Cloning, overexpression, and purification of glucose-6-phosphate dehydrogenase of Pseudomonas aeruginosa.
Glucose-6-phosphate dehydrogenase (G6PDH) (EC 188.8.131.523) plays an important role in the human pathogen Pseudomonas aeruginosa because it generates NADPH, an essential cofactor for several biosynthetic pathways and antioxidant enzymes. P. aeruginosa G6PDH is also a key enzyme in the metabolism of various carbon sources, such as glucose, glycerol, fructose, and mannitol. Understanding the kinetic characteristics and mechanisms that control the activity of this enzyme is crucial for future studies in this context. However, one of the impediments to achieving this goal is the limited amount of protein obtained when current purification protocols are implemented, a factor curtailing its biochemical characterization. In this study, we report a fast, efficient and reproducible procedure for the purification of P. aeruginosa G6PDH that can be implemented in a short period (2 days). In order to establish this protocol, the zwf gene, which encodes for this enzyme, was cloned and overexpressed in Escherichia coli cells. In contrast to other procedures, our method is based on protein precipitation with CaCl2 and further purification by ion exchange chromatography. Using this protocol, we were able to obtain 31 mg/L of pure protein that manifested specific activity of 145.7 U/mg. The recombinant enzyme obtained in this study manifested similar physicochemical and kinetic properties to those reported in previous works for this molecule. The large quantities of active enzyme obtained using this procedure will facilitate its structural characterization and identify differences between P. aeruginosa- and human G6PDH, thus contributing to the search for selective inhibitors against the bacterial enzyme.


Control of glucose metabolism in isolated acini of the lactating mamary gland of the rat. Effects of oleate on glucose utilization and lipogenesis.
Oleate (1mM) had only small inhibitory effects on glucose utilization and lipogenesis in acini isolated from rat mammary gland. Esterification of [1-14C]oleate was unaffected by insulin but were decreased by 60% by acetoacetate (2mM). Glycerol (1mM), but not insulin, relieved this inhibition. These experiments provide further support for the role of acetoacetate in regulating substrate utilization by the gland.


Risk factors for Aujeszky's disease in pig herds and detection of field virus antibodies in fattening pigs in the state of Yucatan, Mexico.
Two epidemiological studies were conducted from August 1997 to May 1998: a case-control study to identify herd level risk factors for antibodies to Aujeszky's disease virus (ADV) in sows in the state of Yucatan, Mexico and a cross-sectional study to determine the prevalence of antibodies against ADV in fattening pigs. In the case-control study, data on herd management and biosecurity were obtained from all the 27 ADV known field-virus-seropositive farms (cases) and 62 randomly selected seronegative farms (controls) by questionnaire. Breeding animals of these seropositive farms had received a gE-deletion vaccine. In the cross-sectional study, 26 farrow-to-finish farms of the 27 seropositive farms were used and blood samples taken from 60 fattening pigs per herd (15 pigs for each stage of production). Serum samples were analyzed by the screening-ELISA and gE-ELISA tests. In the case-control study, three of the 15 risk factors were significant. Odds ratios for distance to the nearest farm (< or = 2.5km), not sampling for the detection of ADV and herds with origin of breeding animals within the state were 9.5, 18.1 and 8.7. In the cross-sectional study, 11 (42.3%) of the 26 sampled farms were seropositive to vaccine antibodies. None of the piglets were positive to antibodies against field virus risk--suggesting that the strategy of vaccinating only the breeding animals reduced the ADV infection of the piglets.


Phenotyping Whole Forests Will Help to Track Genetic Performance.
Phenotyping is the accurate and precise physical description of organisms. Accurate and quantitative phenotyping underpins the delivery of benefits from genetic improvement programs in agriculture. In forest trees, phenotyping at an equivalent precision has been impossible because trees and forests are large, long-lived, and highly variable. These facts have restricted the delivery of genetic gains in forestry compared to other agricultural sectors. We describe a landscape-scale phenotyping platform that integrates remote sensing, spatial information systems, and genomics to facilitate the delivery of greater gains enabling forestry to catch up with other sectors. Combining remote sensing at a range of spatial and temporal scales with genomics will ultimately impact on tree breeding globally.


Brain death in children: Part II.
The determination of brain death in children has increasingly relied on a variety of neurodiagnostic studies to confirm the clinical diagnosis. This second article on brain death reviews the relevant pediatric electroencephalographic, evoked response, and cerebral blood flow studies, provides our recommendations and protocol for the determination of brain death in children, and considers some of the problems associated with physiologic stabilization of the brain dead child who is considered for organ donation.


Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children.
Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccine to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine.


Blood cell-derived tissue factor influences host response during murine endotoxemia.
During endotoxemia, blood coagulation becomes activated due to tissue factor (TF) expression on leukocytes and/or endothelial cells. We investigated the influence of blood cell-derived tissue factor on murine endotoxemia. Therefore, we generated mice that lack tissue factor on their blood cells by transplanting tissue factor-deficient hematopoietic stem cells into lethally irradiated wild-type recipients. Control mice were also irradiated but were injected with stem cells from wild-type littermate embryos. Seven weeks after transplantation, the mice received 250 microg of endotoxin intraperitoneally. Three hours later, the mice were bled and plasma and organs were collected to assess inflammation, coagulation, and apoptosis. Mice that lack tissue factor on their blood cells still reacted to endotoxemia, but markedly less than wild-type controls. Blood cell-derived tissue factor-deficient mice showed significantly less clinical symptoms than control mice. Levels of circulating inflammatory mediators and thrombin-antithrombin (TAT) complexes were lower in blood cell-derived tissue factor-deficient mice than in controls. Surprisingly, inflammation was seen more often in blood cell-derived tissue factor-deficient mice than in control mice, but signs of apoptosis were more pronounced in controls. In summary, our data clearly indicate that endotoxin-induced coagulation and inflammation are strongly influenced by blood cell-derived tissue factor.


Intercellular movement of transcription factors.
Intercellular communication by the direct trafficking of transcription factors has been reported in plant developmental events such as root radial or epidermal cell patterning and shoot organogenesis. Investigations of this novel communication system have just begun and have highlighted the structural requirements for and mechanisms of transcription factor movement. Early studies suggest that plants employ both targeted (selective) and non-targeted (non-selective) intercellular movement of transcription factors. Factors that affect the intercellular movement of transcription factors through plasmodesmata have been explored.


Indomethacin-induced blood flow distribution in premature and full-term piglets.
Indomethacin (IND), widely used in premature infants to effect nonoperative closure of patent ductus arteriosus (PDA), has been implicated in gastrointestinal tract (GI) perforations and necrotizing enterocolitis (NEC). The vasoactive effects of IND could simultaneously affect regional blood flow distribution, specifically a decrease in intestinal blood flow. This study determined blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and regional blood flows (mL/min/g) at baseline, 15, 60, and 120 minutes after intravenous infusion of IND (0.4 mg/kg) in three groups: preterm piglets delivered 7 to 10 days before term; 1- to 2-day-old piglets; and 7- to 14-day-old piglets. IND did not significantly affect hemodynamic parameters (BP, HR, CO, TPR) or regional blood flows to the heart, central nervous system, kidney or GI tract in the premature animals. In 1- to 2-day-old animals, a significant increase in BP and TPR occurred at 120 minutes, with significant decreases in blood flow to the GI tract in the esophagus, stomach, and rectosigmoid. In the 7- to 14-day group CO significantly decreased while TPR increased. Significant decreases in blood flow occurred throughout the GI tract, most pronounced in the small intestine and colon, essentially due to decreased mucosal blood flow. Our study indicates that indomethacin can cause selective GI tract mucosal ischemia, and that the effect is increased in the more developed animal. This effect on mucosal blood flow suggests the GI tract disturbances seen after IND administration are due to an ischemic injury to mucosa previously affected by ischemia-reperfusion injury from other stresses.


Virus contamination and infectivity in beach environment: Focus on sand and stranded material.
To assess the exposure of beachgoers to viruses, a study on seawater, sand, and beach-stranded material was carried out, searching for human viruses, fecal indicator organisms, and total fungi. Moreover, for the first time, the genome persistence and infectivity of two model viruses was studied in laboratory-spiked sand and seawater samples during a one-week experiment. Viral genome was detected in 13.6 % of the environmental samples, but it was not infectious (Human Adenovirus - HAdV, and enterovirus). Norovirus and SARS-CoV-2 were not detected. The most contaminated samples were from sand and close to riverine discharges. In lab-scale experiments, the infectivity of HAdV5 decreased by ~1.5-Log10 in a week, the one of Human Coronavirus-229E disappeared in <3 h in sand. The genome of both viruses persisted throughout the experiment. Our results confirm viral contamination of the beach and suggest HAdV as an index pathogen for beach monitoring and quantitative risk assessment.


Pharmacological management of cancer pain in the elderly.
Existing studies indicate a high prevalence rate and poor management of cancer pain in the elderly. Pain is often considered an expected concomitant of aging, and older patients are considered more sensitive to opioids. Despite the well known pharmacokinetic changes in the elderly, the complex network of factors involved in the opioid response make the evaluation of a single element, such as age, more difficult. Notwithstanding such difficulties, appropriate analgesic treatment is able to control cancer pain in the elderly in most cases. Skills necessary to optimise pain control in older cancer patients include the ability to objectively assess functional age (not necessarily related to chronological age since the rate of decline is variable), understand the impact of coexisting conditions, carefully manage the numbers and types of drugs taken at the same time and adequately communicate with patients and relatives. The most common treatment of cancer pain consists of the use of regularly given oral analgesics. The elderly are at increased risk of developing toxicity from NSAIDs, and the overall safety of these drugs in frail elderly patients should be considered. When older patients have clear contraindications to NSAIDs, manifest signs of toxicity from these agents, or find that pain is no longer controlled with this class of drugs, opioids should be started. A variety of opioids are available, and they differ widely with respect to analgesic potency and adverse effects among the elderly. Although the aged population requires lower doses of opioids, only careful titration based on individual response can ensure the appropriate response to clinical demand. Elderly patients are potentially more likely to be affected by opioid toxicity because of the physiological changes associated with aging. Nevertheless, appropriate dosage and administration may limit these risks. Cancer patients with pain who do not respond to increasing doses of opioids because they develop adverse effects before achieving acceptable analgesia may be switched to alternative opioids. Despite the favourable effects reported with opioid switching, monitoring is crucial, particularly in the elderly or patients who are switched from high doses of opioids. Adjuvant analgesics, including antidepressants, antiepileptics, corticosteroids and bisphosphonates may help in the treatment of certain types of chronic pain. With an appropriate and careful approach, it should be possible to reduce or eliminate unrelieved cancer pain in most elderly patients and, consequently, to enhance their quality of life. Older patients with cancer should be continuously assessed for cancer pain, both before and after analgesic treatment.


