or 5 micrograms/kg estradiol benzoate (EB). Forty-four hours after administration of the TP or the EB, all females received 0.5 mg P, and the first behavioral test was carried out four hours later. TP-treated animals showed lordosis responses in a dose dependent manner. Two weeks after the first test, the animals were retested by using the same hormonal regime as in the first test, except that an additional 5 mg P was administered 1 h prior to the TP or the EB. As a result, significant reductions in sexual receptivity were observed in the TP-treated as well as in the EB-treated females. These results indicate that progesterone can inhibit androgen-induced lordosis behavior in female rats.


Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.
HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells. Small molecule CCR5 antagonists are currently being developed for the treatment of HIV-1 infection. Because HIV-1 may also use CXCR4 for entry, the use of CCR5 entry inhibitors is controversial for patients harboring CCR5-using and CXCR4-using (dual/mixed-tropic) viruses. The goal of the present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses in dual/mixed-tropic virus isolates from drug-naïve patients and the phenotypic and genotypic relationships of viruses that use CCR5 or CXCR4 or both. Fourteen antiretroviral-naive HIV-1-infected patients were identified as having population coreceptor tropism readout of dual/mixed-tropic viruses. Intrapatient comparisons of coreceptor tropism and genotype of env clones were conducted on plasma virus from each patient. Population HIV-1 envelope tropism and susceptibility to the CCR5 entry inhibitor, aplaviroc, were performed using the Monogram Biosciences Trofile Assay. Twelve env clones from each patient were analyzed for coreceptor tropism, aplaviroc sensitivity, genotype, and intrapatient phylogenetic relationships. Viral populations from antiretroviral-naive patients with dual/mixed-tropic virus are composed primarily of CCR5-tropic env clones mixed with those that use both coreceptors (R5X4-tropic) and, occasionally, CXCR4-tropic env clones. Interestingly, the efficiency of CXCR4 use by R5X4-tropic env clones varied with their genetic relationships to CCR5-tropic env clones from the same patient. These data show that the majority of viruses in these dual/mixed-tropic populations use CCR5 and suggest that antiretroviral-naive patients may benefit from combination therapy that includes CCR5 entry inhibitors.


Some Haliotrema (Monogenea: Dactylogyridae) from cultured grouper (Epinephelus Spp.) with emphasis on the phylogenetic position of Haliotrema cromileptis.
Three Haliotrema spp. are reported from the Vietnamese grouper. Morphological and morphometric characters show minor deviations from original descriptions of H. cromileptis Young, 1968 and H. epinepheli Young, 1968 . The third encountered species ( Haliotrema sp.) appears to be new to science. Genetically, H. cromileptis clusters with Bravohollisia , Pseudohaliotrema , and Haliotrema . The group is well supported by partial large subunit rDNA (LSU), complete small subunit rDNA (SSU), and partial SSU + ITS1 rDNA analyses. Ingroup phylogenetic relationships are not well resolved. Haliotrema cromileptis , H. fleti Young, 1968 , and Pseudohaliotrema sphincteroporus Yamaguti, 1953 are closely related to a monophyletic group of 5 Haliotrema spp. characterized by bell- or horn-shaped bases of the male copulatory organ (MCO), which contains an accessory piece. Based on SSU rDNA, H. cromileptis is a sister species to P. sphincteroporus and, together, they form a clade to 3 other Haliotrema spp. characterized by a bell-shape based MCO with an accessory piece. Data analysis conducted on partial SSU + ITS1 rDNA confirms the close phylogenetic relationship of H. cromileptis , H. fleti , H. chenhsintaoi Zhang, 2001 (possessing a horn-shaped base of the MCO), and Bravohollisia rosetta Lin, 1995. However, because major differences in diagnostic characters exist, this genetic relationship needs further elucidation.


Tinnitus Suppression by Intracochlear Electrical Stimulation in Single-Sided Deafness: A Prospective Clinical Trial - Part I.
Cochlear implantation is a viable treatment option for tinnitus, but the underlying mechanism is yet unclear. Is the tinnitus suppression due to the reversal of the assumed maladaptive neuroplasticity or is it the shift in attention from the tinnitus to environmental sounds and therefore a reduced awareness that reduces tinnitus perception? In this prospective trial, 10 patients with single-sided deafness were fitted with a cochlear implant to investigate the effect of looped intracochlear electrical stimulation (i.e. stimulation that does not encode environmental sounds) on tinnitus, in an effort to find optimal stimulation parameters. Variables under investigation were: amplitude (perceived stimulus loudness), anatomical location inside the cochlea (electrode/electrodes), amplitude modulation, polarity (cathodic/anodic first biphasic stimulation) and stimulation rate. The results suggest that tinnitus can be reduced with looped electrical stimulation, in some cases even with inaudible stimuli. The optimal stimuli for tinnitus suppression appear to be subject specific. However, medium-to-loud stimuli suppress tinnitus significantly better than soft stimuli, which partly can be explained by the masking effect. Although the long-term effects on tinnitus would still have to be investigated and will be described in part II, intracochlear electrical stimulation seems a potential treatment option for tinnitus in this population.


The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta.
The receptor Notch and its ligands of the Delta/Serrate/LAG2 (DSL) family are the central components in the Notch pathway, a fundamental cell signaling system that regulates pattern formation during animal development. Delta is directly ubiquitinated by Drosophila and Xenopus Neuralized, and by zebrafish Mind bomb, two unrelated RING-type E3 ubiquitin ligases with common abilities to promote Delta endocytosis and signaling activity. Although orthologs of both Neuralized and Mind bomb are found in most metazoan organisms, their relative contributions to Notch signaling in any single organism have not yet been assessed. We show here that a Drosophila ortholog of Mind bomb (D-mib) is a positive component of Notch signaling that is required for multiple Neuralized-independent, Notch-dependent developmental processes. Furthermore, we show that D-mib associates physically and functionally with both Serrate and Delta. We find that D-mib uses its ubiquitin ligase activity to promote DSL ligand activity, an activity that is correlated with its ability to induce the endocytosis and degradation of both Delta and Serrate (see also Le Borgne et al., 2005). We further demonstrate that D-mib can functionally replace Neuralized in multiple cell fate decisions that absolutely require endogenous Neuralized, a testament to the highly similar activities of these two unrelated ubiquitin ligases in regulating Notch signaling. We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development.


Electrophoretic karyotyping of typical and atypical Candida albicans.
Electrophoretic karyotypes of atypical isolates of Candida albicans, e.g., strains that were germ tube negative, failed to express proteinase activity, demonstrated low virulence for mice, formed hyperchlamydoconidia, produced hyperhyphae, or were sucrose negative (including the type strain of Candida stellatoidea), were compared with those of typical C. albicans. Karyotypes of whole-cell DNA of classical C. albicans examined with transverse alternating-field electrophoresis under specific conditions were composed of seven DNA bands with a specific migration pattern. Certain atypical strains and representatives of the three serotypes of C. stellatoidea produced discrete karyotypes with 5 to 10 bands. All isolates demonstrated a significant degree of DNA relatedness, suggesting their conspecificity. Densitometric tracings of DNA bands provided an objective and standardized method for comparing bands within the gels.


Modified surgical technique for the treatment of idiopathic spinal cord herniation.
Spinal cord herniation is not a common disease and only 80 cases have been reported to the best of our knowledge. The treatment of this lesion is thought to be difficult and a better surgical technique has not been established. A 57-year-old man presented with gradually worsening spastic gait and hypoesthesia in the bilateral lower extremities suspected to be due to Brown-Séquard syndrome. Magnetic resonance imaging showed a thoracic spinal cord herniation into the anterior hiatus at T2 - 3. A modified technique of closure of the hiatus in front of the herniation was performed. A surgical artificial dural membrane was introduced between the herniated portion of the thoracic cord and the dural hiatus and was placed to cover the whole dural defect in order to minimize the operative procedure at the ventral side of the spinal cord. On subsequent magnetic resonance imaging, the herniation was remarkably improved and patient's symptoms were abolished. The direct widening of the dural defect has been reported to be the only treatment providing a good outcome. We suggest that our modified technique for its closure can be as safe and effective as the direct widening method.


Cloning and growth-regulated expression of the gene encoding the hepatitis B virus middle surface antigen in Yarrowia lipolytica.
Expression of the gene encoding the hepatitis B virus middle surface antigen (pre-HBsAg) in the yeast Yarrowia lipolytica has been studied. The preS2-HBsAg gene was expressed from the alkaline extracellular protease-encoding gene (XPR2) promoter. In the fusion construct, the membrane-spanning 'a' domain of preS2-HBsAg has been replaced by the leader peptide and the proI region of the alkaline protease, thus eliminating the epitope responsible for the immune escape mechanism. Expression has been found to be growth-stage dependent with the highest protein accumulation during the stationary phase, accounting for around 2.35% of the total soluble intracellular proteins. The produced protein was assembled into Dane particles and was immunogenic in mice. The expression vector was found to be stable for at least 100 generations under non-selective conditions.


