The therapy of infantile malignant brain tumors: current status?
Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors. Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d'Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. * The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae.


Correction: An Empirical Biomarker-Based Calculator for Cystic Index in a Model of Autosomal Recessive Polycystic Kidney Disease-The Nieto-Narayan Formula.
[This corrects the article DOI: 10.1371/journal.pone.0163063.].


Regional and global impact of CO2 uptake in the Benguela Upwelling System through preformed nutrients.
Eastern Boundary Upwelling Systems (EBUS) are highly productive ecosystems. However, being poorly sampled and represented in global models, their role as atmospheric CO2 sources and sinks remains elusive. In this work, we present a compilation of shipboard measurements over the past two decades from the Benguela Upwelling System (BUS) in the southeast Atlantic Ocean. Here, the warming effect of upwelled waters increases CO2 partial pressure (pCO2) and outgassing in the entire system, but is exceeded in the south through biologically-mediated CO2 uptake through biologically unused, so-called preformed nutrients supplied from the Southern Ocean. Vice versa, inefficient nutrient utilization leads to preformed nutrient formation, increasing pCO2 and counteracting human-induced CO2 invasion in the Southern Ocean. However, preformed nutrient utilization in the BUS compensates with ~22-75 Tg C year-1 for 20-68% of estimated natural CO2 outgassing in the Southern Ocean's Atlantic sector (~ 110 Tg C year-1), implying the need to better resolve global change impacts on the BUS to understand the ocean's role as future sink for anthropogenic CO2.


Water Temperature Affects Susceptibility to Ranavirus.
The occurrence of emerging infectious diseases in wildlife populations is increasing, and changes in environmental conditions have been hypothesized as a potential driver. For example, warmer ambient temperatures might favor pathogens by providing more ideal conditions for propagation or by stressing hosts. Our objective was to determine if water temperature played a role in the pathogenicity of an emerging pathogen (ranavirus) that infects ectothermic vertebrate species. We exposed larvae of four amphibian species to a Frog Virus 3 (FV3)-like ranavirus at two temperatures (10 and 25°C). We found that FV3 copies in tissues and mortality due to ranaviral disease were greater at 25°C than at 10°C for all species. In a second experiment with wood frogs (Lithobates sylvaticus), we found that a 2°C change (10 vs. 12°C) affected ranaviral disease outcomes, with greater infection and mortality at 12°C. There was evidence that 10°C stressed Cope's gray tree frog (Hyla chrysoscelis) larvae, which is a species that breeds during summer-all individuals died at this temperature, but only 10% tested positive for FV3 infection. The greater pathogenicity of FV3 at 25°C might be related to faster viral replication, which in vitro studies have reported previously. Colder temperatures also may decrease systemic infection by reducing blood circulation and the proportion of phagocytes, which are known to disseminate FV3 through the body. Collectively, our results indicate that water temperature during larval development may play a role in the emergence of ranaviruses.


Can Neural Activity Propagate by Endogenous Electrical Field?
It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds.


Treatment of arsenical keratosis with etretinate.
Treatment with oral etretinate is reported in a case of arsenical keratosis with Bowen's disease. Good (80%) clearance in keratoses was obtained, which is maintained after 15 months' follow up.


Neuroleptic malignant syndrome (parkinsonism-hyperpyrexia syndrome) after deep brain stimulation of the subthalamic nucleus.
Neuroleptic malignant syndrome (NMS), also called parkinsonism-hyperpyrexia syndrome (PHS), is a severe, general, sometimes fatal, physical reaction, induced by sudden and strong blockade of dopamine receptors. When subthalamic nucleus (STN)-deep brain stimulation (DBS) is used on patients with Parkinson disease (PD), dopaminergic medications are transiently stopped prior to the procedure, and a reduction in the use of drugs is routinely attempted after the procedure. Although a sudden stop or abrupt reduction of dopaminergic medications may set the stage for NMS/PHS, only three cases have been reported after STN-DBS surgery. Here, we describe a 75-year-old woman with PD who experienced delayed onset, yet fatal, PHS after STN-DBS. Although STN-DBS might prevent or suppress PHS, its protective effect is not always complete. We must be aware that fatal PHS can occur when the use of medication for PD is reduced or altered, even when patients are under continuous STN stimulation.


Cloning, purification, and characterization of β-galactosidase from Bacillus licheniformis DSM 13.
The gene encoding homodimeric β-galactosidase (lacA) from Bacillus licheniformis DSM 13 was cloned and overexpressed in Escherichia coli, and the resulting recombinant enzyme was characterized in detail. The optimum temperature and pH of the enzyme, for both o-nitrophenyl-β-D: -galactoside (oNPG) and lactose hydrolysis, were 50°C and 6.5, respectively. The recombinant enzyme is stable in the range of pH 5 to 9 at 37°C and over a wide range of temperatures (4-42°C) at pH 6.5 for up to 1 month. The K(m) values of LacA for lactose and oNPG are 169 and 13.7 mM, respectively, and it is strongly inhibited by the hydrolysis products, i.e., glucose and galactose. The monovalent ions Na(+) and K(+) in the concentration range of 1-100 mM as well as the divalent metal cations Mg²(+), Mn²(+), and Ca²(+) at a concentration of 1 mM slightly activate enzyme activity. This enzyme can be beneficial for application in lactose hydrolysis especially at elevated temperatures due to its pronounced temperature stability; however, the transgalactosylation potential of this enzyme for the production of galacto-oligosaccharides (GOS) from lactose was low, with only 12% GOS (w/w) of total sugars obtained when the initial lactose concentration was 200 g/L.


Comparison of binocular game and patching in treating mild to moderate anisometropic amblyopia: a study protocol for a randomized controlled trial.
Amblyopia, as a neurodevelopmental preventable visual disorder, affects approximately 1.1 % in Asia. A binocular approach to treating amblyopia has been recently proposed. Whether the binocular playing game treatment is comparable to patching treatment needs further randomized clinical trials. To address this, the present research, designs, develops, and evaluates a new binocular game to treat amblyopia. This study has been designed as a non-inferiority, randomized, two parallel-group, controlled trial. Forty-four patients between 4 and 12 years diagnosed with amblyopia will be randomly assigned to the control and intervention groups. In the intervention group, amblyopia treatment is provided with red-green anaglyphic glasses and a red filter placed in front of the amblyopic eye, along with a game to be played for 30 min twice a day. Those in the control group will receive patch therapy according to amblyopia treatment study protocol. The primary outcome is to change visual acuity in the amblyopic eye from the baseline to 3 months after randomization. The Ethics Committee of Mashhad University of Medical sciences' approval date was February 28, 2018, with a reference code of IR.MUMS.fm.REC.1396.783. Thus far, the recruitment of participants has not been completed and is scheduled to end in September 2021. The results will be disseminated in a peer-reviewed journal. Iranian Registry of Clinical Trials IRCT20180217038768N1 . Registered on 22 April 2019.


