Recurrent micronucleation through cell cycle progression in the presence of microtubule inhibitors.
Although most cell lines undergo mitotic arrest after prolonged exposure to microtubule inhibitors, some cells subsequently exit this state and become tetraploid. Among these cells, limited numbers of rodent cells are known to undergo multinucleation to generate multiple small independent nuclei, or micronuclei by prolonged colcemid treatment. Micronuclei are thought to be formed when cells shift to a pseudo G1 phase, during which the onset of chromosomal decondensation allows individual chromosomes distributed throughout the cell to serve as sites for the reassembly of nuclear membranes. To better define this process, we used long-term live cell imaging to observe micronucleation induced in mouse A9 cells by treating with the microtubule inhibitor colcemid. Our observations confirm that nuclear envelope formation occurs when mitotic-arrested cells shift to a pseudo G1 phase and adopt a tetraploid state, accompanied by chromosome decondensation. Unexpectedly, only a small number of cells containing large micronuclei were formed. We found that tetraploid micronucleated cells proceeded through an additional cell cycle, shifting to a pseudo G1 phase and forming octoploid micronucleated cells that were smaller and more numerous compared with the tetraploid micronucleated cells. Our data suggest that micronucleation occur when cells shift from mitotic arrest to a pseudo G1 phase, and demonstrate that, rather than being a single event, micronucleation is an inducible recurrent process that leads to the formation of progressively smaller and more numerous micronuclei.


Molecular pathways: autophagy in cancer--a matter of timing and context.
Autophagy is an intracellular self-digestion mechanism, by which cellular components are sorted into double-membrane autophagosomes and delivered to lysosomes for degradation. Cells use autophagy to dispose of wastes and eliminate hazards, while recycling nutrients and tuning metabolism in the process. Through these functions, autophagy promotes cell fitness, genome integrity, tissue homeostasis, and cell survival and growth under stress. Both autophagy upregulation and downregulation have been found in human cancers, suggesting a complex role in tumor development. Accumulating results from autophagy-deficient mice and mouse models of human cancers have demonstrated that autophagy generally suppresses tumor initiation, but promotes tumor progression, in a manner that is dependent on timing and context and modified by specific tumorigenic events. Given the role of autophagy in facilitating tumor growth, autophagy inhibition has gained wide attention as a potential anticancer therapy. Here, we summarize relevant genetic, preclinical, and clinical studies and discuss the multifaceted role of autophagy in cancer, as well as the prospects of autophagy inhibition for cancer therapy.


Anterior interhemispheric approach for 100 tumors in and around the anterior third ventricle.
We report our experience with anterior interhemispheric approach for tumors in and around the anterior third ventricle, including surgical technique, instrumentation, pre- and postoperative hormonal disturbances, and resection rate. One hundred patients with 46 craniopharyngiomas, 12 hypothalamic gliomas, 12 meningiomas, 6 hypothalamic hamartomas, and 24 other lesions were operated on using an anterior interhemispheric approach with or without opening of the lamina terminalis. This surgical approach involves no frontal sinus opening; a narrow (approximately 15-20 mm in width) access between the bridging veins, which is sufficient to remove the tumor totally; and sparing of the anterior communicating artery. Specially designed long bipolar forceps and scissors are necessary for this approach, and concomitant use of angled instruments (endoscope, aspirator, and microforceps) is required frequently. The postsurgical follow-up period varied from 4 months to 18 years. Total removal of the neoplasm was accomplished in 37 of 46 patients with craniopharyngiomas (80.4%), whereas subtotal resection was performed in hypothalamic gliomas. No significant differences in pre- and postoperative hormonal disturbances were observed in 37 craniopharyngiomas and 10 hypothalamic gliomas. There was no operative mortality. Visual acuity was preserved or improved in 68 of 75 patients assessed. The Karnofsky Performance Scale score did not deteriorate in 72 of 75 patients tested. The minimally invasive anterior interhemispheric approach, with or without opening of the lamina terminalis, is useful for removal of tumors in and around the anterior third ventricle, such as craniopharyngiomas and hypothalamic gliomas.


[Production of hepatitis B virus core particles protein in plants, by using cowpea mosaic virus-based vector].
The core antigen of hepatitis B virus (HBcAg) has attracted considerable attention as a carrier for antigenic sequences for various diagnostic and vaccine applications. The hepatitis B core protein has been expressed in different expression systems. At present, for reasons of cost, scale, and safety, the plant-based expression systems are attracting increasing interest. The expression and assembly for the hepatitis B core protein were investigating in N. benthamiana plants using the new expression system based on deleted version of cowpea mosaic virus RNA-2. Analysis of HBcAg expression revealed that the core protein expressed in plants and could self-assemble into virus-like particles. Virus-like particles could be purified by differential and sucrose gradient centrifugation. This expression system has the advantage of biocontainment and can be used for the rapid production of HBcAg virus-like particles for immunological and vaccine applications.


Insights into the development of fungal biomarkers for metal ecotoxicity assessment: case of Trametes versicolor exposed to copper.
The relationship between the physiological state of fungi and the response of their functional system to metals is not known, limiting the use of fungal enzymes as tools for assessing metal ecotoxicity in terrestrial ecosystems. The present study attempts to establish how the development phases modulate the secretion of enzymes in the filamentous fungus Trametes versicolor after exposure to Cu. For that purpose, extracellular hydrolases (acid and alkaline phosphatases, aryl-sulfatase, beta-glucosidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) and oxidoreductases (laccase, manganese and lignin peroxidases) were monitored in liquid cultures for 2 weeks. Copper was added during either the growth or the stationary phases at 20 or 200 ppm. Results of the present study showed that Cu at the highest concentration modifies the secretion of enzymes, regardless of the development phase to which the fungus was exposed. However, the sensitivity of enzyme responses to Cu depended on the phase development and the type of secreted enzyme. In a general way, the production of hydrolases was decreased by Cu, whereas that of oxidoreductases was highly increased. Furthermore, lignin peroxidase was not detected in control cultures and was specifically produced in the presence of Cu. In conclusion, fungal oxidoreductases may be enzymatic biomarkers of copper exposure for ecotoxicity assessment.


Parenting Behaviors after Moderate - Severe Traumatic Injury in Early Childhood.
Purpose: Examine the impact of traumatic brain injury (TBI) on parenting behavior over time. Method: Included 206 children (3-7 years old) with moderate to severe TBI or orthopedic injury, using a prospective longitudinal cohort study design. Assessments completed at baseline, 6-months, 12-months, 18-months, 3.5 years, and 6.8 years after injury. Dependent variables included authoritative, permissive, and authoritarian parenting. Results: Injury characteristics had limited impact on parenting behaviors over time. Levels of authoritative parenting remained stable over time; however, levels of warmth and involvement declined over time for those with TBI. Levels of permissive and authoritarian parenting declined for all participants by 3.5 years post injury. SES and stressors impacted parenting behaviors. Conclusions: While there was limited effect of TBI on parenting behavior over time, it remains unclear how individuals respond to these parenting behaviors years after injury. Clinicians should monitor family and parenting behaviors to foster an environment to promote positive recovery.


Prospective, randomized comparison of two biphasic waveforms for the efficacy and safety of transthoracic biphasic cardioversion of atrial fibrillation.
The purpose of this study was to determine if there is a difference in commercially available biphasic waveforms. Although the superiority of biphasic over monophasic waveforms for external cardioversion of atrial fibrillation (AF) is established, the relative efficacy of available biphasic waveforms is less clear. We compared the effectiveness of a biphasic truncated exponential (BTE) waveform and a biphasic rectilinear (BR) waveform for external cardioversion of AF. Patients (N = 188) with AF were randomized to receive transthoracic BR shocks (50, 75, 100, 120, 150, 200 J) or BTE shocks (50, 70, 100, 125, 150, 200, 300, 360 J). Shock strength was escalated until success or maximum energy dose was achieved. If maximum shock strength failed, patients received the maximum shock of the opposite waveform. Analysis included 141 patients (71 BR, 70 BTE; mean age 66.5 +/- 13.7. Forty-seven randomized patients were excluded because of flutter on precardioversion ECG upon blinded review (n = 25), presence of intracardiac thrombus (n = 7), or protocol deviation (n = 15). Groups were similar with regard to clinical and echocardiographic characteristics. The success rate was similar for the two waveforms (93% BR vs 97 BTE, P = .44), although cumulative selected and delivered energy was less in the BTE group. Only AF duration was significantly different between successful and unsuccessful patients. No significant complications occurred. Biphasic waveforms were very effective in transthoracic cardioversion of AF, and complication rates were low. No significant difference in efficacy was observed between BR and BTE waveforms. Impedance was not an important determinant of success for either biphasic waveform.