Supervised dimension reduction of intrinsically low-dimensional data.
High-dimensional data generated by a system with limited degrees of freedom are often constrained in low-dimensional manifolds in the original space. In this article, we investigate dimension-reduction methods for such intrinsically low-dimensional data through linear projections that preserve the manifold structure of the data. For intrinsically one dimensional data, this implies projecting to a curve on the plane with as few intersections as possible. We are proposing a supervised projection pursuit method that can be regarded as an extension of the single-index model for nonparametric regression. We show results from a toy and two robotic applications.


Synaptotagmin-7 Is Essential for Ca2+-Triggered Delayed Asynchronous Release But Not for Ca2+-Dependent Vesicle Priming in Retinal Ribbon Synapses.
Most synapses release neurotransmitters in two phases: (1) a fast synchronous phase lasting a few milliseconds; and (2) a delayed "asynchronous" phase lasting hundreds of milliseconds. Ca(2+) triggers fast synchronous neurotransmitter release by binding to synaptotagmin-1, synaptotagmin-2, or synaptotagmin-9, but how Ca(2+) triggers delayed asynchronous release has long remained enigmatic. Recent results suggested that consistent with the Ca(2+)-sensor function of synaptotagmin-7 in neuroendocrine exocytosis, synaptotagmin-7 also functions as a Ca(2+) sensor for synaptic vesicle exocytosis but operates during delayed asynchronous release. Puzzlingly, a subsequent study postulated that synaptotagmin-7 is not a Ca(2+) sensor for release but mediates Ca(2+)-dependent vesicle repriming after intense stimulation. To address these issues, we here analyzed synaptic transmission at rod bipolar neuron-AII amacrine cell synapses in acute mouse retina slices as a model system. Using paired recordings, we show that knock-out of synaptotagmin-7 selectively impairs delayed asynchronous release but not fast synchronous release. Delayed asynchronous release was blocked in wild-type synapses by intracellular addition of high concentrations of the slow Ca(2+)-chelator EGTA, but EGTA had no effect in synaptotagmin-7 knock-out neurons because delayed asynchronous release was already impaired. Moreover, direct measurements of vesicle repriming failed to uncover an effect of the synaptotagmin-7 knock-out on vesicle repriming. Our data demonstrate that synaptotagmin-7 is selectively essential for Ca(2+)-dependent delayed asynchronous release in retinal rod bipolar cell synapses, that its function can be blocked by simply introducing a slow Ca(2+) buffer into the cells, and that synaptotagmin-7 is not required for normal vesicle repriming. How Ca(2+) triggers delayed asynchronous release has long remained enigmatic. Synaptotagmin-7 has been implicated recently as Ca(2+) sensor in mediating delayed asynchronous release, or vesicle repriming, in cultured neurons. To test the precise function of synaptotagmin-7 in a physiologically important synapse in situ, we have used pair recordings to study the synaptic transmission between retinal rod bipolar cells and AII amacrine cells. Our data demonstrate that the knock-out of synaptotagmin-7 selectively impaired delayed asynchronous release but not synchronous release. In contrast, the readily releasable vesicles after depletion recover normally in knock-out mice. Therefore, our findings extend our knowledge of synaptotagmins as Ca(2+) sensors in vesicle fusion and support the idea that synapses are governed universally by different synaptotagmin Ca(2+) sensors mediating distinct release.


Surgical management of spontaneous pneumothorax.
Despite the promising potential of video-assisted thoracoscopic pleurectomy in the treatment of pneumothoraces, conventional surgical intervention by a thoracotomy and pleurodesis with ligation/stapling of bullae remains the main form of treatment in many hospitals. It is with this in mind that we present our experience of 250 patients who have undergone surgical pleurodesis for treatment of a persistent or recurrent spontaneous pneumothorax. Of these patients, 74 had undergone parietal pleurectomy (PP), 93 pleural abrasion (PA), 60 transaxillary apical pleurectomy (TAP), and 23 had undergone apical pleurectomy via a posterolateral or submammary thoracotomy (APT). In general, there were few complications and we could show no discernible difference in the rate of complications between the groups. Despite there being no significant difference in the median period of postoperative intercostal tube drainage, there was a significant difference between the groups in the number of patients with a postoperative hospital stay equal to or greater than seven days and a postoperative serosanguinous volume loss greater than 500 ml. Those patients that had undergone parietal pleurectomy tended to remain in hospital for a longer period (> or = 7 days) and to have a heavier serosanguinous volume loss (> 500 ml). There have been no recurrent cases in the PP and APT groups. Their respective median follow up periods are 62 (range 15-83) and 32 (range 15-54) months. The median follow up period in the PA group was 42 (range 13-69) months, one recurrence occurred after 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)


Positive effects of computer-based cognitive training in adults with mild cognitive impairment.
Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a 12-week computer-based memory-attention training program based on recognition in subjects with A-MCI and compared their performances with those of A-MCI controls trained in cognitively stimulating activities. The effect of training was assessed by comparing outcome measures in pre- and post-tests 15 days before and after training. To evaluate the duration of training benefits, a follow-up test session was performed 6 months after memory and attention training or cognitively stimulating activities. Outcome measures showed that the trained group, compared to control group, improved episodic recall and recognition. Six months after training, scores remained at the level of the post-test. Since the training program was exclusively based on recognition, our results showed a generalization from recognition to recall processes, which are memory components that represent part of the core cognitive impairments in individuals at risk of converting to AD. Thus, cognitive training based on recognition holds promise as a preventive therapeutic method and could be proposed as a non-pharmacological early-intervention strategy. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action.


Cortical blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage: three-dimensional N-isopropyl-p-[(123)I]iodoamphetamine single photon emission CT findings.
The relationship between regional cerebral blood flow (rCBF) during cerebral vasospasm after subarachnoid hemorrhage (SAH) and angiographic vasospasm and the value of rCBF in predicting vasospasm and the prognosis are not fully delineated. Our aim was to investigate the changes in extent of vasospasm-induced decreased cortical rCBF on three-dimensional (3D) displays of single photon emission CT (SPECT) findings. The clinical usefulness of these assessments was analyzed. In 58 cases of SAH, SPECT and digital subtraction angiography were performed on the same day, 5-9 days after SAH or within 24 hours after the onset of delayed ischemic neurologic deficit (DIND). Cerebral blood flow data were assessed by measuring the area of decreased cortical rCBF on 3D SPECT images. The area of decreased cortical rCBF on the 3D images was significantly increased in cases with DIND (P <.001), in cases with a large infarction due to vasospasm (P =.006), and in cases with a poor prognosis after vasospasm (P =.045). These increases were also related to the type of angiographic vasospasm; the greatest decrease in cortical rCBF occurred in the combined type (combination of the peripheral and proximal types) of vasospasm, followed by cases with the peripheral type, proximal type, and no angiographic vasospasm. In cases with DIND, patchy decreased cortical rCBF areas were seen before the onset of DIND. Combined-type vasospasm leads to reductions in CBF greater than those due to isolated peripheral or proximal vasospasm. Two-dimensional and mean-hemispheric CBF analyses are less sensitive for this change than is 3D SPECT.


Correlation of electron transport and photocatalysis of nanocrystalline clusters studied by Monte-Carlo continuity random walking.
In this research, Monte-Carlo Continuity Random Walking (MC-RW) model was used to study the relation between electron transport and photocatalysis of nano-crystalline (nc) clusters. The effects of defect energy disorder, spatial disorder of material structure, electron density, and interfacial transfer/recombination on the electron transport and the photocatalysis were studied. Photocatalytic activity is defined as 1/τ from a statistical viewpoint with τ being the electron average lifetime. Based on the MC-RW simulation, a clear physical and chemical "picture" was given for the photocatalytic kinetic analysis of nc-clusters. It is shown that the increase of defect energy disorder and material spatial structural disorder, such as the decrease of defect trap number, the increase of crystallinity, the increase of particle size, and the increase of inter-particle connection, can enhance photocatalytic activity through increasing electron transport ability. The increase of electron density increases the electron Fermi level, which decreases the activation energy for electron de-trapping from traps to extending states, and correspondingly increases electron transport ability and photocatalytic activity. Reducing recombination of electrons and holes can increase electron transport through the increase of electron density and then increases the photocatalytic activity. In addition to the electron transport, the increase of probability for electrons to undergo photocatalysis can increase photocatalytic activity through the increase of the electron interfacial transfer speed.