The attitude of maternity staff to, and smoking cessation interventions with, childbearing women in London.
To explore the self-reported smoking-cessation interventions of maternity staff with pregnant smokers, and their attitudes towards smoking in pregnancy. Postal survey of all 137 maternity staff (clinical grades A-H) at a large acute hospital in London; 78 questionnaires were completed (response rate: 57%). Over two-thirds of respondents (71%) reported not advising any pregnant women to give up smoking within the previous 7 days. However, nearly two-thirds (64%) felt that women should not be left to make up their own minds about whether or not to smoke during pregnancy, and even more (81%) agreed or strongly agreed that many pregnant women would like to give up smoking but need help and advice on how to succeed. Helping a pregnant woman to give up smoking was seen as being one of the most important things a midwife can do by 73% of the respondents. Although the reported attitudes were supportive of the midwife's role in smoking cessation, they did not translate into practice. The level of smoking cessation interventions was low. The findings from this study indicate some deficits in knowledge among maternity staff that training may address. Raising awareness of the local smoking-cessation service, and how to refer women to it, may increase the number of referrals maternity staff make.


[Positron emission tomography with [18 F]-2-fluoro-2-deoxy-D-glucose (18FDG-PET) in diagnosis of retroperitoneal lymph node metastases of testicular tumors].
In 1991, this prospectively designed study was started to assess the potentials of positron emission tomography with 18FDG in the diagnostic workup for the detection of lymph node metastases in testicular cancer, since there were no data available concerning this subject at this time. In 54 patients (27 patients with pure seminoma, 27 patients with non-seminomatous tumors) 18FDG-PET results were compared with the findings obtained with abdominal computed tomography, serum level of tumor markers (AFP, beta-HCG), and the histopathological findings after primary or post-chemotherapy retroperitoneal lymph node dissection. In 21 patients with pure seminoma (clinical stage I according to the Lugano classification) 18FDG-PET results were identical with those of the abdominal computed tomography, so PET does not add relevant informations in this group of patients. In 7 patients presenting with non-seminomatous testicular cancer (stage I), PET was not able to detect the existing micrometastases in 4 patients. In 1/7 case PET examination showed a suspicious focal lesion, this lymph node had 2 micrometastases within inflammatory changes. In 1/7 patient 18FDG-PET definitely revealed metastatic lesions, while the CT scans where judged to be unobtrusive and tumor marker levels were within the normal range. In the 4 patients with pure seminomas stage II B and II C (N = 6), that have undergone retroperitoneal lymph node dissection following chemotherapy, 18FDG-PET correctly predicted absence of tumor in 3 out of these 4, and in 1/4 patient the benign nature of a persistent large tumor after two cycles of polychemotherapy was correctly identified which eventually turned out to be a ganglioneuroma. This lesion falsely was classified as malignant tumor with abdominal computed tomography, and in 2/4 patients post-chemotherapy residual retroperitoneal lesions in the CT scans could not be assessed exactly whether or not malignant tumor was present. In 20 patients presenting with non-seminomatous testicular cancer (stage II and III) 18FDG-PET was able to demonstrate therapeutic effects of chemotherapy by showing decreasing tracer activity in those regions, that had hypermetabolic foci prior to chemotherapy. It became evident in testicular cancer that there is a single entity which is not characterized by increased glucose metabolism, the mature teratoma. In lesions detected by abdominal computed tomography which do not present increased 18FDG uptake, mature teratoma as well as scar/necrosis or rare other tumors with normal glucose metabolism can be supposed, but additional characteristics based on different 18FDG uptake were not observed. In 1/20 case post-chemotherapy PET scan detected a hypermetabolic lesion, which was suspicious for metastatic spread, but in the histopathological examination this lesion was identified as inflammatory tissue reaction. Based on the data reported here in 18FDG-PET cannot be considered a standard diagnostic tool in the staging examinations in testicular cancer. It is of clinical relevance in patients who present residual tumor after chemotherapy. In this situation 18FDG-PET is helpful in deciding whether or not a residual mass post-chemotherapy contains active tumor. 18FDG-PET can not replace retroperitoneal lymph node dissection for staging purposes.


Medication therapy management services provided by student pharmacists.
To evaluate the impact of student pharmacists delivering medication therapy management (MTM) services during an elective advanced pharmacy practice experience (APPE). Student pharmacists provided MTM services at community pharmacy APPE sites, documented their recommendations, and then made follow-up telephone calls to patients to determine the impact of the MTM provided. Students were surveyed about the MTM experience. Forty-seven students provided MTM services to 509 patients over 2 years and identified 704 drug-related problems (average of 1.4 problems per patient). About 53% of patients relayed the recommendations to their physician and 205 (75%) physicians accepted the recommendations. Eighty-eight percent of patients reported feeling better about their medications after receiving MTM services. A majority of the students perceived their provision of MTM services as valuable to their patients. Providing MTM services to patients in a pharmacy practice setting allowed student pharmacists to apply skills learned in the doctor of pharmacy (PharmD) curriculum.


The relationship between central venous pressure and pulmonary capillary wedge pressure during aortic surgery.
Twenty-three ASA physical status II-III patients scheduled for elective abdominal aortic surgery were studied preoperatively with multiple unit gated acquisition angiography (MUGA) scan to determine the resting left ventricular and right ventricular ejection fractions (LVEF and RVEF respectively). Intraoperatively pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) were measured in each patient at five different time periods in the horizontal, 24 degrees head up, and 24 degrees head down table tilt positions. The correlation between absolute values and changes in PCWP and CVP, and the degree to which preoperative knowledge of LVEF and RVEF predicted these correlations were examined. Resting LVEF ranged from 0.1 to 0.84. Thirteen of the 23 patients failed to show significant correlation (p less than 0.05) between the absolute values of PCWP and CVP either before and/or after aortic crossclamp. When the correlation coefficients from this analysis were ranked against LVEF, there was a weak but significant correlation before aortic crossclamp (r = 0.41), but not after. The correlation between a change in PCWP and a change in CVP was significant for the 23 patients at all time intervals, before and after aortic crossclamp. However, the prediction of a change of PCWP value from a known change of CVP value ranged in accuracy from +/- 3 mmHg to +/- 12.5 mmHg. The study suggests that if the filling pressures of both ventricles need to be assessed during aortic surgery, then the PCWP and CVP must be independently measured.(ABSTRACT TRUNCATED AT 250 WORDS)


Focal seizures in a patient with myotonic disorder type 2 co-segregating with a chloride voltage-gated channel 1 gene mutation: a case report.
Myotonic dystrophy type 2 is a multisystem disorder with both neurological and non-neurological signs and symptoms. Seizures are not a commonly associated neurological feature of this disorder. A 57-year-old white American man presented with a long history of clinical and electrophysiological features of a myotonic disorder. He also developed multiple episodes of focal seizures and underwent a series of investigations which showed no structural or metabolic etiology. Genetic testing revealed that he had an expansion mutation in CCHC-type zinc finger, nucleic acid binding protein gene confirming the diagnosis of myotonic disorder type 2 and carried a mutation in the chloride voltage-gated channel 1 gene. We report a rare association between myotonic dystrophy type 2 and a seizure disorder. The pathophysiology of a possible relationship between these two neurological conditions is discussed.