Investigation of Molecular Mechanisms of Polyvinylidene Fluoride under the Effects of Temperature, Electric Poling, and Mechanical Stretching Using Molecular Dynamics Simulations.
This study uses molecular dynamics (MD) simulations to investigate the molecular mechanisms of polyvinylidene fluoride (PVDF) influenced by temperature, electric poling, and mechanical stretching. The β-phase, with all-trans ⟨T⟩ planar zigzag conformation, is known to have the best potential of energy harvesting, while α-phase, with alternating trans ⟨T⟩ and gauche ⟨G⟩ linkages, is more stable in terms of potential energy. By applying an electric field and uniaxial deformation to an amorphous PVDF system, we study the transformation from α- to β-phase and corresponding molecular mechanisms by tracking the molecular chain conformation using the trans percentages (PT). After complete relaxation of molecular chains, the chain conformations and PT values indicate a typical distribution pattern of α-phase. Next, we observe that the dipole moment of the system increases significantly with the presence of a strong electric field without immediately affecting the chain conformations. The increment of dipole moment is due to the aligning of side atoms within the chains and the increment becomes more significant with elevated temperature. In contrast, chain conformations change significantly under mechanical stretching. Specifically, before yielding, the total dipole moments are still governed by local orientations of atoms. Later, the chain segments begin to straighten in the large deformation stage, which leads to the increment of the total dipole moment. Our results also show that there exists an optimal temperature window for maximum ⟨G⟩ to ⟨T⟩ transformation rate. Moreover, we look into the synergistic effect of electric poling and mechanical stretching and explain molecular-level mechanisms for this effect. This study contributes to the fundamental understanding of the underlying molecular mechanisms for the piezoelectric PVDF system under different processing conditions.


[Treatment of cytomegalovirus disease].
For years, intravenous ganciclovir has been the recommended treatment for cytomegalovirus (CMV) in transplant recipients. Recently, oral valganciclovir has been shown to induce a response to CMV similar to that produced by intravenous ganciclovir and could consequently be an alternative to ganciclovir in patients with non-severe disease. Sequential therapy with ganciclovir followed by valganciclovir, after the onset of clinical improvement, reduces costs and avoids prolonged hospital stays, thus benefitting patients. Optimal treatment duration is guided by clinical response and virological monitoring (polymerase chain reaction or antigenemia) and is maintained until the results are negative. Some groups use secondary prophylaxis in patients with risk factors for recurrence of CMV disease. Reducing the intensity of immunosuppression or complementing antiviral therapy with immunoglobulins can be considered in patients with severe disease or immunodepression. There are no conclusive data on the most effective treatment in ganciclovir-resistant CMV. Therapeutic decisions should be based on genotypic resistance studies, the patient's immune status and disease severity. Treatment consists of foscarnet alone or in combination with ganciclovir in the most severe forms and in high-resistance mutations, or in increasing the dose of ganciclovir in clinical forms or in mild resistance. There are no conclusive data on alternative antiviral drugs or complementary therapy with mTOR inhibitors. Several CMV vaccines are under development and the preclinical results are encouraging.


Organizational culture and affective commitment to e-learning' changes during COVID-19 pandemic: The underlying effects of readiness for change.
Higher education institutions (HEIs) have been embracing digital transformation for years, but the disruptive influence of the global COVID-19 pandemic has accelerated it. Despite the importance of organizational culture (OC) for the successful delivery of e-learning, empirical studies looking at its impact on academics' readiness and affective commitment to e-learning-induced changes are scant. This study unveils the underlying impacts of multiple employee readiness for change (ERFC) dimensions in the OC-employee affective commitment to change (EACC) relationship. Survey data were obtained from 1,200 Jordanian public HEIs' academics. Structural equation modelling was used to analyze the data, testing the study's six hypotheses. The findings offer a novel contribution by showing that OC types influence different dimensions of ERFC, each having a distinctive impact on EACC. It further shows that two ERFC dimensions, namely self-efficacy and personal valence, function as full mediators in the relationships between group culture/adhocracy culture and EACC.


NF1 Gene Novel Splicing Mutations in a Chinese Family with Neurofibromatosis Type 1: Case Series.
Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder. NF1 is a multisystemic disease and its pathogenesis involves mutations in the NF1 gene on chromosome 17q11.2 causing RAS overactivation to stimulate abnormal cell proliferation. To identify pathogenic mutation of the NF1 gene in a pedigree of NF1. Collection of clinical data from one NF1 family. Peripheral blood samples were collected from the affected persons and their family members. Potential mutations of NF1 gene were screened by exome and cDNA sequencing. A splice mutation (c.4836-10T>G) was found in exon 37 of the NF1 gene in this NFI family, and no corresponding mutation was found in healthy members of this pedigree or in the human reference genome (GRCh37/hg19). Mutations of NF1 gene is a major cause of NF1. The novel splice mutation in exon 37 of NF1 gene is the underlying cause of the familial c.4836-10T>G.


In vivo toxicity to lymphoid tissue by 2'-deoxycoformycin.
The enzyme adenosine deaminase has an essential role in lymphocyte metabolism. To examine the in vivo effects of inhibition of this enzyme healthy BDF1 mice were injected intraperitoneally with 2'-deoxycoformycin, a stoichiometric tight-binding inhibitor of adenosine deaminase. Of the treated animals, 20% died of overwhelming infection, and histopathological examination of these, and surviving animals sacrificed 10 days following treatment indicated a selective toxicity to lymphoid cells. No toxicity to tissues other than the lymphoid system was observed, which is consistent with the hypothesis that 2'-deoxycoformycin offers a new and selective approach to the treatment of lymphoid malignancies.


Optic nerve tumors: role of magnetic resonance imaging and computed tomography.
Localization and pathologic diagnosis of optic nerve tumors have been greatly improved by high resolution computed tomography and magnetic resonance imaging. Radiologic differentiation of the most common tumors of the optic nerve (meningioma and glioma) can be made by using these new imaging modalities. Early diagnosis of optic nerve lesions has resulted in better prognosis and surgical outcome.


The impact of focused ion beam induced damage on scanning spreading resistance microscopy measurements.
Scanning Spreading Resistance Microscopy is a well-established technique for obtaining quantitative two- and three-dimensional carrier profiles in semiconductor devices with sub-nm spatial resolution. However, for sub-100 nm devices, the use of focused ion beam becomes inevitable for exposing the region of interest on a sample cross section. In this work, we investigate the impact of the focused ion beam milling on spreading resistance analysis and we show that the electrical effect of the focused ion beam extends far beyond the amorphous region and depends on the dopant concentration, ion beam energy, impact angle, and current density. For example, for dopant concentrations between 1.0 × 1020 and 1.5 × 1016 cm-3 we observe dopant deactivation at least between 23 and 175 nm for a glancing 30 keV ion beam. Further, we show that dopant deactivation is caused by defect diffusion during milling and is not directly impacted by the presence of Gallium in the sample. Later, we also discuss potential ways to mitigate these effects.


Enhanced Ethanol Production from CO2 Electroreduction at Micropores in Nitrogen-Doped Mesoporous Carbon.
Efficient formation of valuable multicarbon products in CO2 electrochemical reduction is challenging, owing to the difficulty of C-C coupling. Medium micropores embedded in the channel walls of nitrogen-doped ordered mesoporous carbon are found to capably promote ethanol production from CO2 electroreduction. By scaling up the medium micropore content, the yield of ethanol is increased to 2.3 mmol gcat -1 h-1 , far outperforming previously reported state-of-the-art electrocatalysts. The intrinsically higher activity is attributed to the desolvation effect induced by the medium micropores, facilitating the coupling reaction of C1 intermediates to form ethanol.


Enhanced Purkinje cell survival in granuloprival cerebellar cultures.
The number of large cortical neurons that survived in cerebellar cultures in which granule cells had been destroyed by exposure to cytosine arabinoside was 3-4 times the number in normal cultures. Transplantation of granuloprival cerebellar cultures with granule cells and glia resulted in a reduction of the large cortical neuron population (predominantly Purkinje cells) to normal, while the number of such neurons remained elevated after transplantation with glia alone. These results indicated that granule cells were critical for the reduction of large cortical neurons. The rescue of large cortical neurons in granuloprival cultures was attributed to an expanded target field for Purkinje cell axon collateral projections.


Clinical trial simulation to evaluate power to compare the antiviral effectiveness of two hepatitis C protease inhibitors using nonlinear mixed effect models: a viral kinetic approach.
Models of hepatitis C virus (HCV) kinetics are increasingly used to estimate and to compare in vivo drug's antiviral effectiveness of new potent anti-HCV agents. Viral kinetic parameters can be estimated using non-linear mixed effect models (NLMEM). Here we aimed to evaluate the performance of this approach to precisely estimate the parameters and to evaluate the type I errors and the power of the Wald test to compare the antiviral effectiveness between two treatment groups when data are sparse and/or a large proportion of viral load (VL) are below the limit of detection (BLD). We performed a clinical trial simulation assuming two treatment groups with different levels of antiviral effectiveness. We evaluated the precision and the accuracy of parameter estimates obtained on 500 replication of this trial using the stochastic approximation expectation-approximation algorithm which appropriately handles BLD data. Next we evaluated the type I error and the power of the Wald test to assess a difference of antiviral effectiveness between the two groups. Standard error of the parameters and Wald test property were evaluated according to the number of patients, the number of samples per patient and the expected difference in antiviral effectiveness. NLMEM provided precise and accurate estimates for both the fixed effects and the inter-individual variance parameters even with sparse data and large proportion of BLD data. However Wald test with small number of patients and lack of information due to BLD resulted in an inflation of the type I error as compared to the results obtained when no limit of detection of VL was considered. The corrected power of the test was very high and largely outperformed what can be obtained with empirical comparison of the mean VL decline using Wilcoxon test. This simulation study shows the benefit of viral kinetic models analyzed with NLMEM over empirical approaches used in most clinical studies. When designing a viral kinetic study, our results indicate that the enrollment of a large number of patients is to be preferred to small population sample with frequent assessments of VL.