Effects of age and obesity on fasting gastric electrical activity in man: a cutaneous electrogastrographic study.
We investigated the effects of age and obesity on the fasting cutaneous electrogastrogram (EGGc) by studying both young and aged, healthy men. All subjects underwent an electrogastrographic recording lasting 1 h, and frequency and power data were obtained by means of spectral analysis. In order to make a precise comparison of the data, each subject's body mass index (BMI) was calculated and each age group was subdivided into nonobese subjects, those with a BMI of less than 24.9 kg/m2, and obese subjects, those with a BMI of more than 25 kg/m2. Comparison of the mean frequency values of the gastric spectral peak did not reveal statistically significant differences among the groups (young vs. old, nonobese vs. obese). Comparison of the mean power values of the gastric spectral peak, on the other hand, showed that there was a statistically significant reduction in spectral power in the aged subjects compared with the young (p = 0.017 in the aged vs. young nonobese subjects and p = 0.009 in the aged vs. young obese subjects), and in the obese subjects compared with the nonobese (p = 0.00021 in the young and p = 0.00029 in the aged). Frequency, therefore, is the parameter of gastric electrical activity which may best be studied by means of EGGc as it is only very slightly affected by physiological parameters, such as age and the adiposity of subjects. EGGc, therefore, could be useful in the study of those gastric diseases associated with disorders in gastric electrical rhythm and rate.


Seed maturation in Arabidopsis thaliana is characterized by nuclear size reduction and increased chromatin condensation.
Most plant species rely on seeds for their dispersal and survival under unfavorable environmental conditions. Seeds are characterized by their low moisture content and significantly reduced metabolic activities. During the maturation phase, seeds accumulate storage reserves and become desiccation-tolerant and dormant. Growth is resumed after release of dormancy and the occurrence of favorable environmental conditions. Here we show that embryonic cotyledon nuclei of Arabidopsis thaliana seeds have a significantly reduced nuclear size, which is established at the beginning of seed maturation. In addition, the chromatin of embryonic cotyledon nuclei from mature seeds is highly condensed. Nuclei regain their size and chromatin condensation level during germination. The reduction in nuclear size is controlled by the seed maturation regulator ABSCISIC ACID-INSENSITIVE 3, and the increase during germination requires two predicted nuclear matrix proteins, LITTLE NUCLEI 1 and LITTLE NUCLEI 2. Our results suggest that the specific properties of nuclei in ripe seeds are an adaptation to desiccation, independent of dormancy. We conclude that the changes in nuclear size and chromatin condensation in seeds are independent, developmentally controlled processes.


Trivalent antimonials induce degradation of the PML-RAR oncoprotein and reorganization of the promyelocytic leukemia nuclear bodies in acute promyelocytic leukemia NB4 cells.
Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) chromosomal translocation that fuses the genes encoding the promyelocytic leukemia protein (PML) and the retinoic acid receptor (RAR). The resulting PML-RAR protein induces a block in the differentiation of the myeloid progenitor cells, which can be released by retinoic acid (RA) in vitro and in vivo. The RA-induced differentiation of APL blasts is paralleled by the degradation of the fusion protein and the relocation of wild-type PML from aberrant nuclear structures to its normal localization in nuclear bodies. Recently, arsenic trioxide (As2O3) treatment was proposed as an alternative therapy in APL, because it can induce complete remission in both RA-sensitive and -resistant APL patients. Intriguingly, As2O3 was also shown to induce degradation of the PML-RAR chimera and to reorganize PML nuclear bodies. Here we show that trivalent antimonials also have striking effects on RA-sensitive and RA-resistant APL cells. Treatment of the APL-derived NB4 cells and the RA-resistant subclone NB4R4 with antimony trioxide or potassium antimonyl tartrat triggers the degradation of the fusion protein and the concomitant reorganization of the PML nuclear bodies. In addition, as reported for As2O3, the antimonials provoke apoptosis of NB4 and NB4R4 cells. The mechanism of antimony action is likely to be similar to that of As2O3, notably both substances induce the attachment of the ubiquitin-like SUMO-1 molecule to the PML moiety of PML-RAR. From these data, we propose that, in analogy to As2O3, antimonials might have a beneficial therapeutic effect on APL patients, perhaps with less toxicity than arsenic.


Computer-automated structure evaluation of flavonoids and other structurally related compounds as glyoxalase I enzyme inhibitors.
The Computer-Automated Structure Evaluation (CASE) methodology has been applied to a set of flavonoids and other structurally related compounds tested for glyoxalase I enzyme inhibition. CASE identified several structural features believed to be responsible for activity. A total of five fragments were isolated. The most important structural feature is the alpha-hydroxy-alpha,beta-unsaturated carbonyl group attached to a fused ring carbon atom. This fragment tautomerizes into a transition state analog of the substrate of the enzyme. Five tested compounds initially removed from the database were submitted to CASE in the predictive mode. The predictions generally matched the tested values for enzyme inhibition. A set of chromones and phenyl-pyrones, although untested, were also submitted to CASE. CASE predicts that, as a class of compounds, chromones would be more effective inhibitors than phenyl-pyrones.


Source monitoring for actions in adolescents with 22q11.2 deletion syndrome (22q11DS).
Source monitoring consists in identifying the origin of mental events. Recent research suggests that confusions over internally generated mental events may represent a cognitive marker for increased proneness to psychotic symptoms and disorders. We have examined source monitoring for actions in adolescents with the 22q11.2 deletion syndrome (22q11DS), a neurogenetic disease associated with high rates of schizophrenia during adulthood, and expected to observe source monitoring deficits in comparison to IQ-matched and typically developing controls. Eighteen adolescents with 22q11DS, 17 adolescents matched for age and IQ, and also 17 adolescents matched for age participated in this study. Our adapted action monitoring paradigm asked subjects to visualize a series of actions in three different conditions: (1) visualize themselves performing the action; (2) visualize the experimenter performing the action; or (3) simply repeat the action statements without visualization of the action performer. The adolescents with 22q11DS performed adequately in terms of recognition (hits), but in comparison to both control groups, they committed more source confusions on correctly recognized items. Further examination revealed that the adolescents were more likely to demonstrate confusions between exterior sources in which the self was not involved. Source monitoring deficits can be observed in adolescents with 22q11DS, a syndrome putting them at high risk for developing schizophrenia. These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia.


Water gelation of an amino acid-based amphiphile.
The water immobilization by a simple amino acid-containing cationic surfactant was investigated. A variety of techniques, such as (1)H NMR spectroscopy, circular dichroism (CD), steady-state fluorescence spectroscopy, and field-emission scanning electron microscopy (FESEM) were applied to determine the formation and architecture of the hydrogel. The new gelator with a minimum gelation concentration (MGC) of 0.3 % w/v shows prolonged stability and a low melting temperature (39 degrees C). (1)H NMR experiments revealed that intermolecular hydrogen bonding between the amide groups and pi-pi stacking of the indole rings are the two regulating parameters for gelation. Furthermore, fluorescence studies with 8-anilino-1-naphthalenesulfonic acid (ANS) as the probe indicate the participation of hydrophobicity during gelation. The luminescence study using both ANS and pyrene, along with FESEM results, indicate a critical concentration, well below the MGC, at which fibres begin to form. These cross-link further to give thicker fibers, leading to the formation of a hydrogel (0.3 % w/v). This new hydrogelator expresses high supramolecular chirality, as evidenced by the CD spectra. In addition, the gelator molecule was found to be nontoxic up to a concentration of 4 mM (0.2 % w/v). The high supramolecular chirality, prolonged stability, low melting point, and biocompatibility of the molecule make it a focus of chemical and biological interest.


Evaluation of Trichoderma spp., Pseudomonasfluorescens and Bacillus subtilis for biological control of Ralstonia wilt of tomato.
Background:Ralstonia spp. is a major pathogenic microbe for tomato, which invades the roots of diverse plant hosts and colonizes xylem vessels causing wilt, especially in tropical, subtropical and warm-temperate regions. Ralstonia spp. produces several virulence factors helping it to invade the plant's natural defense mechanism. Native isolates of Trichoderma spp., Pseudomonas fluorescens and Bacillus subtilis can be used as biocontrol agents to control the bacterial wilt and combined application of these beneficial microbes can give better results. Methods: Bacterial wilt infection in the field was identified by field experts and the infected plant part was used to isolate Ralstonia spp. in CPG media and was positively identified. Subsequently, the efficacy of the biocontrol agents was tested and documented using agar well diffusion technique and digital microscopy. 2ml of the microbial concentrate (10 9 cells/ml) was mixed in one liter of water and was applied in the plant root at the rate of 100 ml per plant as a treatment method. Results: It was observed that the isolated Trichoderma spp. AA2 and Pseudomonas fluorescens PFS were most potent in inhibiting the growth of Ralstonia spp. , showing ZOI 20.67 mm and 22.33 mm, respectively. Digital microscopy showed distinct inhibitory effect on the growth and survival of Ralstonia spp . The results from the field data indicated that Trichoderma spp. and Pseudomonas fluorescens alone were able to prevent 92% and 96% of the infection and combination of both were more effective, preventing 97% of infection. Chemical control methods prevented 94% of infection. Bacillus subtilis could only prevent 84 % of the infection. Conclusions: Antagonistic effect against Ralstonia spp. shown by native isolates of Trichoderma spp. and P. fluorescens manifested the promising potential as biocontrol agents. Combined application gave better results. Results shown by Bacillus subtilis were not significant.


