Persistent pesticides in human breast milk and cryptorchidism.
Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. Within a prospective birth cohort, we performed a case-control study; 62 milk samples from mothers of cryptorchid boys and 68 from mothers of healthy boys were selected. Milk was collected as individual pools between 1 and 3 months postpartum and analyzed for 27 organochlorine pesticides. Eight organochlorine pesticides were measurable in all samples (medians; nanograms per gram lipid) for cases/controls: 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (p,p -DDE) : 97.3/83.8; beta-hexachlorocyclohexane (beta-HCH) : 13.6/12.3; hexachlorobenzene (HCB) : 10.6/8.8; alpha-endosulfan: 7.0/6.7; oxychlordane: 4.5/4.1; 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p -DDT) : 4.6/4.0; dieldrin: 4.1/3.1 ; cis-heptachloroepoxide (cis-HE) : 2.5/2.2. Five compounds [octachlorostyrene (OCS); pentachlorobenzene, 1,1-dichloro-2,2-bis(4-chlorophenyl) ethane(p,p -DDD) ; o,p -DDT ; mirex] were measurable in most samples (detection rates 90.8-99.2%) but in lower concentrations. For methoxychlor, cis-chlordane, pentachloroanisole (PCA), gamma-HCH, 1,1-dichloro-2-(2-chlorophenyl) -2,2(4-chlorophenyl) ethane, trans-chlordane, alpha-HCH, and o,p -DDE, both concentrations and detection rates were low (26.5-71.5%). Heptachlor, HCH (lc delta, epsilon), aldrin, beta-endosulfan and trans-heptachloroepoxide were detected at negligible concentrations and low detection rates and were not analyzed further. Seventeen of 21 organochlorine pesticides [p,p -DDT, p,p-DDE, p,p-DDD, o,p-DDT, HCH (alpha, beta, gamma), HCB, PCA, alpha-endosulfan, cis-HE, chlordane (cis-, trans-) oxychlordane, methoxychlor, OCS, and dieldrin] were measured in higher median concentrations in case milk than in control milk. Apart from trans-chlordane (p = 0.012), there were no significant differences between cryptorchid and healthy boys for individual chemicals. However, combined statistical analysis of the eight most abundant persistent pesticides showed that pesticide levels in breast milk were significantly higher in boys with cryptorchidism (p = 0.032). The association between congenital cryptorchidism and some persistent pesticides in breast milk as a proxy for maternal exposure suggests that testicular descent in the fetus may be adversely affected.


An endoscope for ophthalmology.
An endoscope with a 1.7-mm diameter shaft has unique properties of focus, magnification, and large field of view that make it useful for both orbital and intraocular surgery.


Polydatin mediates Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in acute respiratory distress syndrome.
Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin-/- mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.


Management of Male Urethral Emergencies.
We provide an overview of the terminology, anatomical considerations, pathophysiology, diagnostic evaluation and contemporary management strategies of male urethral emergencies. We reviewed the literature, including the latest EAU (European Association of Urology) guidelines. Iatrogenic injuries are the most common cause of urethral injuries. Traumatic injuries are contusion, stretch or partial or complete injury of the anterior and/or posterior urethra. Blunt injuries are most frequently treated initially with suprapubic urinary drainage and, if necessary, subsequent urethroplasty. Early realignment is controversial and can be attempted in stable patients. Except in rare cases most pelvic fracture urethral injuries are treated with delayed anastomotic urethroplasty. For other injuries such as contusions, depending on the length and localization of the fibrotic gap end-to-end anastomosis or augmented urethroplasty is performed. Penetrating or open injuries are variably managed by initial urinary diversion or wound débridement, hematoma evacuation and, if possible, primary urethral anastomosis. Primary repair of fractured penis is recommended and immediate primary repair is especially important for suspected associated urethral injury.


Phytophthora viruses.
Phytophthora sp. is a genus in the oomycetes, which are similar to filamentous fungi in morphology and habitat, but phylogenetically more closely related to brown algae and diatoms and fall in the kingdom Stramenopila. In the past few years, several viruses have been characterized in Phytophthora species, including four viruses from Phytophthora infestans, the late blight pathogen, and an endornavirus from an unnamed Phytophthora species from Douglas fir. Studies on Phytophthora viruses have revealed several interesting systems. Phytophthora infestans RNA virus 1 (PiRV-1) and PiRV-2 are likely the first members of two new virus families; studies on PiRV-3 support the establishment of a new virus genus that is not affiliated with established virus families; PiRV-4 is a member of Narnaviridae, most likely in the genus Narnavirus; and Phytophthora endornavirus 1 (PEV1) was the first nonplant endornavirus at the time of reporting. Viral capsids have not been found in any of the above-mentioned viruses. PiRV-1 demonstrated a unique genome organization that requires further examination, and PiRV-2 may have played a role in late blight resurgence in 1980s-1990s.


Facile preparation of Artemisia argyi oil-loaded antibacterial microcapsules by hydroxyapatite-stabilized Pickering emulsion templating.
Artemisia argyi oil (AAO)-loaded antibacterial microcapsules with hydroxyapatite (HAp)/poly(melamine formaldehyde) (PMF) hybrid shells were facilely prepared by oil-in-water (O/W) Pickering emulsion templating. AAO-in-water emulsions were stabilized using HAp nanoparticles as the particulate emulsifier. The hybrid shells were fabricated by in situ polymerization of melamine formaldehyde pre-polymer (pre-MF) at the interface of the O/W Pickering emulsions. The prepared microcapsules were characterized in terms of size, morphology, component and thermal stability using scanning electronic microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), respectively. Moreover, both in vitro release and antimicrobial activity of the microcapsules were also evaluated. The results showed that the AAO-loaded microcapsules with HAp/PMF shells had a spherical shape and a rough surface. The microcapsules maintained excellent performances in the thermal stability, controlled release activity, antimicrobial effect and long-term antimicrobial activity. The release curves of AAO from the microcapsules could be well described by Higuchi kinetic model. The microcapsules may find applications as antibacterial agents in the areas of textiles, leather, rubber and coatings. In situ polymerization based on Pickering emulsion droplets opens up a new route to prepare a variety of hybrid microcapsules with a core-shell structure.


Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card!
Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients' self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.


Corrigendum: Bias in measurement of autism symptoms by spoken language level and non-verbal mental age in minimally verbal children with neurodevelopmental disorders.
[This corrects the article DOI: 10.3389/fpsyg.2022.927847.].


Novel use of the Bakri balloon to minimize empty pelvis syndrome following laparoscopic total pelvic exenteration.
Pelvic exenteration is the only surgical option for locally advanced pelvic malignancies infiltrating the surrounding organs. The resultant pelvic void after the procedure is responsible for a number of complications, collectively termed empty pelvis syndrome (EPS). We aim to show how EPS can be minimized by presenting a case series demonstrating the surgical technique of laparoscopic total pelvic exenteration with bilateral pelvic node dissection along with a novel use of the Bakri balloon. This is a case series of three successive patients undergoing laparoscopic total pelvic exenteration for locally advanced primary, nonmetastatic rectal adenocarcinoma over a period of 1 month in a specialized colorectal unit at a tertiary cancer centre. The Bakri balloon was deployed in all three patients and retained for variable time intervals postoperatively. Features of EPS were prospectively documented. In the first patient, the Bakri balloon was completely deflated and removed on postoperative day (POD) 5. The patient developed subacute intestinal obstruction which resolved with conservative management by POD 12. In the second and third patients, the Bakri balloon was deflated in a sequential manner, beginning on POD 8, until it was finally removed on POD 11. Neither of these patients had any abdominal complaints. A postoperative CT scan of both these patients showed the small bowel loops clearly above the pelvic inlet. The Bakri balloon is a simple, safe and cost-effective method to reduce the complications of EPS following laparoscopic total pelvic exenteration. A prospective study is ongoing to objectively quantify the benefits of this technique.


Effect of mini-implant diameter on fracture risk and self-drilling efficacy.
The aim of this study was to evaluate the effect of mini-implant diameter on fracture risk and self-drilling efficacy. A sample of 405 mini-implants with 9 diameters from 1.2 to 2.0 mm was used. Ten mini-implants of each diameter were placed in artificial bone, and 25 were placed in pig iliac bone to evaluate placement torque (PT) and axial placement load (APL), which represents self-drilling efficacy. Ten mini-implants of each diameter were used to determine fracture torque (FT). The different diameters were compared regarding PT, FT, and APL. The fracture risk of each diameter was evaluated by the fracture resistance index (FT/PT × [FT-PT]). The PT and APL changes during placement were correlated. Only PT and FT were different for all mini-implant diameter changes. PT and FT showed a strong correlation with the mini-implant diameter, but the APL was weakly to moderately correlated. The fracture resistance index was remarkably greater for each 0.1 mm added in diameter. The PT increased significantly, whereas the APL was progressively reduced during placement. Increases in mini-implant diameters significantly influenced the increases of PT and FT on quantities that progressively reduced the fracture risk. The self-drilling efficacy was not strongly influenced by diameter.


Further studies on the potent positive chronotropic effect of (15S)-15-methyl-prostaglandin E1 on the guinea-pig isolated spontaneously beating right atrium.
1. 15-Me-PGE1 (10(-14)-10(-11) M) elicited a concentration-dependent and long-lasting increase in heart rate without an effect on contractility of the isolated spontaneously beating guinea-pig right atria. 2. Noradrenaline, histamine and PGE1 produced a concentration-dependent increase in both heart rate and contractility with relatively higher concentrations. 3. beta-Adrenoceptor blocker propranolol and histamine H2-receptor blocker cimetidine inhibited the effects of noradrenaline and histamine respectively without altering the positive chronotropic effect of 15-Me-PGE1. 4. Prazosin and lidocaine partially inhibited the effect of 15-Me-PGE1, while reducing Na+ concentration in the medium to 50 mM almost completely inhibited the positive chronotropic effect of the analog. 5. Calcium channel blocker, nicardipine, decreased the positive chronotropic effect of 15-Me-PGE1 in a concentration-dependent manner. 6. These results were taken as an evidence for the specific and unique effect of 15-Me-PGE1 in the guinea-pig sinoatrial node interacting with Na+ and Ca2+ fluxes probably through their specific exchangers.