Psychological characteristics and development of narcotic-addicted infants.
This paper reviews neonatal and developmental behavioral characteristics of children born to heroin- and methadone-addicted women. Evidence of behavioral effects is clearer and more consistent for the neonatal period than in later infancy and childhood. It has not been shown that additional risk for psychological disturbance in childhood is contributed by passive addiction in utero. Methodologic problems in this literature are described and suggestions for strategies and directions in research are offered.


Color change of some aesthetic dental materials: Effect of immersion solutions and finishing of their surfaces.
The purpose of this research was to evaluate the color change of five aesthetic dental materials, before and after immersion in distilled water and blue food color solution for 7 and 21 days, and to study the effect of finishing the surfaces on any color change. Disc shaped samples of five types of light curing composite (A2) (n = 10 samples/composite) were prepared and all samples were light-cured with a Plasma Arc light cure unit for ten seconds. One side of each sample disc was finished and polished with a Super-Snap system all samples. After 24 h, color measurements of each sample were conducted using a digital spectrophotometer. Five sample discs from each composite group were immersed in 30 ml of food color solution for 7 and 21 days, while the remaining five sample discs were immersed in 30 ml of distilled water as a control. Color measurements were repeated for all samples at 7 and 21 days after immersion. The color changes were statistically analyzed using t-tests within the same group. A result was considered statistically significant at α = 0.05. The color differences (ΔE) ranged from 0.4 to 4.66 and statistically significant differences on the finished and unfinished surfaces were observed after immersion in the food color solution for 7 days. No significant differences were found in any group after immersion in the food color solution for 21 days. The Tetric EvoCeram and Arabesk groups showed less color differences after 7 and 21 days than other composites. Finished composite surfaces showed less coloration than unfinished surfaces after 7 days, but all surfaces (finished and unfinished) were highly colored for all composite types after 21 days.


Doppler ultrasound measurement of cerebral blood flow in healthy pregnant women.
To compare global cerebral blood supply in healthy pregnant women and nonpregnant women. Flow volumes in the common, internal, and external carotid, arteries and the vertebral arteries were determined using color Doppler ultrasonography in 17 nonpregnant women, 55 healthy pregnant women at 10 to 40 weeks gestation, and 24 puerperal women within 1 week after spontaneous delivery. Global cerebral blood flow was defined as the sum of flow volumes in the bilateral internal carotid and vertebral arteries. In the nonpregnant group, mean flow volumes of the common, internal, and external carotid arteries and the vertebral arteries, and mean global cerebral blood flow volume were (mean±SD) 863±108 ml/min, 554 ±94 ml/min, 386±65 ml/min, 115±24 ml/min, and 669±104 ml/min, respectively. During the second trimester, flow volumes of the common and external carotid arteries increased significantly in the healthy pregnant women, to about 130 percent and 140 percent of the nonpregnant level, respectively. Global cerebral blood flow volume remained unchanged during pregnancy. During pregnancy, increase in flow volumes in the common carotid arteries were accompanied by elevated flow volumes of the external carotid arteries but not the internal carotid arteries. This distribution would tend to regulate the volume of global cerebral blood flow throughout the period of pregnancy.


Knowledge of malocclusion supports comprehensive dental hygiene care.
Occlusal assessments are often missed or neglected by dentists and dental hygienists. This short communication discusses how these assessments can be implemented through 4 planes of space: anterior-posterior/anteroposterior, vertical, transverse, and perimeter. Expanded occlusal knowledge can improve the referral process for early preventive care. A chairside guide has been defined for dental hygienists to conduct a systematic occlusal exam.


Choroidal melanomas near the optic disk or macula. Long-term results after proton beam irradiation: a report of 3 cases.
Three patients with choroidal melanomas of the posterior pole were treated with proton beam irradiation. One tumor was medium-sized, two were large-sized. Two of the three eyes were functionally single eyes. 60 CGE (cobalt gray equivalents) was delivered in 4 equal treatments during 4 consecutive days. The minimum follow-up period for each patients is 4 years, the average time 4.8 years. Functionally, we lost both eyes with the large-sized tumors owing to severe radiogenic side effects; the eye containing the largest tumor had to be enucleated after 48 months because of phthisis bulbi. No metastases have developed up to now.


Disease recognition is related to specific autobiographical memory deficits in alcohol-dependence.
The particularly high treatment gap in alcohol-dependence suggests the existence of important barriers to treatment decision and in particular difficulties in problem recognition. This study tested the relation between problem recognition and self-related memories. Forty-one recently detoxified alcohol-dependent individuals (AD) were compared to twenty alcoholic subjects that were abstinent for 6 months or more (recruited among alcoholics-anonymous (AA)), and to twenty controls on autobiographical memories elicited by pictures depicting or not alcohol using the autobiographical memory test. Autonoetic consciousness was measured with the Remember/Know paradigm. We tested whether memories performances were related with data obtained on the readiness to change questionnaire (RCQ) or with consciousness of the severity of drinking. AD subjects provided less specific memories than control and AA subjects, and fewer Remember responses than controls. The deficits in AD subjects were not specific for memories elicited by pictures depicting alcohol, suggesting a global deficit. Autobiographical memories specificity was negatively correlated to scores of consciousness of the severity of drinking but not to RCQ. Our results support potential recovery of autobiographical memory with abstinence. AD's deficits in autobiographical memory were related to capacities to recognize the severity and therefore may be a barrier to treatment decision.


Double J stent malposition in the inferior vena cava: Two case reports and a literature review.
Double J stent (DJS) malposition in the vascular system is a rare and severe complication. We present two cases in our department who went through DJS malposition in the inferior vena cava and our experience in treatment, and we reviewed the previous case reports to further summarize its underlying reasons and prevention and treatment methods.


[Competency-based Neurosurgery Residency Programme].
A programme proposal for competency-based Neurosurgery training adapted to the specialization project is presented. This proposal has been developed by a group of neurosurgeons commissioned by the SENEC (Spanish Society of Neurosurgery) and could be modified to generate a final version that could come into force coinciding with the implementation of the specialization programme. This document aims to facilitate the test of the new programme included in the online version of our journal. Total training period is 6 years; initial 2 years belong to the surgery specialization and remaining 4 years belong to core specialty period. It is a competency-based programmed based on the map used by the US Accreditation Council for Graduate Medical Education (ACGME) including the following domains of clinical competency: Medical knowledge, patient care, communication skills, professionalism, practice-based learning and improvement, health systems, interprofessional collaboration and professional and personal development. Subcompetencies map in the domains of Knowledge and Patient care (including surgical competencies) was adapted to the one proposed by AANS and CNS (annex 1 of the programme). A subcompetency map was also used for the specialization rotations. Resident's training is based on personal study (self-learning) supported by efficient use of information sources and supervised clinical practice, including bioethical instruction, clinical management, research and learning techniques. Resident evaluation proposal includes, among other instruments, theoretical knowledge tests, objective and structured evaluation of the level of clinical competency with real or standardised patients, global competency scales, 360-degree evaluation, clinical record audits, milestones for residents progress and self-assessment (annex 2). Besides, residents periodically assess the teaching commitment of the department's neurosurgeons and other professors participating in rotations, and annually assess the overall operation of the programme. Results of evaluations are registered, together with other relevant data, in the Resident's Book. The creation of a Programme Committee directly attached to the SENEC (National Commission) that, aside from generating a final version of the programme, monitors its implementation (level of adherence and operation in the different departments), assumes the creation of test banks and the centralized administration of knowledge tests (in the middle of the residency and/or at the end of it) and centralizes information collected by tutors that could be used for re-accreditation of the services, is proposed.