Effects of L-type calcium channel and human ether-a-go-go related gene blockers on the electrical activity of the human heart: a simulation study.
Class III and IV drugs affect cardiac human ether-a-go-go related gene (IKr) and L-type calcium (ICaL) channels, resulting in complex alterations in repolarization with both anti- and pro-arrhythmic consequences. Interpretation of their effects on cellular and electrocardiogram (ECG)-based biomarkers for risk stratification is challenging. As pharmaceutical compounds often exhibit multiple ion channel effects, our goal is to investigate the simultaneous effect of ICaL and IKr block on human ventricular electrophysiology from ionic to ECG level. Simulations are conducted using a human body torso bidomain model, which includes realistic representation of human membrane kinetics, anatomy, and fibre orientation. A simple block pore model is incorporated to simulate drug-induced ICaL and IKr blocks, for drug dose = 0, IC50, 2× IC50, 10× IC50, and 30× IC50. Drug effects on human ventricular activity are quantified for different degrees and combinations of ICaL and IKr blocks from the ionic to the body surface ECG level. Electrocardiogram simulations show that ICaL block results in shortening of the QT interval, ST elevation, and reduced T-wave amplitude, caused by reduction in action potential duration and action potential amplitude during the plateau phase, and in repolarization times. In contrast, IKr block results in QT prolongation and reduced T-wave amplitude. When ICaL and IKr blocks are combined, the degree of ICaL block strongly determines QT interval whereas the effect of IKr block is more pronounced on the T-wave amplitude. Our simulation study provides new insights into the combined effect of ICaL and IKr blocks on human ventricular activity using a multiscale computational human torso model.


Characteristics of enzyme-linked immunosorbent assay for detection of IgG antibodies specific to Сhlamydia trachomatis heat shock protein (HSP-60)
The goal of this work was to study sensitivity and specificity of the developed ELISA set for the identification of IgG antibodies against Chlamydia trachomatis HSP-60 (using biotinylated tyramine-based signal amplification system). The study was conducted using a panel of characterized sera, as well as two reference ELISA sets of similar purpose. According to the results of ELISA informative value parameters, the ELISA we have developed showed the highest specificity and sensitivity parameters (no false negative or false positive results were registered). In 4 out of 15 intralaboratory panel serum samples initially identified as negative, anti-HSP-60 IgG-antibodies test result in reference ELISA sets upon dilution changed from negative to positive. The nature of titration curves of false negative sera and commercial monoclonal antibodies А57-В9 against C. trachomatis HSP-60 after incubation for 24 h was indicative of the presence of anti-idiotypic antibodies in these samples. Upon sera dilution, idiotypic-anti-idiotypic complexes dissociated, which caused the change of test result. High informative value of the developed ELISA set for identification of IgG antibodies against C. trachomatis HSP-60 has been proven. Anti-idiotypic antibodies possessing C. trachomatis anti-HSP-60 activity and being one of the causes of false negative results of the relevant ELISA-based tests have been identified in blood sera of individuals infected with chlamydial genitourinary infection agents.


Implementation and Short-term Adverse Events of Anti-SARS-CoV-2 Vaccines in Inflammatory Bowel Disease Patients: An International Web-based Survey.
Anti-SARS-CoV-2 vaccine clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease [IBD]. We aimed to describe the implementation of anti-SARS-CoV-2 vaccination among IBD patients, patients' concerns, and the side effect profile of the anti-SARS-CoV-2 vaccines, using real-world data. An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of the patient characteristics, concerns, vaccination status, and side effect profile were analysed. In all 3272 IBD patients completed the survey, 79.6% had received at least one dose of anti-SARS-CoV-2 vaccine, and 71.7% had completed the vaccination process. Patients over 60 years old had a significantly higher rate of vaccination [p < 0.001]. Patients' main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD [24.6%], an IBD flare after vaccination [21.1%], and reduced vaccine efficacy due to IBD or associated immunosuppression [17.6%]. After the first dose of the vaccine, 72.4% had local symptoms and 51.4% had systemic symptoms [five patients had non-specified thrombosis]. Adverse events were less frequent after the second dose of the vaccine and in older patients. Only a minority of the patients were hospitalised [0.3%], needed a consultation [3.6%], or had to change IBD therapy [13.4%] after anti-SARS-CoV-2 vaccination. Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD.


Free boundary problem for cell protrusion formations: theoretical and numerical aspects.
In this paper, a free boundary problem for cell protrusion formation is studied theoretically and numerically. The cell membrane is precisely described thanks to a level set function, whose motion is due to specific signalling pathways. The aim is to model the chemical interactions between the cell and its environment, in the process of invadopodia or pseudopodia formation. The model consists of Laplace equation with Dirichlet condition inside the cell coupled to Laplace equation with Neumann condition in the outer domain. The actin polymerization is accounted for as the gradient of the inner signal, which drives the motion of the interface. We prove the well-posedness of our free boundary problem under a sign condition on the datum. This criterion ensures the consistency of the model, and provides conditions to focus on for any enrichment of the model. We then propose a new first order Cartesian finite-difference method to solve the problem. We eventually exhibit the main biological features that can be accounted for by the model: the formation of thin and elongated protrusions as for invadopodia, or larger protrusion as for pseudopodia, depending on the source term in the equation. The model provides the theoretical and numerical grounds for single cell migration modeling, whose formulation is valid in 2D and 3D. In particular, specific chemical reactions that occurred at the cell membrane could be precisely described in forthcoming works.


Zinc starvation induces a stress response in Saccharomyces cerevisiae that is mediated by the Msn2p and Msn4p transcriptional activators.
During the production of wine and beer, the yeast Saccharomyces cerevisiae can encounter an environment that is deficient in zinc, resulting in a 'sluggish' or a 'stuck' ferment. It has been shown that the Zap1p-transcription factor induces the expression of a regulon in response to zinc deficiency; however, it was evident that a separate regulon was also activated during zinc deficiency in a Zap1p-independent manner. This study discovered the Msn2p and Msn4p (Msn2/4p) transcriptional activator proteins to be an additional control mechanism inducing the stress response during zinc deficiency. Promoter sequence analysis identified the stress-response element (STRE) motif, recognized by Msn2/4p, and was significantly enriched in the promoters of genes induced by zinc deficiency. An investigation using genome-wide analyses revealed a distinct regulon consisting of STRE-containing genes whose zinc-responsive expression was abolished in an msn2 msn4 double mutant. An STRE-driven lacZ reporter construct confirmed that expression of the genes within this regulon was perturbed by the deletion of MSN2 and MSN4 and also implicated Hog1p as a contributing factor. This research provides a better understanding of the molecular mechanisms involved in the yeast response to zinc deficiency during fermentation.


Experimental investigation of the quality of ghost imaging via sparsity constraints.
Sampling number and detection signal-to-noise ratio (SNR) are two major factors influencing imaging quality. Combining the image's sparsity in the representation basis with the ghost imaging (GI) approach, GI via sparsity constraints (GISC) can nonlocally image the object even when the measurement number is far fewer than the Nyquist criteria required for the conventional GI reconstruction algorithm. The influence of receiving the system's numerical aperture and detection SNR in the test path to GISC is studied through experiments. It is also shown that the quality of GISC depends on the object's sparse representation basis.


How pooling fragmented healthcare encounter data affects hospital profiling.
People receiving healthcare from multiple payers (eg, Medicare and the Veterans Health Administration [VA]) have fragmented health records. How the use of more complete data affects hospital profiling has not been examined. Retrospective cohort study. We examined 30-day mortality following acute myocardial infarction at 104 VA hospitals for veterans 66 years and older from 2006 through 2010 who were also Medicare beneficiaries. Using VA-only data versus combined VA/Medicare data, we calculated 2 risk-standardized mortality rates (RSMRs): 1 based on observed mortality (O/E) and the other from CMS' Hospital Compare program, based on model-predicted mortality (P/E). We also categorized hospital outlier status based on RSMR relative to overall VA mortality: average, better than average, and worse than average. We tested whether hospitals whose patients received more of their care through Medicare would look relatively better when including those data in risk adjustment, rather than including VA data alone. Thirty-day mortality was 14.8%. Adding Medicare data caused both RSMR measures to significantly increase in about half the hospitals and decrease in the other half. O/E RSMR increased in 53 hospitals, on average, by 2.2%, and decreased in 51 hospitals by -2.6%. P/E RSMR increased, on average, by 1.2% in 56 hospitals, and decreased in the others by -1.3%. Outlier designation changed for 4 hospitals using O/E measure, but for no hospitals using P/E measure. VA hospitals vary in their patients' use of Medicare-covered care and completeness of health records based on VA data alone. Using combined VA/Medicare data provides modestly different hospital profiles compared with those using VA-alone data.


Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients.
The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC). The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance. Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC. The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available.


Antimicrobial 3D Printed Objects in the Fight Against Pandemics.
The uncharted nature of the COVID-19 pandemic has caused uncertainty globally, resulting in many health care professionals and key-workers being left with supply shortages in medical consumables and personal protective equipment, exacerbated by supply line issues and in some cases delays resulting from governmental policies. 3D printing (3DP) has played an important role in providing essential items to hospitals and the wider communities, such as visors, face masks, and ventilator components. This short-review article covers the potential of antimicrobial materials in the manufacturing of 3DP essential products, as an approach for added protection against pandemics.