Classification of the extracellular fields produced by activated neural structures.
Classifying the types of extracellular potentials recorded when neural structures are activated is an important component in understanding nerve pathophysiology. Varying definitions and approaches to understanding the factors that influence the potentials recorded during neural activity have made this issue complex. In this article, many of the factors which influence the distribution of electric potential produced by a traveling action potential are discussed from a theoretical standpoint with illustrative simulations. For an axon of arbitrary shape, it is shown that a quadrupolar potential is generated by action potentials traveling along a straight axon. However, a dipole moment is generated at any point where an axon bends or its diameter changes. Next, it is shown how asymmetric disturbances in the conductivity of the medium surrounding an axon produce dipolar potentials, even during propagation along a straight axon. Next, by studying the electric fields generated by a dipole source in an insulating cylinder, it is shown that in finite volume conductors, the extracellular potentials can be very different from those in infinite volume conductors. Finally, the effects of impulses propagating along axons with inhomogeneous cable properties are analyzed. Because of the well-defined factors affecting extracellular potentials, the vague terms far-field and near-field potentials should be abandoned in favor of more accurate descriptions of the potentials.


Analysis of pathogenic factors of Candida albicans and the effect of vaginal immunization on recurrent vulvovaginal candidiasis in mice.
The role of fungal pathogenic factors and the immune response of the vaginal epithelium in vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are still unclear. Our study wants to clarify whether there are differences in pathogenic factors between VVC and RVVC strains, confirm the roles of pathogenic factors in the pathogenesis of RVVC, and analyze the influence of pathogenic factors on vaginal host immunity. VVC- and RVVC-causing Candida albicans strains were genotyped with 25S rDNA. Drug susceptibility assays using a modified alamarBlue broth microdilution method were carried out. Milk culture medium and egg yolk culture medium were used to measure the secreted aspartate protease (Sap) and phospholipase (Plb) activity of the samples. We used C. albicans with different Sap activity levels to induce RVVC in mice and measured interleukin 4 (IL4), interleukin 8 (IL8), and interleukin 17 (IL17) in vaginal lavage fluid at different stages of RVVC infection. There were no significant differences between VVC and RVVC fungi except that the Sap activity was lower for RVVC-causing C. albicans than for VVC-causing C. albicans. C. albicans with both strong Sap and weak Sap induced RVVC in mice. C. albicans with strong Sap had a reduced RVVC infection rate. In addition, C. albicans with strong Sap stimulated the vaginal epithelium to secrete more IL4, IL8, and IL17. Compared with that of VVC-causing C. albicans, the Sap activity of RVVC-causing C. albicans was lower. C. albicans with strong Sap was less capable of causing repeated vaginal infections than that with weak Sap and stimulated the vaginal epithelium to produce more cytokines.


Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state.
On the basis of the findings of the electrophysiological evaluation of vegetative state (VS) and minimally conscious state (MCS), the effect of deep brain stimulation (DBS) was examined according to long-term follow-up results. The results of spinal cord stimulation (SCS) on MCS was also examined and compared with that of DBS. One hundred seven patients in VS and 21 patients in MCS were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury. Among the 107 VS patients, 21 were treated by DBS. Among the 21 MCS patients, 5 were treated by DBS and 10 by SCS. Eight of the 21 patients recovered from VS and were able to follow verbal instructions. These eight patients showed desynchronization on continuous electroencephalographic frequency analysis. The Vth wave of the auditory brainstem response and N20 of somatosensory evoked potential were recorded even with a prolonged latency, and pain-related P250 was recorded with an amplitude of more than 7 μV. In addition, DBS and SCS induced a marked functional recovery in MCS patients who satisfied the electrophysiological inclusion criteria. DBS for VS and MCS patients and SCS for MCS patients may be useful, when the candidates are selected on the basis of the electrophysiological inclusion criteria. Only 16 (14.9%) of the 107 VS patients and 15 (71.4%) of the 21 MCS patients satisfied the electrophysiological inclusion criteria.


Microperimetry as a diagnostic tool for the detection of early, subclinical retinal damage and visual impairment in multiple sclerosis.
A majority of multiple sclerosis patients experience visual impairment, often as the initial presenting symptom of the disease. While structural changes in the retinal nerve fiber layer and optic nerve have demonstrated correlations with brain atrophy in multiple sclerosis using magnetic resonance imaging, a non-invasive, cost-effective, and clinically efficacious modality to identify early damage and facilitate prompt therapeutic intervention to slow the progression of multiple sclerosis and its ocular manifestations, is still urgently needed. In this study, we sought to determine the role of macular sensitivity measured by microperimetry in the detection of subclinical multiple sclerosis-related retinal damage and visual dysfunction. This cross-sectional observational case-control study involved population-based samples of multiple sclerosis patients and age-, race-, and gender-matched healthy control subjects. Among the key criteria for the multiple sclerosis patients were diagnosis by the McDonald criteria, visual acuity greater than 20/25, and no history of optic neuritis. Macular sensitivity and average macular thickness were measured in all subjects using microperimetry and spectral-domain optical coherence tomography, respectively. Pearson correlation coefficients were measured using bivariate correlations. Sample means, mean differences, and 95% confidence intervals were calculated using independent sample t-tests. Twenty-eight eyes from 14 MS patients and 18 eyes from 9 control subjects were included. Mean macular sensitivity of control subjects and multiple sclerosis patients in decibels was 18.2 ± 0.4 and 16.5 ± 0.4, respectively, corresponding to a mean difference of 1.7 (95% CI, 1.1-2.4; P < 0.001). Macular sensitivity was positively correlated with macular thickness in multiple sclerosis patients (r = 0.49, P = 0.01) but not control subjects (r = 0.15, P = 0.55). Macular sensitivity as measured by microperimetry was decreased in multiple sclerosis patients with normal visual acuity and no history of optic neuritis. Furthermore, macular sensitivity demonstrated a positive correlation with macular thickness as measured by optical coherence tomography. As such, microperimetry may represent a non-invasive and efficient method to identify signs of subclinical visual dysfunction that correspond with early macular architectural changes characteristic of multiple sclerosis.


Dietary modifications in Parkinson's disease: A neuroprotective intervention?
Parkinson's disease (PD) is the second most common neurodegenerative disease, with the prevalence increasing as the population ages. Many mechanisms have been implicated in the pathogenesis of PD including oxidative stress, mitochondrial dysfunction, protein aggregation, and inflammation. Current treatment strategies focus on symptomatic improvement. However, therapies to modify disease progression are lacking. A whole food, plant-based diet contains many compounds that fight oxidative stress and inflammation. Evidence from animal models show that various phytochemicals may alter the mechanisms contributing to PD pathophysiology. Epidemiological studies show a relationship between reduced risk of PD and diet. We hypothesize that phytochemicals in plant-based foods may contribute to neuroprotection in PD and that adopting a plant-based diet may provide symptomatic improvement and alter disease progression in PD.


American Society for Pain Management Nursing position statement with clinical practice guidelines: authorized agent controlled analgesia.
The American Society for Pain Management Nursing (ASPMN) has updated its 2007 position statement on the use of authorized agent controlled analgesia (AACA) for patients who are unable to independently utilize patient-controlled analgesia (PCA). ASPMN continues to support the use of AACA to provide timely and effective pain management while promoting equitable care for vulnerable patient populations who are unable to utilize PCA. ASPMN does not support the use of "PCA by Proxy" in which unauthorized individuals activate PCA for a patient. The background of the development of the position statement, definitions related to AACA, and application of ethical principles to the use of AACA are presented in the document. This position statement includes an updated review of the evidence related to AACA and a call for further research. Clinical practice recommendations for authorized agents, nurses, prescribers, and organizations are provided with an emphasis on the importance of appropriate authorized agent selection, education, diligent patient assessment and medication management.


From 'conductor' to 'second fiddle': older adult care recipients' perspectives on transitions in family caring at hospital admission.
Family carers provide strong support for many older adults, often enabling older adults to remain at home. Little is known about the care recipients' perspectives of the role and contributions of family carers, particularly when hospital admissions occur as part of end of life care. This paper explores the meanings of family caring for care recipients by drawing on older adults' perspectives about the impact of hospital admission on established family caring relationships. Exploratory semi-structured qualitative interviews. Key findings reported in this paper emerged from within the inductive research design. Interviews were conducted in older adults' place of residence in northwest England between June 2009 and July 2010. Participants were 27 older adults living with heart failure (n=13) or lung cancer (n=14), aged 69-89 years (mean 79 ± 4.3 years) and considered by their health professionals to be in their last year of life. In 12 of the interviews, a family carer was also present and made contributions. For community-dwelling older adults, family carers are conceptualised as 'conductors'; making strong contributions to maintaining the rhythm of good care throughout the illness trajectory. Following older adults' hospital admission, family carers find themselves in the role of 'second fiddle', their ability to work with the individual and to make or influence decisions vastly reduced. Despite this, carers continue to invest considerable effort in maintaining continuity in the carer relationship to maximise the individual's wellbeing by identifying needs, filling gaps in provision and advocating on patients' behalf. Family carers act flexibly to provide continuity, support and take responsibility for older adults' wellbeing across settings. Nurses and family carers working together, and greater appreciation of the contribution and role of family carers by health professionals may contribute to improving the quality and continuity of care for older adults.