Second-generation three-dimensional reconstruction for rotational three-dimensional angiography.
The purpose of this study was to assess the feasibility and accuracy of three-dimensional (3D) reconstruction techniques for digital subtraction angiography (DSA) in planning and evaluation of minimally invasive image-controlled therapy. Using a standard, commercially available system, the authors acquired DSA images and corrected them for inherent distortions. They designed and implemented parallel and multiresolution versions of cone-beam reconstruction techniques to reconstruct high-resolution targeted volumes in a short period of time. Testing was performed on anatomically correct, calibrated in vitro models of a cerebral aneurysm. These models were used with a pulsatile circulation circuit to allow for blood flow simulation during DSA, computed tomographic (CT) angiography, and magnetic resonance (MR) angiography image acquisitions. The multiresolution DSA-based reconstruction protocol and its implementation allowed the authors to achieve reconstruction times and levels of accuracy for the volume measurement of the aneurysmal cavities that were considered compatible with actual clinical practice. Comparison with data obtained from other imaging modalities shows that, besides vascular tree depiction, the DSA-based true 3D technique provides volume estimates at least as good as those obtained from CT and MR angiography. The authors demonstrated the feasibility and potential of true 3D reconstruction for angiographic imaging with DSA. On the basis of the model testing, this work addresses both the timing and quantification required to support minimally invasive image-controlled therapy.


The role of hypoxia inducible factor-1alpha in gynecological cancer.
Understanding the mechanisms of carcinogenesis and progression of gynecological tumors is important as these insights might lead to improved diagnostic tools for the pathologist, improved prediction of prognosis, response to therapy, and eventually better biology-based disease management, thereby improving prognosis and quality of life for the individual patient. Hypoxia is an important event in carcinogenesis because it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases and poorer survival. Although selecting patients with hypoxic tumors may therefore be clinically important, there is no consensus as to the method best suited for routine assessment of hypoxia. One of the potential tumor hypoxia markers is hypoxia inducible factor 1 (HIF-1). HIF-1 is the key cellular survival protein under hypoxia, and is associated with tumor progression and metastasis in various solid tumors. In this review, we show that in gynecological cancers, HIF-1A is emerging as an important factor in carcinogenesis, and that overexpression of HIF-1A and its target genes CA9 and SLC2A1 seems associated with shorter progression free- and overall survival. Since hypoxia and HIF-1A expression are associated with treatment failure, targeting HIF-1A could be an attractive therapeutic strategy with the potential for disrupting multiple pathways crucial for tumor growth. Currently, HIF-1A inhibitors are being studied in clinical trials in recurrent ovarian- and cervical cancer, and trials in other gynecological cancers are expected.


Time-dependent influence of procaine hydrochloride on cisplatin antitumor activity in P388 tumor bearing mice.
In previous papers (1,2) we demonstrated that procaine hydrochloride may increase the therapeutic index of cisplatin by an improvement of its antitumor activity and a reduction of its nephrotoxicity. In the present study we investigated the relationship between the antitumor activity obtained by cisplatin associated with procaine hydrochloride and the relative time of administration of these two agents. When procaine hydrochloride (40 mg/Kg body wt) was administered 30 or 120 minutes before cisplatin (16 mg/kg) diluted in normal saline (i.e. clinical condition) it increased, although not significantly, its percent increase in life span (%ILS) and cure rate (%ILS: +292 and +217 vs +150; cure rate: 46.2% and 42.3% vs 23%, respectively), compared to cisplatin alone treatment. These results became statistically significant when procaine hydrochloride was given either simultaneously with cisplatin or 30 and 120 minutes thereafter (%ILS: > 400 vs +150; cure rate: 65.4%, 73.1% and 68% vs 23%, respectively). In conclusion procaine hydrochloride increased the antitumor activity of cisplatin independently from its timing of administration, although it seemed to be a better potentiating agent when administered after cisplatin.


Many approved drugs have bioactive analogs with different target annotations.
Close structural relationships between approved drugs and bioactive compounds were systematically assessed using matched molecular pairs. For structural analogs of drugs, target information was assembled from ChEMBL and compared to drug targets reported in DrugBank. For many drugs, multiple analogs were identified that were active against different targets. Some of these additional targets were closely related to known drug targets while others were not. Surprising discrepancies between reported drug targets and targets of close structural analogs were often observed. On one hand, the results suggest that hypotheses concerning alternative drug targets can often be formulated on the basis of close structural relationships to bioactive compounds that are easily detectable. It is conceivable that such obvious structure-target relationships are frequently not considered (or might be overlooked) when compounds are developed with a focus on a primary target and a few related (or undesired) ones. On the other hand, our findings also raise questions concerning database content and drug repositioning efforts.


Chlorambucil induction of HsRad51 in B-cell chronic lymphocytic leukemia.
Our previous studies with B-cell chronic lymphocytic leukemia (B-CLL) have suggested that one of the mechanisms of nitrogen mustard (NM) drug resistance is increased repair of drug-induced damage. We have postulated that recombination may play a crucial role in this process. The human homologue of Rad51, (HsRad51), has homology to the RecA protein in Escherichia coli, which is implicated in recombination repair and induction of DNA repair enzymes. In this report, we have examined the expression and distribution of HsRad51 protein in lymphocytes from patients with B-CLL to see whether the expression of HsRad51 is associated with NM damage to the malignant B lymphocytes, specifically chlorambucil (CLB), which is the standard alkylating agent used to treat patients with B-CLL. We have analyzed the intracellular distribution of HsRad51 protein in these lymphocytes before and after treatment with CLB by immunofluorescence. In vitro CLB treatment induces Rad51 expression, as measured by increased immunopositive staining in all CLL samples. In the CLB-resistant CLL lymphocytes, there was a linear correlation between induction of Rad51 protein at 5.4 microM CLB and the in vitro LD50 dose of CLB. Surprisingly, although it has been reported that Rad51 is induced in S phase and only 10% of cells from cell lines expressed positive immunostaining for Rad51, our CLL lymphocytes, which were not subjected to in vitro drug exposure, were 90% positive for Rad51, despite their nonproliferative state, which suggests that there is chronic activation of the protein. Our results suggest that CLB activates HsRad51-directed recombination repair and that this process may be important in NM drug-induced cytotoxicity.


Application of polychromatic flow cytometry to identify novel subsets of circulating cells with angiogenic potential.
Defining whether human circulating proangiogenic cells represent a subset of the hematopoietic system and express CD45 or are hematopoietic derivatives that do not express CD45 (and are called endothelial progenitor cells) remains controversial. We have previously developed a polychromatic flow cytometry (PFC) protocol to isolate subsets of hematopoietic cells and we now identify the circulating pool of CD34(+)CD45(dim) cells representing functional circulating hematopoietic stem and progenitor cells (CHSPCs) that can be separated on the basis of AC133 expression and report that the AC133(+) subset of the CHSPCs enhances the growth of tumor blood vessels in vivo in immunodeficient mice. In addition, the ratio of AC133(+) proangiogenic CHSPCs to AC133(-) nonangiogenic CHSPCs unambiguously correlates with the severity of the clinical state of patients with peripheral arterial disease. In sum, a PFC protocol validated via in vitro and in vivo analyses, can be used to interrogate the roles of human hematopoietic elements in the growth and maintenance of the vasculature.


Dual microsporidial infection due to Vittaforma corneae and Encephalitozoon hellem in a patient with AIDS.
A 46-year-old human immunodeficiency virus-infected Swiss citizen living in Tanzania presented with respiratory, abdominal, and urogenital complaints. Microsporidial spores were isolated from urine and a sinunasal aspirate and were propagated in MRC-5 cell cultures. Western blot analysis and riboprinting identified the sinunasal isolate as Encephalitozoon hellem. Electron microscopic investigation of the urine isolate revealed spores with diplokaryotic nuclei and five to six isofilar coils of the polar tube and sporonts with two or three diplokarya. All stages were enveloped by two membranes, corresponding to a cisterna of host endoplasmic reticulum studded with ribosomes. These characteristics have been described for the genus Vittaforma. Western blot analysis of this isolate revealed a banding pattern identical to that of the Vittaforma corneae reference isolate. Part of the small subunit rRNA gene was amplified, sequenced (239 base pairs), and found to be identical to that of V. corneae. This is the second isolation of V. corneae and the first description of urinary tract infection due to V. corneae in a patient with AIDS.


Kneeling ability after total knee arthroplasty. Perception and reality.
Kneeling as one of the knee's capabilities required for many activities of daily living has not been examined in detail after total knee replacement. The purpose of the present study was to question the patients' ability to kneel and their perception of factors affecting this ability after total knee arthroplasty, and to objectively assess their kneeling ability. Seventy patients with 100 total knee arthroplasties were asked to comment on their ability to kneel. Thirty-one patients with 44 knees said they could kneel easily, 29 patients with 41 knees said they were able to kneel but avoided doing so, and 10 patients with 15 knees said they were unable to kneel. Regarding observed kneeling ability, all patients were able to kneel under supervision: 56 patients with 82 knees knelt easily and got up easily from this position, 11 patients with 14 knees showed slight difficulties in kneeling or in getting up, and three patients with four knees had marked difficulties with kneeling. The patients' perceived ability to kneel after total knee arthroplasty was less than their observed ability. Fear of harming the prosthesis and lack of information prevented kneeling in 49% of the patients (27 of 56 knees) with perceived inability to kneel. Of those patients with observed difficulty in kneeling, scar pain and back related problems seemed to be major factors in limiting the kneeling ability. Kneeling, as an important function of the knee, should be given additional consideration in relation to the functional results of total knee arthroplasty. Patients should be counseled regarding factors affecting future ability to kneel.