Predictors of extubation failure in myasthenic crisis.
The ideal timing for extubation of patients with myasthenic crisis (MC) and the factors that influence extubation outcome are not well established. To assess the risk of extubation failure in MC and to identify predictors of extubation failure. We reviewed consecutive episodes of MC treated with endotracheal intubation from January 1, 1987, through December 31, 2006. Mayo Clinic. Patients Forty patients with 46 episodes of MC underwent endotracheal intubation and mechanical ventilation. The main outcome measures were extubation failure and reintubation. Extubation failure was defined as reintubation, tracheostomy, or death while intubated. Reintubation was also analyzed as a separate end point. Univariate logistic regression was used to identify predictors of extubation failure and reintubation. Of the 46 episodes of MC, extubation failure occurred in 20 (44%), including 9 of 35 episodes (26%) of reintubation. Male sex, history of previous crisis, atelectasis, and intubation for more than 10 days were associated with extubation failure. Lower pH and lower forced vital capacity on the time of extubation, atelectasis, and bilevel intermittent positive airway pressure use after extubation predicted the need for reintubation. Atelectasis showed the strongest association with both end points. Extubation failure and reintubation were associated with significant prolongation in intensive care unit and hospital length of stay. Extubation failure is relatively common in patients with MC. Atelectasis is the strongest predictor of this complication.


Biological design in science classrooms.
Although evolutionary biology is replete with explanations for complex biological structures, scientists concerned about evolution education have been forced to confront "intelligent design" (ID), which rejects a natural origin for biological complexity. The content of ID is a subset of the claims made by the older "creation science" movement. Both creationist views contend that highly complex biological adaptations and even organisms categorically cannot result from natural causes but require a supernatural creative agent. Historically, ID arose from efforts to produce a form of creationism that would be less vulnerable to legal challenges and that would not overtly rely upon biblical literalism. Scientists do not use ID to explain nature, but because it has support from outside the scientific community, ID is nonetheless contributing substantially to a long-standing assault on the integrity of science education.


[Knowledge and use of Pap-smear among HIV-positive women].
HIV-positive women are at increased risk for preneoplastic lesions and invasive cervical cancer (ICC). The occurrence of these lesions can be substantially reduced by appropriate cervico-vaginal screening protocols (i.e., Pap-test). The aim of study was to assess: 1) awareness of Pap-smear and 2) the association between awareness of Pap-smear and screening attitudes of HIV-positive women. Three-hundred and ninety HIV-positive women who attended the HIV outpatient gynecological unit of the National Institute for Infectious Diseases, Rome, from January 2003 to April 2005 were included in this investigation. These 390 women were interviewed to assess whether they were aware that Pap-test was a preventive tool against cervical cancer. In addition, past history of Pap-test, socioeconomic condition, history of HIV infection, and sexual habits were investigated. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association between knowledge of Pap-test and covariates. Of these 390 HIV-positive women, 54.6% were not aware that Pap-test could prevent ICC. Women with a low educational level (OR = 6.6) or women who originated from Africa (OR = 6.5) were more likely to be unaware of Pap-test. Lack of Pap-test awareness was strongly associated with negative history for lifetime Pap-test (OR = 4.7). We showed that a large proportion of HIV-infected women are not aware that ICC could be prevented through Pap-test screening, and that lack of Pap-test screening is strongly associated with lack of awareness. The need for Pap-test counseling targeted to HIV-infected women clearly emerges from our findings.


Synthesis of a 3-methyluridine phosphoramidite to investigate the role of methylation in a ribosomal RNA hairpin.
The synthesis of a 5'-O-BzH-2'-O-ACE-protected-3-methyluridine phosphoramidite is reported [BzH, benzhydryloxy-bis(trimethylsilyloxy)silyl; ACE, bis(2-acetoxyethoxy)methyl]. The phosphoramidite was employed in solid-phase RNA synthesis to generate a series of RNA hairpins containing single or multiple modifications, including the common nucleoside pseudouridine. Three 19-nucleotide hairpin RNAs that represent the 1920-loop region (G(1906)-C(1924)) of Escherichia coli 23S ribosomal RNA were generated. Modifications were present at positions 1911, 1915, and 1917. The stabilities and structures of the three RNAs were examined by using thermal melting, circular dichroism, and NMR spectroscopy


Apparent ionophoric effects of red blood cell deformation.
Normal human RBCs in vitro demonstrated increased utilization of ATP in when subjected to shear stress. Much of the increased ATP utilization appeared to be due to stimulation of membrane ion pumps. Thus, there was an apparent ionophoric effect of RBC deformation. Whether deformation-induced increases in membrane permeability occur in the circulation remains to be determined. It is suggested that in addition to chemically and electrically coupled channels, mechanically coupled "channels" may be modifiers of cellular functions under some conditions.


Fibrotic response as a distinguishing feature of resistance and susceptibility to pulmonary infection with Mycobacterium tuberculosis in mice.
The differential susceptibility of inbred mouse strains DBA/2J (susceptible) and C57BL/6J (resistant) to pulmonary tuberculosis following aerosol infection is under complex genetic control. In this report, transcriptional profiling with RNAs from Mycobacterium tuberculosis-infected lungs was used to investigate the physiological response, cell type, and biochemical pathways underlying differential susceptibility to infection. Statistical analysis of cDNA-based microarrays revealed that 1,097 transcripts showed statistically significant changes in abundance (changes of > or = 1.5-fold) in at least one of four experimental group comparisons (C57BL/6J [day 0] versus DBA/2J [day 0] mice, C57BL/6J [day 90] versus DBA/2J [day 90] mice, C57BL/6J [day 90] versus C57BL/6J [day 0] mice, or DBA/2J [day 90] versus DBA/2J [day 0] mice). A group of genes showing very high degrees of significance (changes of > or = 2.0-fold) displayed enrichment for transcripts associated with tissue remodeling and the fibrotic response. The differential expression of fibrotic response genes (Sparc, Col1a1, Col1a2, Col4a1, and Col4a2) in the infected lungs of the two mouse strains was validated by another microarray platform (Affymetrix oligonucleotide chips) and by reverse transcription-PCR. Furthermore, the differential expression of additional genes known to be associated with fibrosis (Mmp2, Timp1, and Arg1) was also validated by these approaches. Overall, these results identify the differential fibrotic response as a pathological basis for the high susceptibility of DBA/2J mice to pulmonary tuberculosis.


Management of myocardial revascularisation failure: an expert consensus document of the EAPCI.
Myocardial revascularisation represents the most frequently performed therapeutic intervention worldwide. Current percutaneous and surgical revascularisation techniques provide excellent short- and long-term clinical outcomes. However, despite the technological and procedural advances with the widespread use of drug-eluting stents and arterial bypass grafts in contemporary practice, a considerable proportion of patients require repeat revascularisation procedures during long-term follow-up. The need for repeat revascularisation has a major impact on patients' quality of life and is associated with a significant economic burden. This consensus document summarises the views on the management of myocardial revascularisation failure of an expert panel of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). The present document provides a broad and pragmatic overview of the clinical management of myocardial revascularisation failure with a focus on the three key underlying mechanisms leading to repeat revascularisation: 1) failure of percutaneous coronary interventions, 2) failure of coronary artery bypass grafting, and 3) progression of coronary artery disease in native coronary segments previously untreated. The aim of the present position document is to provide a patient-oriented approach for the management of myocardial revascularisation failure.


Real-time quantitative RT-PCR assay of GADD45 gene expression changes as a biomarker for radiation biodosimetry.
To assess the efficacy of fluorescent-based quantitative reverse transcription-polymerase chain reaction (QRT-PCR) technology to measure gene expression changes (GEC) for rapid, point-of-care radiation dose assessment. A real-time QRT-PCR assay based on 5'-fluorogenic nuclease TaqMan(TM) methodology was developed, which employs both relative and absolute quantification of a candidate mRNA biomarker. Growth arrest and DNA damage gene 45 (GADD45), a cell-cycle regulation and DNA repair gene, served as the paradigm because of the reported linear dose-response relationship for mRNA induction in the human myeloid tumor cell line (ML-1) over the range of 2-50 cGy. Using an ex vivo whole-blood model, GEC was measured from total blood RNA at 24h and 48 h after (60)Co gamma-ray exposures (0-3 Gy; 0.1 Gy/min). A linear and reproducible up-regulation representing a twofold to fourfold change in GADD45 relative and absolute GEC was confirmed in both intra- and inter-assay analyses. Primer and probes to detect GADD45 targets using real-time PCR were developed. This is the first report using realtime QRT-PCR to measure radiation-induced GEC dose response. Real-time QRT-PCR using GEC as biomarkers offers rapidity, sensitivity, and reproducibility as a potential efficient biological dosimetry tool applicable in radiation therapy applications and early-response accident biodosimetry.


Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner.
Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C+ monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusion-compression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.