Hierarchical domain structures associated with oxygen octahedra tilting patterns in lead-free (Bi1/2Na1/2)TiO3.
Hierarchical domain structures associated with oxygen octahedra tilting patterns were observed in lead-free (Bi1/2Na1/2)TiO3ceramics using aberration-corrected high-resolution transmission electron microscopy (HRTEM). Three types of domains are induced by distinct mechanisms: the 'orientation-domain' is induced at micrometer scale formed by different tilting orientations of the oxygen octahedra, the 'meso-chemical-domain' occurs at a few tens of nanometer scale by chemical composition variation on the A-site in the ABO3perovskite structure, and the 'nano-cluster-region' runs across several unit-cells with apparent A-site cation segregation with oxygen vacancies clustering around Na cations. Based on HRTEM amplitude contrast imaging (ACI), the correlation between the oxygen octahedral tilting pattern and compositional non-stoichiometry was established. The role of the hierarchical domain structure associated with the tilting patterns of the oxygen octahedra on the ferroelectric behavior of (Bi1/2Na1/2)TiO3is also discussed.


Monoamine levels within the orbitofrontal cortex and putamen interact to predict reversal learning performance.
The compulsive and inflexible behaviors that are present in many psychiatric disorders, particularly behavioral addictions and obsessive-compulsive disorder, may be due to neurochemical dysfunction within the circuitry that enables goal-directed behaviors. Experimental removal of serotonin or dopamine within the orbitofrontal cortex or dorsal striatum, respectively, impairs flexible responding in a reversal learning test, suggesting that these neurochemical systems exert important modulatory influences on goal-directed behaviors. Nevertheless, the behavioral impairments present in psychiatric disorders are likely due to subtle neurochemical differences, and it remains unknown whether naturally occurring variation in neurochemical levels associate with individual differences in flexible, reward-directed behaviors. The current study assessed the ability of 24 individual juvenile monkeys to acquire, retain, and reverse discrimination problems and examined whether monoamine levels in the orbitofrontal cortex, caudate nucleus, and putamen could explain variance in behavior. The interaction between dopamine levels in the putamen and serotonin levels in the orbitofrontal cortex explained 61% of the variance in a measure of behavioral flexibility but not measures of associative learning or memory. The interaction mirrored that of a hyperbolic function, with reversal learning performance being poorest in either monkeys with relatively low levels of orbitofrontal serotonin and putamen dopamine or in monkeys with relatively high levels of orbitofrontal serotonin and putamen dopamine levels. These results support the hypothesis that subcortical and cortical neuromodulatory systems interact to guide aspects of goal-directed behavior, providing insight into the neurochemical dysfunction that may underlie the inflexible and compulsive behaviors present in psychiatric disorders.


[3H]imipramine binding in subcellular fractions of rat cerebral cortex after chemical lesion of serotonergic neurons.
The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.


Atraumatic removal of teeth and root fragments in dental implantology.
A technique that facilitates the removal of teeth or retained root fragments without traumatizing the alveolar bone of the socket is described. This technique may be employed whenever such extractions are envisaged, but it is particularly important when the subsequent placement of dental implants is planned.


Bovine ocular squamous cell carcinoma: ultrastructural characteristics in vitro.
The ultrastructure of cells obtained from bovine ocular squamous cell carcinoma is described. Cells were observed in pelleted form and in monolayer in situ on film liners. Both preparations consistently showed the ultrastructural features of transformed epithelium in vitro.


Dietary supplementation with a microencapsulated complex of thymol, carvacrol, and cinnamaldehyde improves intestinal barrier function in weaning piglets.
The authors previously prepared a microencapsulated complex of thymol, carvacrol, and cinnamaldehyde (MEEO). This study aimed to evaluate the effect of MEEO on the intestinal mucosal barrier and homeostasis in weaning piglets. A comparison of the effect of MEEO versus chlortetracycline (CTC) was performed in this study. Piglets were divided into three groups - control (Con), MEEO, and CTC groups - and raised for 28 days. The results showed that MEEO significantly elevated the ratio of the villus height and the crypt depth in the jejunum and decreased the crypt depth in the ileum compared with the other groups (P < 0.05); it also upregulated the messenger ribonucleic acid (mRNA) expression of tight junction protein in the small intestine. Compared with the Con group, MEEO increased the concentration of secretory immunoglobulin A (sIgA), cathelicidin antimicrobial peptides (CAMP), and interleukin 10 (IL-10), while decreasing the interleukin 1 beta (IL-1β) concentration in both jejunal and ileal mucosa (P < 0.05). The mRNA expression of jejunal mucosal MUC1 and ileal mucosal MUC2 was increased in the MEEO group compared with the other groups (P < 0.05). Intestinal microbial analysis showed that dietary treatment had little impact on the ileal microbial structure. A significant rise in the genus Lactobacillus was, however, found in the MEEO group. There is a positive correlation between the Lactobacillus and sIgA, and between the Lactobacillus and CAMP, indicating that an improvement in the mucosal barrier function by the addition of MEEO may be associated with the proliferation of Lactobacillus. Dietary supplementation with MEEO improves intestinal barrier function in weaning piglets, the effect of which was superior to CTC. © 2022 Society of Chemical Industry.