Electrocoiling-guided printing of multiscale architectures at single-wavelength resolution.
The rope coiling observed in liquid ink with high viscosity has been exploited in additive printing to fabricate architectures with periodically curled structures and tune their mechanical properties. However, the control over the coiling path relying on mechanical motion restricts the spatiotemporal resolution. We develop an electrically assisted high-resolution technique to manipulate coiling paths of viscous ink and structures of the deposited filament. By spatially programming the voltage applied onto the viscous ink, we show that the switching between different filament structures can be accomplished at single wavelength resolution, facilitating the rapid and accurate construction of sophisticated patterns. Furthermore, translational guiding of the electrocoiling enables rapid printing of filaments with complex structures at a line speed of 102 mm s-1. With a simplified trajectory of the printing head, large-area and multiscale patterns can be printed at an unprecedented speed; for instance, centimeter-sized architectures constructed from nanofibers with micron-sized curled structures can be completed in a few minutes. By enabling the printing of complex fiber networks with tunable shape and density, our work provides a route towards custom-design of fiber architectures with unique features such as spatially varying mechanical properties.


EEG decoding for datasets with heterogenous electrode configurations using transfer learning graph neural networks.
Objective. Brain-machine interfacing (BMI) has greatly benefited from adopting machine learning methods for feature learning that require extensive data for training, which are often unavailable from a single dataset. Yet, it is difficult to combine data across labs or even data within the same lab collected over the years due to the variation in recording equipment and electrode layouts resulting in shifts in data distribution, changes in data dimensionality, and altered identity of data dimensions. Our objective is to overcome this limitation and learn from many different and diverse datasets across labs with different experimental protocols.Approach. To tackle the domain adaptation problem, we developed a novel machine learning framework combining graph neural networks (GNNs) and transfer learning methodologies for non-invasive motor imagery (MI) EEG decoding, as an example of BMI. Empirically, we focus on the challenges of learning from EEG data with different electrode layouts and varying numbers of electrodes. We utilize three MI EEG databases collected using very different numbers of EEG sensors (from 22 channels to 64) and layouts (from custom layouts to 10-20).Main results. Our model achieved the highest accuracy with lower standard deviations on the testing datasets. This indicates that the GNN-based transfer learning framework can effectively aggregate knowledge from multiple datasets with different electrode layouts, leading to improved generalization in subject-independent MI EEG classification.Significance. The findings of this study have important implications for brain-computer-interface research, as they highlight a promising method for overcoming the limitations posed by non-unified experimental setups. By enabling the integration of diverse datasets with varying electrode layouts, our proposed approach can help advance the development and application of BMI technologies.


Evaluation of a new ultrasonic device in thyroid surgery: comparative randomized study.
Conventional techniques for hemostasis during thyroidectomy rely on knot tying, clips, and electrocoagulation. Recently, the Harmonic FOCUS Shear (Ethicon Endo-Surgery, Inc, Cincinnati, OH) was developed for thyroidectomy. Between December 2007 and March 2008, 62 consecutive patients (45 women, 17 men; mean age 50.9 years) undergoing thyroidectomy were randomized into 2 groups: group A, where the FOCUS was used, and group B, where electrocoagulation and clamp-and-tie technique were used. The 2 groups were similar in terms of age, sex ratio, indication for surgery, and thyroid volume. Operative time was significantly shorter in group A. Significantly fewer clips and ties were used, and postoperative pain and suction balloon amount were also significantly lower in the FOCUS group. The only postoperative complication was a patient with transient hypocalcemia in group B. FOCUS is a reliable and safe tool for thyroidectomy. Its utilization is associated with a shorter operative time, less blood loss, and less postoperative pain.


[Maltreatment: study from the perspective of the police department for the protection of the child and the adolescent in Salvador, Bahia].
This cross-sectional study describes the occurrences of maltreatment recorded over three years (1997-1999) in a Brazilian Police Department for the Protection of the Child and the Adolescent. Socio-demographic and physical data of victims, aggressors and denouncers were investigated in a sample consisting of 2073 cases. The victims were aged between 0-18 years, of which 56.1% were girls. Data were entered into EPI INFO 2000 software and analyzed using descriptive statistics and chi-square test to determine significant differences (p<0.05). All manifestations of abuse, except physical abuse, tend to occur more frequently in females, and tend to be more prevalent in the 11-to-15 year-old subgroup. Physical abuse was the most common offense (64.7%). Injuries of face and jaw were found in 65.3% of the cases. Most of the aggressors were males (71.8%). There was a positive correlation between gender (female) and sexual abuse. Physical violence against boys was more intensive, as indicated by the presence of more severe body lesions. Health professionals should increase their diagnostic skills and raise the awareness of their communities to take action for reducing the incidence and the impact of violence upon children and adolescents.


A case of elephantiasis nostras verrucosa treated successfully by a new type of compressive garment.
Elephantiasis nostras verrucosa (ENV) is a clinical manifestation composed of hyperkeratotic, verrucous, and papillomatous lesions and dermal fibrosis, which complicate chronic lymphedema. There is currently no cure for ENV, however, several measures have been used to reduce lymphedema and the resultant pseudoepidermal hyperplasia. Supportive dressings and compression therapy still constitute an important part of the treatment. In this report, we present a 69-year-old male patient with ENV developed due to chronic lymphedema caused by venous insufficiency. After failure of healing with conventional two- and three-layered bandages, and elastic stockings, he was successfully treated by a new type of compression garment. We recommend this user friendly garment for prevention of frictional trauma, contact dermatitis, and secondary infection, which all may complicate compression treatments.


Maternal childhood trauma, postpartum depression, and infant outcomes: Avoidant affective processing as a potential mechanism.
Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation. A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes. Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism. Limitations included modest sample size, self-report measures, and unmeasured potential confounders. Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa.


Tooth Size in Patients with Mild, Moderate and Severe Hypodontia and a Control Group.
To compare tooth size between subjects with mild, moderate and severe hypodontia and a control group. The study comprised 120 patients with hypodontia divided into three groups of 40 mild (≤2 teeth congenitally missing), 40 moderate (3-5 teeth congenitally missing) and 40 severe (≥6 teeth congenitally missing) hypodontia; and 40 age and sex matched controls. Tooth size was recorded by measuring the mesiodistal and buccolingual dimensions of all fully erupted teeth on study models using digital callipers and compared between all hypodontia and control groups using Two-way ANOVA and Post Hoc Tests of subgroup comparison. Two-way ANOVA revealed patients with hypodontia had significantly smaller mesiodistal and buccolingual tooth dimensions compared with controls (p<0.05). Furthermore patients with more severe hypodontia demonstrated significantly smaller tooth dimensions than those in the mild and moderate hypodontia subgroups (p<0.05). The most affected tooth in terms of tooth size reduction was the maxillary lateral incisor and the least affected tooth was the mandibular first molar. Patients with hypodontia have smaller tooth dimensions than control. Tooth size appears to be affected by the degree of hypodontia, with severe hypodontia having a greater effect on tooth size reduction. The findings of this study may contribute to understanding the aetiology of hypodontia and aid the multidisciplinary management of this complex condition.


Association Between Uric Acid and Renal Hemodynamics: Pathophysiological Implications for Renal Damage in Hypertensive Patients.
The role of vascular renal changes in mediating the association between serum uric acid (SUA) and renal damage is unclear. The purposes of this study were to investigate the relationship between SUA and renal resistive index (RRI), assessed by duplex Doppler ultrasonography, and to assess whether hemodynamic renal changes may explain the association between SUA and renal damage in hypertensive patients. A total of 530 hypertensive patients with and without chronic kidney disease were enrolled and divided into SUA tertiles based on sex-specific cutoff values. RRI and albuminuria were greater and glomerular filtration rate (GFR) was lower in the uppermost SUA tertile patients when compared with those in the lowest tertiles (all P<.001). Moreover, SUA strongly correlated with RRI (P<.001) in all patients. However, RRI did not seem to explain the relationship between SUA and renal damage, and GFR significantly related with SUA in the overall population (P<.001) even after adjustment for RRI.