The Periotest method for determining implant success.
The purpose of this paper is to show that the currently accepted methods for the determination of implant stability are unpredictable. It describes those techniques that are currently utilized for the assessment of implant success and discusses the problems they present. The paper will propose the Periotest method as a reliable and reproducible alternative to the methods currently available to the clinician for determining implant stability.


[Mechanical performance of non slotted small diameter nails of Gross and Kempf].
The goal of this study was to evaluate the mechanical properties of closed section small diameter Grosse-Kempf tibia nails. This type of implant has been advocated for an unreamed nailing of open tibia fractures in order to avoid further damage of bone blood supply and an increased risk for compartment syndrome. Static and dynamic tests were performed on 9 and 10 mm nonslotted Grosse-Kempf (G-K) and Russel-Taylor (R-T) nails. Results were compared with the properties of a 11 mm slotted G-K nail, considered as the reference nail. Axial loading tests were realized on nailed cadaver tibiae after resection of a midshaft bone segment. 3 points bending tests have shown a mean diminution of the elastic limit of 50 per cent, and a 25 per cent decrease of the bending rigidity for the closed section nails, as compared with the slotted reference nail. The rigidity in torsion was on the other hand 10 times higher with the nonslotted nails, which is a direct consequence of the elimination of the slot. Axial loading tests performed on isolated implants have given comparable results for all types of nails, including the reference nail. Nailed tibiae axially loaded demonstrated a stable bone-implant interface for loads up to 200 daN, with a mean displacement of 2 mm for a 50 daN load, whatever the type of the nail. Bending tests achieved on locking screws have indicated that G-K screws are twice as rigid as R-T screws.(ABSTRACT TRUNCATED AT 250 WORDS)


Cranioplasty of large cranial defect at an early stage after decompressive craniectomy performed for severe head trauma.
Large cranial defects resulting from decompressive craniectomy performed for refractory intracranial hypertension after head trauma is one of the indications for cranioplasty, and this procedure is commonly performed 3 months after craniectomy. However, the large cranial defect would lead to the kinds of complications early during the phase of these patients' recovery, which would go against rehabilitation. This study retrospectively reviewed 23 patients undergoing early cranioplasty (5-8 weeks after craniectomy) in the last 4 years with a detailed choice of patients, outcome of complications after head trauma and large craniectomy, as well as assessment of prognosis. The early outcome (1 month later) revealed most of the patients who had conscious disturbance before the cranioplasty recovered their consciousness and presented an improved neurologic function. The long-dated prognosis (18 months later) revealed that 17 patients were good (independent patients) in this series (74%), whereas four patients survived with a severe disability (17%) and two remained in a vegetative state (9%). No dead patients or intracranial infection after the procedure were found in this study. Most patients' complications were relieved after the cranioplasty with improvements of symptoms or image of computed tomography scan. In conclusion, we consider that with the appropriate choice of patients and materials, early cranioplasty for large cranial defects after decompressive craniectomy would be safe and helpful for the improvement of patients' neurologic function and prognosis. To our knowledge, this series may be the first detailed report in English about early cranioplasty after decompressive craniectomy. We are going to perform prospective and retrospective contrastive studies to further confirm the effects of this procedure on the patients with large cranial defects after decompressive craniectomy.


Psychogenic nonepileptic spells in chronic epilepsy patients with moderate cognitive impairment: the need for video EEG monitoring for adequate diagnosis.
The objective of our study was to emphasize the importance of intensive video EEG monitoring in patients with a well-established diagnosis of epilepsy with moderate cognitive impairment. The idea was to diagnose new onset frequent atypical events prompting the need for frequent emergency room and clinic visits and hospital admissions. Retrospective chart reviews were conducted on patients with chronic epilepsy with moderate cognitive impairment who had an increased incidence of new onset episodes different from the baseline seizures. Data were acquired from electronic medical records. The hospital's Institutional Review Board gave approval for this retrospective analysis of patient records. We retrospectively analyzed data from three patients with an established diagnosis of epilepsy. Extensive chart reviews were performed with emphasis on type and duration of epilepsy and description of baseline seizures and description of new events. There were two men and one woman with moderate cognitive impairment. One subject had generalized epilepsy and other two had temporal lobe epilepsy. The patients were on an average of two to three antiepileptic medicines. The duration of follow-up in our neurology clinic ranged from 9 months to 5 years. The occurrence of increased frequency of these atypical events as described by the caregivers, despite therapeutic anticonvulsant levels, prompted the need for 5-day intensive video EEG monitoring. New atypical spells were documented in all three patients and the brain waves were normal during those episodes. The diagnosis of pseudoseizures was made based on the data acquired during the epilepsy monitoring unit stay. Our data analysis showed that intensive video EEG monitoring is an important tool to evaluate change in frequency and description of seizures even in cognitively impaired patients with an established diagnosis of epilepsy for adequate seizure management.


Metabolite Cross-Feeding Promoting NADH Production and Electron Transfer during Efficient SMX Biodegradation by a Denitrifier and S. oneidensis MR-1 in the Presence of Nitrate.
Antibiotics often coexist with other pollutants (e.g., nitrate) in an aquatic environment, and their simultaneous biological removal has attracted widespread interest. We have found that sulfamethoxazole (SMX) and nitrate can be efficiently removed by the coculture of a model denitrifier (Paracoccus denitrificans, Pd) and Shewanella oneidensis MR-1 (So), and SMX degradation is affected by NADH production and electron transfer. In this paper, the mechanism of a coculture promoting NADH production and electron transfer was investigated by proteomic analysis and intermediate experiments. The results showed that glutamine and lactate produced by Pd were captured by So to synthesize thiamine and heme, and the released thiamine was taken up by Pd as a cofactor of pyruvate and ketoglutarate dehydrogenase, which were related to NADH generation. Additionally, Pd acquired heme, which facilitated electron transfer as heme, was the important composition of complex III and cytochrome c and the iron source of iron sulfur clusters, the key component of complex I in the electron transfer chain. Further investigation revealed that lactate and glutamine generated by Pd prompted So chemotactic moving toward Pd, which helped the two bacteria effectively obtain their required substances. Obviously, metabolite cross-feeding promoted NADH production and electron transfer, resulting in efficient SMX biodegradation by Pd and So in the presence of nitrate. Its feasibility was finally verified by the coculture of an activated sludge denitrifier and So.


Potential for nutrient removal by integrated remediation methods in a eutrophicated artificial lake - a case study in Dishui Lake, Lingang New City, China.
A new integrated water remediation technology, including a floating bed, a buffer zone of floating plants, enclosed 'water hyacinth' purification, economic aquatic plants and near-shore aquatic plant purification, was used in Dishui Lake to improve its water quality. A channel of 1,000 m length and 30 m width was selected to implement pilot-scale experiments both in the static period and the continuous water diversion period. The results showed that the new integrated water remediation technology exhibited the highest removal rate for permanganate index in a static period, which achieved 40.6%. The average removal rates of total nitrogen (TN), ammonia nitrogen (NH3-N) and total phosphorus (TP) in a static period were 23.2, 21.6 and 19.1%, respectively. However, it did not exhibit an excellent removal rate for pollutants in the continuous water diversion period. The average removal rates for all pollutants were below 10%. In winter, the new integrated remediation technology showed efficient effects compared to others. The average removal rate for CODMn, TN, NH3-N and TP were 7, 5.3, 7.6 and 6.5%, respectively. Based on our results, the new integrated water remediation technology was highly efficient as a purification system, especially during the static period in winter.


Elevated Homocysteine Levels Are Associated With the Metabolic Syndrome and Cardiovascular Events in Hypertensive Patients.
Hyperhomocysteinemia and the metabolic syndrome are established cardiovascular risk factors and are frequently associated with hypertension. The relationship of plasma homocysteine (Hcy) with the metabolic syndrome and insulin resistance, however, is debated and studies in hypertensive patients are limited. In this study, we have investigated the association of Hcy with the metabolic syndrome and cerebro- cardiovascular events in hypertension. In 562 essential hypertensive patients who underwent accurate assessment of fasting and postload glucose metabolism, insulin sensitivity, and renal function, we measured plasma levels of Hcy, vitamin B12, folate, and fibrinogen and assessed the prevalence of the metabolic syndrome and of coronary heart and cerebrovascular disease (CVD). Patients with the metabolic syndrome had significantly higher plasma Hcy levels. After correction for covariates, increasing Hcy levels were associated with an increasing prevalence of the metabolic syndrome, coronary heart disease, and CVD. Plasma Hcy was directly correlated with age, waist circumference, fasting glucose, triglyceride, uric acid, and fibrinogen levels, and homeostatic model assessment index and inversely with creatinine clearance and high-density lipoprotein cholesterol, vitamin B12, and folate levels. Logistic regression analysis showed an independent association of Hcy levels with age, male gender, vitamin B12 and folate levels, and the metabolic syndrome. Logistic regression indicated also an independent association of Hcy with cerebro-cardiovascular disease that was independent of the metabolic syndrome. Elevated plasma Hcy is associated with the metabolic syndrome in hypertensive patients. Prevalence of events increases with increasing plasma Hcy levels suggesting a contribution of Hcy to cerebro-cardiovascular diseases in these patients.