Using omics approaches to understand pulmonary diseases.
Omics approaches are high-throughput unbiased technologies that provide snapshots of various aspects of biological systems and include: 1) genomics, the measure of DNA variation; 2) transcriptomics, the measure of RNA expression; 3) epigenomics, the measure of DNA alterations not involving sequence variation that influence RNA expression; 4) proteomics, the measure of protein expression or its chemical modifications; and 5) metabolomics, the measure of metabolite levels. Our understanding of pulmonary diseases has increased as a result of applying these omics approaches to characterize patients, uncover mechanisms underlying drug responsiveness, and identify effects of environmental exposures and interventions. As more tissue- and cell-specific omics data is analyzed and integrated for diverse patients under various conditions, there will be increased identification of key mechanisms that underlie pulmonary biological processes, disease endotypes, and novel therapeutics that are efficacious in select individuals. We provide a synopsis of how omics approaches have advanced our understanding of asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH), and we highlight ongoing work that will facilitate pulmonary disease precision medicine.


Mathematical model of oxygen transport in the cerebral cortex.
To estimate the magnitude of hyperemia necessary to support oxidative metabolism in the cerebral cortex during functional activation, a mathematical model of O2 transport from capillary to tissue was developed. Radial and axial gradients of O2 pressure in tissue surrounding a single capillary were calculated at normal and increased cerebral metabolic rates for O2. Cone-shaped tissue geometry and nonlinear oxyhemoglobin dissociation were assumed. Local O2 consumption was assumed to be supported with local tissue pO2 greater than 1 mmHg. The distribution of tissue pO2 was also calculated during moderate hypoxemia (paO2=42 mmHg), using experimental values of red blood cell velocity measured in individual capillaries of the rat cerebral cortex using intravital video-microscopy. The model predicted that moderate increases (</=50%) in cerebral O2 consumption were supported by proportional increases in capillary blood flow. Large increases in O2 consumption (50-110%) were supported by disproportional increases in flow. During moderate hypoxemia, average tissue pO2 decreased but oxygen utilization was sustained when capillary flow was increased to a level measured in experiments. The results suggest a proportional relationship between cerebrocortical blood flow and oxygen consumption in the normal physiological range of functional activation.


Priming Seeds with Indole and (Z)-3-Hexenyl Acetate Enhances Resistance Against Herbivores and Stimulates Growth.
A striking feature of plant ecology is the ability of plants to detect and respond to environmental cues such as herbivore-induced plant volatiles (HIPVs) by priming or directly activating defenses against future herbivores. However, whether seeds also respond to compounds that are common constituents of HIPV blends and initiate future plant resistance is unknown. Considering that seeds depend on other environmental cues to determine basic survival traits such as germination timing, we predicted that seeds exposed to synthetic constituents of HIPV blends would generate well-defended plants. We investigated the effect of seed exposure to common volatiles on growth, reproduction, and resistance characteristics in the model plants Arabidopsis thaliana and Medicago truncatula using herbivores from two feeding guilds. After seed scarification and vernalization, we treated seeds with one of seven different plant-derived volatile compounds for 24 h. Seeds were then germinated and the resulting plants were assayed for growth, herbivore resistance, and expression of inducible defense genes. Of all the synthetic volatiles tested, indole specifically reduced both beet armyworm growth on A. thaliana and pea aphid fecundity on M. truncatula. The induction of defense genes was not affected by seed exposure to indole in either plant species, indicating that activation of direct resistance rather than inducible resistance is the mechanism by which seed priming operates. Moreover, neither plant species showed any negative effect of seed exposure to any synthetic volatile on vegetative and reproductive growth. Rather, M. truncatula plants derived from seeds exposed to (Z)-3-hexanol and (Z)-3-hexenyl acetate grew larger compared to controls. Our results indicate that seeds are sensitive to specific volatiles in ways that enhance resistance profiles with no apparent costs in terms of growth. Seed priming by HIPVs may represent a novel ecological mechanism of plant-to-plant interactions, with broad potential applications in agriculture and seed conservation.


Perihematomal edema after minimally invasive surgery: a matter of concern to neurosurgeons.
The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.


Endoscopic ultrasound-guided choledochoantrostomy as an alternative extrahepatic bile duct drainage method in pancreatic cancer with duodenal invasion.
Recently, endoscopic ultrasonography-guided bile duct drainage (EUS-BD) has become popular as an alternative method of biliary drainage in cases of failed endoscopic retrograde cholangiopancreatography. In terms of EUS-guided extrahepatic bile duct drainage, recently, EUS-guided choledochoantrostomy has been reported as a variation of EUS-BD. We describe a case of successful choledochoantrostomy using a fully covered self-expandable metallic stent. We conclude that EUS-guided choledochoantrostomy should be one option for biliary decompression. In particular, if patients have duodenal strictures, with or without a duodenal metal stent, it seems to be an ideal alternative to choledochoduodenostomy.


White matter microstructural changes of thalamocortical networks in photosensitivity and idiopathic generalized epilepsy.
Photosensitivity or photoparoxysmal response (PPR) is an electroencephalography trait that is highly associated with idiopathic generalized epilepsies (IGEs) and characterized by changes in cortical excitability in response to photic stimulation. Studying functional and structural changes of PPR might provide important insights into the pathogenesis of IGE. Recent studies revealed a functional network consisting of occipital, parietal, and precentral areas that might be implicated in PPR. Herein, we investigate the microstructural changes associated with PPR. Twelve healthy subjects with PPR, nine patients with IGE and PPR (IGE-PPR group), and 18 healthy controls were studied with diffusion magnetic resonance imaging. Tract-based spatial statistics were used to test for regional differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity between groups. Subjects with PPR exhibited higher FA in the right precentral juxtacortical white matter and higher MD in lateral occipital areas relative to controls. Patients with IGE-patients showed additional increases in regional FA in the thalamus and juxtacortical precentral and parietal areas. Both subjects with PPR and patients with IGE-PPR presented axial and radial diffusivity changes in the occipital regions. Our results show that PPR is associated with subcortical microstructural changes in precentral, parietal, and occipital regions. The coexistence of PPR and IGE is associated with white matter abnormalities in the thalamus and precuneus. PPR and epilepsy share similar functional and structural networks in widespread cortical and subcortical areas.


Type 2 diabetes can undermine driving performance of middle-aged male drivers through its deterioration of perceptual and cognitive functions.
It has been widely agreed that it is risky for patients with diabetes to drive during hypoglycemia. However, driving during non-hypoglycemia may also bring certain safety hazards for some patients with diabetes. Based on previous studies on diabetes-related to early aging effect, as well as gender differences in health belief and driving behavior, we have hypothesized that middle-aged male drivers with type 2 diabetes, compared with the control healthy ones, may experience a decline in driving performance without awareness. And the decline is caused by impaired perceptual and cognitive driving-related functions. To verify these hypotheses, we recruited 56 non-professional male drivers aged between 40 and 60 (27 patients with type 2 diabetes and 29 healthy controls) to perform a simulated car-following task and finish behavioral tests of proprioception, visual search, and working memory abilities during non-hypoglycemia. They also reported their hypoglycemia experience and perceived driving skills. We found that the patients had equal confidence in their driving skills but worse driving performance as shown in larger centerline deviation (t = 2.83, p = .006), longer brake reaction time (t = 3.77, p = .001) and shorter minimum time-to-collision (t = -3.27, p = .002). Such between-group differences in driving performance could be fully mediated by proprioception, visual search ability, and working memory capacity but not by hypoglycemia experience. Regarding the effect sizes of the mediation, the visual search ability played the most important role, and then followed the working memory and the proprioception. This initial study provides original and first-hand evidence demonstrating that the middle-aged male drivers with type 2 diabetes have deteriorated driving performance, but they are unaware of it. We will also discuss the possible measures to identify people of the highest risk and improve their safety awareness by using the findings of the current study.


Evaluation of breastfeeding and infant feeding attitudes among syrian refugees in Turkey: observations of Syrian healthcare workers.
The influx of Syrian refugees into Turkey has highlighted the importance of supporting breastfeeding practices among this vulnerable population. We aimed to evaluate the breastfeeding and infant feeding attitudes of Syrian mothers based on the observations of Syrian healthcare workers (HCWs). An online form including 31 questions was prepared in Turkish, Arabic, and English languages and distributed to HCWs, working in refugee health centers via e-mail, WhatsApp, or text message with the help of Ministry of Health in Turkey between January 2020 and March 2020. The questions were about HCWs' characteristics (occupation, region of employment, duration of employment, participation in breastfeeding counseling course) and about HCWs' observations of Syrian mothers' breastfeeding and infant feeding practices. A total of 876 HCWs were included in the study; about 37.3% were physicians. Only 40.0% of HCWs reported that babies were predominantly fed with breast milk in the first three days after birth, 45.2% of HCWs indicated that mothers typically used sugary water as a prelacteal food, and 30.5% believed that breastfeeding was discontinued before 12 months. The main barriers to breastfeeding identified by HCWs included the lack of education, mental and physical health issues in the mother, food insecurity, low income, inadequate housing, lack of family planning, sociocultural environment, and limited access to quality health services. For complementary feeding, 28.0% of HCWs stated early introduction and 7.4% remarked delayed. HCWs believed grains, fruits and vegetables, and dairy products as top three foods for starting complementary food (59.5%, 47.8%, and 30.3% respectively). Healthcare challenges of Syrian pregnant and lactating mothers were reported to be associated primarily with "food, finance, and housing difficulties", low maternal education, and cultural and environmental issues. HCWs recommended various solutions, such as supporting breastfeeding, offering nutrition and health support, promoting family planning, improving healthcare systems through legislation, and addressing cultural barriers. To address breastfeeding issues among Syrian mothers, it is crucial to provide breastfeeding training to both HCWs and mothers. Expanding interventions that support breastfeeding-friendly practices, including community support and food aid for breastfeeding mothers, should also be considered to address the social determinants of breastfeeding.