Update on the defensive chemicals of the little black ant, Monomorium minimum (Hymenoptera: Formicidae).
Alkaloids, including 2,5-dialkylpyrrolidines and 2,5-dialkylpyrrolines, have been reported to be components in the venom of little black ants, Monomorium minimum (Buckley). Two fatty amines were recently reported as minor compounds. By analyzing the discharge collected from the stinger apparatus (milking), this study revealed the presence of an additional seven compounds in the defensive secretion of this ant species. Compounds identified were 9-decenyl-1-amine, N-methylenedecan-1-amine, N-methylenedodecan-1-amine, 2-(1-non-8-enyl)-5-(1-hex-5-enyl)-1-pyrroline, N-methyl-2-(hex-5-enyl)-5-nonanyl-1-pyrrolidine, β-springene ((E,E)-7,11,15-trimethyl-3-methylene-1,6,10,14-hexadecatetraene) and neocembrene ((E,E,E)-1-isopropenyl-4,8,12-trimethylcyclotetradeca-3,7,11-triene). β-springene and neocembrene were found only in the defensive secretion of queens. Analyses of the contents of isolated poison and Dufour's glands of the queen indicated that all amines and alkaloids were from the poison gland and that β-springene and neocembrene were from the Dufour's gland. This demonstrated that the defensive secretion in M. minimum queens consists of components from both glands. This is also the first report on the natural occurrence of 9-decenyl-1-amine, N-methylenedecan-1-amine, and N-methyllenedodecan-1-amine.


Writing, dictating, and speaking letters.
It is commonly assumed that dictation requires a long time to learn, but authors eventually dictate much faster than they write. Performance results now show that novice dictators can learn in a few hours to dictate with the speed and quality with which they write. However, they do not think they perform this well. Dictators with years of experience are from 0 to 25 percent faster than novices, depending upon the complexity of the letters. Planning time is about two-thirds of composition time, regardless of the method of composition.


Treatment of suprachoroidal hemorrhage with tissue plasminogen activator.
We evaluated the efficacy of tissue plasminogen activator in treating experimental suprachoroidal hemorrhage. Suprachoroidal hemorrhage was created in 30 white rabbit eyes by implanting four pieces of small, exogenously formed blood coagula into the suprachoroidal space. Animals were randomized for treatment with a surgical sponge soaked in 25, 50, or 75 microg of tissue plasminogen activator (tPA) or balanced salt solution (BSS) as a control. The time when initiation and completion of clot dissolution occurred was established, and histological examination was performed to assess damage. Clot dissolution started within 30 min in the 50- and 75-microg tPA group, whereas it took 2.75 days in the control group; complete dissolution of blood clots took 4.5 h in the 75-microg tPA group and 14 days in the control group. Histological examination revealed a minimal change in photoreceptors within 6 h after treatment with 75 microg tPA. Treatment of suprachoroidal hemorrhage with tPA seems to be effective, but further investigations for determining the effective and nontoxic dose are required.


Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index.
To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar PIs (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.


Identifying the challenges of interdisciplinary research on pornography use.
This paper explores some the difficulties in undertaking a large-scale systematic review of pornography research literature. Its authors come from different disciplines across the humanities and social sciences, and work within an interdisciplinary team. The research project aims to understand pornography's relationship with its audiences, particularly considering the relationship between pornography consumption and healthy sexual development. Offering a conversational account of research experiences on the project so far, the paper illustrates some key tensions and ongoing points of discussion in research committed to interdisciplinary scholarship, featuring disciplinary perspectives that do not easily correlate. We disagree on definitions, data-gathering methods and modes of data analysis. This paper does not aim to deliver solutions to these problems but presents two different voices describing our experiences of interdisciplinary porn research so far. In order to challenge and extend our disciplinary thinking, we offer an example of dialogue, and highlight the potential of listening across disciplinary frameworks. We encourage scholars from different disciplines to work together as this generates broader research perspectives and offers challenging conditions that can usefully interrogate and extend upon traditional research practice and methods. We hope this paper will generate further reflection among research peers about how best to strengthen interdisciplinary research practice, including, but not limited to, porn research.


Estimating radiofrequency power deposition in body NMR imaging.
Simple theoretical estimates of the average, maximum, and spatial variation of the radiofrequency power deposition (specific absorption rate) during hydrogen nuclear magnetic resonance imaging are deduced for homogeneous spheres and for cylinders of biological tissue with a uniformly penetrating linear rf field directed axially and transverse to the cylindrical axis. These are all simple scalar multiples of the expression for the cylinder in an axial field published earlier (Med. Phys. 8, 510 (1981]. Exact solutions for the power deposition in the cylinder with axial (Phys. Med. Biol. 23, 630 (1978] and transversely directed rf field are also presented, and the spatial variation of power deposition in head and body models is examined. In the exact models, the specific absorption rates decrease rapidly and monotonically with decreasing radius despite local increases in rf field amplitude. Conversion factors are provided for calculating the power deposited by Gaussian and sinc-modulated rf pulses used for slice selection in NMR imaging, relative to rectangular profiled pulses. Theoretical estimates are compared with direct measurements of the total power deposited in the bodies of nine adult males by a 63-MHz body-imaging system with transversely directed field, taking account of cable and NMR coil losses. The results for the average power deposition agree within about 20% for the exact model of the cylinder with axial field, when applied to the exposed torso volume enclosed by the rf coil. The average values predicted by the simple spherical and cylindrical models with axial fields, the exact cylindrical model with transverse field, and the simple truncated cylinder model with transverse field were about two to three times that measured, while the simple model consisting of an infinitely long cylinder with transverse field gave results about six times that measured. The surface power deposition measured by observing the incremental power as a function of external torso radius was comparable to the average value. This is consistent with the presence of a variable thickness peripheral adipose layer which does not substantially increase surface power deposition with increasing torso radius. The absence of highly localized intensity artifacts in 63-MHz body images does not suggest anomalously intense power deposition at localized internal sites, although peak power is difficult to measure.


Misexpression of full-length HMGA2 induces benign mesenchymal tumors in mice.
The high-mobility group AT-hook 2 (HMGA2) protein is a member of the high-mobility group family of the DNA-binding architectural factors and participates in the conformational regulation of active chromatin on its specific downstream target genes. HMGA2 is expressed in the undifferentiated mesenchyme and is undetectable in their differentiated counterparts, suggesting its functional importance in mesenchymal cellular proliferation and differentiation. Interestingly, it is a frequent target of chromosomal translocations in several types of human benign differentiated mesenchymal tumors, including lipomas, fibroadenomas of the breast, salivary gland adenomas, and endometrial polyps. The translocations lead to a variety of HMGA2 transcripts, which range from wild-type, truncated, and fusion mRNA species. However, it is not clear whether alteration of the HMGA2 transcript is required for its tumorigenic potential. To determine whether misexpression of HMGA2 in differentiated mesenchymal cells is sufficient to cause tumorigenesis, we produced transgenic mice that misexpressed full-length or truncated human HMGA2 transcript under the control of the differentiated mesenchymal cell (adipocyte)-specific promoter of the adipocyte P2 (Fabp4) gene. Expression of the full-length HMGA2 transgene was observed in a number of tissues, which produced neoplastic phenotype, including fibroadenomas of the breast and salivary gland adenomas. Furthermore, transgenic misexpression of the truncated version of HMGA2, containing only the three DNA-binding domains, produced similar phenotypes. These results show that misexpression of HMGA2 in a differentiated mesenchymal cell is sufficient to cause mesenchymal tumorigenesis and is independent of the nature of the HMGA2 transcript that results from chromosomal translocations observed in humans.


Same-sex sexual behaviors among male migrants in a context of male "marriage squeeze": results from an exploratory survey in urban Xi'an, China.
The male marriage squeeze in China may increase the prevalence of male same-sex sexual behaviors among unmarried male migrants who lack stable female sexual partners. The same-sex sexual behaviors among unmarried male migrants appear to be at high risk of transmission of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs), mainly because of a lack of knowledge of these diseases. Using data from the "Survey on Reproductive Health and Family Life of Migrant Male Bachelors in Urban Areas" conducted in Xi'an City, Shaanxi Province, in December 2009 and January 2010, this study compares same-sex sexual behaviors of unmarried with that of married male migrants (including married but separated men who are migrating without their spouse or partner and cohabitating men who are migrating with their spouse or partner). It is reported that the prevalence of same-sex sexual behaviors among unmarried males reaches 11%, more than twice the 5.1% reported by married but separated men and thrice the 3.8% reported by cohabitating men. It also appears that the same-sex sexual behaviors is significantly associated with men's attitudes toward same-sex sexual behaviors (odds ratio = 1.59, p < .001), toward life-long bachelorhood (odds ratio = 1.35, p < .01), and with marital status (odds ratio = 0.37, p < .01). The frequency of condom use appears to be higher among unmarried men than among men who are married, whether or not they migrated with their wives, and is significantly associated with scores on knowledge about HIV/AIDS (estimated coefficient = .12, p < .001) and STIs (estimated coefficient = .22, p < .01). It is also associated with the likelihood of same-sex sexual behaviors (estimated coefficients = .83, p < .01) and marital status (estimated coefficients for married but separated = -.50, p < .05; estimated coefficients for cohabitating = -.77, p < .001).