Displaced intracapsular hip fractures in fit, older people: a randomised comparison of reduction and fixation, bipolar hemiarthroplasty and total hip arthroplasty.
To compare internal fixation, bipolar hemiarthroplasty and total hip arthroplasty for the management of displaced subcapital fracture of the hip in previously fit patients of 60 years or older. A prospective randomised clinical trial. This multicentre trial was carried out in 11 Scottish hospitals with acute orthopaedic trauma units. The participants were 298 previously fit patients of 60 years or older with displaced subcapital hip fractures. The three surgical interventions for comparison were reduction and fixation, bipolar hemiarthroplasty and total arthroplasty (total hip replacement). Participating surgeons elected to randomise patients either among all three types of operation (three-way randomisation) or just between fixation and hemiarthroplasty (two-way randomisation). Clinical outcomes were mortality rates, reoperation rates and the complication rates associated with each procedure. Functional outcome was measured using a hip specific questionnaire [Johanson Hip Rating Questionnaire (HRQ)] and a general health status questionnaire [EuroQol 5 Dimensions (EQ-5D)]. Economic analysis compared the costs in the randomised groups of hospital treatment for the initial and subsequent admissions for up to 2 years. Altogether, 207 patients were randomised among all three trial operations, and 91 between just fixation and bipolar hemiarthroplasty. There were no statistically significant differences in clinical outcomes, but confidence intervals (CIs) were wide. At 2 years fixation failure reached 37% among those allocated fixation and 39% had undergone further surgery. Further surgery rates after hemiarthroplasty and total hip replacement were 5% and 9%, respectively. The group allocated fixation had significantly worse HRQ and EQ-5D scores than both arthroplasty groups at 4 and 12 months. At 24 months the results still favoured arthroplasty, but the overall HRQ and EQ-5D scores were no longer statistically significant. Total hip replacement had the best patient-assessed outcome scores. At 24 months the overall HRQ and EQ-5D scores for total hip replacement were significantly better than for hemiarthroplasty. The mean costs for the initial episode ranged from 6384 pounds Sterling for fixation to 7633 pounds Sterling for total hip replacement. The cost differences were largely due to differences in theatre costs and the cost of prostheses and hardware. The cumulative cost over 2 years of hemiarthroplasty was around 3000 pounds Sterling lower than for fixation (95% CI 1227 pounds Sterling to 7192 pounds Sterling). Compared with total hip replacement, both fixation and hemiarthroplasty were characterised by increased costs arising from hip-replacement admissions. When total (initial episode and subsequent hip-related admissions) hip-related costs are compared, total hip replacement conferred a cost advantage of around 3000 pounds Sterling per patient (versus hemiarthroplasty, 95% CI -pounds Sterling 1400 to 7420 pounds Sterling). In fit, older patients the results of the study show a clear advantage for arthroplasty over fixation; arthroplasty was more clinically effective and probably less costly over a 2-year period postsurgery. The results suggest that total hip replacement has long-term advantages over bipolar hemiarthroplasty, but these findings are less definite. This study provided support for the use of total hip replacement to treat displaced intracapsular hip fractures in fit, older patients. A larger trial comparing total versus hemiarthroplasty for these fractures could help to verify these findings. It would also be useful to know whether the findings of this study apply to patients aged 60 years or less who are usually treated with reduction and fixation. A clinical trial comparing arthroplasty versus fixation in patients older than 40 years would be a logical extension of the current study.


From surveillance to surgery: The delayed implications of non-operative and operative management of pancreatic injuries.
Our study compares the delayed outcomes of operative versus nonoperative management of pancreatic injuries. We analyzed the 2017 Nationwide Readmissions Database on adult (≥18 years) trauma patients with pancreatic injuries. Patients who died on index admission were excluded. Patients were stratified into operative (OP) and non-operative (NOP) groups and compared for outcomes within 90 days of discharge. Multivariable regression analyses were performed. We identified 1553 patients (NOP = 1092; OP = 461). The Mean (SD) age was 39 (17.0) years, 31% of patients were female, and 77% had blunt injuries. Median ISS was 17 [9-25] and 74% had concomitant non-pancreatic intraabdominal injuries. On multivariable analysis, operative management was independently associated with increased odds of 90-day readmissions (aOR = 1.47; p = 0.03), intraabdominal abscesses (aOR = 2.7; p < 0.01), pancreatic pseudocyst (aOR = 2.4; p = 0.04), and need for percutaneous or endoscopic management (aOR = 5.8; p < 0.001). Operative management of pancreatic injuries is associated with higher rates of delayed complications compared to non-operative management. Surgically treated pancreatic trauma patients may need close surveillance even after discharge.


Gastric femoral hernia in a male cadaver with gastroptosis: case report and review of the literature.
The shape and the position of the stomach and its anatomic relations to the round viscera vary from individual to individual, but they also vary in the same subject depending on many factors. The downward displacement of the stomach is called gastroptosis. In the literature, there are only five case reports where the stomach constituted the content of a femoral hernia. The current study presents a case of a gastric femoral hernia in a cadaver along with a review of the relevant literature. During routine dissection of a 67-year-old male cadaver with a very large stomach and gastroptosis, a femoral hernia containing a part of the great curvature of the stomach was found. The length of the hernia sac was 5 cm, and its width was 3.5 cm. There was a disposition of the intestinal coils to the posterior wall and the lesser pelvis. The cadaver's former medical history and skin observation before dissection excluded any previous abdominal surgery. This is the second case of stomach herniation through the femoral ring in a male subject ever reported. The symptoms in this pathology vary from complete absence to symptoms due to high stenosis of the digestive tract, stomach strangulation and stomach wall necrosis.


Mobile echogenicities on scrotal sonography: is the finding associated with vasectomy?
The purpose of this study was to determine whether mobile echogenicities seen in the epididymis on scrotal sonography are associated with prior vasectomy. We prospectively obtained a sonographic video clip of each epididymal body in outpatients sent for scrotal sonography. The presence of punctate mobile echogenicities in the epididymal body was noted, and the indication for the sonogram, patient age, and history of vasectomy were recorded. This study was compliant with the Health Insurance Portability and Accountability Act and was approved by the Institutional Review Board. Of 345 patients (mean age, 44.9 years), 56 (16.2%) had undergone vasectomy and 289 had not. Mobile echogenicities were found in 8 patients, 7 of whom were postvasectomy. The rates of mobile echogenicities appearing were 12.5% (7 of 56) in the vasectomy group and 0.3% (1 of 289) in the nonvasectomy group (P < .0001, Fisher exact test). Epididymal cysts were seen in 184 of 345 patients (53.3%). There was no significant difference in the presence of epididymal cysts in the patients who had undergone vasectomy compared to those who had not (P = .34), including 30 of 56 postvasectomy patients (53.6%) and 154 of 289 patients without vasectomy (53.3%). Pain was reported by 177 patients (51.3%), including 34 of 56 (60.7%) in the postvasectomy group and 143 of 289 (49.5%) without vasectomy. The presence of pain was similar in both groups (P = .15). The presence of mobile echogenicities in the epididymis is almost always a postvasectomy finding and occurs in approximately 12.5% of such patients. There is no significant difference in the rate of epididymal cysts or pain after vasectomy compared to those who have not had vasectomies.


Lead phytoextraction by Pelargonium hortorum: Comparative assessment of EDTA and DIPA for Pb mobility and toxicity.
Soil amendments like ethylene-diamine-tetraacetic-acid (EDTA) have extensively been used for enhancing lead (Pb) phytoextraction. But due to its toxic effects, environment friendly substitute is required. Therefore, the present study was conducted to investigate the effect of EDTA and Di-iso-propanol-amine (DIPA) to enhance Pb phytoavailability and uptake by Pelargonium hortorum along with comparative toxicities of both organic amendments. For this purpose, soil was spiked with Pb concentrations (0, 500, 750, 1000 and 1500 mg kg1) and amended with EDTA and DIPA at dosage levels (0, 1.5, 3, 5, 7.5, 10 mmol kg-1) for plantation of Pelargonium hortorum. Soil samples were extracted with MgCl2, plant samples were acid digested and analyzed for metal content. Biomass and root/shoot length of Pelargonium hortorum was decreased with increase in concentration of Pb and chelating agents. Phytoavailability of Pb at 1500 mg kg-1 with EDTA 10 mmol kg-1 was 0.3-folds in comparison to DIPA at the same dosage. Pelargonium hortorum plants amended with EDTA and DIPA at 10 mmol kg-1 with Pb 1000 mg kg-1 were found to uptake Pb 5.3-fold and 2.5-folds, respectively in comparison to Pb 1000 mg kg-1 alone. Pb uptake decreased at 1500 mg kg-1 with both chelating agents. The EDTA alone and in combination with 1500 mg Pb kg-1 showed maximum genotoxicity by reducing the mitotic index and increasing the micronuclei formation. EDTA+Pb showed maximum toxicity followed by Pb and DIPA. Overall, 10 mmol kg-1 of EDTA and DIPA performed better among all dosages in enhancing phytoavailability and uptake of Pb. DIPA showed less toxicity than that caused by EDTA, with comparable ability to promote Pb phytoextraction.


Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients.
To describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.3 % otic solution alone (CIPRO), and fluocinolone acetonide 0.025 % otic solution alone (FLUO) administered into the middle ears of pediatric patients with Acute Otitis Media with Tympanostomy Tubes (AOMT). We performed a PK analysis of patients who participated in two multicenter, randomized, double-blind AOMT clinical trials (SALVAT studies CIFLOTIII/10IA02 and CIFLOTIII/10IA04). Each patient received 0.25 mL of CIPRO+FLUO, CIPRO, or FLUO twice a day instilled into the ear canal(s) for 7 days to treat AOMT. Blood samples of patients with unilateral AOMT were collected before the administration of the first dose of study medication at Visit 1 (day 1) and within 1-2 h after the last dose on day 7. Blood samples were analyzed to detect ciprofloxacin and fluocinolone acetonide concentrations using two validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods, with the lower limit of quantification for ciprofloxacin and fluocinolone acetonide in plasma samples being 1 ng/mL. Thirty randomly selected patients between 10 months and 10 years of age (mean age, 4.4 years) were included in the study. Although all available samples were analyzed, only PK data of the 22 patients with both samples and unilateral disease were considered for study purposes. No detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). These results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.


Templated Synthesis of 2D Polyimide Covalent Organic Framework for Rechargeable Sodium-Ion Batteries.
Covalent organic frameworks (COFs) hold great promise for electrochemical energy storage because of their high surface area, readily accessible redox-active sites, and environment-friendly chemical composition. In this study, the synthesis of a redox-active pyrene-containing polyimide COF (PICOF-1) by linker exchange using an imine-linked COF as a template is reported and its performance in sodium-ion batteries (SIBs) is demonstrated. The reported synthetic route based on linker exchange mitigates the challenges typically encountered with crystallizing chemically stable polyimide COFs from typical condensation reactions; thus, facilitating their rapid synthesis and purification. Using this approach, PICOF-1 exhibits high crystallinity with very low refinement parameters RP and RWP of 0.415% and 0.326%, respectively. PICOF-1 has a high Brunauer-Emmette-Teller (BET) surface area of 924 m2 g-1 and well-defined one-dimentional (1D) channels of 2.46 × 1.90 nm, which enable fast ion transport and charge transfer, reaching a capacity at 0.1 C of almost nearly as its theoretical capacity and maintaining 99% Coulombic efficiency over 175 cycles at 0.3 C. The study demonstrates that imine-linked COFs are effective templates for integrating carbonyl-rich polyimide moieties into high-surface COFs to advance electrochemical energy storage applications.