Anti-Vpr activities of homodrimane sesquiterpenoids and labdane diterpenoids from Globba sherwoodiana rhizomes.
Two new homodrimane sesquiterpenoids, globbatones A and B (1 and 2), and one 16-norlabdane diterpenoid, globbatone C (3), together with two new naturally occurring, (E)-labda-8(17),12-diene-15,16-olide (4) and γ-bicyclohomofarnesen-12-ol (5), and one known homodrimane sesquiterpenoid (6), nine known labdane diterpenoids (7-15), and one isospongian diterpenoid (16), were isolated from the chloroform extract of Globba sherwoodiana rhizomes. The structures of the new compounds 1-3 were elucidated based on 1D and 2D NMR and HRESIMS spectroscopic analyses. The chloroform extract of G. sherwoodiana rhizomes and 10 μM concentrations of some of its constituents 1, 3, 4, 8, 9, 12, and 14 showed the moderate anti-Vpr activities, without cytotoxic effects on the TREx-HeLa-Vpr cell line.


Minor-myosin, a novel myosin isoform synthesized preferentially in Drosophila testis is encoded by the muscle myosin heavy chain gene.
Searching for structural proteins involved in spermatogenesis of Drosophila, we found a novel myosin isoform in the testis of Drosophila hydei and D. melanogaster. The transcript encoding this isoform, which we called 'minor-myosin', initiates within the intron between exons 12 and 13 of the muscle myosin heavy chain (mMHC) gene. Minor-myosin contains a common myosin tail but no ordinary myosin head domain. Instead, it has a short N-terminal domain which displays similarity with the N-termini of certain myosin light chain proteins. Western blots with male germ line mutants showed that the novel mMHC isoform is synthesized in the male germ cells, mainly postmeiotically. However, minor-myosin is not testis-specific, as it is expressed at a low level in the fly carcasses. The possible functions of the myosin isoform in the male germ line are discussed.


Evidence for the phosphorylation of a proenkephalin-derived peptide, peptide B.
The potential phosphorylation of a proenkephalin-derived peptide, Peptide B, was investigated in primary cultures of bovine adrenal chromaffin cells and fresh adrenal medullary tissue. Cultures were labeled with [32P]phosphate for 24 h and extracts subjected to immunoprecipitation using affinity-purified anti-serum directed against the carboxyl terminus of Peptide B. A 4.6-kDa-labeled peptide was observed in autoradiograms of immunoprecipitates separated by sodium dodecyl sulfate-polyacrylamide electrophoresis; this peptide was not observed when excess antigen was present during the immunoprecipitation. Radioimmunoassay of extracts prepared from adrenal medullary tissue and separated by isoelectric focusing revealed the presence of four isoelectric forms of Peptide B-immunoreactive peptides; these peptides also exhibited Met-enkephalin-Arg-Phe immunoreactivity. The isoelectric points of these peptides (4.5, 4.3, 4.1, and 3.9) were consistent with the predicted pI values for phosphorylated derivatives of Peptide B. Treatment of samples with alkaline phosphatase prior to isoelectric focusing resulted in the conversion of the more acidic forms to the least acidic form. The presence of phosphate in the more acidic peaks was additionally verified by isoelectric focusing of 32P-labeled immunoprecipitates; the pI values of the radioactive peptides corresponded precisely to the peaks of immunoreactivity. In adrenal medullary tissue, the relative contributions of the various phosphorylated species to the total Peptide B immunoreactivity were as follows: unphosphorylated form, 13%; singly phosphorylated, 31%; doubly phosphorylated, 37%; and triply phosphorylated, 17%. Thus more than 85% of the Peptide B molecules present in the bovine adrenal medulla are phosphorylated.


Permeability of Intestinal and Blood-Tissue Barriers in Rats for Evans Blue Dye under Conditions of Acute Intoxication with Cyclophosphamide.
Myeloablative therapy was modeled by administration of cyclophosphamide to rats in a dose of 2.1 LD50 for 14 days. Under these conditions, increased accumulation of Evans blue dye given by gavage was observed in the blood, brain, lung, liver, kidney, and ileum (by 34, 1.6, 149, 46, 30, and 6.2 times, respectively). After intravenous injection of the dye, its accumulation was increased only in the lung and ileum. Thus, simulation of myeloablation cytostatic therapy by cyclophosphamide injection to rats is associated with impairment of the intestinal and lung-blood barriers. These alterations predispose to penetration of biologically active substances from the small intestine, gastrointestinal chyme, and lungs to the blood, thus contributing to the development of the early toxic effects of cyclophosphamide.


Optimizing Expectations About Endocrine Treatment for Breast Cancer: Results of the Randomized Controlled PSY-BREAST Trial.
Medication side effects are strongly determined by non-pharmacological, nocebo mechanisms, particularly patients' expectations. Optimizing expectations could minimize side effect burden. This study evaluated whether brief psychological expectation management training (EXPECT) optimizes medication-related expectations in women starting adjuvant endocrine therapy (AET) for breast cancer. In a multisite randomized controlled design, 197 women were randomized to EXPECT, supportive therapy (SUPPORT), or treatment as usual (TAU). The three-session cognitive-behavioral EXPECT employs psychoeducation, guided imagery, and side effect management training. Outcomes were necessity-concern beliefs about AET, expected side effects, expected coping ability, treatment control expectations, and adherence intention. Both interventions were well accepted and feasible. Patients' necessity-concern beliefs were optimized in EXPECT compared to both TAU and SUPPORT, d = .41, p < .001; d = .40, p < .001. Expected coping ability and treatment control expectations were optimized compared to TAU, d = .35, p = .02; d = .42, p < 001, but not to SUPPORT. Adherence intention was optimized compared to SUPPORT, d = .29, p = .02, but not to TAU. Expected side effects did not change significantly. Expectation management effectively and partly specifically (compared to SUPPORT) modified medication-related expectations in women starting AET. Given the influence of expectations on long-term treatment outcome, psychological interventions like EXPECT might provide potential pathways to reduce side effect burden and improve quality of life during medication intake.


Oxidative Stress Induced by 30 Days of Mercury Exposure Accelerates Hypertension Development in Prehypertensive Young SHRs.
Mercury is considered a risk factor for the development of hypertension and other cardiovascular diseases. We investigated whether the effects of mercury exposure on haemodynamic parameters of young Wistar rats and prehypertensive SHRs might alter the time course of hypertension development. Young (4 weeks) male Wistar rats and SHRs were randomly assigned to four groups: untreated Wistar rats (Wistar Ct), Wistar rats exposed to mercury chloride for 30 days (Wistar Hg), untreated SHRs (SHR Ct) and SHRs exposed to mercury chloride (SHR Hg) for 30 days. Non-invasive and invasive arterial pressures were measured to investigate pressure reactivity; nitrite/nitrate levels, ACE activity, and lipid peroxidation were measured in plasma. The systolic blood pressure (SBP) of the Wistar rat groups did not change but increased in the SHRs from the second week to the last week. Hg exposure accelerated the increase in the SBP of SHRs. L-NAME administration increased SBP and diastolic blood pressure (DBP) in all groups, but this increase was smaller in SHRs exposed to Hg. A decrease in plasma nitrite and nitrate levels in the SHR Hg group suggested that mercury reduced NO bioavailability. Tempol-reduced blood pressure suggesting that the superoxide anion played a role in the marked increase in this parameter. These findings provide evidence that Hg exposure might activate mechanisms to accelerate hypertension development, including a reduction in NO bioavailability. Therefore, predisposed individuals under mercury exposure are at greater risk from an enhanced development of hypertension.


Diagnostic accuracy of 2- and 3-dimensional computed tomography and solid modeling of coronoid fractures.
This study measured the diagnostic performance characteristics and reliability of 2-dimensional (2DCT) and 3-dimensional (3DCT) computed tomography images and modeling of coronoid fractures. The treating surgeon and first assistant evaluated 28 fractures for fracture type, specific characteristics, and proposed treatment. The observers evaluated the fractures 4 times: first based upon 2DCT computed images and radiographs; second with the addition of 3DCT images; third with the addition of 3D models; and finally based upon intra-operative exposure, which was considered the reference standard. The diagnostic performance characteristics did not improve with more sophisticate imaging and models. The addition of 3DCT reconstructions improved the inter-observer reliability for fracture classification, characteristics, and proposed treatment. More sophisticated images and modeling improved reliability but not accuracy when characterizing coronoid fractures.


Enzastaurin renders MCF-7 breast cancer cells sensitive to radiation through reversal of radiation-induced activation of protein kinase C.
Enzastaurin (LY317615.HCI), a protein kinase C (PKC)-beta inhibitor, has a radiosensitising effect on 4T1 murine breast cancer and human glioma cells; however, the exact mechanism of this action has not been evaluated. The present study investigated the effects of enzastaurin and gamma irradiation on PKC activity in MCF-7 human breast cancer cells in vitro and in vivo. Enzastaurin (5 microM) in combination with irradiation (2-8 Gy) produced a synergistic decline in MCF-7 clonogenic cell survival. Analysis of MCF-7 cells stained with Annexin V and 7-aminoactinomycin D showed a dose-dependent increase in apoptosis in response to enzastaurin (3, 5 and 7 microM) and irradiation (10 Gy) compared to irradiation alone. This pro-apoptotic effect was confirmed by increases in caspase-3 and -9 activity. In a MCF-7 xenograft model, irradiation with 25 Gy increased PKC-alpha activity by 2.5-fold compared to untreated controls, whereas PKC-epsilon and -betaII activity was increased by 1.8-fold. Radiation-induced activation of all three anti-apoptotic isoforms of PKC was reversed by pre-treatment with enzastaurin (75 mg/kg, twice daily for 3 days). We conclude that enzastaurin has a radiosensitising effect on MCF-7 human xenograft tumours through the reversal of anti-apoptotic activation of PKC isoforms.


Reliability and validity of the parent form of the social competence scale in Chinese preschoolers.
The Parent Form of the Social Competence Scale (SCS-PF) was translated into Chinese and validated in a sample of Chinese preschool children (N = 443). Results confirmed a single dimension and high internal consistency in the SCS-PF. Mothers' ratings on the SCS-PF correlated moderately with teachers' ratings on the Teacher Form of the Social Competence Scale and weakly with teachers' ratings on the Student-Teacher Relationship Scale.