Psychological ramifications of facial change in relation to orthodontic treatment and orthognathic surgery.
A patient who undergoes orthodontic treatment or orthognathic surgery should be prepared psychologically for the difficulties involved. Information that would assist in communicating with potential patients was compiled from questionnaires distributed by orthodontic and oral surgery departments and by practitioners. Of the patients questioned 14 months after treatment, 93% were satisfied with the results.


The anion gap of patients receiving bicarbonate maintenance hemodialysis.
To compare the effect of maintenance bicarbonate hemodialysis on the serum anion gap (AG) and the serum HCO3, the authors retrospectively evaluated the data of 28 patients using the first-of-the-month blood chemistries. Data were available for at least 9 of the previous 12 months in each case. For the entire group, the average AG was 15.8 +/- 0.1 mEq/L and the HCO3 21.7 +/- 0.2 mEq/L. Comparing these values with the data compiled recently by three different groups of investigators in undialyzed patients with severe chronic renal failure indicates that the AG of the dialyzed patients was similar to that of untreated patients, but the HCO3 levels of dialyzed patients averaged 2 to 3 mEq/L higher. Separate prospective evaluation of the acute effect of two consecutive bicarbonate dialyses in 31 patients revealed that the average acute (immediate postdialysis) decrease (from predialysis values) in AG was only about 40% of that of the increase in HCO3. The authors conclude that bicarbonate dialysis is more effective in improving serum HCO3 than AG.


Maintaining a Safe Blood Supply in an Era of Emerging Pathogens.
Coming shortly after outbreaks of dengue and chikungunya virus in related locations, the recent outbreak of Zika virus in the southern part of the western hemisphere is yet another reminder that infectious pathogens continue to emerge rapidly and can adversely affect public health, including the safety of the blood supply. In response to Zika virus, public health measures that rely largely on donor deferral and sourcing of blood from non-outbreak areas until a blood donor screening test becomes available have been implemented to address the safety of the blood supply in the United States. However, a more universal approach to ensuring blood safety in the setting of rapidly emerging infectious diseases is needed.


Parental age effects, but no evidence for an intrauterine effect in the transmission of myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat (g.17294_17296(45_1000)) with more repeats associated with increased disease severity and reduced age at onset. Expanded disease-associated alleles are highly unstable in both the germline and soma. Germline instability is expansion biased, providing a molecular explanation for anticipation. Somatic instability is expansion biased, size- and age-dependent, features that have compromised genotype-phenotype correlations and intergenerational studies. We corrected these confounding factors by estimating the progenitor allele length in 54 father-offspring and 52 mother-offspring pairs in Costa Rican DM1 families. Not surprisingly, we found major parental allele length effects on the size of the allele transmitted, the magnitude of the intergenerational length change, the age at onset in the next generation and the degree of anticipation in both male and female transmissions. We also detected, for the first time, an age-of-parent effect for both male and female transmission. Interestingly, we found no evidence for an intrauterine effect in the transmission of congenital DM1, suggesting previous reports may have been an artefact of age-dependent somatic instability and sampling bias. These data provide new insights into the germline dynamics of the CTG repeat and opportunities for providing additional advice and more accurate risk assessments to prospective parents in DM1 families.


Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET.
The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis). DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti-angiogenic therapies.


FineStr: a web server for single-base-resolution nucleosome positioning.
The DNA in eukaryotic cells is packed into the chromatin that is composed of nucleosomes. Positioning of the nucleosome core particles on the sequence is a problem of great interest because of the role nucleosomes play in different cellular processes including gene regulation. Using the sequence structure of 10.4 base DNA repeat presented in our previous works and nucleosome core DNA sequences database, we have derived the complete nucleosome DNA bendability matrix of Caenorhabditis elegans. We have developed a web server named FineStr that allows users to upload genomic sequences in FASTA format and to perform a single-base-resolution nucleosome mapping on them. FineStr server is freely available for use on the web at http:/www.cs.bgu.ac.il/ approximately nucleom. The site contains a help file with explanation regarding the exact usage. email@example.com.


Influence of sense of coherence on oral health-related quality of life: a systematic review.
The aim of the present study was to perform a systematic review of the literature for scientific evidence regarding the association between a sense of coherence (SOC) and oral health-related of quality of life (OHRQoL). Electronic searches were performed in five databases. Manual searches were also performed. To be included, studies needed to address the relationship between SOC and OHRQoL. The risk of bias was evaluated using the Newcastle-Ottawa scales for cross-sectional and cohort studies and the Physiotherapy Evidence Database scale for clinical trials. Seven cross-sectional studies, four cohort studies, and one clinical trial were included in the present review. Two independent reviewers selected the studies, extracted that data, and performed the evaluations of methodological quality based on the standardized scales. The majority of authors found a significant association between a weak SOC and greater impact on OHRQoL, but some methodological flaws were found in the execution of the studies. Based on the analysis of the studies included in the present systematic review, there is scientific evidence that a sense of coherence exerts an influence on oral health-related quality of life, but further population-based studies are needed to confirm such evidence.


Right anterior insula is associated with pain generalization in patients with fibromyalgia.
Despite diffuse tenderness, patients with fibromyalgia (FM) have reported a wide range of areas with musculoskeletal pain. This study investigated the neural structures and neuroanatomical networks associated with self-reported widespread pain in FM using magnetic resonance imaging. We collected clinical profiles and brain magnetic resonance imaging data of newly diagnosed patients with FM. A total of 138 patients with FM were divided into 3 subgroups based on the number of pain areas, with 3 to 8, 9 to 12, and 13 to 19 areas, respectively. Using voxel-based morphometry analysis, we first identified the neural structure that showed a trend of volumetric change across the 3 subgroups. We then used it as a candidate seed of interest with a seed-to-voxel analytical approach to explore the structural covariance (SC) networks of the whole brain. Finally, we studied the trend of changes in the distribution and strength of SC networks across subgroups of patients. We found a decreasing trend in the volumes of the right anterior insular cortex (rAIC) across the 3 subgroups that had an increased number of pain areas. An increasing trend in the number of neural substrates over the subcortical regions, especially the basal ganglion, showed SC to the rAIC, and a decreasing trend of SC strength was shown between the rAIC and the precuneus, frontal cortex, anterior and posterior cingulate, and lingual gyri, across the patient subgroups with increased pain areas. The rAIC and its altered connection with specific brain regions indicates widespread pain in patients with FM.


Evaluation of the Ultrastructural and In Vitro Flow Properties of the PRESERFLO MicroShunt.
To measure the in vitro flow properties of the PRESERFLO implant for comparison with the theoretical resistance to flow. The PRESERFLO was designed to control the flow of aqueous humor according to the Hagen-Poiseuille (HP) equation. Scanning electron microscopy (SEM) was performed to analyze the ultrastructure, and flow measurements were carried out using a gravity-flow setup. SEM images of the PRESERFLO showed luminal diameters of 67.73 × 65.95 µm and 63.66 × 70.54 µm. The total diameter was 337.2 µm, and the wall was 154 µm wide. The theoretical calculation of the resistance to flow (R) for an aqueous humor (AH) viscosity of 0.7185 centipoises (cP) was 1.3 mm Hg/(µL/min). Hence, assuming a constant AH flow of 2 µL/min, the pressure differential across the device (ΔP) was estimated to be 2.6 mm Hg. The gravity-flow experiment allowed us to measure the experimental resistance to flow, which was RE = 1.301 mm Hg/(µL/min), in agreement with the theoretical resistance to flow R given by the HP equation. The experimental and theoretical flow testing showed that the pressure drop across this device would not be large enough to avoid hypotony unless the resistance to outflow of the sub-Tenon space was sufficient to control the intraocular pressure in the early postoperative period. The fluid properties of glaucoma subconjunctival drainage devices determine their specific bleb-forming capacity and ability to avoid hypotony and therefore their safety and efficacy profile.


Regulation of insulin granule turnover in pancreatic beta-cells by cleaved ICA512.
Insulin maintains homeostasis of glucose by promoting its uptake into cells from the blood. Hyperglycemia triggers secretion of insulin from pancreatic beta-cells. This process is mediated by secretory granule exocytosis. However, how beta-cells keep granule stores relatively constant is still unknown. ICA512 is an intrinsic granule membrane protein, whose cytosolic domain binds beta2-syntrophin, an F-actin-associated protein, and is cleaved upon granule exocytosis. The resulting cleaved cytosolic fragment, ICA512-CCF, reaches the nucleus and up-regulates the transcription of granule genes, including insulin and ICA512. Here, we show that ICA512-CCF also dimerizes with intact ICA512 on granules, thereby displacing it from beta2-syntrophin. This leads to increased granule mobility and insulin release. Based on these findings, we propose a model whereby the generation of ICA512-CCF first amplifies insulin secretion. The ensuing reduction of granule stores would then increase the probability of newly generated ICA512-CCF to reach the nucleus and enhance granule biogenesis, thus allowing beta-cells to constantly adjust production of granules to their storage size and consumption. Pharmacological modulation of these feedback loops may alleviate deficient insulin release in diabetes.