Modeling limit order trading with a continuous action policy for deep reinforcement learning.
Limit Orders allow buyers and sellers to set a "limit price" they are willing to accept in a trade. On the other hand, market orders allow for immediate execution at any price. Thus, market orders are susceptible to slippage, which is the additional cost incurred due to the unfavorable execution of a trade order. As a result, limit orders are often preferred, since they protect traders from excessive slippage costs due to larger than expected price fluctuations. Despite the price guarantees of limit orders, they are more complex compared to market orders. Orders with overly optimistic limit prices might never be executed, which increases the risk of employing limit orders in Machine Learning (ML)-based trading systems. Indeed, the current ML literature for trading almost exclusively relies on market orders. To overcome this limitation, a Deep Reinforcement Learning (DRL) approach is proposed to model trading agents that use limit orders. The proposed method (a) uses a framework that employs a continuous probability distribution to model limit prices, while (b) provides the ability to place market orders when the risk of no execution is more significant than the cost of slippage. Extensive experiments are conducted with multiple currency pairs, using hourly price intervals, validating the effectiveness of the proposed method and paving the way for introducing limit order modeling in DRL-based trading.


Death from within: apoptosis and the secretory pathway.
Recent studies have highlighted the importance of the secretory pathway in stress-induced apoptotic signaling. Sensing stress at the endoplasmic reticulum and Golgi might first trigger recovery mechanisms, followed by apoptosis if repair is unsuccessful. Cleavage of endoplasmic-reticulum- or Golgi-resident proteins can signal repair or apoptosis and promote organelle disassembly during apoptosis. Initiation of apoptosis from the secretory pathway requires components of the death machinery localized to these membranes. Extensive trafficking between compartments of the secretory pathway might allow the cell to integrate signals and to determine the proper response to a particular stress.


The C2 entity of chitosugars is crucial in molecular selectivity of the Vibrio campbellii chitoporin.
The marine bacterium Vibrio campbellii expresses a chitooligosaccharide-specific outer-membrane channel (chitoporin) for the efficient uptake of nutritional chitosugars that are externally produced through enzymic degradation of environmental host shell chitin. However, the principles behind the distinct substrate selectivity of chitoporins are unclear. Here, we employed black lipid membrane (BLM) electrophysiology, which handles the measurement of the flow of ionic current through porins in phospholipid bilayers for the assessment of porin conductivities, to investigate the pH dependency of chitosugar-chitoporin interactions for the bacterium's natural substrate chitohexaose and its deacetylated form, chitosan hexaose. We show that efficient passage of the N-acetylated chitohexaose through the chitoporin is facilitated by its strong affinity for the pore. In contrast, the deacetylated chitosan hexaose is impermeant; however, protonation of the C2 amino entities of chitosan hexaose allows it to be pulled through the channel in the presence of a transmembrane electric field. We concluded from this the crucial role of C2-substitution as the determining factor for chitoporin entry. A change from N-acetylamino- to amino-substitution effectively abolished the ability of approaching molecules to enter the chitoporin, with deacetylation leading to loss of the distinctive structural features of nanopore opening and pore access of chitosugars. These findings provide further understanding of the multistep pathway of chitin utilization by marine Vibrio bacteria and may guide the development of solid-state or genetically engineered biological nanopores for relevant technological applications.


Local distribution of the lycaenid butterfly, Jalmenus evagoras, in response to host ants and plants.
The caterpillars of Jalmenus evagoras are tended by ants as they feed upon Acacia trees. In the area of Brisbane, Australia, J. evagoras require ants of the Iridomyrmex anceps species group; predation and parasitism are so intense that larvae and pupae deprived of attendant ants cannot survive (Pierce 1983). We investigated the efficiency with which J. evagoras locate and exploit the "host ant" resource by sampling 737 quadrats in 30 sampling grids and six study sites containing appropriate host plants; ants were collected at baits located in the center of each quadrat. J. evagoras was found in all habitats where I. anceps cooccurred with host Acacia. Nine of the ten sampling grids which had three or more I. anceps/Acacia "host" quadrats also had colonies of J. evagoras present (or immediately adjacent), including sites as far as 35 km apart. Of 19 sampling grids on which "host" quadrats were rare (i.e., less than three quadrats), none had J. evagoras (P<0.001). Within sample grids, I. anceps was distributed indepedently from Acacia trees, suggesting that they are not dependent for their survival on either Acacia or on J. evagoras. Within montane pasture habitats, I. anceps and at least one other ground-dwelling Iridomyrmex species were distributed in mutually exclusive "ant mosaic" territories which were stable during a one month period. I. anceps did not colonize or tend pupae of J. evagoras experimentally placed in adjacent territories of a different, nontending species of Iridomyrmex, demonstrating the integrity of territory boundaries. Sampling of ants in Acacia trees revealed that, in the absence of J. evagoras, Iridomyrmex workers are not common above ground level, and that their numbers decline in larger trees (P=0.02). In I. anceps territories, eight of nine J. evagoras pupae placed in trees over 3.0 m tall were not found after 24 h whereas all ten controls placed in low trees were found and tended (P=0.00012). This may explain why J. evagoras tends to oviposit in trees less than 2.0 m tall. An alternative hypothesis, that smaller trees have higher content of total nitrogen, and are threfore more nutritious, was not supported. We conclude that the local distribution and host tree selection by J. evagoras is dependent upon the distribution, patchiness, and foraging behavior of the host ant, I. anceps, and its spatial overlap with a number of species of host Acacia.


Review and Evaluation of the J100-10 Risk and Resilience Management Standard for Water and Wastewater Systems.
Risk analysis standards are often employed to protect critical infrastructures, which are vital to a nation's security, economy, and safety of its citizens. We present an analysis framework for evaluating such standards and apply it to the J100-10 risk analysis standard for water and wastewater systems. In doing so, we identify gaps between practices recommended in the standard and the state of the art. While individual processes found within infrastructure risk analysis standards have been evaluated in the past, we present a foundational review and focus specifically on water systems. By highlighting both the conceptual shortcomings and practical limitations, we aim to prioritize the shortcomings needed to be addressed. Key findings from this study include (1) risk definitions fail to address notions of uncertainty, (2) the sole use of "worst reasonable case" assumptions can lead to mischaracterizations of risk, (3) analysis of risk and resilience at the threat-asset resolution ignores dependencies within the system, and (4) stakeholder values need to be assessed when balancing the tradeoffs between risk reduction and resilience enhancement.


A tuberculosis nationwide prevalence survey in Gambia, 2012.
To estimate the population prevalence of active pulmonary tuberculosis in Gambia. Between December 2011 and January 2013, people aged ≥ 15 years participating in a nationwide, multistage cluster survey were screened for active pulmonary tuberculosis with chest radiography and for tuberculosis symptoms. For diagnostic confirmation, sputum samples were collected from those whose screening were positive and subjected to fluorescence microscopy and liquid tuberculosis cultures. Multiple imputation and inverse probability weighting were used to estimate tuberculosis prevalence. Of 100 678 people enumerated, 55 832 were eligible to participate and 43 100 (77.2%) of those participated. A majority of participants (42 942; 99.6%) were successfully screened for symptoms and by chest X-ray. Only 5948 (13.8%) were eligible for sputum examination, yielding 43 bacteriologically confirmed, 28 definite smear-positive and six probable smear-positive tuberculosis cases. Chest X-ray identified more tuberculosis cases (58/69) than did symptoms alone (43/71). The estimated prevalence of smear-positive and bacteriologically confirmed pulmonary tuberculosis were 90 (95% confidence interval, CI: 53-127) and 212 (95% CI: 152-272) per 100 000 population, respectively. Tuberculosis prevalence was higher in males (333; 95% CI: 233-433) and in the 35-54 year age group (355; 95% CI: 219-490). The burden of tuberculosis remains high in Gambia but lower than earlier estimates of 490 per 100 000 population in 2010. Less than half of all cases would have been identified based on smear microscopy results alone. Successful control efforts will require interventions targeting men, increased access to radiography and more accurate, rapid diagnostic tests.


Hydrolysis of 4-methylumbelliferyl-beta-D-glucuronide in differing sample fractions of river waters and its implication for the detection of fecal pollution.
The hydrolysis rate of 4-methylumbelliferyl-beta-D-glucuronide (MUG-HR) was determined in unamended samples, filtered samples, and in corresponding buffer resuspended filter residues of various river waters of slight to excessive fecal pollution covering a four orders of magnitude range. Regression analysis of the log MUG-HR of the unamended water samples versus the log MUG-HR of the filter residues revealed a highly significant linear relationship (R2 = 0.94; p<0.001). The median of the MUG-HR of the filtrated water samples was about 10% the MUG-HR of the corresponding unamended water samples. If MUG-HR determinations were used as a surrogate for estimating fecal coliform contamination, both the MUG-HR of the unamended water samples and the MUG-HR of the filter residues would have been equally adequate techniques at river sites of higher fecal pollution levels. However, at river locations of decreased fecal pollution, MUG-HR determination of filter residues appeared to be the more sensitive technique in order to estimate fecal coliform concentrations.


Regulatory effects of matrix protein variations on influenza virus growth.
Influenza virus A/WSN/33 forms large plaques (> 3 mm diameter) on MDCK cells whereas A/Aichi/2/68 forms only small plaques (< 1 mm diameter). Fast growing reassortants (AWM), isolated by mixed infection of MDCK cells with these two virus strains in the presence of anti-WSN antibodies, all carried the M gene from WSN. On MDCK cells, these reassortants produced progeny viruses as rapidly as did WSN, and the virus yield was as high as Aichi. The fast-growing reassortants overcame the growth inhibitory effect of lignins. Pulse-labeling experiments at various times after virus infection showed that the reassortant AWM started to synthesize viral proteins earlier than Aichi. Taken together, we conclude that upon infecting MDCK cells, the reassortant viruses advance rapidly into the growth cycle, thereby leading to an elevated level of progeny viruses in the early period of infection. Possible mechanisms of the M gene involvement in the determination of virus growth rate are discussed, in connection with multiple functions of the M proteins.