A half century of high-altitude studies in anthropology: introduction to the plenary session.
Until 50 years ago, high-altitude terrestrial research was conducted largely within the realm of environmental physiology, where interests were focused on physiological mechanisms and mountain exploration. Scientists from the United States, Europe, and Peru had developed sophisticated physiological models of adaptation and acclimatization to the hypoxia of high altitude, but very little research had been conducted on permanent residents, particularly natives of high altitude in the two major regions of the world-the Andes and the Himalayas. In 1962, Raul T. Baker initiated a project at the Pennsylvania State University to explore the responses of indigenous Peruvians to the major stresses at altitude: hypoxia and cold. Approaches to this early research were anthropological in perspective and centered on population-level studies with an evolutionary approach. Studies were conducted by applying a combination of physiological experimental methods, simulated field experiments, and extended anthropological field observations. Early hypotheses at this time were that heredity played a major role in the adaptive complexes in native high-altitude residents. These early hypotheses were later modified to incorporate or replace the genetic hypotheses with developmental adaptation models. A half century of research within anthropology and research in other fields has presented a vastly more complex and integrated picture of high-altitude adaptation in native residents. Recent studies incorporate physiology and oxygen transport, population and molecular genetics, reproduction, growth, and development. The history and current status of high-altitude research and its anthropological applications are treated in papers from this plenary symposium.


International Medical Graduates and the Shortage of US Pathologists: Challenges and Opportunities.
Physician shortages are affecting many communities across the United States and all medical specialties, including pathology. International medical graduates (IMGs) make up a significant proportion of US physicians and graduate medical education (GME) trainees, including pathologists. However, noncitizen IMGs continue to face great challenges in entering the US health care workforce. To show recent and historical data on noncitizen IMGs in pathology GME training, and current limitations on remaining in the US health care workforce. Compared with applicants who do not need a visa, applicants who need a visa to train in the United States have a greatly reduced chance of matching to a residency program. After completion of residency and fellowship, noncitizen IMGs with J-1 visas face the 2-year home country residence requirement unless they obtain a waiver. H-1B visas facilitate the transition to independent practice but have limited availability. Job announcements for pathologists often do not indicate whether J-1 and H-1B visa holders are considered, which makes the job search process difficult for noncitizen IMGs. Academic and nonacademic institutions with departments of pathology should increase awareness of the pathologist shortage in the United States and the rules and regulations that limit hiring of non-US IMGs. Such institutions should also actively educate policymakers to promote durable solutions to these issues. One potential solution to these shortages may be to make it easier for noncitizen IMGs to access GME and join and remain in the US physician workforce.


Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury.
Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.


Blockage of Central Sphingosine-1-phosphate Receptor does not Abolish the Protective Effect of FTY720 in Early Brain Injury after Experimental Subarachnoid Hemorrhage.
Although sphingosine 1-phosphate (S1P) receptor activation by FTY720 (fingolimod) has been suggested to improve the prognosis of experimental stroke, the effect of the drug in early brain injury (EBI) after subarachnoid hemorrhage (SAH) and the precise mechanism of the effect are undetermined. In this study, we investigated the protective effect of systemic administration of FTY720 in EBI after SAH and assessed the mechanism using intracerebroventricular infusion of VPC23019 which is the S1P receptor antagonist. SAH rats were produced by the endovascular perforation model and injected saline or 1mg/kg FTY720 intraperitoneally at 30 minutes after SAH induction. Neurological function, cerebral blood flow, amount of subarachnoid blood, and brain edema were evaluated to confirm the protective effect of systemic administration of FTY720. SAH rats also received VPC23019 intraventricularly before SAH induction to abolish the central S1P receptor activation. Systemic administration of FTY720 significantly ameliorated SAH-induced neurological deficits and brain edema without modulation of CBF and the amount of subarachnoid blood. Blockage of central S1P receptor with VPC23019 did not abolish the protective effects of FTY720. The present study suggests that systemic administration of FTY720 reduces EBI after SAH and that the effect might not come from central S1P activation but be associated with pleiotropic actions of the drug.


Quitline Information Included on Cigarette Packaging: An Assessment of Country Adherence to WHO FCTC Guidelines, 2007 to 2018.
The purpose of this study is to evaluate country adherence to the World Health Organization's (WHO) Framework Convention on Tobacco Control (FCTC) guidelines in terms of including quitline information on cigarette packaging. Data were gathered from the WHO's Global Health Observatory database. The study included countries that were signatories to the FCTC, had a toll-free quitline, and required health warnings on cigarette packaging. Countries were then classified by income level according to the World Bank. From 2007 to 2018, the number of countries that established a quitline increased from 34 to 60. During the same timeframe among those countries, the number of countries that included information about the quitline on cigarette packaging increased from 5 to 37, with a larger proportion (79%) of high-income countries promoting their quitlines on cigarette packaging compared to middle-income (45%) countries. Although there was an increase in adherence to the WHO FCTC guidelines, there is still a need for several countries to include quitline information on cigarette packaging.


Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster.
During chronic obstructive pulmonary disease (COPD) diaphragm and peripheral muscle weakness occur. Muscle remodeling and wasting may be a result of apoptosis and changes in muscle-specific transcription factors, such as MyoD, altering muscle-specific gene transcription and muscle regenerative capacity. To investigate this, we instilled under ketamine/xylazine anesthesia porcine elastase in the lungs of hamsters to induce emphysema. The emphysematous hamster is an accepted model for COPD. In the diaphragm and peripheral muscles we assessed the occurrence of apoptosis, and in the diaphragm and soleus also the expression of MyoD and inhibitor of differentiation protein 2 (Id2). There was no significant muscle atrophy in emphysematous hamsters. The mRNA levels of TNF-alpha and markers of apoptosis were significantly elevated in the diaphragm and soleus muscles during emphysema. This was accompanied by an increased presence of nucleosomes in the cytosol. Caspase 3 activity and the DNA-binding activity of the p65 subunit of NF-kappaB, however, were unaltered in all muscles. The protein expression of MyoD and Id2 were decreased and increased in the diaphragm and the soleus muscle, respectively. Thus, despite the absence of muscle atrophy in emphysematous hamsters, there was evidence of increased TNF-alpha expression, apoptosis, and altered muscle-specific transcriptional regulation as reflected by decreased MyoD and elevated Id2 levels at least in the soleus and diaphragm muscle. These alterations may impair the regenerative capacity of skeletal muscles and ultimately contribute to muscle wasting.


Direct and remote sensing observations of the effects of ships on clouds.
Under certain conditions ships can affect the structure of shallow layer clouds. Simultaneous observations of two ship track signatures in stratus clouds from a satellite and in situ from an aircraft show that in the ship tracks the droplet sizes were reduced and total concentrations of both droplets and particles were substantially increased from those in adjacent clouds. In situ measurements of the upwelling radiance within the ship tracks was significantly enhanced at visible wavelengths, whereas radiance at 2.2 micrometers was significantly reduced. Cloud reflectivity along the tracks was enhanced at 0.63 and 3.7 micrometers. These observations support the contention that ship track signatures in clouds are produced primarily by particles emitted from ships.


Efficacy of hearing conservation education programs for youth and young adults: a systematic review.
Many youth and young adults experience high noise exposure compounded by lack of access to hearing health education. Although the need for hearing health education programs is evident, the efficacy of these programs for youth is unclear. We evaluated the literature for efficacy of various hearing conservation programs aimed at youth and young adults, and analyzed their strengths and limitations. Studies reporting results of hearing conservation or hearing loss prevention programs with youth or young adults, using randomized controlled trials, quasi-experimental designs, experimental design, or qualitative research, and published in peer-reviewed journals in English between 2001 and 2018 were included. Studies were found through searches of selected literature databases (i.e., PubMed, Google Scholar, NIOSH Toxline, and Scopus). Identified publications were assessed for relevance, and data were extracted from the studies deemed relevant. A total of 10 studies were included. Very little evidence of efficacy of hearing conservation educational programs was found in these studies. Several methodological limitations including lack of rigorous study designs, inadequate power, and application of inappropriate statistical analysis were noted. Some use of technology in programs (e.g., smartphone apps, mobile phone text messages, and computers) was observed, but conclusions as to the effectiveness of these tools were limited by the small number of studies and small sample sizes. The number of studies of educational hearing conservation programs for youth and young adults was low. The efficacy of the program was not reported in most studies, and it is difficult to draw public health conclusions from these studies due to their multiple methodological limitations. While use of technology in hearing conservation educational programs offers promise, its effectiveness has not been studied.


Anatomy and physiology as a predictor of success in baccalaureate nursing students.
The purpose of this two-part study was to identify early indicators of students' success (N = 98) in a baccalaureate nursing program. Part I determined how well six variables predicted competence on a criterion-referenced anatomy and physiology (A/P) examination. A multiple regression model was used to analyze the relationships among the predictor and the criterion variables. Data analyses show that only two predictors, grade point average and type of college in which the A/P course was taken, were significantly related (p = 0.0001) to A/P test scores. Part II used students' A/P score to predict success in the didactic component of clinical nursing coursework. In part II, a simple regression model was used to predict the relationship between A/P test score and success in the second clinical nursing course. These results indicated that A/P test score was significantly related (p = 0.003) to success in the second clinical nursing course.