Production and properties of nanocellulose-reinforced methylcellulose-based biodegradable films.
Methylcellulose (MC)-based films were prepared by casting from its 1% aqueous solution containing 0.5% vegetable oil, 0.25% glycerol, and 0.025% Tween 80. Puncture strength (PS), puncture deformation (PD), viscoelasticity coefficient, and water vapor permeability (WVP) were found to be 147 N/mm, 3.46 mm, 41%, and 6.34 g.mm/m(2).day.kPa, respectively. Aqueous nanocellulose (NC) solution (0.1-1%) was incorporated into the MC-based formulation, and it was found that PS was improved (117%) and WVP was decreased (26%) significantly. Films containing 0.25% NC were found to be the optimum. Then films were exposed to gamma radiation (0.5-50 kGy), and it was revealed that mechanical properties of the films were slightly decreased after irradiation, whereas barrier properties were further improved with a decrease of WVP to 28.8% at 50 kGy. Molecular interactions due to incorporation of NC were supported by FTIR spectroscopy. Thermal properties of the NC-containing films were improved, confirmed by TGA and DSC. Crystalline peaks appeared due to NC addition, found by XRD. Micrographs of films containing NC were investigated by SEM.


Technical Note: Integrating an open source Monte Carlo code "MCsquare" for clinical use in intensity-modulated proton therapy.
To commission an open source Monte Carlo (MC) dose engine, "MCsquare" for a synchrotron-based proton machine, integrate it into our in-house C++-based I/O user interface and our web-based software platform, expand its functionalities, and improve calculation efficiency for intensity-modulated proton therapy (IMPT). We commissioned MCsquare using a double Gaussian beam model based on in-air lateral profiles, integrated depth dose of 97 beam energies, and measurements of various spread-out Bragg peaks (SOBPs). Then we integrated MCsquare into our C++-based dose calculation code and web-based second check platform "DOSeCHECK." We validated the commissioned MCsquare based on 12 different patient geometries and compared the dose calculation with a well-benchmarked GPU-accelerated MC (gMC) dose engine. We further improved the MCsquare efficiency by employing the computed tomography (CT) resampling approach. We also expanded its functionality by adding a linear energy transfer (LET)-related model-dependent biological dose calculation. Differences between MCsquare calculations and SOBP measurements were <2.5% (<1.5% for ~85% of measurements) in water. The dose distributions calculated using MCsquare agreed well with the results calculated using gMC in patient geometries. The average 3D gamma analysis (2%/2 mm) passing rates comparing MCsquare and gMC calculations in the 12 patient geometries were 98.0 ± 1.0%. The computation time to calculate one IMPT plan in patients' geometries using an inexpensive CPU workstation (Intel Xeon E5-2680 2.50 GHz) was 2.3 ± 1.8 min after the variable resolution technique was adopted. All calculations except for one craniospinal patient were finished within 3.5 min. MCsquare was successfully commissioned for a synchrotron-based proton beam therapy delivery system and integrated into our web-based second check platform. After adopting CT resampling and implementing LET model-dependent biological dose calculation capabilities, MCsquare will be sufficiently efficient and powerful to achieve Monte Carlo-based and LET-guided robust optimization in IMPT, which will be done in the future studies.


Which Subspecialties Do Female Orthopaedic Surgeons Choose and Why?: Identifying the Role of Mentorship and Additional Factors in Subspecialty Choice.
Limited data exist delineating the reasons women choose subspecialties within orthopaedics. (1) To perform a survey that determines subspecialties female orthopaedic surgeons select and (2) to analyze the motivations behind their choices. A 10-question survey was distributed via e-mail to the Ruth Jackson Orthopaedic Society (RJOS), Texas Orthopaedic Association (TOA), and to a private internet page for women in Orthopaedics, which covered the area of subspecialty practice, motivations, and demographic data. Practicing female orthopaedic surgeons, fellows, or fellowship-matched residents were included. Respondents' ranked motivations when deciding for or against a subspecialty were analyzed and comparisons made. Of the 304 survey responses, 288 met inclusion criteria. The most common subspecialties were hand (24.0%), pediatrics (22.6%), and sports medicine (16.3%). A higher proportion of younger surgeons are electing to subspecialize in sports medicine, whereas a lower proportion of younger surgeons are pursuing general orthopaedics. Top-ranked reasons for selecting a subspecialty were personal satisfaction (50.8%), intellectual stimulation (42.1%), and strong mentorship (37.4%). The most common reason for not selecting a subspecialty was lack of interest (60.6%). Strong mentorship was the largest extrinsic/modifiable factor that affected the decision-making process. A continued focus on mentorship will be necessary to encourage future female orthopaedic surgeons to enter this field and inspire them to explore a different set of subspecialties.


Thromboelastogram evaluation of the impact of hypercoagulability in trauma patients.
Admission hypocoagulability has been associated with negative outcomes after trauma. The purpose of this study was to determine the impact of hypercoagulability after trauma on the need for blood product transfusion and mortality. Injured patients meeting our level I trauma center's highest activation criteria had a thromboelastography (TEG) performed at admission, +1 h, +2 h, and +6 h using citrated blood. Hypercoagulability was defined as any TEG parameter in the hypercoagulable range, and hypocoagulability as any parameter in the hypocoagulable range. Patients were followed up prospectively throughout their hospital course. A total of 118 patients were enrolled: 26.3% (n = 31) were hypercoagulable, 55.9% (n = 66) had a normal TEG profile, and 17.8% (n = 21) were hypocoagulable. After adjusting for differences in demographics and clinical data, hypercoagulable patients were less likely to require un-cross-matched blood (11.1% for hypercoagulable vs. 20.4% for normal vs. 45.7% for hypocoagulable, adjusted P = 0.004). Hypercoagulable patients required less total blood products, in particular, plasma at 6 h (0.1 [SD, 0.4] U for hypercoagulable vs. 0.7 [SD, 1.9] U for normal vs. 4.3 [SD, 6.3] U for hypocoagulable, adjusted P < 0.001) and 24 h (0.2 [SD, 0.6] U for hypercoagulable vs. 1.1 [SD, 2.9] U for normal vs. 8.2 [SD, 19.3] U for hypocoagulable, adjusted P < 0.001). Hypercoagulable patients had lower 24-h mortality (0.0% vs. 5.5% vs. 27.8%, adjusted P < 0.001) and 7-day mortality (0.0% vs. 5.5% vs. 36.1%, adjusted P < 0.001). Bleeding-related deaths were less likely in the hypercoagulable group (0.0% vs. 1.8% vs. 25.0%, adjusted P < 0.001). Approximately a quarter of trauma patients presented in a hypercoagulable state. Hypercoagulable patients required less blood products, in particular plasma. They also had a lower 24-h and 7-day mortality and lower rates of bleeding-related deaths. Further evaluation of the mechanism responsible for the hypercoagulable state and its implications on outcome is warranted.


Factors associated with work outcome after anterior temporal lobectomy for intractable epilepsy.
Whereas the effect of anterior temporal lobectomy on seizure frequency is well recognized, less is known about its impact on work status. One hundred thirty-four of 190 consecutive patients with temporal lobectomy participated in this study. Eligibility criteria were developed to ensure that only patients with the potential of achieving specific outcomes were included in the corresponding analyses. After surgery, significantly more patients were independent in activities of daily living (p < 0.001) or able to drive (p < 0.001). Income from work also increased (p < 0.01). Nearly one fifth of the patients who were eligible for analysis had either a gain (8%) or a loss (11%) of full- or of part-time work. Univariate analyses revealed the following factors to be associated with full-time work after surgery: student or full-time work within a year before surgery, full-time work experience before surgery, full- or part-time employment experience before surgery, no disability benefits before surgery, low postsurgical seizure frequency, improved postsurgical seizure control, excellent postsurgical seizure control, driving after surgery, and further education after surgery (p < 0.05). Significant factors on multivariate analysis were being a student or having full-time work within a year before surgery [odds ratio, 16.2 (95% CI, 4.3-60.5)], driving after surgery [15.2 (3.2-72.0)], and obtaining further education after surgery [9.2 (2.2-53.0)]. Anterior temporal lobectomy for intractable epilepsy improves activities of daily living and the ability to drive. Work outcome of this surgery is influenced by presurgical work experience, successful postsurgical seizure control especially to allow driving, and obtaining further education after surgery.