Analysis of Drosophila cardiac hypertrophy by microcomputerized tomography for genetic dissection of heart growth mechanisms.
Heart failure is often preceded by pathological cardiac hypertrophy, a thickening of the heart musculature driven by complex gene regulatory and signaling processes. The Drosophila heart has great potential as a genetic model for deciphering the underlying mechanisms of cardiac hypertrophy. However, current methods for evaluating hypertrophy of the Drosophila heart are laborious and difficult to carry out reproducibly. Here, we demonstrate that microcomputerized tomography (microCT) is an accessible, highly reproducible method for nondestructive, quantitative analysis of Drosophila heart morphology and size. To validate our microCT approach for analyzing Drosophila cardiac hypertrophy, we show that expression of constitutively active Ras (Ras85DV12), previously shown to cause hypertrophy of the fly heart, results in significant thickening of both adult and larval heart walls when measured from microCT images. We then show using microCT analysis that genetic upregulation of store-operated Ca2+ entry (SOCE) driven by expression of constitutively active Stim (StimCA) or Orai (OraiCA) proteins also results in significant hypertrophy of the Drosophila heart, through a process that specifically depends on Orai Ca2+ influx channels. Intravital imaging of heart contractility revealed significantly reduced end-diastolic and end-systolic dimensions in StimCA- and OraiCA-expressing hearts, consistent with the hypertrophic phenotype. These results demonstrate that increased SOCE activity is an important driver of hypertrophic cardiomyocyte growth, and demonstrate how microCT analysis combined with tractable genetic tools in Drosophila can be used to delineate molecular signaling processes that underlie cardiac hypertrophy and heart failure.NEW & NOTEWORTHY Genetic analysis of Drosophila cardiac hypertrophy holds immense potential for the discovery of new therapeutic targets to prevent and treat heart failure. This potential has been hindered by a lack of rapid and effective methods for analyzing heart size in flies. Here, we demonstrate that analysis of the Drosophila heart with microcomputerized tomography yields accurate and highly reproducible heart size measurements that can be used to analyze heart growth and cardiac hypertrophy in Drosophila.


The biochemical and biological functions of human papillomavirus type 16 E5 protein.
Human papillomavirus type 16 (HPV-16) E5 protein, along with the more publicized E6 and E7 proteins of this virus, has been found to be oncogenic. E5 is a highly hydrophobic membrane-bound protein of 83 amino acids associated with the Golgi apparatus, endoplasmic reticulum, and nuclear membrane in infected cells. E5 can activate epidermal growth factor receptor (EGFR) through binding to the 16 kD subunit of protein pump ATPase leading to a reduced downregulation of EGFR receptors. The activation of EGFR can initiate biochemical cascades that lead to overexpression of a variety of protooncogenes and stimulate rapid cell growth. Moreover, E5 can inhibit the expression of tumor suppressor gene p21((WafI/SdiI/CipI)) and impair the control of cell cycle checkpoint. E5 protein has been identified as a potential tumor vaccine target antigen.


Cluster-Based Ensemble Learning Model for Aortic Dissection Screening.
Aortic dissection (AD) is a rare and high-risk cardiovascular disease with high mortality. Due to its complex and changeable clinical manifestations, it is easily missed or misdiagnosed. In this paper, we proposed an ensemble learning model based on clustering: Cluster Random under-sampling Smote-Tomek Bagging (CRST-Bagging) to help clinicians screen for AD patients in the early phase to save their lives. In this model, we propose the CRST method, which combines the advantages of Kmeans++ and the Smote-Tomek sampling method, to overcome an extremely imbalanced AD dataset. Then we used the Bagging algorithm to predict the AD patients. We collected AD patients' and other cardiovascular patients' routine examination data from Xiangya Hospital to build the AD dataset. The effectiveness of the CRST method in resampling was verified by experiments on the original AD dataset. Our model was compared with RUSBoost and SMOTEBagging on the original dataset and a test dataset. The results show that our model performed better. On the test dataset, our model's precision and recall rates were 83.6% and 80.7%, respectively. Our model's F1-score was 82.1%, which is 4.8% and 1.6% higher than that of RUSBoost and SMOTEBagging, which demonstrates our model's effectiveness in AD screening.


Editorial Commentary: Platelet-Rich Plasma for Rotator Cuff Repairs: No Evidence for Improved Long-Term Outcomes … Yet!
Platelet-rich plasma (PRP) is an autologous blood product containing a high concentration of platelets, growth factors, and cytokines, which basic science studies have shown may improve tendon healing by promoting angiogenesis, cellular migration, proliferation, and matrix deposition. However, there is still controversy over its clinical efficacy, with randomized controlled trials and subsequent meta-analyses finding mixed results when PRP is used to augment rotator cuff repair. Meta-analyses have found that leukocyte-poor PRP significantly reduces the rate of incomplete tendon healing and retear, but the evidence does not support the use of leukocyte-rich PRP or platelet-rich fibrin matrix compositions. Optimizing PRP use may be as simple as the right PRP preparation or the right concentration of the important cytokines.


Biphasic dose-response curve to muscarine on the rat superior cervical ganglion.
The dose-response curve for the muscarine-induced depolarisation of the rat isolated superior cervical ganglion, studied over the concentration range of 3 nM-1 mM, was biphasic. An apparent maximum was obtained at around 1-3 microM muscarine, but this was only a plateau between the two parts of the curve. Two cardioselective antagonists, gallamine (10 microM) and AF-DX 116 (1 microM) had a complex action on this dose-response curve. The dose-response curve between 0.01 and 0.3 microM was shifted to the right, the responses around 3 microM muscarine were enhanced, but the dose-response curve over 30 microM muscarine was unaffected. The M1-selective antagonist pirenzepine (0.05 microM) depressed all parts of the dose-response curve, but it still appeared biphasic. Pretreatment of the ganglion with pertussis toxin (1 microgram/ml) enhanced the depolarisation to muscarine 0.01-1000 microM and the dose-response curve became less biphasic. Like gallamine and AF-DX 116, pertussis toxin abolished the muscarinic M2-mediated hyperpolarisation of the ganglion recorded in 0.3 microM pirenzepine. It is concluded that the presence of an underlying M2-mediated hyperpolarisation contributes to the biphasic nature of the dose-response curve to muscarine.


Purification of neuronal inclusions of patients with Huntington's disease reveals a broad range of N-terminal fragments of expanded huntingtin and insoluble polymers.
Huntington's disease resulting from huntingtin containing an expanded polyglutamine is associated with aggregates largely confined to neuronal inclusions, and with neuronal death. Inclusions are thought to originate from discrete N-terminal fragments of expanded huntingtin produced by specific endopeptidases. We have now purified the neuronal inclusions of Huntington's disease brain. When incubated in concentrated formic acid, purified inclusions release a polymer, an oligomer and a broad range of N-terminal fragments of expanded huntingtin. The fragments and the polymeric forms are linked to each other by non-covalent bonds as they are both released by formic acid, whereas the polymeric forms themselves are presumably stabilized by covalent bonds, as they are resistant to formic acid. We also demonstrate the presence in affected areas of the brain but not in unaffected areas of a broad range of soluble N-terminal fragments of expanded huntingtin not yet associated with the inclusions and which are likely to be the precursors of the inclusions. Fragmentation of expanded huntingtin in Huntington's disease must result from the operation of multiple proteolytic activities with little specificity and not from that of a specific endopeptidase; subsequent aggregation of the fragments by covalent and non-covalent bonds leads to the formation of the inclusions.