Platelet adhesion on commercially pure titanium plates in vitro III: effects of calcium phosphate-blasting on titanium plate biocompatibility.
Platelet-rich plasma (PRP) is often used to improve surface biocompatibility. We previously found that platelets rapidly adhere to plain commercially pure titanium (cp-Ti) plates in the absence, but not in the presence, of plasma proteins. To further expand on these findings, in the present study, we switched titanium plates from a plain surface to a rough surface that is blasted with calcium phosphate (CaP) powder and then examined platelet adhesion and activation. Elemental distribution in CaP-blasted cp-Ti plates was analyzed using energy-dispersive X-ray spectroscopy. PRP samples prepared from anticoagulated blood samples of six healthy, non-smoking adult male donors were loaded on CaP-blasted cp-Ti plates for 1 h and fixed for examination of platelet morphology and visualization of PDGF-B and platelet surface markers (CD62P, CD63) using scanning electron microscopy and fluorescence microscopy. Plain SUS316L stainless steel plates used in injection needles were also examined for comparison. Significant amounts of calcium and phosphate were detected on the CaP-blasted cp-Ti surface. Platelets rapidly adhered to this surface, leading to higher activation. Platelets also adhered to the plain stainless surface; however, the levels of adhesion and activation were much lower than those observed on the CaP-blasted cp-Ti plate. The CaP-blasted cp-Ti surface efficiently entraps and activates platelets. Biomolecules released from the activated platelets could be retained by the fibrin matrix on the surface to facilitate regeneration of the surrounding tissues. Thus, PRP immersion could not only eliminate surface air bubbles but also improve the biocompatibility of the implant surface.


Evaluation of a stair-climbing power wheelchair in 25 people with tetraplegia.
To compare the performance of a power wheelchair with stair-climbing capability (TopChair) and a conventional power wheelchair (Storm3). A single-center, open-label study. A physical medicine and rehabilitation hospital. Patients (N=25) who required power wheelchairs because of severe impairments affecting the upper and lower limbs. Indoor and outdoor driving trials with both devices. Curb-clearing and stair-climbing with TopChair. Trial duration and Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) tool; number of failures during driving trials and ability to climb curbs and stairs. All 25 participants successfully completed the outdoor and indoor trials with both wheelchairs. Although differences in times to trial completion were statistically significant, they were less than 10%. QUEST scores were significantly better with the Storm3 than the TopChair for weight (P=.001), dimension (P=.006), and effectiveness (P=.04). Of the 25 participants, 23 cleared a 20-cm curb without help, and 20 climbed up and down 6 steps. Most participants felt these specific capabilities of the TopChair--for example, curb clearing and stair climbing-were easy to use (22/25 for curb, 21/25 for stairs) and helpful (24/25 and 23/25). A few participants felt insecure (4/25 and 6/25, respectively). The TopChair is a promising mobility device that enables stair and curb climbing and warrants further study.


Sluggish cognitive tempo (Cognitive Disengagement Syndrome) symptoms are more associated with a higher risk of internet addiction and internet gaming disorder than ADHD symptoms: A study with medical students and resident doctors.
The purpose of this study was to examine the relationships between Attention Deficit Hyperactivity Disorder (ADHD), Sluggish Cognitive Tempo (SCT), demographic factors, and Internet Addiction (IA) and internet gaming disorder (IGD) among medical students and resident doctors. The study included 274 medical students and resident doctors. (Ages:18-35, 70.4% female). Fisher exact test, Contingency Table analyses, Mann Whithey-U Test and structural equation model-path analysis were used for analysis. The Sociodemographic Information Form, ASRS Scale, Barkley SCT Scale, Young Internet Addiction Test-Short Form and The Digital Game Addiction Scale were utilized to collect data. In the sample, 48 participants (17.51%, 22 female, 26 male) were classified as having a high-risk internet gaming disorder (IGD+), while 53 participants (19.3%, 37 female, 16 male) were classified as having a high-risk internet addiction (IA+). SCT Scale Daydreaming and Sluggishness scores, as well as ASRS Scale Inattention and Hyperactivity/Impulsivity ratings, were all substantially higher in high-risk groups (for all, p < 0.05). Instead of age, there was no difference between high and low-risk groups, but men had a significantly greater rate of high risk- IGD (%32.1 vs. 11.4; p = 0.001). Path analysis revealed that while older age has a substantial negative effect (β = -0.37, p = 0.001) on increased risk of IA, Inattention (β = 0.19, p = 0.028), Daydreaming (β = 0.62, p0.001), and Sluggishness ( β = 1.12, p0.001) had significant positive effects. On the other hand, results revealed that male gender (β = 5.08, p0.001), IA scores (β = 0.21, p0.001), and only Sluggishness ( = 0.52, p = 0.002), but not Inattention, Hyperactivity/impulsivity, or Daydreaming, have positive effects on greater risk of internet gaming disorder (IGD). Our study is the first to show that SCT symptoms increase the risk of Internet addiction and Internet Gaming Disorder even when ADHD symptoms are controlled. To date, many research have highlighted the necessity of ADHD treatment when evaluating IA and IGD. However, SCT symptoms have a greater impact on people who are predisposed to these behavioral addictions, and despite high comorbidity rates, various treatment approaches for ADHD and SCT are effective. SCT should be kept in mind when assessing treatment-resistant individuals with IA and IGD.


A two-component histidine kinase, MoSLN1, is required for cell wall integrity and pathogenicity of the rice blast fungus, Magnaporthe oryzae.
A two-component signal transduction system is a common mechanism for environmental sensing in bacteria. The functions of the two-component molecules have been also well characterized in the lower eukaryotic fungi in recent years. In Saccharomyces cerevisiae, the histidine kinase Sln1p is a major component of the two-component signaling pathways and a key regulator of the osmolarity response. To determine the function of MoSLN1, a Sln1 homolog of Magnaporthe oryzae, we cloned the MoSLN1 gene and generated specific mutants using gene knock-out strategy. Disruption of MoSLN1 resulted in hypersensitivity to various stresses, reduced sensitivity to cell wall perturbing agent Calcofluor white, and loss of pathogenicity, mainly due to a penetration defect. Additionally, we showed that MoSLN1 is involved in oxidative signaling through modulation of intra- and extracellular peroxidase activities. These results indicate that MoSLN1 functions as a pathogenicity factor that plays a role in responses to osmotic stress, the cell wall integrity, and the activity of peroxidases.


The effects of ACE inhibitor and angiotensin receptor blocker on clusterin and apoptosis in the kidney tissue of streptozotocin-diabetic rats.
Our first aim was to determine the effects of secreted clusterin (sCLU) and nuclear clusterin (nCLU) in diabetic nephropathy. We also aimed to investigate the post-effects of angiotensin II blockage treatment on clusterin expression and to compare these with apoptosis. Five groups of Wistar albino rats were used: First group consisted of healthy controls; the second group included the untreated STZ-diabetics; 30 days of irbesartan or perindopril treated STZ-diabetics formed the third and the fourth groups, respectively; while the subjects receiving a combined treatment with irbesartan and perindopril for 30 days consisted the fifth group. TUNEL method for apoptosis and immunohistochemical staining for TGF-beta1, alpha-SMA, clusterin-beta and clusterin-alpha/beta antibodies were performed. Apoptotic cells especially increased in the kidney tubuli of untreated diabetic group and on the contrary, a significant decrease was observed in the group that received a combined drug treatment. While sCLU was increased in the glomeruli and tubuli of the untreated diabetic group, it was decreased in all the treated groups. An increase in the nCLU immunoreactivity was observed in the podocytes, mesangial cells, and the injured tubule cells of the untreated diabetic group. nCLU immunopositive cells were decreased in all treated diabetic groups. In addition to this, the distribution of nCLU was similar to the distribution of apoptotic cells in the diabetic groups. Our results indicate that sCLU expression in diabetic nephropathy was induced due to renal tissue damage, and the nCLU expression increase in renal tubuli was related to apoptosis. Although irbesartan and perindopril prevented further renal injury in diabetes, a combined application of low-dose ACEI and AT1R blockers revealed more efficient measures, by means of renal damage prevention.


In vitro cytocompatibility of porcine type I atelocollagen crosslinked by oxidized glycogen.
Oxidized glycogen is used as collagen crosslinker to obtain materials with defined crosslinking degrees. These materials are characterized by their swelling ratio. calorimetric properties and the crosslinking level. Direct and indirect cytotoxicities of the materials obtained as sheets, are evaluated in vitro in cultures of human fibroblasts. The crosslinking degree depends on the ratio CHO glycogen/NH2 glycogen, but whatever this ratio (4.0, 2.0 or 0.4), an important percentage of the introduced CHO groups remains free and these groups are responsible for the cytotoxicity observed with the strongly crosslinked materials. This cytotoxicity appears in cell shape modification and in significant reduction of cell growth. Whatever the crosslinking degree, this toxicity can be suppressed by a single treatment with sodium borohydride, which reduced the remaining free CHO groups in OH functions and stabilizes the materials by a concomitant reduction of the crosslinking imine bonds. After reduction, all materials allow cellular adhesion and proliferation. This new crosslinking method of the collagen by the oxidized glycogen could be promising in the preparation of matrix for in vitro and in vivo tissue regeneration.


Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations.
Pregnancy is proposed to aggravate cyst progression in autosomal dominant polycystic kidney disease (ADPKD) but Tolvaptan, the only FDA-approved drug for adult ADPKD, is not recommended for pregnant ADPKD patients because of potential fetal harm. Since pregnancy itself may increase the risk for ADPKD progression, we investigated the safety and efficacy of Elamipretide, a mitochondrial-protective tetrapeptide. Elamipretide was found to ameliorate the progression of kidney disease in pregnant Pkd1RC/RC mice, in parallel with attenuation of ERK1/2 phosphorylation and improvement of mitochondrial supercomplex formation. Furthermore, Elamipretide was found to pass through the placenta and breast milk and ameliorate aggressive infantile polycystic kidney disease without any observed teratogenic or harmful effect. Elamipretide has an excellent safety profile and is currently tested in multiple phase II and phase III clinical trials. These preclinical studies support a potential clinical trial of Elamipretide for the treatment of ADPKD, particularly for patients that cannot take Tolvaptan.