Variation in end-stage renal disease patient outcomes: what we know, what should we know, and how do we find it out?
The size and expense of the ESRD program exceed all predictions made when the program was first initiated. Although the effectiveness of dialytic therapy is unquestioned, its value (quality/cost) is actively debated in this era of constricting resources. To better evaluate the quality of the ESRD program, it is essential to first define and quantitate the outcomes of dialytic care. Although mortality is a convenient outcome measure, it may be affected by many patient-specific as well as other factors that must be considered when evaluating and comparing new and existing technologies or advances. Quality of life is only beginning to be used in depth as an outcome measure, and much work is needed to standardize research methodology and thus move this area forward. The following review describes the current state of knowledge regarding outcomes of ESRD patients and proposes areas for future investigation, which should help increase the understanding of the value of the ESRD program to patients, providers, and payors.


Adaptation and Preliminary Validation of the Advance Care Planning Engagement Survey for Surrogate Decision Makers.
Although measures that assess patient engagement in the advance care planning (ACP) process exist, there are no validated tools to assess surrogate decision makers' (SDMs') role in ACP. The objective of this study was to adapt and begin to validate a patient-oriented questionnaire for use with SDMs of patients with chronic illness. Questions from the 55-item patient-oriented ACP engagement survey were adapted for SDMs and assessed for face validity. The resultant 47-item questionnaire was administered to 65 SDMs of patients with chronic illness. Responses were assessed and items were flagged for removal based on item redundancy, nonresponses, and ceiling effects. A preliminary exploratory factor analysis was performed, internal consistency was assessed, and domains were constructed based on findings. The 47-item questionnaire was administered to 65 participants (mean age 51.8; 81% female; 96% Caucasian). Seventeen items were removed owing to redundancy (r > 0.80), and 13 items lacking face validity were removed. In a preliminary exploratory factor analysis of the resultant 17-item questionnaire, a three-factor solution was deemed most statistically and conceptually sound. Items were organized into domains: 1) serving as an SDM (seven items); 2) contemplation (four items); 3) readiness (six items). Internal consistency for each domain was high (Cronbach alpha 0.90-0.91). The 17-item ACP engagement survey for SDMs (ACP-17-SDM) is a conceptually sound and reliable questionnaire adaptation of the original ACP engagement survey. This questionnaire may be used by researchers in parallel with the patient-oriented ACP engagement survey to more fully understand the impact of ACP interventions on SDMs. Larger studies are needed to more closely examine construct validity.


Gamification as an approach to improve resilience and reduce attrition in mobile mental health interventions: A randomized controlled trial.
Forty percent of all general-practitioner appointments are related to mental illness, although less than 35% of individuals have access to therapy and psychological care, indicating a pressing need for accessible and affordable therapy tools. The ubiquity of smartphones offers a delivery platform for such tools. Previous research suggests that gamification-turning intervention content into a game format-could increase engagement with prevention and early-stage mobile interventions. This study aimed to explore the effects of a gamified mobile mental health intervention on improvements in resilience, in comparison with active and inactive control conditions. Differences between conditions on changes in personal growth, anxiety and psychological wellbeing, as well as differences in attrition rates, were also assessed. The eQuoo app was developed and published on all leading mobile platforms. The app educates users about psychological concepts including emotional bids, generalization, and reciprocity through psychoeducation, storytelling, and gamification. In total, 358 participants completed in a 5-week, 3-armed (eQuoo, "treatment as usual" cognitive behavioral therapy journal app, no-intervention waitlist) randomized controlled trial. Relevant scales were administered to all participants on days 1, 17, and 35. Repeated-measures ANOVA revealed statistically significant increases in resilience in the test group compared with both control groups over 5 weeks. The app also significantly increased personal growth, positive relations with others, and anxiety. With 90% adherence, eQuoo retained 21% more participants than the control or waitlist groups. Intervention delivered via eQuoo significantly raised mental well-being and decreased self-reported anxiety while enhancing adherence in comparison with the control conditions. Mobile apps using gamification can be a valuable and effective platform for well-being and mental health interventions and may enhance motivation and reduce attrition. Future research should measure eQuoo's effect on anxiety with a more sensitive tool and examine the impact of eQuoo on a clinical population.


When and how does cell division order influence cell allocation to the inner cell mass of the mouse blastocyst?
Aggregate 8-cell embryos were constructed from four 2/8 pairs of blastomeres, one of which was marked with a short-term cell lineage marker and was also either 4 h older (derived from an early-dividing 4-cell) or 4 h younger (derived from a late-dividing 4-cell) than the other three pairs. The aggregate embryos were cultured to the 16-cell stage, at which time a second marker was used to label the outside cell population. The embryos were then disaggregated and each cell was examined to determine its labelling pattern. From this analysis, we calculated the relative contributions to the inside cell population of the 16-cell embryo of older and younger cells. Older cells were found to contribute preferentially. However, if the construction of the aggregate 8-cell embryo was delayed until each of the contributing 2/8 cell pairs had undergone intercellular flattening and then had been exposed to medium low in calcium to reverse this flattening immediately prior to aggregation, the advantage possessed by the older cells was lost. These results support the suggestion that older cells derived from early-dividing 4-cell blastomeres contribute preferentially to the inner cell mass as a result of being early-flattening cells.


Nonspecific suppressor function in rheumatoid arthritis.
Patients with rheumatoid arthritis (RA) have diminished peripheral blood cellular immune responses in vivo and in vitro. To determine whether these changes reflected excessive peripheral blood suppressor function, we compared suppressor function in 52 patients with RA with 57 normal subjects. We examined suppressor cell function for (i) preincubation sensitivity, (ii) glass adherence, (iii) indomethacin sensitivity, (iv) concanavalin (con) A inducibility, (v) aggregated IgG inducibility and (vi) quantitated Tmu and Tgamma cell populations. Con A-generated suppressor cell function was further studied by evaluating unseparated-, T-cell, glass adherent-, indomethacin sensitive-, radiosensitive-, and radioresistant-suppressor cell effects upon mitogen-stimulated allogeneic and autologous unseparated, T-cell, B-cell and IM9 lymphoblastoid cell line responses, the latter representing a newly devised and simplified assay system. We found that patients with RA exhibited: (i) significantly increased incubation-sensitive suppressor function; (ii) generally normal nonspecific suppression function in other assays, although individual patients were strikingly abnormal; and (iii) significantly increased sensitivity of B-cell proliferation to aggregated-IgG-induced T-cell suppressor function.


Clinico-pathological profile of vulva cancer in southern Thailand: analysis of 66 cases.
To evaluate the clinico-pathologic findings and treatment outcome of women with vulva cancer in Southern Thailand. The authors retrospectively reviewed the medical records of 66 women who had been treated with surgery from June 1984 to October 2003 at the Department of Obstetrics and Gynecology, Prince of Songkla University. The patients' age ranged from 30 to 87 years, mean 58.2 years. Two most common presentations were vulva mass (89.4%) and pruritus (57.6%). Duration of symptoms at presentation ranged form 1 month to 5 years. Most cases were squamous cell carcinoma (82.0%). The distribution by FIGO surgical stage I, II, III and IV was 9.1%, 47.0%, 34.8% and 9.1%, respectively. The most common complication was wound infection (45.5%), followed by wound dehiscence, lymphosis and leg edema (each 15.2%). The 5-year survival (and 95% CI) for stages I, II, III and IV was 100%, 96% (76-99%), 94% (63-99%) and 60 (13-88%), respectively. The 5-year survival for node-positive cases was 82% (54-94%) versus 100% for node-negative cases (p = 0.0003). Stage was a significant predictor of survival (p = 0.0142) and disease-free survival (p = 0.0112). Stage and nodal involvement are predictors of survival, and stage is a predictor of disease-free survival.


Weight loss and biomedical health improvement on a very low calorie diet: the moderating role of history of weight cycling.
In this study, the authors examined biomedical consequences of participation in a professionally delivered, multifaceted very low calorie diet (VLCD) program and whether the degree of benefit associated with treatment was moderated by history of weight cycling. The authors monitored body weight and biomedical health indicators in 66 severely obese outpatients on a VLCD liquid fast. Participants remained on the VLCD for a median of 55 (range 9 to 247) days. Treatment was associated with significant pre-to-post improvements on body weight, systolic and diastolic blood pressure, triglycerides, and cholesterol. History of weight cycling (independent of age) was inversely related to the magnitude of absolute pre-to-post treatment changes in systolic and diastolic blood pressure, as well as to the rate of weight change. More intensive, longer term, and explicit maintenance components, especially aimed at individuals with multiple weight loss-regain episodes, may be necessary to facilitate weight loss and attain optimal health benefits from VLCDs.