Automatic shape quantification of freely suspended red blood cells by isodensity contour tracing and tangent counting.
In several blood diseases, the resting red blood cells show deviations from the normal discoidal shape. This is of great diagnostic importance. Similar shape changes occur if cells are subjected to various physical and chemical treatments. An automatic on-line method is introduced which can quantify the mean shape of such cells, freely suspended and unaltered by the method. With the cells inside a special flow chamber, pictures are taken in the form of optical sections using a CCD camera. The image processing includes digitization, cumulation of regions of interest (ROI), contour determination by two-dimensional histogram and isodensity contour tracing, chain coding and tangent counting. The method determines the mean of the absolute number of tangents per section Ts, a quantitative unique shape factor, which allows quantification of pathological red blood cell shapes and follow-up shape changes in experiments, and makes different experiments quantitatively comparable.


Mechanism of garlic (Allium sativum) induced reduction of hypertension in 2K-1C rats: a possible mediation of Na/H exchanger isoform-1.
Garlic causes reduction in blood pressure (BP), however the role of Na/H exchanger (NHE) which mediates hypertension and related tissue-damage is poorly understood. In this study the effect of an established dose of raw garlic extract was investigated on the expression of NHE-1 and -3 and sodium pump activity in a 2K-1C model of hypertension in rats. 2K-1C animals showed high BP, increased serum concentration of PGE2 and TxB2, hypertrophy of the unclipped kidneys, but not in the clipped kidneys In addition, NHE-1 and NHE-3 isoforms were increased in both the 2K-1C kidneys, whereas alpha-actin was increased in the clipped but not in unclipped kidneys. Sodium pump activity was decreased in the clipped kidneys, but remained unchanged in the unclipped kidneys. Garlic treatment reduced the induction of NHE-1 only in the unclipped 2K-1C kidneys, whereas garlic treatment increased the sodium pump activity in both the 2K-1C kidneys. These findings demonstrate that the antihypertensive action of garlic is associated with a reversal of NHE-1 induction in the unclipped kidneys. Induction of NHE isoforms together with a reduced sodium pump activity might cause necrosis in the 2K-1C clipped kidneys due to cellular retention of Na+. On the other hand, activation of sodium pump by garlic extract in the kidneys should reduce intracellular Na+ concentration and normalize BP. These findings signify the use of garlic in the treatment of hypertension.


Comparison of ab externo trabeculotomy in primary open-angle glaucoma and uveitic glaucoma: long-term outcomes.
The aim of this study was to compare the long-term outcomes of ab externo trabeculotomy in primary open-angle glaucoma (POAG) and uveitic glaucoma (UG). This was a retrospective single-center case series study. Twenty eyes of 17 patients with POAG and 22 eyes of 18 patients with UG were included in this study. The medical records of all consecutive patients with POAG and UG who underwent ab externo trabeculotomy since 2004 were reviewed. The main outcome measure was change in median intraocular pressure (IOP). Success was defined as IOP ≤21 mmHg (success 1) and IOP ≤21 mmHg and at least 25% reduction from baseline (success 2). In the POAG group, the median IOP decreased significantly from 22 mmHg (95% CI 21-25 mmHg; n=20) at baseline to 14 mmHg (95% CI 12-16; n=13) after 4 years, P<0.001. In the UG group, the median IOP decreased significantly from 27 mmHg (95% CI 24.5-30.5 mmHg; n=22) at baseline to 12 mmHg (95% CI 9-15 mmHg; n=15) after 4 years, P<0.001. Seven eyes in the UG group failed within the first year after surgery compared to none in the POAG group. Of these, four eyes had Fuchs' uveitis syndrome and two had granulomatous uveitis. No sight-threatening complications occurred in both POAG and UG groups. Ab externo trabeculotomy effectively reduced IOP in both UG and POAG groups. However, the success rates in the UG group were significantly lower due to the high failure rate in patients with Fuchs' uveitis syndrome and granulomatous uveitis. The procedure demonstrated a high safety profile in both UG and POAG patients.


Handling drug-related problems in rehabilitation patients: a randomized study.
Drug-related problems (DRPs) have been found to be associated with increased morbidity, mortality, and health costs. To investigate whether the inclusion of pharmacists in a rehabilitation team influences the handling of DRPs in the ward and whether an intervention in hospital affects drug use after discharge. The rehabilitation ward of a general hospital in Oslo, Norway. Patients were randomized into an intervention group (IG) or a usual care group (CG). The IG patients were followed prospectively by a pharmacist, who reviewed the patients' drug therapies using information from their medical records and patient interviews. The pharmacist identified DRPs and suggested solutions during multidisciplinary team meetings. The IG patients received targeted drug counselling from the pharmacist before discharge. The drug therapy in the CG, for the period from study randomization to discharge, was assessed retrospectively by the pharmacist, who identified DRPs and recorded how they were acted upon. Three months after discharge, pharmacists who were blinded to the patient randomization, visited the patients at home and interviewed them about their medication. Types and frequencies of DRPs in the IG and CG were compared at hospital admission, at discharge, and 3 months after discharge. Of the 77 patients included, 40 belonged to the IG and 37 to the CG. Patient characteristics (IG vs CG) were as follows: age 73.5 versus 76.8 years; female 58 versus 68%; mean number of drugs at admission 8.3 versus 7.8; and mean number of drugs at discharge 8.5 versus 7.7. At admission, 4.4 DRPs per patient were recorded in the IG and 4.2 in the CG. Significantly more DRPs were acted upon and resolved in the IG; at discharge, the IG had 1.2 DRPs per patient and the CG had 4.0 (P < 0.01). At the home visit, a significant difference between the groups was found: 1.63 versus 2.62 DRPs (P = 0.02) for the IG and the CG, respectively. Involvement of a pharmacist in drug-therapy management, including participation in multidisciplinary team discussions, markedly improved the identification and resolution of DRPs during a hospital stay. The benefit persisted after discharge.


Collection of the International Hip Outcome Tool-12 Using a Smartphone Application Format Is Faster and Preferred When Compared With the Paper Version: A Pilot Study of rHip.
To evaluate the agreeability between the mobile application-based International Hip Outcome Tool-12 (iHOT-12) survey with the paper version, as well as compare the time it takes patients each of the versions, and patient preferences between the two. Patients seen with symptomatic femoroacetabular impingement syndrome were prospectively enrolled in February 2019 and completed both the paper and application-based iHOT-12, in randomized order. Outcomes scores and time to completion were recorded for each version, and patients were also asked which they preferred. Intraclass correlation coefficient was calculated to assess for absolute agreement between the 2 versions. Bland-Altman plots were constructed to evaluate the agreeability between paper and application-based iHOT-12 scores. Bland-Altman plots were evaluated to identify systematic bias and data stratification was performed to identify sequence bias between the application and paper-based collection modalities. Twenty-nine patients (aged15-56 years) completed both the paper and application-based versions of the iHOT-12. Between the application-based and paper versions, the intraclass correlation coefficient was 0.98, and Bland-Altman analysis showed agreement without bias between versions. There was no sequence bias. Accounting for completion order, the application-based iHOT-12 was faster for patients when compared to the paper version (61.4 ± 20.3 vs 71.9 ± 23.6 seconds, P = .02). Twenty-two patients reported a version preference where 19 of 22 (86%) chose application-based (P < .001). The application-based iHOT-12 demonstrated absolute agreement with the paper iHOT-12, and is faster for patients to complete. Patients preferred using the application-based iHOT-12 over the paper-based version. Application-based PROs allow for collection of patient data at more frequent time points, which may be helpful in tracking the recovery progress of patients and predicting outcomes. As electronic-based outcome surveys become more common, it is important to know how the results may differ from traditional paper-based surveys.


International study on the comparability of Apo A-1 and Apo B methods.
Apo A-1 and Apo B levels have become increasingly important as a mean of assessing risk and susceptibility to cardiovascular diseases. These proteins are measured routinely in numerous clinical and research laboratories due primarily to the ability to mechanise the immunological assay method and to the ready availability of commercially produced antisera and standards which are often sold in kit form. However, if these variables are to be used to assess the clinical risk of disease reliably, the test methods should have a low degree of imprecision and inaccuracy, to reduce false positive and negative results. The 'normal' and 'pathological' ranges for both proteins also need to be clearly defined. In order to be able to define clinical ranges and establish quality control limits on both a national and international level the inaccuracy and imprecision of the different methods used to assay the parameters need to be established. Since the technical expertise and the equipment and reagents used vary between laboratories, and because there is no internationally recognized calibration material, a survey conducted to establish imprecision and inaccuracy must include many laboratories to take these variations into account. At the WHO Collaborating Lipid Reference Centre, The Institute for Clinical and Experimental Medicine in Prague, Czechoslovakia, we have been involved in the external quality control programme for cholesterol, triglyceride, HDL-cholesterol and thiocyanate methods for more than 15 yr. Although the Centre was originally created as a European Reference Centre, laboratories participating in our quality control scheme now come from Asia, the USA and New Zealand as well as Europe due to their involvement in the large scale population studies like 'MONICA', 'ERICA' and 'CINDI'. In addition we also cooperate with some laboratories expected to join WHO projects and with others running either national or their own research programmes. Due to the increasing need to learn more about the methods used for Apo A-1 and Apo B assays in both research and preventive schemes for cardiovascular diseases, we decided, following the combined IUIS and NHLBI-CDC Apolipoprotein standardization surveys, to arrange for an international survey to determine the precision and relative accuracy of EIA, ELISA, INA, TURB and RID methods. Our survey originally intended to include only European laboratories but the number of participants increased (Table I) and we believe it supplies complementary information to the IUIS-NHLBI-CDC surveys because both research and routine clinical laboratories were included in our survey.