Co-regulative effects of chitosan-fennel seed extract system on the hormonal and biochemical factors involved in the polycystic ovarian syndrome.
There is a renewed interest in the application of chitosan-based drug delivery systems over the last few years. In this study, the ionic gelation method was used to prepare chitosan-engaged tripolyphosphate ions, as the cross-linking molecule, (Chit-TPP) and concurrent loading of the biomolecules of the ethanolic extract of fennel, Foeniculum vulgare, seed (FEC@NBC). The samples were characterized by SEM, DLS, TGA, FTIR, XRD, GC-MS, and zeta potential, and their effects on the related hormonal and biochemical factors of the rats with polycystic ovarian syndrome (PCOS) were assessed. The estradiol valerate-induced PCOS in female rats was confirmed by vaginal smear test and subsequent histological screening. The PCOS-induced rats were treated by fennel seed extract (FSX), Chit-TPP, and FEC@NBC. The process of treatment was monitored by measuring the serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, insulin, glucose, high-density lipoprotein cholesterol, total cholesterol, and total triglyceride after 16 days of treatment and compared with healthy control and untreated PCOS-control groups. The FEC@NBC administration contributed to the remarkable hormonal, glucose, and lipid profile regulation in the rats with PCOS. The significance of FEC@NBC performance in dealing with PCOS complications compared to that of the only extract could be resulted from the effective targeted delivery and stability of phytomolecules when encapsulated in Chit-TPP.


Percutaneous gene therapy heals cranial defects.
Nonhealing bone defects are difficult to treat. As the bone morphogenic protein and transforming growth factor beta pathways have been implicated in bone healing, we hypothesized that percutaneous Smad7 silencing would enhance signaling through both pathways and improve bone formation. Critical sized parietal trephine defects were created and animals received percutaneous injection of: agarose alone or agarose containing nonsense or Smad7 small interfering RNA (siRNA). At 12 weeks, SMADs1, 2, 3, 5, 7 and 8 levels were assessed. Smad1/5/8 osteogenic target, Dlx5, and SMAD2/3 angiogenic target, plasminogen activator inhibitor-1 (Pai1), transcription levels were measured. Noncanonical signaling through TGFβ activated kinase-1 (Tak1) and target, runt-related transcription factor 2 (Runx2) and collagen1α1 (Col1α1), transcription were also measured. Micro-computed tomography and Gomori trichome staining were used to assess healing. Percutaneous injection of Smad7 siRNA significantly knocked down Smad7 mRNA (86.3 ± 2.5%) and protein levels (46.3 ± 3.1%). The SMAD7 knockdown resulted in a significant increase in receptor-regulated SMADs (R-SMAD) (Smad 1/5/8 and Smad2/3) nuclear translocation. R-SMAD nuclear translocation increased Dlx5 and Pai1 transcription. Additionally, noncanonical signaling through Tak1 increased Runx2 and Col1α1 target transcription. Compared with animals treated with agarose alone (33.9 ± 2.8% healing) and nonsense siRNA (31.5 ± 11.8% healing), animals treated Smad7 siRNA had significantly great (91.2 ± 3.8%) healing. Percutaneous Smad7 silencing increases signal transduction through canonical and noncanonical pathways resulting in significant bone formation. Minimally invasive gene therapies may prove effective in the treatment of nonhealing bone defects.


Enantiospecific synthesis and insect feeding activity of sulfur-containing cyclitols.
The first syntheses of two deoxythiocyanocyclitols (4-deoxy-4-thiocyano-L-chiro-inositol and deoxythiocyanoconduritol F) and two deoxysulfonylcyclitol acetals are reported by a chemoenzymatic enantioselective route. The compounds were prepared by a sequence of enzymatic and ruthenium-catalyzed dihydroxylations, and the results were studied regarding reaction conditions and co-catalyst for different derivatives. The new compounds were included in a minilibrary of deoxygenated cyclitols and evaluated for their capacity to influence the feeding behavior of Epilachna paenulata (Coleoptera: Coccinellidae), a common pest of the Curcubitaceae crops.


Graphene Symmetry Amplified by Designed Peptide Self-Assembly.
We present a strategy for designed self-assembly of peptides into two-dimensional monolayer crystals on the surface of graphene and graphite. As predicted by computation, designed peptides assemble on the surface of graphene to form very long, parallel, in-register β-sheets, which we call β-tapes. Peptides extend perpendicularly to the long axis of each β-tape, defining its width, with hydrogen bonds running along the axis. Tapes align on the surface to create highly regular microdomains containing 4-nm pitch striations. Moreover, in agreement with calculations, the atomic structure of the underlying graphene dictates the arrangement of the β-tapes, as they orient along one of six directions defined by graphene's sixfold symmetry. A cationic-assembled peptide surface is shown here to strongly adhere to DNA, preferentially orienting the double helix along β-tape axes. This orientational preference is well anticipated from calculations, given the underlying peptide layer structure. These studies illustrate how designed peptides can amplify the Ångstrom-level atomic symmetry of a surface onto the micrometer scale, further imparting long-range directional order onto the next level of assembly. The remarkably stable nature of these assemblies under various environmental conditions suggests applications in enzymelike catalysis, biological interfaces for cellular recognition, and two-dimensional platforms for studying DNA-peptide interactions.


High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men.
A high body mass index (BMI) is associated with an increased risk for severe liver disease. It is unclear if this risk differs across BMI categories, and if the association is partially attributed to development of type 2 diabetes mellitus (T2DM). We used register data from more than 1.2 million Swedish men enlisted for conscription between 1969 and 1996. Data regarding new events of severe liver disease and T2DM during follow-up were obtained by record-linkage of population-based registers. We used Cox regression to estimate adjusted HRs for future inpatient care and mortality in severe liver disease and incidence of hepatocellular carcinoma (HCC) across BMI categories, using BMI of 18.5-22.5 kg/m2 as reference. During a follow-up of more than 34 million person-years, 5281 cases of severe liver disease including 251 cases of HCC were identified. An association with severe liver disease was found for overweight (HR 1.49, 95% CI 1.35 to 1.64) and for obese men (HR 2.17, 95% CI 1.82 to 2.59). Development of T2DM further increased the risk for severe liver disease across all BMI categories, for instance, men with obesity and T2DM had a higher risk of severe liver disease (HR 3.28, 95% CI 2.27 to 4.74) than men with obesity free of T2DM (HR 1.72, 95% CI 1.72 to 2.54). A high BMI in late adolescent men was associated with an increased risk of future severe liver disease, including HCC. Development of T2DM during follow-up was associated with a further increased risk of severe liver disease, independent of baseline BMI.