The metal hyperaccumulators from New Caledonia can broaden our understanding of nickel accumulation in plants.
While an excess of metals such as zinc, cadmium or nickel (Ni) is toxic for most plants, about 500 plant species called hyperaccumulators are able to accumulate high amounts of these metals. These plants and the underlying mechanisms are receiving an increasing interest because of their potential use in sustainable biotechnologies such as biofortification, phytoremediation, and phytomining. Among hyperaccumulators, about 400 species scattered in 40 families accumulate Ni. Despite this wide diversity, our current knowledge of the mechanisms involved in Ni accumulation is still limited and mostly restricted to temperate herbaceous Brassicaceae. New Caledonia is an archipelago of the tropical southwest pacific with a third of its surface (5500 km(2)) covered by Ni-rich soils originating from ultramafic rocks. The rich New Caledonia flora contains 2145 species adapted to these soils, among which 65 are Ni hyperaccumulators, including lianas, shrubs or trees, mostly belonging to the orders Celastrales, Oxalidales, Malpighiales, and Gentianales. We present here our current knowledge on Ni hyperaccumulators from New Caledonia and the latest molecular studies developed to better understand the mechanisms of Ni accumulation in these plants.


Functional analysis of RF2a, a rice transcription factor.
RF2a is a bZIP transcription factor that regulates expression of the promoter of rice tungro bacilliform badnavirus. RF2a is predicted to include three domains that contribute to its function. The results of transient assays with mutants of RF2a from which one or more domains were removed demonstrated that the acidic domain was essential for the activation of gene expression, although the proline-rich and glutamine-rich domains each played a role in this function. Studies using fusion proteins of different functional domains of RF2a with the 2C7 synthetic zinc finger DNA-binding domain showed that the acidic region is a relatively strong activation domain, the function of which is dependent on the context in which the domain is placed. Data from transgenic plants further supported the conclusion that the acidic domain was important for maintaining the biological function of RF2a. RF2a and TBP (TATA-binding protein) synergistically activate transcription in vitro (Zhu, Q., Ordiz, M. I., Dabi, T., Beachy, R. N., and Lamb, C. (2002) Plant Cell 14, 795-803). In vitro and in vivo assays showed that RF2a interacts with TBP through the glutamine-rich domain but not the acidic domain. Functional analysis of such interactions indicates that the acidic domain activates transcription through mechanisms other than via the direct recruitment of TBP.


Perceptions of family learning environments: the influence of sibling background.
Longitudinal data from 240 female and 260 male Australians were used to examine relationships among birth order, sibsize, and adolescents' perceptions of family learning environments after taking into account the correlation of intellectual ability and social status on those perceptions. For the analysis, regression models were investigated that included terms to test for possible linear, interaction and curvilinear relationships. The findings provided tentative support for the sibling dilution theory, that is, after accounting for the effects of children's ability and family social status, the sibling variables continued to have some modest associations with the adolescents' perceptions of their parents' support for learning.


Outcomes of French's Corrective Osteotomy of the Humerus for Cubitus Varus Deformity in Children.
Supracondylar humerus fractures are the most common elbow fractures in the pediatric population. To evaluate the outcomes of French's corrective osteotomy for correction of post-traumatic cubitus varus deformity in children. We conducted a retrospective review of medical charts of all patients who had undergone French's corrective osteotomy in our institution from 1998 to 2012. We recorded range of motion, cosmetic deformity, carrying angle, lateral cortex prominence index, hyperextension, and lateral cortex step before and after the surgery. Seven patients were enrolled the study. Average follow-up time was 4.6 years (range 2-9 years). An average of 18.3º of limited flexion (range 5º-35º) compared to the healthy elbow was recorded in three patients. Lateral condylar prominence was recorded in one patient. The average preoperative carrying angle was -20.5º (range -15º-30º) and postoperative angle was 9.6º (range 7º-13º). In comparison, the average carrying angle in the healthy elbow was 8.5º (range 4º-13º). No lateral cortex prominence was recorded. An average of 27.5º (range 15º-35º) of hyperextension of the distal fragment was recorded immediately postoperatively in four patients; however, during postoperative follow-up, the hyperextension was corrected spontaneously in all patients. As described by French, osteotomy has the ability to correct the varus deformity only in the coronal plane. However, our research supports the assumption that hyperextension in the sagittal plane might be corrected spontaneously.


Metabolic response of vetiver grass (Chrysopogon zizanioides) to acid mine drainage.
Acid mine drainage (AMD) is a sulfuric discharge containing metals and particulates that can spread to nearby water sources, imposing toxicity and physical stress to living things. We have shown that vetiver grass (Chrysopogon zizanioides) is capable of tolerating and treating AMD-impacted water from the abandoned Tab-Simco mining site from southern Illinois, though little is known about its tolerance mechanisms. We conducted metabolomic analyses of vetiver shoots and roots after relatively short- and long-term periods of exposure to Tab-Simco AMD. The metabolic shift of vetiver shoots was dramatic with longer-term AMD exposure, including upregulation of amino acid and glutathione metabolism, cellular respiration and photosynthesis pathways, with downregulation of phosphorylated metabolites. Meanwhile, the roots demonstrated drastic downregulation of phospholipids and phosphorylated metabolites, cellular respiration, glyoxylate metabolism, and amino acid metabolism. Vetiver accumulated ornithine and oxaloacetate in the shoots, which could function for nitrogen storage and various intracellular functions, respectively. Organic acids and glutathione were secreted from the roots for rhizospheric metal-chelation, whereas phosphorylated metabolites were recycled for phosphorus. These findings reveal AMD-induced metabolic shifts in vetiver grass, which are seemingly unique in comparison to independent abiotic stresses reported previously.


Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease.
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.


Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model.
Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.


Citric Juice-mediated Synthesis of Tellurium Nanoparticles with Antimicrobial and Anticancer Properties.
Bacterial infections and cancer are two of the most significant concerns that the current healthcare system should tackle nowadays. Green nanotechnology is presented as a feasible solution that is able to produce materials with significant anticancer and antibacterial activity, while overcoming the main limitations of traditional synthesis. In the present work, orange, lemon and lime extracts were used as both reducing and capping agents for the green synthesis of tellurium nanoparticles (TeNPs) using a microwave-assisted reaction. TeNPs showed a uniform size distribution, and rod- and cubic-shapes, and were extensively characterized in terms of morphology, structure and composition using TEM, SEM, XPS, XRD, FTIR and EDX analysis. TeNPs showed an important antibacterial activity against both Gram-negative and -positive bacteria in a range concentrations from 5 to 50 μg/mL over a 24-hour time period. Besides, nanoparticles showed anticancer effect towards human melanoma cells over 48 hours at concentrations up to 50 μg/mL. Moreover, the Te nanostructures showed no significant cytotoxic effect towards human dermal fibroblast at concentrations up to 50 μg/mL. Therefore, we present an environmentally-friendly and cost-effective synthesis of TeNPs using only fruit juices and showing enhanced and desirable biomedical properties towards both infectious diseases and cancer.


[Driving: What is the relevance and usability of the Reisberg scale in 2023?]
The publication of the decree on the care of people with neurocognitive disorders brought to the fore the Reisberg's Global Deterioration Scale, a scale that only few clinicians use in memory centers or in geriatric. This scale has a number of limitations, not least of which is that it is obsolete, since it does not take into account disease advances in scientific knowledge with biomarkers. Consequently, the stages evoked no longer correspond to current descriptions. Moreover, it only concerns Alzheimer's disease, whereas in our practice we encounter other neurodegenerative pathologies. Even if we decide to use another global assessment scale, such as the Clinical Dementia Rating or the Functional Assessment Staging, they cannot replace a personalized assessment. Indeed, it is important to stress that this decree does not take into account the relevance of personalized assessments using, for example, neuropsychological tests to estimate driving ability. A personalized assessment accompanied by a real-life driving test would be preferable than a score on a global scale. This article therefore presents the Global Deterioration Scale, highlighting its unsuitability for assessing whether or not to continue driving.


Proteomic and biomarker studies and neurological complications of pediatric sickle cell disease.
Biomarker analysis and proteomic discovery in pediatric sickle cell disease has the potential to lead to important discoveries and improve care. The aim of this review article is to describe proteomic and biomarker articles involving neurological and developmental complications in this population. A systematic review was conducted to identify relevant research publications. Articles were selected for children under the age of 21 years with the most common subtypes of sickle cell disease. Included articles focused on growth factors (platelet-derived growth factor), intra and extracellular brain proteins (glial fibrillary acidic protein, brain-derived neurotrophic factor), and inflammatory and coagulation markers (interleukin-1β, l-selectin, thrombospondin-1, erythrocyte, and platelet-derived microparticles). Positive findings include increases in plasma brain-derived neurotrophic factor and platelet-derived growth factor with elevated transcranial Dopplers velocities, increases in platelet-derived growth factor isoform AA with overt stroke, and increases in glial fibrillary acidic protein with acute brain injury. These promising potential neuro-biomarkers provide insight into pathophysiologic processes and clinical events, but their clinical utility is yet to be established. Additional proteomics research is needed, including broad-based proteomic discovery of plasma constituents and blood cell proteins, as well as urine and cerebrospinal fluid components, before, during and after neurological and developmental complications.