Delayed presentation of mons pubis abscess formation following MUS-case report and surgical video.
Mid-urethral sling (MUS) surgery for stress urinary incontinence (SUI) has relatively low complication rates. However, although rare, complications such as bladder wall, prepubic and thigh abscess occur. We present an unusual case of MUS vaginal mesh exposure followed by mons pubis abscess formation occurring 18 years postoperatively because of inadvertent prepubic insertion of the right arm. Our objectives were to raise awareness about such a rare complication and to describe the approach for sling removal. A 75-year-old woman presented with gradual swelling on the mons pubis followed by pain with a past history of MUS insertion. Examination revealed a palpable, tender, non-fluctuant mass, extending about 10-15 cm from mons pubis to the right labia. There was a 2 × 2-cm vaginal mesh exposure. Following imaging, an examination under anaesthesia was performed with vaginal exploration and complete removal of the right arm of the MUS and closure of the vagina. Six months postoperatively, all surgical sites had healed well, and there was no recurrent SUI or persistent mesh exposure. Unusual long-term complications of MUS should be considered and recognized. Thorough evaluation is crucial for informed decision-making related to treatment strategies. The vaginal approach to mesh removal is safe and should be practised by experienced surgeons. Patients should be informed regarding the possibility of incontinence after sling removal.


Comparison of Superpulse Thulium Fiber Laser vs Holmium Laser for Ablation of Renal Calculi in an In Vivo Porcine Model.
Introduction and Objectives: We sought to compare the effectiveness and efficiency of the superpulse thulium fiber laser (sTFL to the holmium: yttrium-aluminum-garnet [Ho:YAG] laser for ureteroscopic "dusting" of implanted renal stones in an in vivo porcine model. Methods: Twenty-four porcine kidneys (12 juvenile female Yorkshire pigs) were randomized to Ho:YAG or sTFL treatment groups. Canine calcium oxalate stones were scanned with computed tomography to calculate stone volume and stone density; the stones were randomized and implanted into each renal pelvis via an open pyelotomy. In all trials, a 14F, 35 cm ureteral access sheath was placed. With a 9.9F dual lumen flexible ureteroscope, laser lithotripsy was performed using dusting settings: Ho:YAG 200 μm laser fiber at 16 W (0.4 J, 40 Hz) or sTFL 200 μm laser fiber at 16 W (0.2 J, 80 Hz). Lithotripsy continued until no fragments over 1 mm were observed. No stone basketing was performed. Throughout the procedures, intrarenal and renal pelvis temperatures were measured using two percutaneously positioned K-type thermocouples, one in the upper pole calyx and one in the renal pelvis. After the lithotripsy, the ureteropelvic junction was occluded, the kidneys were bivalved, and all residual fragments were collected, dried, weighed, and then measured with an optical laser particle sizer. Results: Implanted stones were similar in volume and density in both groups. Intraoperative collecting system temperatures were similar for both groups (all <44°C). Compared to Ho:YAG, sTFL ablated stones faster (9 vs 27 minutes, p < 0.001) with less energy expenditure (8 vs 26 kJ, p < 0.001), and a greater stone clearance rate (73% vs 45%, p = 0.001). After sTFL lithotripsy, 77% of the remaining fragments were ≤1 mm vs 17% of fragments ≤1 mm after Ho:YAG treatment (p < 0.001). Conclusions: In an in vivo porcine kidney, using dusting settings, sTFL lithotripsy resulted in shorter ablation times, higher stone clearance rates, and markedly smaller stone fragments than Ho:YAG lithotripsy.


Treatment of endometriosis by vaginal administration of gestrinone.
The effectiveness and acceptability of gestrinone administered by vaginal route was evaluated in a group of 110 patients with endometriosis. Patients were divided into four groups. The first three groups were treated by vaginal route. Group I (n = 17) received two 2.5-mg tablets weekly; group II (n = 31) received three 2.5-mg tablets weekly; group III (n = 35) received two 5.0-mg tablets weekly. Group IV consisted of 27 patients who received 2.5 mg of gestrinone orally twice weekly. Ninety-eight women completed the 6- to 8-month treatment period. Amenorrhea developed in all treatment groups, including group I (34%). The disappearance of both dyspareunia and dysmenorrhea occurred in most patients in all treatment groups soon after the second month of therapy. Patients treated by vaginal route had significantly less seborrhea and acne than those treated by oral route. Weight gain was also significantly less in vaginally treated women than in those treated orally. Pregnancy rate following discontinuation was not significantly different for the various groups.


Prioritization of organic contaminants in a reclaimed water irrigation system using wide-scope LC-HRMS screening.
A prioritization procedure was developed and implemented at the local level to identify the most relevant organic contaminants of emerging concern (CECs) in an agricultural area irrigated with reclaimed water. A wide-scope screening methodology based on UPLC-HRMS analysis was applied to holistically characterize the CEC footprint in water and its spatial and temporal variations. One hundred and fifty-eight CECs, including pharmaceuticals, industrial chemicals, and pesticides, among others, were identified with a confidence level of 2 in the water samples investigated. After water treatment in the reclamation plant and transport within the irrigation channel network, more than a hundred compounds were still detected at the location where water is abstracted for crop irrigation. Compound ecotoxicity and occurrence (semi-quantified concentrations or peak intensity) were the parameters used to prioritize CECs in the water used for irrigation. Results pointed at venlafaxine, O-desmethyl-venlafaxine, galaxolidone, theophylline/paraxanthine, oxybenzone, and N-phenyl-1-naphtylamine, among others, as CECs of concern in the investigated area. This study provides a simple and cost-effective approach to detecting site-specific priority pollutants that could otherwise be overlooked by national or European regulations. The prioritization tool provided contributes to rationally designing monitoring and attenuation programs and efficiently managing water resources, by ensuring the safety of reclaimed water applications.


Pervasive decreases in living vegetation carbon turnover time across forest climate zones.
Forests play a major role in the global carbon cycle. Previous studies on the capacity of forests to sequester atmospheric CO2 have mostly focused on carbon uptake, but the roles of carbon turnover time and its spatiotemporal changes remain poorly understood. Here, we used long-term inventory data (1955 to 2018) from 695 mature forest plots to quantify temporal trends in living vegetation carbon turnover time across tropical, temperate, and cold climate zones, and compared plot data to 8 Earth system models (ESMs). Long-term plots consistently showed decreases in living vegetation carbon turnover time, likely driven by increased tree mortality across all major climate zones. Changes in living vegetation carbon turnover time were negatively correlated with CO2 enrichment in both forest plot data and ESM simulations. However, plot-based correlations between living vegetation carbon turnover time and climate drivers such as precipitation and temperature diverged from those of ESM simulations. Our analyses suggest that forest carbon sinks are likely to be constrained by a decrease in living vegetation carbon turnover time, and accurate projections of forest carbon sink dynamics will require an improved representation of tree mortality processes and their sensitivity to climate in ESMs.


The modifying effect of multiple generation selection and dietary cadmium on methyl mercury toxicity in Japanese quail.
Japanese quails were exposed to dietary methyl mercury chloride in graded amounts from 2--8 ppm through a series of multiple-generation experiments with the experimental periods lasting from 6--12 weeks, starting with the experimental diets when the birds were 6 weeks old. Cadmium chloride was added to diets with and without mercury and fed to groups in three of the five experiments. Hatchability was depressed at 8 ppm mercury. The mortality of chicks from 8 ppm exposed parents was 100% in the first two generations, while chick mortality at the 4 ppm level in the same experiments was 54--63%. After six generations mortality in chicks hatched in 8 ppm group was reduced to about 50%. Cadmium supplementation at a level of 5 ppm counteracted the mercury-induced toxicity but failed to be effective in preventing the effects of mercury toxicity when added at 15 ppm level. Significant toxic effects of cadmium alone did not occur until the level was raised to 60 ppm. The morphology of mercury-induced encephalopathy was similar to the brain lesions reported in other bird species, with the injuries predominantly being localized to the cerebellar cortex and medulla.


Temozolomide induces senescence but not apoptosis in human melanoma cells.
Temozolomide (TMZ), a DNA alkylating agent used in the treatment of melanoma, is believed to mediate its effect by addition of a methyl group to the O(6) position of guanine in DNA. Resistance to the agent may be in part due to the activity of O(6)-methylguanine-DNA methyl transferase (MGMT). In the present study, we show that sensitivity of melanoma cells to TMZ was dependent on their p53 status and levels of MGMT. Analysis of the mechanisms underlying reduced viability showed no evidence for induction of apoptosis even though marked levels of apoptosis was seen in TK6 lymphoma cells. Sensitivity of melanoma cells was associated with p53-dependent G2/M cell cycle arrest and induction of senescence. To verify the role of p53, the assays were repeated in presence of pifithrin-alpha, an inhibitor of p53. This resulted in increased viability of melanoma cells with wild-type p53 and reversed G2/M cell cycle arrest. Paradoxically, apoptosis was increased in melanoma but decreased as expected in TK6 lymphoma cells. These results are consistent with the view that TMZ is relatively ineffective against melanoma due to defective apoptotic signalling resulting from activation of p53. The nature of the defects in apoptotic signalling remains to be explored.


WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring.
Neural type-specific expression of clustered Protocadherin (Pcdh) proteins is essential for the establishment of connectivity patterns during brain development. In mammals, deterministic expression of the same Pcdh isoform promotes minimal overlap of tiled projections of serotonergic neuron axons throughout the brain, while stochastic expression of Pcdh genes allows for convergence of tightly packed, overlapping olfactory sensory neuron axons into targeted structures. How can the same gene locus generate opposite transcriptional programs that orchestrate distinct spatial arrangements of axonal patterns? Here, we reveal that cell type-specific Pcdh expression and axonal behavior depend on the activity of cohesin and its unloader, WAPL (wings apart-like protein homolog). While cohesin erases genomic-distance biases in Pcdh choice, WAPL functions as a rheostat of cohesin processivity that determines Pcdh isoform diversity.


Falling spells in normal pressure hydrocephalus: a favourable prognostic sign?
Two patients with idiopathic normal pressure hydrocephalus are described suffering from so called 'falling spells'. Both patients showed marked improvement after ventriculoatrial shunting, and the falling spells ceased. The literature concerning falling spells is reviewed. The possible pathogenesis and the relationship to shunting are discussed.