Postresuscitation care and prognostication after cardiac arrest-Does sex matter?
There are conflicting results concerning sex-specific differences in the post-cardiac arrest period. We investigated the sex distribution of patients after successful cardiopulmonary resuscitation (CPR), differences in treatment, complications, outcome and sex-specific performance of biomarkers for prognostication of neurological outcome. Prospective observational study including cardiac-arrest (CA) patients treated with mild therapeutic hypothermia (MTH) at 33 °C for 24 h or normothermia. We investigated common complications including pneumonia and acute kidney injury (AKI) and neuron-specific enolase, secretoneurin and tau protein as biomarkers of neurological outcome, which was assessed with the cerebral performance categories score at hospital discharge. Out of 134 patients 26% were female. Women were significantly older (73 years, interquartile range (IQR) 56-79 years vs. 62 years, IQR 53-70 years; p = 0.038), whereas men showed a significantly higher rate of pneumonia (29% vs. 6%; p = 0.004) and a trend towards higher rates of AKI (62% vs. 45%; p = 0.091). Frequency of MTH treatment was not significantly different (48% vs. 31%; p = 0.081). Female sex was not associated with neurological outcome in multivariable analysis (p = 0.524). There was no significant interaction of sex with prognostication of neurological outcome at 24, 48 and 72 h after CPR. At the respective time intervals pinteraction for neuron-specific enolase was 0.524, 0.221 and 0.519, for secretoneurin 0.893, 0.573 and 0.545 and for tau protein 0.270, 0.635, and 0.110. The proportion of female patients was low. Women presented with higher age but had fewer complications during the post-CA period. Female sex was not associated with better neurological outcome. The performance of biomarkers is not affected by sex.


Selection towards different adaptive optima drove the early diversification of locomotor phenotypes in the radiation of Neotropical geophagine cichlids.
Simpson envisaged a conceptual model of adaptive radiation in which lineages diversify into "adaptive zones" within a macroevolutionary adaptive landscape. However, only a handful of studies have empirically investigated this adaptive landscape and its consequences for our interpretation of the underlying mechanisms of phenotypic evolution. In fish radiations the evolution of locomotor phenotypes may represent an important dimension of ecomorphological diversification given the implications of locomotion for feeding and habitat use. Neotropical geophagine cichlids represent a newly identified adaptive radiation and provide a useful system for studying patterns of locomotor diversification and the implications of selective constraints on phenotypic divergence in general. We use multivariate ordination, models of phenotypic evolution and posterior predictive approaches to investigate the macroevolutionary adaptive landscape and test for evidence of early divergence of locomotor phenotypes in Geophagini. The evolution of locomotor phenotypes was characterized by selection towards at least two distinct adaptive peaks and the early divergence of modern morphological disparity. One adaptive peak included the benthic and epibenthic invertivores and was characterized by fishes with deep, laterally compressed bodies that optimize precise, slow-swimming manoeuvres. The second adaptive peak resulted from a shift in adaptive optima in the species-rich ram-feeding/rheophilic Crenicichla-Teleocichla clade and was characterized by species with streamlined bodies that optimize fast starts and rapid manoeuvres. Evolutionary models and posterior predictive approaches favoured an early shift to a new adaptive peak over decreasing rates of evolution as the underlying process driving the early divergence of locomotor phenotypes. The influence of multiple adaptive peaks on the divergence of locomotor phenotypes in Geophagini is compatible with the expectations of an ecologically driven adaptive radiation. This study confirms that the diversification of locomotor phenotypes represents an important dimension of phenotypic evolution in the geophagine adaptive radiation. It also suggests that the commonly observed early burst of phenotypic evolution during adaptive radiations may be better explained by the concentration of shifts to new adaptive peaks deep in the phylogeny rather than overall decreasing rates of evolution.


Search for Higgs-like bosons decaying into long-lived exotic particles.
A search is presented for massive long-lived particles, in the 20-60 [Formula: see text] mass range with lifetimes between 5 and 100 [Formula: see text]. The dataset used corresponds to 0.62[Formula: see text] of proton-proton collision data collected by the LHCb detector at [Formula: see text]. The particles are assumed to be pair-produced by the decay of a Higgs-like boson with mass between 80 and 140 [Formula: see text]. No excess above the background expectation is observed and limits are set on the production cross-section as a function of the long-lived particle mass and lifetime and of the Higgs-like boson mass.


Proteomic profiling of medulloblastoma reveals novel proteins differentially expressed within each molecular subgroup.
The objective of the study was to identify novel medulloblastoma (MB) biomarkers through proteomic profiling, correlate it with the molecular subgroups of MB and assess the clinical significance. Archived paraffin embedded tumor tissue blocks from 118 MB patients, operated at our institute were retrieved. Clinical information was documented from the hospital database. Tumours were stratified into molecular subgroups using the IHC markers- β Catenin, GAB-1, YAP-1 and p53. Six fresh MB tumour tissues and two control cerebellar tissues were subjected to proteomic profiling to study differential protein expression in molecular subgroups using high resolution mass spectrometry. Prominent signalling pathways activated in each subgroup were identified using the Panther pathway software. Non WNT/SHH group was the most common (61.1 %), followed by SHH and WNT. p53 immunopositivity did not correlate with prognosis in any subgroup. Proteomic profiling revealed several novel proteins differentially expressed between MB molecular subgroups. Signalling pathways exclusively enriched in each molecular subgroup were also identified. The top upregulated proteins were PMEL and FBN2 in the WNT subgroup, SYNGR2 in the SHH subgroup and GFAP, IMPG2 and MAGEA10 in the Non WNT/Non SHH group. We validated GFAP by immunohistochemistry on the archived samples (n = 118) and noted two types of staining pattern in MBs - reactive (stellate) astrocytes and tumour cell staining. GFAP immunopositivity in tumor cells of SHH subgroup correlated with a better prognosis. Proteomic profile identified several novel proteins differentially regulated within the molecular subgroups that could serve as potential diagnostic /prognostic biomarkers. Notably, GFAP, which was derived from proteomics data, when validated by IHC, revealed a variable staining pattern in MB tumours. The prognostic significance of GFAP in SHH tumor patients further points at the heterogeneity of this subgroup. The study also throws light on the signaling pathways activated in MB and in turn its plausible role in the tumorigenesis.


Simultaneous determination of nitrated and oligomerized proteins by size exclusion high-performance liquid chromatography coupled to photodiode array detection.
Chemical modifications such as nitration and cross-linking may enhance the allergenic potential of proteins. The kinetics and mechanisms of the underlying chemical processes, however, are not yet well understood. Here, we present a size-exclusion chromatography/spectrophotometry method (SEC-HPLC-DAD) that allows a simultaneous detection of mono-, di-, tri-, and higher protein oligomers, as well as their individual nitration degrees (NDs). The ND results of proteins from this new method agree well with the results from an alternative well-established method, for the analysis of tetranitromethane (TNM)- and nitrogen dioxide and ozone (NO2/O3)-nitrated protein samples. Importantly, the NDs for individual oligomer fractions can be obtained from the new method, and also, we provide a proof of principle for the calculation of the concentrations for individual protein oligomer fractions by their determined NDs, which will facilitate the investigation of the kinetics and mechanism for protein tyrosine nitration and cross-linking.