Some Misconceptions in the Treatment of Cubital Tunnel Syndrome, Radial Tunnel Syndrome, and Median Nerve Compression in the Forearm.
This article discusses ulnar, median, and radial nerve compression in the proximal forearm and elbow and some possible common misconceptions. In particular, the ligament of Struthers extremely rarely causes ulnar neuropathy. Lacertus syndrome and flexor superficialis-pronator syndrome can be diagnosed separately. Surgical release can be through a small incision. Acronyms for compression to radial nerve in proximal forearm can be simplified to radial tunnel syndrome, which includes a mild type (classical radial tunnel syndrome) and a severe type (posterior interosseous nerve (PIN) compression).


Myopia Control with a Novel Peripheral Gradient Soft Lens and Orthokeratology: A 2-Year Clinical Trial.
To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. The baseline refractive sphere was correlated significantly (Spearman's Rho (ρ) correlation = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were -0.56 ± 0.51, -0.32 ± 0.53, and -0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased 27% and 38% less in the SRRG and OK groups, respectively compared with the SV group at the 2-year visit (P < 0.05). Axial elongation was not significantly different between SRRG and OK (P = 0.430). The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent.


Administration of granulocyte-macrophage colony-stimulating factor enhanced chimeric antigen receptor T-cell expansion and cellular immunity recovery without inducing cytokine release syndrome.
Neutropenia and cytokine release syndrome (CRS) are two major toxicities of chimeric antigen receptor (CAR)-T cell therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an ideal candidate treatment for neutropenia except for its potential aggravation of CRS. We hypothesized that the optimal timing of supplemental with GM-CSF in a shortage of host immunity and CAR T-cell was chosen as avoidance of CRS. In the study we evaluated the safety and efficacy of GM-CSF intervention post-CAR T-cell therapy while circulating CAR T-cell declined. Nine patients received GM-CSF therapy who displayed moderate neutropenia with absolute neutrophil counts (ANC) < 1,500 cells/mm3 with concomitant declination of circulating CAR T-cell. The median duration of GM-CSF intervention was 15 days (4-30). CAR T-cell expansion was observed in peripheral blood (PB) of seven patients (7/9). The median baseline and peak CAR T cells count in PB of the seven patients with CAR T-cell expansion were 0.85 × 106/L (0-50.9) and 6.06 × 106/L (1.43-112.55). And the peaks of CAR T-cell levels in PB appeared in day 7 (2-11) following the initiation of GM-CSF administration with increases of 2.84 × 106/L (0.38-61.65). Also, increased white blood cells in PB were observed in all patients. The median onset and duration time of WBC recovery were 9 (1-14) and 17 (3-53) days. Moreover, the increment of WBC, neutrophil, lymphocyte and CD3-CD16 + CD56 + natural killer cell in PB was observed. In addition, no CRS or fatal infection occurred during GM-CSF treatment. This study provides evidence for the clinical feasibility of combining CAR T-cell therapy with the GM-CSF to treat neutropenia patients with concomitant declination of circulating CAR T-cell.


Development and characterization of a plant-derived norovirus-like particle vaccine.
Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains. NoV VLPs (NoVLP) composed of the surface viral protein (VP) 1 of the GI and GII genogroups were produced in Nicotiana benthamiana using an Agrobacterium tumefaciens-based recombinant transient expression system. Leaves from infiltrated plants were harvested and NoVLPs were extracted and purified. The safety and immunogenicity of the GII.4 NoVLP, the genotype currently causing most human disease, were subsequently examined in rabbits and mice. Fifteen GI and GII NoVLPs were successfully expressed in N. benthamiana and were structurally similar to NoV virions, as determined by cryogenic transmission electron microscopy. The NoVLP was well-tolerated, with no local or systemic signs of toxicity in rabbits. Three intramuscular doses of the GII.4 NoVLP adjuvanted with aluminum hydroxide induced robust IgG titers, IgG-secreting cells, histo-blood group antigen blocking titers, and IFNγ-secreting T cells in mice. In addition to circulating antibodies, oral administration of the NoVLP in mice induced significant IgA levels in feces, indicative of a mucosal response. The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses.


Contributions of general practitioners in China facing the COVID-19 outbreak.
During the COVID-19 pandemic, general practitioners have played the crucial part of health gatekeepers, which should be acknowledged and appreciated.


[Experimental study of periosteal osteoblasts coculture with freeze-dried demineralized bone matrix].
To investigate the feasibility of freeze-dried demineralized bone matrix (FDBM) as scaffold material in bone tissue engineering. Osteoblasts which were isolated from cranial periosteum of New Zealand rabbits were cultured as the seeding cells, then the cells were cocultured with heterogenous FDBM in vitro. The cell-material complex was observed under phase microscope, light microscope and electronic scanning microscope in order to evaluate the interaction between cells and FDBM. Eight hours after coculture, the osteoblasts adhered to FDBM scaffolds. Seven days later, the osteoblasts differentiated and proliferated in FDBM network. Extracellular matrix was secreted and calcium nodes were formed among osteoblasts. FDBM is a good scaffold material for the bone tissue engineering.


Ecological and evolutionary forces shaping microbial diversity in the human intestine.
The human gut is populated with as many as 100 trillion cells, whose collective genome, the microbiome, is a reflection of evolutionary selection pressures acting at the level of the host and at the level of the microbial cell. The ecological rules that govern the shape of microbial diversity in the gut apply to mutualists and pathogens alike.


The section-Golgi-impregnation procedure--3. Combination of Golgi-impregnation with enzyme histochemistry and electron microscopy to characterize acetylcholinesterase-containing neurons in the rat neostriatum.
Three morphologically distinct types of neuron that contain acetylcholinesterase have been distinguished by Golgi-impregnation of sections of the rat neostriatum that had been incubated to reveal acetylcholinesterase activity. The neuron that stained most intensely for acetylcholinesterase was a large cell, with smooth or sparsely spiny dendrites; the axon of one these neurons was partially impregnated by the Golgi stain and had local axon collaterals (type 1). Another acetylcholinesterase-containing neuron had a small to medium-size cell body with long sparsely spiny dendrites emerging from opposite poles (type 2). The third type of neuron that contained acetylcholinesterase was medium to large size and had many primary, sparsely spiny dendrites that branched frequently (type 3). Examination of the same Golgi-impregnated, acetylcholinesterase-stained neurons that had been studied in the light microscope by electron microscopy allowed us to distinguish several other differences between the three types of neuron. Whereas all three types had acetylcholinesterase reaction product in the endoplasmic reticulum and along the nuclear envelope, only neurons of type 1 displayed reaction product in the Golgi apparatus. All three types of neuron received synaptic input, mainly along their dendrites. It is concluded that the combination of Golgi-impregnation with histochemical procedures that demonstrate endogenous enzyme activity can be applied to reveal the morphological characteristics, synaptic input and local synaptic output of neurons with specific biochemical properties.


Diseases with oral manifestations among adult asthmatics in Finland: a population-based matched cohort study.
Many comorbidities are associated with adult asthma and may exacerbate the asthma burden of disease. This study aims to investigate the risk for major oral diseases or oral-manifesting diseases in asthmatic compared with non-asthmatic adults. We conducted a population-based matched cohort study with a 13.8-year follow-up. A baseline questionnaire was completed by participants in 1997 and follow-up data were extracted from the national hospital discharge registry of the National Institute for Health and Welfare in Finland from 1997 to 2014. A total of 1394 adults with asthma were matched with 2398 adults without asthma based on sex, age and area of residence. Asthmatic adults were identified from the Drug Reimbursement Register of the Finnish Social Insurance Institution based on a special drug reimbursement right resulting from asthma. Participants without asthma were identified from the Population Register. Oral health-related primary diagnoses were retrieved using codes from the International Classification of Diseases, 10th edition and divided into groups of diseases. Cox's proportional hazards models stratified by matching unit and models matched and adjusted for pack-years, education level and body mass index (when possible) were used to evaluate the matched and further adjusted HRs for diseases comparing asthmatic and non-asthmatic cohorts. Adult asthma was associated with a higher risk for any oral-manifesting disease (adjusted HR 1.41, 95% CI 1.11 to 1.80), herpes zoster (adjusted HR 6.18, 95% CI 1.21 to 31.6), benign tumours of the oral cavity and pharynx (matched HR 1.94, 95% CI 1.05 to 3.56) and dermatological diseases (pemphigus, pemphigoid, dermatitis herpetiformis, psoriasis and lichen planus, HR 1.67, 95% CI 1.01 to 2.78). In this study, adult asthmatics experienced a higher risk for a major oral disease or oral-manifesting disease.


Nasal chondromesenchymal hamartoma causing sleep-disordered breathing in an infant.
Nasal chondromesenchymal hamartoma is an extremely rare neoplasm of the nasal and paranasal sinuses. We present the case of a 10-month-old boy with a huge nasal chondromesenchymal hamartoma that was complicated by sleep-disordered breathing. The mass was completely resected by image-guided endoscopic surgery and confirmed histopathologically as a chondromesenchymal hamartoma. In this report, we discuss the characteristics and treatment of this unusual tumor.


New Roles for an Ancient Factor.
In 1996, Hyejin Kang and Erin Schuman, in search of new functions for the secreted growth factor brain-derived neurotrophic factor (BDNF), identified the protein synthesis requirement of BDNF in regulating synaptic plasticity. This landmark paper identified one of the first tractable pathways in the quest to dissect the complex process of synaptic remodeling and revealed the critical role for this neurotrophin in regulating long-term memory.