Development of a topical protein therapeutic for human papillomavirus and associated cancers.
Human papillomaviruses (HPVs) are the causative agents of several disease states, including genital warts and cervical cancer. There are around 500 million cases of genital warts per annum worldwide and around 450,000 cases of cervical cancer. Although HPV vaccines should eventually reduce the incidence of these diseases, new and effective treatments are still urgently required. The E2 (early) proteins from some HPV types induce growth arrest and apoptosis, and these proteins could be used as therapeutics for HPV-induced disease. A major obstacle to this approach concerns the delivery of the protein to HPV-transformed cells and/or HPV-infected cells in vivo. One possible solution is to use recombinant viruses to deliver E2. Another possible solution is to use purified E2 proteins or E2 fusion proteins. The herpes simplex virus VP22 protein is one of a small number of proteins that have been shown to cross the cell membrane with high efficiency. VP22-E2 fusion proteins produced in bacterial cells are able to enter mammalian cells and induce apoptosis. This suggests that VP22-E2 fusion proteins could be topically applied as a treatment for HPV-induced diseases, most probably post-surgery. In this review, we discuss this and other approaches to the topical delivery of selective therapeutic agents against HPV-associated conditions.


Effects of several preoperative medications on fat cell lipolysis, and activity of adipose tissue cyclic AMP phosphodiesterase.
Effects were examined of atropine, diazepam, pethidene, promethazine, scopolamine, omnopon and papaverine on basal and noradrenaline-stimulated lipolysis in rat isolated fat cells and on rat adipose tissue cyclic AMP phosphodiesterase activity. Papaverine at high concentration (1 mM) inhibited both basal and hormone-stimulated lipolysis, whereas diazepam enhanced basal lipolysis. At a 'clinical dose', omnopon increased both basal and noradrenaline-stimulated lipolysis. Adipose tissue cAMP phosphodiesterase activity was strongly inhibited by 1 mM diazepam, papaverine, promethazine and omnopon (280 microgram ml-1). Lack of enhancement of lipolysis by the established cAMP phosphodiesterase antagonist papaverine, is compatible with simultaneous inhibition also of adipose adenyl cyclase. Diazepam-stimulated lipolysis is compatible with its phosphodiesterase inhibitory activity. It is proposed that papaverine-containing omnopon may offer some survival advantages during surgical stress by facilitating a caloric supply.


Burn surgery.
The challenges posed by thermal injury often are daunting emotionally and physically for the survivor, family, and staff. Morbidity and mortality have improved with advances in emergent and multidisciplinary care; the establishment of dedicated burn centers; and increased education, prevention, and experience. The role of surgery in the treatment of these complex injury patterns continues to evolve, incorporating refined concepts of tissue preservation, wound bed preparation, and early attention to functional and esthetic parameters. Societal reintegration, psychosocial support, and new pain control strategies have dramatically improved the quality of life for our patients during and after the acute course of care. With improved survivability and a changing demographic, fundamental reconstructive surgical principles have found increased applicability and are instituted at the time of admission whenever possible.


Endogenous antisense RNA curbs CD39 expression in Crohn's disease.
CD39 is an ectonucleotidase that initiates conversion of extracellular nucleotides into immunosuppressive adenosine. CD39 is expressed by regulatory T (Treg)-cells, where it mediates immunosuppression, and by a subset of T-helper (Th) 17-cells, where it limits pathogenicity. CD39 is regulated via single-nucleotide-polymorphisms and upon activation of aryl-hydrocarbon-receptor and oxygen-mediated pathways. Here we report a mechanism of CD39 regulation that relies on the presence of an endogenous antisense RNA, transcribed from the 3'-end of the human CD39/ENTPD1 gene. CD39-specific antisense is increased in Treg and Th17-cells of Crohn's disease patients over controls. It largely localizes in the cell nucleus and regulates CD39 by interacting with nucleolin and heterogeneous-nuclear-ribonucleoprotein-A1. Antisense silencing results in CD39 upregulation in vitro and amelioration of disease activity in a trinitro-benzene-sulfonic-acid model of colitis in humanized NOD/scid/gamma mice. Inhibition/blockade of antisense might represent a therapeutic strategy to restore CD39 along with immunohomeostasis in Crohn's disease.


Wavelet-based processing of neuronal spike trains prior to discriminant analysis.
Investigations of neural coding in many brain systems have focused on the role of spike rate and timing as two means of encoding information within a spike train. Recently, statistical pattern recognition methods, such as linear discriminant analysis (LDA), have emerged as a standard approach for examining neural codes. These methods work well when data sets are over-determined (i.e., there are more observations than predictor variables). But this is not always the case in many experimental data sets. One way to reduce the number of predictor variables is to preprocess data prior to classification. Here, a wavelet-based method is described for preprocessing spike trains. The method is based on the discriminant pursuit (DP) algorithm of Buckheit and Donoho [Proc. SPIE 2569 (1995) 540-51]. DP extracts a reduced set of features that are well localized in the time and frequency domains and that can be subsequently analyzed with statistical classifiers. DP is illustrated using neuronal spike trains recorded in the motor cortex of an awake, behaving rat [Laubach et al. Nature 405 (2000) 567-71]. In addition, simulated spike trains that differed only in the timing of spikes are used to show that DP outperforms another method for preprocessing spike trains, principal component analysis (PCA) [Richmond and Optican J. Neurophysiol. 57 (1987) 147-61].


Reduced density of functional 5-HT1A receptors in the brain, medulla and spinal cord of monoamine oxidase-A knockout mouse neonates.
Abnormally high brain 5-HT levels in monoamine oxidase-A knockout (MAO-A KO) mouse neonates raise the question of whether the distribution and density of the 5-HT1A receptors (5-HT1AR) expressed in the brain by postnatal day P7 are affected and, if so, whether the 5-HT1A autoreceptors in the dorsal raphe are modified in the same way as the postsynaptic 5-HT1AR present in raphe target structures. [3H]8-OH-DPAT binding and quantitative autoradiography were performed to answer these questions. Binding specificity was first confirmed in adult wild-type mice and rat brain sections. 5-HT1AR binding was then analyzed in four MAO-A mutant vs. five wild-type neonatal brains, from olfactory bulb to cervical cord. Among 12 structures expressing postsynaptic 5-HT1AR in wild-type neonates, the highest densities involved the retrosplenial cortex, entorhinal cortex, and septum (52-46 fmol/mg tissue); low densities occurred in the hippocampus and spinal cord (24 fmol/mg tissue); in addition, the raphe autoreceptor density was only 20 fmol/mg tissue. In mutants, the distribution of postsynaptic 5-HT1AR was unchanged, but an overall decrease in density occurred (-32% to -63%); the raphe autoreceptors decreased in mutants by at least -79%. Data are discussed with reference to the ectopic 5-HT uptake and accumulation reported to occur during the first 10 postnatal days in wild-type and MAO-A KO mice. As previously suggested to explain the raphe autoreceptor loss in 2-month-old MAO-A KO mice, the overall 5-HT1AR down-regulation in mutant pups probably results from extracellular 5-HT excess in both raphe and target structures. The greater the 5-HT excess, the more the functional receptor density decreases.


Influence of injection site, microvascular pressure and ultrasound variables on microbubble-mediated delivery of microspheres to muscle.
Our objective was to test the hypothesis that the ultrasound pulsing interval (PI), microbubble injection site and microvascular pressure significantly influence the transport of 100-nm microspheres to muscle through extravasation sites created by the destruction of microbubbles with ultrasound. Microbubbles show promise as targeted drug and gene delivery agents; however, designing optimal microbubble-based therapies will require an understanding of the factors that influence the transport of microbubble-delivered, gene-bearing vehicles to tissue. Ultrasound at 1 MHz, with a peak negative pressure amplitude of 0.75 MPa, was applied to microbubbles and 100-nm microspheres in exteriorized rat spinotrapezius muscle. Ultrasound PIs of 1, 3, 5 and 10 s, arterial microsphere injection times of 10 or 40 s and arterial versus venous injection sites were tested. Extravasation point creation and microsphere delivery were greatest when the ultrasound PI was 5 or 10 s. No significant differences in extravasation point creation or microsphere delivery were observed with arterial versus venous microbubble injection, but a trend toward increased microsphere delivery with arterial injection may exist. Decreasing the arterial injection time from 40 to 10 s increased microvascular pressure, which, in turn, substantially enhanced microsphere transport to tissue, without a concomitant increase in the number of extravasation points. The ultrasound PI and microvascular pressure significantly influence the creation of extravasation points and the transport of microspheres to tissue. These factors may be important in designing and optimizing contrast ultrasound-based therapies.


Sleep associated monitoring on awakening mediates the relationship between cutaneous body image dissatisfaction and insomnia symptoms.
This study examined the relationship between dissatisfaction with cutaneous body image and insomnia symptoms, incorporating the mediating role of monitoring for signs of poor-sleep on awakening and throughout the day. Two hundred twenty-one participants completed The Insomnia Severity Index, Cutaneous Body Image Scale, and subscales of the Sleep Associated Monitoring Index. The results demonstrated that insomnia symptoms were significantly associated with a greater dissatisfaction with cutaneous body image. Moreover, this relationship was partially mediated by sleep associated monitoring on awakening, but not throughout the day. These findings provide further understanding of the potential mechanisms underlying negative self-perceptions of physical appearance in insomnia.