Disability Among Middle-Aged and Older Persons With Human Immunodeficiency Virus Infection.
Older human immunodeficiency virus (HIV)-infected adults may experience higher rates of frailty and disability than the general population. Improved understanding of the prevalence, risk factors, and types of impairment can better inform providers and the healthcare system. HIV-infected participants within the AIDS Clinical Trials Group A5322 HAILO study self-reported disability by the Lawton-Brody Instrumental Activities of Daily Living (IADL) Questionnaire. Frailty was measured by 4-m walk time, grip strength, self-reported weight loss, exhaustion, and low activity. Logistic regression models identified characteristics associated with any IADL impairment. Agreement between IADL impairment and frailty was assessed using the weighted kappa statistic. Of 1015 participants, the median age was 51 years, 15% were aged ≥60 years, 19% were female, 29% black, and 20% Hispanic. At least 1 IADL impairment was reported in 18% of participants, most commonly with housekeeping (48%) and transportation (36%) and least commonly with medication management (5%). In multivariable models, greater disability was significantly associated with neurocognitive impairment, lower education, Medicare/Medicaid insurance (vs private/other coverage), smoking, and low physical activity. Although a greater proportion of frail participants had IADL impairment (52%) compared to non-frail (11%) persons, agreement was poor (weighted kappa <0.18, 95% confidence interval, 0.13, 0.23). IADL disability occurs frequently among middle-aged and older HIV-infected adults on effective antiretroviral therapy. Potentially modifiable risk factors (smoking, physical activity) provide targets for interventions to maintain independent living. Systematic recognition of persons at greater risk for disability can facilitate connection to resources that may help preserve independence.


Health-Related Quality of Life (HRQoL) in Young Adults with Strabismus in India.
Strabismus has negative psycho-social and functional effects in adults. The impact can be minimised with surgery. However, in a low-income setting, it is important to evaluate the level of impact and prioritise the target population for intervention. The Adult Strabismus (AS-20) questionnaire is a reliable tool for assessment of Health-Related Quality of Life (HRQoL) in strabismic adults. To assess the HRQoL in young adults with manifest strabismus through psychosocial and functional scores according to gender and direction of deviation using the AS-20 questionnaire. In this cross-sectional cohort study, 132 young adults who manifest horizontal strabismus were recruited and the AS-20 questionnaire was administered. Patient's demographic profile and type of strabismus were noted and compared with the overall mean scores of psycho-social and functional subscales. Data was analyzed using SPSS 21 and p-value less than 0.05 was considered statistically significant. The participants comprised of 70 (53.03%) males and 62 (46.97%) females with a mean age of 24.5±3.57 years (range 18 to 38 years). The overall mean AS-20 score of young adults with strabismus was 61.62±12.61. The overall mean score for male and female were 65.54±13.53 and 57.68±13.46, respectively. Similarly, the mean scores for esotropes was 57.03±11.66 and 66.19±15.30 for exotropes. The overall mean scores were statistically significantly reduced (decreased QoL) in females as compared to males (CI 95%; p=0.002) and in esotropes as compared to exotropes (CI 95%; p=0.001). However, there was no significant difference between the psychosocial and functional score for all types of strabismus and genders (for all, p>0.05). The Quality of Life (QoL) is affected through psychosocial and functional factors in adults with strabismus. Females and adults with esotropia faced greater difficulties in the QoL. We recommend clinicians to consider the impact on QoL while managing adult with strabismus.


Adenovirus small e1a alters global patterns of histone modification.
Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.


Brain parenchymal and leptomeningeal metastasis in non-small cell lung cancer.
Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p < 0.0001). The median time to the onset of PM and LM from the diagnosis of advanced NSCLC was 0 months and 8.3 months, respectively. Patients with LM had a statistically shorter over survival (OS) compared to either No-BM or PM patients (p < 0.0001). Based on independent predictive variables, two nomogram models were constructed to predict the development of PM and LM in advanced NSCLC patients, and the C-indexes were 0.656 and 0.767, respectively. Although both considered as BM, PM and LM had different clinical characteristics. And the nomogram showed good performance in predicting LM development, but not PM.


Biological control of soybean damping-off by antagonistic rhizobacteria.
Experiments were carried out with 133 bacterial isolates that were collected from soybean rhizosphere. These strains were used to investigate their biocontrol traits in vitro and their ability to suppress the soybean damping-off in vivo (soil and seed treatments). Three highly effective isolates were selected from these antagonists for subsequent studies. According to the biochemical, physiological and morphological tests, these isolates (B-2, B-12 and B-80) were identified as Bacillus spp. In soil treatment, the isolate B-3 with 70.8%, B-12 with 66.7%, B-80 with 54.2% had the highest effect on reducing the soybean damping-off. In seed treatment, the isolates B-43 with 62.5%, B-12 with 58.4 and B-80 with 45.8%, had the greatest effect on reducing the disease. These isolates produced volatile metabolites that inhibited mycelial growth of Phytophthora sojae.


Arecoline hydrobromide enhances jejunum smooth muscle contractility via voltage-dependent potassium channels in W/Wv mice.
Gastrointestinal motility was disturbed in W/Wv, which were lacking of interstitial cells of Cajal (ICC). In this study, we have investigated the role of arecoline hydrobromide (AH) on smooth muscle motility in the jejunum of W/Wv and wild-type (WT) mice. The jejunum tension was recorded by an isometric force transducer. Intracellular recording was used to identify whether AH affects slow wave and resting membrane potential (RMP) in vitro. The whole-cell patch clamp technique was used to explore the effects of AH on voltage-dependent potassium channels for jejunum smooth muscle cells. AH enhanced W/Wv and WT jejunum contractility in a dose-dependent manner. Atropine and nicardipine completely blocked the excitatory effect of AH in both W/Wv and WT. TEA did not reduce the effect of AH in WT, but was sufficient to block the excitatory effect of AH in W/Wv. AH significantly depolarized the RMP of jejunum cells in W/Wv and WT. After pretreatment with TEA, the RMP of jejunum cells indicated depolarization in W/Wv and WT, but subsequently perfused AH had no additional effect on RMP. AH inhibited the voltage-dependent K+ currents of acutely isolated mouse jejunum smooth muscle cells. Our study demonstrate that AH enhances the contraction activity of jejunum smooth muscle, an effect which is mediated by voltage-dependent potassium channels that acts to enhance the excitability of jejunum smooth muscle cells in mice.


Integrating top-down and bottom-up sensory processing by somato-dendritic interactions.
The classical view of cortical information processing is that of a bottom-up process in a feedforward hierarchy. However, psychophysical, anatomical, and physiological evidence suggests that top-down effects play a crucial role in the processing of input stimuli. Not much is known about the neural mechanisms underlying these effects. Here we investigate a physiologically inspired model of two reciprocally connected cortical areas. Each area receives bottom-up as well as top-down information. This information is integrated by a mechanism that exploits recent findings on somato-dendritic interactions. (1) This results in a burst signal that is robust in the context of noise in bottom-up signals. (2) Investigating the influence of additional top-down information, priming-like effects on the processing of bottom-up input can be demonstrated. (3) In accordance with recent physiological findings, interareal coupling in low-frequency ranges is characteristically enhanced by top-down mechanisms. The proposed scheme combines a qualitative influence of top-down directed signals on the temporal dynamics of neuronal activity with a limited effect on the mean firing rate of the targeted neurons. As it gives an account of the system properties on the cellular level, it is possible to derive several experimentally testable predictions.


Risk of Barrett's oesophagus, oesophageal adenocarcinoma and reflux oesophagitis and the use of nitrates and asthma medications.
To investigate the relationship between use of asthma medication and nitrates and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Data were collected on use of asthma medication and nitrates at least 1 year before interview from patients with reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Associations between use of asthma medications and nitrates and the risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma were estimated using multiple logistic regression. Nine hundred and forty-one subjects were recruited: 230 reflux oesophagitis, 224 Barrett's oesophagus, 227 oesophageal adenocarcinoma patients and 260 population controls. Barrett's oesophagus patients were more likely than controls to have had a diagnosis of asthma (odds ratio 2.15, 95% confidence interval 1.15-4.03) and to have used asthma medications (odds ratio 2.13, 95% confidence interval 1.09-4.16). No significant associations were observed between use of asthma medication or nitrates and reflux oesophagitis or oesophageal adenocarcinoma. Gastro-oesophageal reflux symptoms appear to confound the association between asthma medication use and Barrett's oesophagus. However, it is possible that asthma medications may increase the risk of Barrett's oesophagus by other mechanisms.


Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.
In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association. (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases. Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.


PHI-base in 2022: a multi-species phenotype database for Pathogen-Host Interactions.
Since 2005, the Pathogen-Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.