Effect of long-term equilibration on the toxicity of molybdenum to soil organisms.
To determine if long-term equilibration may alleviate molybdenum toxicity, earthworms, enchytraeids, collembolans and four plant species were exposed to three soils freshly spiked with Na(2)MoO(4).2H(2)O and equilibrated for 6 or 11 months in the field with free drainage. Total Mo concentrations in soil decreased by leaching, most (up to 98%) in sandy soil and less (54-62%) in silty and clayey soils. Changes in residual Mo toxicity with time were inconclusive in sandy soil. In the other two soils, toxicity of residual total Mo was significantly reduced after 11 months equilibration with a median 5.5-fold increase in ED50s. Mo fixation in soil, i.e. the decrease of soil solution Mo concentrations at equivalent residual total soil Mo, was maximally a factor of 2.1 only. This experiment shows natural attenuation of molybdate ecotoxicity under field conditions is related to leaching of excess Mo and other ions as well as to slow ageing reactions.


How Leiomodin and Tropomodulin use a common fold for different actin assembly functions.
How proteins sharing a common fold have evolved different functions is a fundamental question in biology. Tropomodulins (Tmods) are prototypical actin filament pointed-end-capping proteins, whereas their homologues, Leiomodins (Lmods), are powerful filament nucleators. We show that Tmods and Lmods do not compete biochemically, and display similar but distinct localization in sarcomeres. Changes along the polypeptide chains of Tmods and Lmods exquisitely adapt their functions for capping versus nucleation. Tmods have alternating tropomyosin (TM)- and actin-binding sites (TMBS1, ABS1, TMBS2 and ABS2). Lmods additionally contain a C-terminal extension featuring an actin-binding WH2 domain. Unexpectedly, the different activities of Tmods and Lmods do not arise from the Lmod-specific extension. Instead, nucleation by Lmods depends on two major adaptations-the loss of pointed-end-capping elements present in Tmods and the specialization of the highly conserved ABS2 for recruitment of two or more actin subunits. The WH2 domain plays only an auxiliary role in nucleation.


Nerve pathophysiology and mechanisms of pain in causalgia.
In contrast to sensory endings in skin, muscle, etc., afferents in the mid-course of intact nerves are normally incapable of generating impulses upon slow or prolonged depolarization. However, after various types of nerve injury, including complete nerve section and local demyelination, an ectopic pacemaker capability develops. One peculiarity of such abnormal differentiated sites is chemosensitivity to alpha-adrenergic agonists and to sympathetic efferents discharge. Such ectopic chemosensitivity may well be involved in the etiology of paraesthesias and pain in reflex sympathetic dystrophies including causalgia. Specifically, it is proposed that the fundamental cause of these conditions is the development of abnormal electrogenic membrane properties in the region of demyelination and sprout outgrowth. These abnormal properties presumably include the appearance of excess inward current conductances and ectopic alpha-adrenergic receptors. Catecholamines released from sympathetic efferents in the area of injury locally depolarize damaged sensory fibers, and because of the abnormal electrogenic properties of these fibers, an abnormal afferent discharge is generated.


Preservation of and DNA Extraction from Muscle Tissue.
As well as protecting DNA for subsequent analysis, tissue preservation methods ideally should be safe, readily available, and easy to transport at relatively low cost. Formalin (formaldehyde solution), used extensively to preserve medical and museum specimens, irreparably damages DNA. We have found four tissue preservatives (solid salt, salt-saturated dimethyl sulfoxide (DMSO)-EDTA solution, ethanol solution, and ethanol-EDTA solution) that preserved muscle tissue at 35 °C for up to 1 month: full short tandem repeat (STR) profiles were obtained after preservation. In addition, salt-saturated DMSO-EDTA solution yielded full STR profiles from aliquots of the liquid preservative surrounding muscle tissue.


Feminizing Wolbachia: a transcriptomics approach with insights on the immune response genes in Armadillidium vulgare.
Wolbachia are vertically transmitted bacteria known to be the most widespread endosymbiont in arthropods. They induce various alterations of the reproduction of their host, including feminization of genetic males in isopod crustaceans. In the pill bug Armadillidium vulgare, the presence of Wolbachia is also associated with detrimental effects on host fertility and lifespan. Deleterious effects have been demonstrated on hemocyte density, phenoloxidase activity, and natural hemolymph septicemia, suggesting that infected individuals could have defective immune capacities. Since nothing is known about the molecular mechanisms involved in Wolbachia-A. vulgare interactions and its secondary immunocompetence modulation, we developed a transcriptomics strategy and compared A. vulgare gene expression between Wolbachia-infected animals (i.e., "symbiotic" animals) and uninfected ones (i.e., "asymbiotic" animals) as well as between animals challenged or not challenged by a pathogenic bacteria. Since very little genetic data is available on A. vulgare, we produced several EST libraries and generated a total of 28 606 ESTs. Analyses of these ESTs revealed that immune processes were over-represented in most experimental conditions (responses to a symbiont and to a pathogen). Considering canonical crustacean immune pathways, these genes encode antimicrobial peptides or are involved in pathogen recognition, detoxification, and autophagy. By RT-qPCR, we demonstrated a general trend towards gene under-expression in symbiotic whole animals and ovaries whereas the same gene set tends to be over-expressed in symbiotic immune tissues. This study allowed us to generate the first reference transcriptome ever obtained in the Isopoda group and to identify genes involved in the major known crustacean immune pathways encompassing cellular and humoral responses. Expression of immune-related genes revealed a modulation of host immunity when females are infected by Wolbachia, including in ovaries, the crucial tissue for the Wolbachia route of transmission.


[Changes in coronary circulation following reflex excitation of the sympathetic nervous system].
The patterns and efferent mechanisms of coronary blood flow reactions in cats following sympathetic activation after hemorrhage and carotid occlusion, were studied. Like in other vascular regions, the sympathetic activation led to alpha-adrenergic coronary constriction which was particularly clear after blocking of neurogenic and metabolic vasodilatory factors (beta-blockers, atropine). The significance of myogenic constrictory component was elucidated as well.


Ecologically relevant arsenic exposure alters female mate preference and anxiety-like behavior in Betta splendens.
Arsenic is a metalloid pollutant that is commonly found in surface and groundwater worldwide. Toxicological effects of arsenic are relatively well-known, but much less studied are its effects on behavioral endpoints, which may have considerable evolutionary and population-level consequences. Here we investigated the effects of exposure to environmentally relevant concentrations of arsenic (0, 10 and 100 μg/L) for 96-hours on female preference for male color (i.e. red versus blue) in Betta splendens, an increasingly popular fish model for contaminant-induced behavioral dysfunction. Further, we examined whether arsenic exposure altered anxiety-like behaviors using a standard scototaxis test (preference for light or dark), as well as measured tissue cortisol concentrations to increase our understanding of possible mechanisms driving behavioral responses. We found exposure to 100 μg/L arsenic results in a loss of female preference for red males, and arsenic exposed females showed increased anxiety-like behavior. The loss in preference for male coloration may have been driven by anxiety, as preference for red was negatively correlated with anxiety-like behavior for all fish. Interestingly, increase in anxiety-like behavior occurred without a parallel increase in cortisol. Female preference for red colored males may confer fitness benefits, and this study highlights important arsenic-induced behavioral changes that could have population level consequences.


Temporal genomics of vein bypass grafting through oligonucleotide microarray analysis.
Autologous vein is the conduit of choice for small artery reconstruction. Despite excellent patency, these conduits undergo remodeling over time. The purpose of this study was to identify temporal gene expression in vein grafts versus control veins through microarray analysis. Cephalic vein grafts (n = 12) were used to bypass femoral arteries in canines. Vein grafts were harvested after 1, 7, 14, and 30 days. Normal contralateral cephalic vein served as control. Total RNA was isolated; its quantity and quality were confirmed with spectrophotometry and gel electrophoresis. Affymetrix U133A GeneChips, comprising approximately 15,000 genes, were used to analyze differential gene expression at each time point. Statistical analysis was performed with Affymetrix and dChip software to identify consistently upregulated and downregulated genes. Real-time, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to validate microarray data. Statistical analysis revealed that 49 genes were consistently upregulated and 31 genes were consistently downregulated in all three animals at various time points. qRT-PCR to quantitatively assess messenger RNA expression was performed on specific genes to validate the microarray data. Immunohistochemistry to qualitatively assess protein expression was used for further validation. Hierarchical clustering with dChip identified additional genes with similar temporal or functional expression patterns. This is the first study to use microarray analysis with confirmatory qRT-PCR to identify altered genes after vein bypass grafting. Oligonucleotide microarrays and hierarchical clustering are powerful tools to generate hypotheses as the basis for additional research on gene expression in vein graft remodeling. Ultimately, identification of a temporal sequence of differential gene expression may provide insights not preferred into the molecular mechanisms of vein graft remodeling, but also into the pathways leading to intimal hyperplasia.


Remifentanil versus Fentanyl/Midazolam in Painless Reduction of Anterior Shoulder Dislocation; a Randomized Clinical Trial.
Performance of painful diagnostic and therapeutic procedures is common in emergency department (ED), and procedural sedation and analgesia (PSA) is a fundamental skill for every emergency physician. This study was aim to compare the efficacy of remifentanil with fentanyl/midazolam in painless reduction of anterior shoulder dislocation. In this randomized, double blind, clinical trial the procedural characteristics, patients' satisfaction as well as adverse events were compared between fentanyl/midazolam and remifentanil for PSA of 18-64 years old patients, which were presented to ED following anterior shoulder dislocation. 96 cases were randomly allocated to two groups (86.5% male). There were no significant difference between groups regarding baseline characteristics. Remifentanil group had lower duration of procedure (2.5 ± 1.6 versus 4.6 ± 1.8 minutes, p < 0.001), higher pain reduction (53.7 ± 13.3 versus 33.5 ± 19.6, p < 0.001), lower failure rate (1 (2.1%) versus 15 (31.3%), p < 0.001), higher satisfaction (p = 0.005). Adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p = 0.122). It seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulder dislocation.


Correction: Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.
In the original version of this article, author 'Aisha Al-Khinji' was incorrectly listed as 'Aisha Ahmed'. This has now been corrected in both the PDF and HTML versions of the article to 'Aisha Al-Khinji'.