Comparison of automated beam hardening correction (ABHC) algorithms for myocardial perfusion imaging using computed tomography.
Myocardial perfusion imaging using computed tomography (MPI-CT) and coronary CT angiography (CTA) have the potential to make CT an ideal noninvasive imaging gatekeeper exam for invasive coronary angiography. However, beam hardening can prevent accurate blood flow estimation in dynamic MPI-CT and can create artifacts that resemble flow deficits in single-shot MPI-CT. In this work, we compare four automatic beam hardening correction algorithms (ABHCs) applied to CT images, for their ability to produce accurate single images of contrast and accurate MPI flow maps using images from conventional CT systems, without energy sensitivity. Previously, we reported a method, herein called ABHC-1, where we iteratively optimized a cost function sensitive to beam hardening artifacts in MPI-CT images and used a low order polynomial correction on projections of segmentation-processed CT images. Here, we report results from two new algorithms with higher order polynomial corrections, ABHC-2 and ABHC-3 (with three and seven free parameters, respectively), having potentially better correction but likely reduced estimability. Additionally, we compared results to an algorithm reported by others in the literature (ABHC-NH). Comparisons were made on a digital static phantom with simulated water, bone, and iodine regions; on a digital dynamic anthropomorphic phantom, with simulated blood flow; and on preclinical porcine experiments. We obtained CT images on a prototype spectral detector CT (Philips Healthcare) scanner that provided both conventional and virtual keV images, allowing us to quantitatively compare corrected CT images to virtual keV images. To test these methods' parameter optimization sensitivity to noise, we evaluated results on images obtained using different mAs. In images of the static phantom, ABHC-2 reduced beam hardening artifacts better than our previous ABHC-1 algorithm, giving artifacts smaller than 1.8 HU, even in the presence of high noise which should affect parameter optimization. Taken together, the quality of static phantom results ordered ABHC-2> ABHC-3> ABHC-1>> ABHC-NH. In an anthropomorphic MPI-CT simulator with homogeneous myocardial blood flow of 100 ml⋅min-1 ⋅100 g-1 , blood flow estimation results were 122 ± 24 (FBP), 135 ± 24 (ABHC-NH), 104 ± 14 (ABHC-1), 100 ± 12 (ABHC-2), and 108 ± 18 (ABHC-3) ml⋅min-1 ⋅100 g-1 , showing ABHC-2 as a clear winner. Visual and quantitative evaluations showed much improved homogeneity of myocardial flow with ABHC-2, nearly eliminating substantial artifacts in uncorrected flow maps which could be misconstrued as flow deficits. ABHC-2 performed universally better than ABHC-1, ABHC-3, and ABHC-NH in simulations with different acquisitions (varying noise and kVp values). In the presence of a simulated flow deficit, all ABHC methods retained the flow deficit, and ABHC-2 gave the most accurate flow ratio and homogeneity. ABHC-3 corrected phantom flow values were slightly better than ABHC-2, in noiseless images, suggesting that reduced quality in noisy images was due to reduced estimability. In an experiment with a pig expected to have uniform flow, ABHC-2 applied to conventional images improved flow maps to compare favorably to those from 70keV images. The automated algorithm can be used with different parametric BH correction models. ABHC-2 improved MPI-CT blood flow estimation as compared to other approaches and was robust to noisy images. In simulation and preclinical experiments, ABHC-2 gave results approaching gold standard 70 keV measurements.


Evaluation of inhibitory effects of heavy metals on anaerobic ammonium oxidation (anammox) by continuous feeding tests.
To facilitate the application of anaerobic ammonium oxidation (anammox) to a nitrogen removal process, the effects of heavy metals (Ni, Cu, Co, Zn, and Mo) on anammox bacteria entrapped in gel carriers were examined by conducting continuous feeding tests for each metal. The results show that all anammox activities decreased by more than 10 % when influent concentrations of Ni, Cu, Co, Zn, and Mo were 5, 5, 5, 10, and 0.2 mg/L, respectively. It was observed that the effects of Ni, Cu, Co, and Zn on anammox activity were reversible and that of Mo on anammox activity was irreversible. Anammox activity was not affected when influent containing mixed Ni, Cu, Co, and Zn (0.5 mg/L) was fed into the reactor.


Combined magnitude and phase-based segmentation of the cerebral cortex in 7T MR images of the elderly.
To propose a new method that integrates both magnitude and phase information obtained from magnetic resonance (MR) T*(2) -weighted scans for cerebral cortex segmentation of the elderly. This method makes use of K-means clustering on magnitude and phase images to compute an initial segmentation, which is further refined by means of transformation with reconstruction criteria. The method was evaluated against the manual segmentation of 7T in vivo MR data of 20 elderly subjects (age = 67.7 ± 10.9). The added value of combining magnitude and phase was also evaluated by comparing the performance of the proposed method with the results obtained when limiting the available data to either magnitude or phase. The proposed method shows good overlap agreement, as quantified by the Dice Index (0.79 ± 0.04), limited bias (average relative volume difference = 2.94%), and reasonable volumetric correlation (R = 0.555, p = 0.011). Using the combined magnitude and phase information significantly improves the segmentation accuracy compared with using either magnitude or phase. This study suggests that the proposed method is an accurate and robust approach for cerebral cortex segmentation in datasets presenting low gray/white matter contrast.


Flexible device for vertebral body replacement.
A novel vertebral prosthesis is presented. The prosthesis was developed for surgical procedures requiring the resection of a complete vertebral body and the adjacent intervertebral discs, the design objective being to develop a flexible implant that would be robust enough to withstand the in vivo stress environment of the human spine. In theory, a flexible implant should preserve a more normal range of motion and apply less stress to surrounding tissue than a rigid implant. A prototype implant was constructed so as to combine a rigid stainless steel structure with flexible silicon rubber elements in order to form an implant with static and dynamic mechanical characteristics similar to those of the anterior spinal column. Implant flexibility characteristics were determined from ex vivo stress-strain behaviour during bending and compressive creep testing. Results from the bending tests indicated good agreement for the lateral and sagittal bending characteristics in comparison with in vitro bending tests of human lumbar motion segments. Comparison of the implant compressive creep response with similar in vitro tests on human lumbar intervertebral discs also demonstrated similarities in the time-dependent mechanical parameters.


Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma.
Androgen Receptor (AR) signaling is a critical driver of hormone-dependent prostate cancer and has also been proposed to have biological activity in female hormone-dependent cancers, including type I endometrial carcinoma (EMC). In this study, we evaluated the preclinical efficacy of a third-generation AR antagonist, enzalutamide, in a genetic mouse model of EMC, Sprr2f-Cre;Ptenfl/fl. In this model, ablation of Pten in the uterine epithelium leads to localized and distant malignant disease as observed in human EMC. We hypothesized that administering enzalutamide through the diet would temporarily decrease the incidence of invasive and metastatic carcinoma, while prolonged administration would result in development of resistance and loss of efficacy. Short-term treatment with enzalutamide reduced overall tumor burden through increased apoptosis but failed to prevent progression of invasive and metastatic disease. These results suggest that AR signaling may have biphasic, oncogenic and tumor suppressive roles in EMC that are dependent on disease stage. Enzalutamide treatment increased Progesterone Receptor (PR) expression within both stromal and tumor cell compartments. Prolonged administration of enzalutamide decreased apoptosis, increased tumor burden and resulted in the clonal expansion of tumor cells expressing high levels of p53 protein, suggestive of acquired Trp53 mutations. In conclusion, we show that enzalutamide induces apoptosis in EMC but has limited efficacy overall as a single agent. Induction of PR, a negative regulator of endometrial proliferation, suggests that adding progestin therapy to enzalutamide administration may further decrease tumor burden and result in a prolonged response.


What determines the efficacy of landfarming for petroleum-contaminated soils: Significance of contaminant characteristics.
Identifying the cause of inconsistent landfarming efficacy is critical to designing optimal remedial strategies for petroleum-contaminated sites. We assessed contaminated soils collected from two former military bases in South Korea to better understand the role and influence of different factors. Landfarming remediation was simulated in the laboratory by applying comparable practices (such as tillage and bioaugmentation) and the relevant mechanism was examined. We then systematically examined potential factors affecting petroleum-removal efficacy, including the content of fine soil particles, the initial concentration and composition of petroleum contaminants, and the degree of soil-contaminant interaction. The distribution range of total petroleum hydrocarbons (TPHs) and the size of unresolved complex mixture (UCM) found in gas chromatography data showed that petroleum composed of TPHs with lower carbon numbers and having smaller size of UCM could be treated more effectively by landfarming. Incorporating the evaluation of the distribution range and UCM properties of petroleum, rather than simply considering its total concentration, is a more accurate and efficient method for determining the site-specific suitability of landfarming as a remedial option, as well as for assessing the necessity of supplementary processes.


Juvenile didymozoids of the types, Torticaecum and Neotorticaecum (Didymozoidae: Digenea), from new marine fish hosts (Pisces: Teleostei) in the neotropical region of Brazil.
From December 2006 to March 2008, 60 specimens of Paralichthys isosceles and 25 specimens of P. patagonicus were investigated for helminths. One hundred and sixty-nine digeneans were recovered and parasites were identified as juvenile didymozoids of two types. Torticaecum and Neotorticaecum were found in 48 of the 60 P. isosceles (80%) and 10 of the 25 P. patagonicus (40%). Torticaecum and Neotorticaecum are reported for the first time in fish in South America (Brazil), found in the Atlantic Ocean. Morphometrics and illustrations are presented.


Stage-dependent gene expression profiles during natural killer cell development.
Natural killer (NK) cells develop from hematopoietic stem cells (HSCs) in the bone marrow. To understand the molecular regulation of NK cell development, serial analysis of gene expression (SAGE) was applied to HSCs, NK precursor (pNK) cells, and mature NK cells (mNK) cultured without or with OP9 stromal cells. From 170,464 total individual tags from four SAGE libraries, 35,385 unique genes were identified. A set of genes was expressed in a stage-specific manner: 15 genes in HSCs, 30 genes in pNK cells, and 27 genes in mNK cells. Among them, lipoprotein lipase induced NK cell maturation and cytotoxic activity. Identification of genome-wide profiles of gene expression in different stages of NK cell development affords us a fundamental basis for defining the molecular network during NK cell development.


Procoagulant and proinflammatory activity in acute coronary syndromes.
Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes. Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA). FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups. IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.