The articulatory in-out effect: replicable, but inexplicable.
People prefer inward over outward articulation dynamics, a phenomenon referred to as the articulatory in-out effect. It is empirically robust and generalizes across languages, settings, and stimuli. However, the theoretical explanation of the effect is still a matter of lively debate and in need of novel research directions.


A Study on the Stability and Antimicrobial Efficacy of a Newly Modeled Teat Dip Solution Containing Chlorhexidine.
Despite much focus on mastitis as an endemic disease, clinical and subclinical mastitis remains an important problem for many herds. Reducing the usage of antibiotics for mastitis treatment allows the risks to be minimized related to the development of antimicrobial resistance and the excretion of antibiotics into the environment. The aim of the study was to determine the physico-chemical properties, stability and antimicrobial effect of a newly formulated biocide for post-milking udder hygiene containing a thickener made from hydroxypropyl guar gum, an antiseptic chlorhexidine digluconate and teat skin-friendly components including glycerol, Mentha Arvensis herbal oil and Aesculus hippocastanum extract. Hydroxypropyl guar gum was used as a thickener to provide the physical parameters and to retain the viscosity at 1438 mPa.s. The physical and chemical properties of the product, including the 12-month stability, were tested in long-term and accelerated stability studies. The product was effective against the primary mastitis pathogens, including Staphylococcus aureus, Streptococcus uberis, Escherichia coli, Candida albicans and Aspergillus niger.


Covalent grafting of common trihydroxymethylaminomethane in the headgroup region imparts high serum compatibility and mouse lung transfection property to cationic amphiphile.
Clinical success of cationic transfection lipids in nonviral gene therapy continues to remain critically dependent on the use of serum compatible cationic amphiphiles efficient in delivering genes into our body cells. To this end, we demonstrate that covalent grafting of simple Tris-base component of the widely used biological Tris buffer in the headgroup region is capable of imparting high serum compatibility and intravenous mouse lung transfection properties to cationic amphiphile.


A carrier for GABA uptake exists on noradrenaline nerve endings in selective rat brain areas but not on serotonin terminals.
gamma-Aminobutyric acid (GABA) increased in a concentration-dependent way (3-300 microM) the basal release of tritium from rat cerebral cortex and hippocampus synaptosomes, prelabelled with 3H-noradrenaline (3H-NA); however, GABA was ineffective on hypothalamic nerve endings. The effect displayed by low concentrations (less than 10 microM) of GABA was largely bicuculline-sensitive. Muscimol mimicked GABA, while (-)baclofen was inactive. The releasing effects produced by concentrations of GABA higher than 10 microM were largely prevented by SK&F89976A, SK&F100330A and SK&F100561, three novel GABA uptake inhibitors. When present together, GABA uptake blocker and bicuculline counteracted entirely the GABA effects. The basal release of 3H-5-hydroxytryptamine (3H-5-HT) in synaptosomes from various CNS regions was not affected by GABA. GABA can enhance 3H-NA release not only through GABA-A receptors but also by penetrating into NA terminals through a GABA uptake system. This implies coexistence of carriers for NA and GABA uptake on a same nerve terminal. The carrier coexistence occurs in selective CNS areas. The phenomenon appears to be transmitter-selective.


Assessing mitochondrial outer membrane permeabilization during apoptosis.
Mitochondria play a pivotal role in the regulation of apoptosis. An imbalance in apoptosis can lead to disease. Unscheduled apoptosis has been linked to neurodegeneration while inhibition of apoptosis can cause cancer. An early and key event during apoptosis is the release of factors from mitochondria. In apoptosis the mitochondrial outer membrane becomes permeable, leading to release of apoptogenic factors into the cytosol. One such factor, cytochrome c, is an electron carrier of the respiratory chain normally trapped within the mitochondrial intermembrane space. Many apoptotic studies investigate mitochondrial outer membrane permeabilization (MOMP) by monitoring the release of cytochrome c. Here, we describe three reliable techniques that detect cytochrome c release from mitochondria, through subcellular fractionation or immunocytochemistry and fluorescence microscopy, or isolated mitochondria and recombinant Bax and t-Bid proteins in vitro. These techniques will help to identify mechanisms and characterize factors regulating MOMP.


Mercury compounds characterization by thermal desorption.
The ability to accurately determine metal mercury content and identify different mercury species in solid samples is essential for developing remediation and control strategies. The aim of the present study is to characterize mercury compounds based on thermal desorption. For this purpose a series of samples was prepared and the operational parameters-heating velocity, carrier gas-were optimized. Fifteen commercial mercury compounds were analyzed for use as fingerprints. The results of the study show that the identification of mercury species by the method of thermal desorption is possible. The temperature of desorption increased according to the following order HgI2<HgBr2<Hg2Cl2=HgCl2<Hg(CN)2<HgCl2O8·H2O<Hg(SCN)2<HgS (red)<HgF2<Hg2(NO3)2·2H2O<Hg(NO3)2·H2O<HgO (yellow, red)<Hg2SO4<HgSO4. A comparison of the estimated total mercury content with the mercury content calculated by integrating the area of the desorption curve shows that recoveries of 79-104% for HgS can be estimated. The proposed method represents a significant step forward in direct mercury analysis in solid samples.


The incidence of simple renal cyst by computed tomography.
Five hundred and forty-two abdominal computed tomography (CT) scans, including the kidneys, were reviewed to investigate the incidence of simple renal cysts. Increasing frequency with age was clearly demonstrated. The incidence in patients 50 years of age and over was at least 27%. Two thirds of simple renal cysts were 2 cm or less in diameter. Cysts were usually observed as exo-endoparenchymal or endoparenchymal lesions on CT.


Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study.
The goal of this work was to determine whether rheolytic thrombectomy (RT) as an adjunct to primary percutaneous coronary intervention (PCI) reduces infarction size and improves myocardial perfusion during treatment of ST-segment elevation myocardial infarction (STEMI). Primary PCI for STEMI achieves brisk epicardial flow in most patients, but myocardial perfusion often remains suboptimal. Distal embolization of thrombus during treatment may be a contributing factor. This prospective, multicenter trial enrolled 480 patients presenting within 12 h of symptom onset and randomized to treatment with RT as an adjunct to PCI (n = 240) or to PCI alone (n = 240). Visible thrombus was not required. The primary end point was infarct size measured by sestamibi imaging at 14 to 28 days. Secondary end points included final Thrombolysis In Myocardial Infarction (TIMI) flow grade, tissue myocardial perfusion (TMP) blush, ST-segment resolution, and major adverse cardiac events (MACE), defined as the occurrence of death, new Q-wave myocardial infarction, emergent coronary artery bypass grafting, target lesion revascularization, stroke, or stent thrombosis at 30 days. Final infarct size was higher in the adjunct RT group compared with PCI alone (9.8 +/- 10.9% vs. 12.5 +/- 12.13%; p = 0.03). Final TIMI flow grade 3 was lower in the adjunct RT group (91.8% vs. 97.0% in the PCI alone group; p < 0.02), although fewer patients had baseline TIMI flow grade 3 in the adjunct RT group (44% vs. 63% in the PCI alone group; p < 0.05). There were no significant differences in TMP blush scores or ST-segment resolution. Thirty-day MACE was higher in the adjunct RT group (6.7% vs. 1.7% in the PCI alone group; p = 0.01), a difference primarily driven by very low mortality rate in patients treated with PCI alone (0.8% vs. 4.6% in patients treated with adjunct RT; p = 0.02). Despite effective thrombus removal, RT with primary PCI did not reduce infarct size or improve TIMI flow grade, TMP blush, ST-segment resolution, or 30-day MACE.


Odontogenic maxillofacial space infections at a tertiary care center in North India: a five-year retrospective study.
Odontogenic infections contribute to a significant proportion of maxillofacial space infections (MSI) across the world. MSI can cause several life-threatening complications despite skillful management. The objective of this study was to review the clinical characteristics, management, and outcome of odontogenic MSI treated at a tertiary care center, and to identify the factors predisposing to life-threatening complications. A retrospective chart review of all patients treated for MSI from January 2006 to December 2010 at the Christian Medical College Hospital in Ludhiana, North India, was conducted. Out of 137 patients identified, 66.4% were men. Mean patient age was 40 years, and 24.1% of the patients were diabetic. The most common origin was pulpal (70.8%), the most common space involved was the submandibular space, and the most common teeth responsible were the lower third molars. Twenty patients (14.6%) developed complications. Diabetes, multiple space involvement, and a total leukocyte count of ≥15×10(9)/l were associated with complications. Patients with MSI who present with multiple space involvement, a high leukocyte count, and those with diabetes are at higher risk of developing life-threatening complications and need to be closely monitored.


In situ immobilization of a general resolving agent on the magnetic multi-wall carbon nanotube for the direct enantioenrichment of DL-mandelic acid.
L-Threonine (L-thr) as a general chiral selector anchored on the surface of magnetic multi-wall carbon nanotube (MMWCNT) was prepared using an in situ electrostatic adsorption and studied as a new magnetically chiral selector for the separation of chiral DL-mandelic acid (DL-MA) as a model sample. By varying the pH, DL-MA was adsorbed on the surface of magnetic chiral selector through hydrogen bonds. It is recognized that MMWCNT with chiral ligands on its surface simultaneously possesses both magnetic property and direct chiral recognition ability. The successful immobilization of L-thr onto the surface of MMWCNT was confirmed by infrared spectra (FT-IR), X-ray diffraction patterns (XRD) and transmission electron microscopy (TEM). The FT-IR and mass spectra of supernatant and elution solutions also confirmed the immobilization of L-thr onto the surface of MMWCNT. The analysis results of specific rotation, HPLC and ultraviolet-visible spectroscopy reveal that the L-thr-MMWCNT show stronger complexation of (+)-enantiomer than (-)-enantiomer. The functional magnetic nanotubes were easily separated from the racemic solution using an external magnetic field which demonstrated its feasibility of recycling the adsorbent. All processes including in situ immobilization, enantioseparation (enantioenrichment) and magnetic separation were done by single process in a short time (only 10min).


Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L cells in response to ingested nutrients. The first recognized and most important action of GLP-1 is the potentiation of glucose-stimulated insulin secretion in beta-cells, mediated by activation of its seven transmembrane domain G-protein-coupled receptor. In addition to its insulinotropic actions, GLP-1 exerts islet-trophic effects by stimulating replication and differentiation and by decreasing apoptosis of beta-cells. The GLP-1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism, including pancreatic alpha-cells, hypothalamus and brainstem, and proximal intestinal tract. GLP-1 also appears to exert important actions in liver, muscle and fat. Thus, GLP-1 suppresses glucagon secretion, promotes satiety, delays gastric emptying and stimulates peripheral glucose uptake. The impaired GLP-1 secretion observed in type 2 diabetes suggests that GLP-1 plays a role in the pathogenesis of this disorder. Thus, because of its multiple actions, GLP-1 is an attractive therapeutic target for the treatment of type 2 diabetes, and major interest has resulted in the development of a variety of GLP-1 receptor agonists for this purpose. Ongoing clinical trials have shown promising results and the first analogs of GLP-1 are expected to be available in the near future.


"You look sleepy…" The impact of sleep restriction on skin parameters and facial appearance of 24 women.
Total sleep deprivation has a visible impact on subjective facial appearance. However, there is a lack of knowledge on how moderate sleep restriction objectively impairs skin quality and facial aspect. Twenty-four healthy good-sleeping women, aged 30-55, volunteered for this study on the impact of sleep restriction (SR) on their facial skin. SR was limited to 3 h per night for 2 consecutive nights. We assessed the following parameters at the same time of day, before and after SR: sebumetry (Sebumeter SM 815), hydration (Corneometer CM 825), trans-epidermal water loss (Tewameter TM 210), biomechanical properties (Cutometer MPA 580), pH (PH-meter 900), desquamation quantification (D-Squameter and microscopy), and image analysis (ColorFace - Newtone Technologies). We also obtained skin samples (swab) for malondialdehyde quantification (MDA). We observed that some skin parameters are significantly associated with SR in both the morning and afternoon, including: lower hydration (p < 0.001), increased trans-epidermal water loss (PIE) (p < 0.001), and decreased extensibility (Uf; p = 0.015) and viscosity (Uv; p < 0.001) of the skin. The average pH increased from 4.8 (±0.2) to 4.9 ± 0.4; p < 0.001. For face photography, brightness and saturation also significantly decreased with SR in mornings and afternoons (p < 0.001 for all tests). Finally, we observed a significant decrease in isolated corneocytes after desquamation associated with SR (p < 0.001 for all tests). SR was also associated with significantly increased MDA levels (p < 0.001 for all tests). Two nights of SR significantly altered the skin and facial appearances in our test group of typically good-sleeping women.


Ultrasonography training and utilization in surgical critical care fellowships: a program director's survey.
Intensivist-performed ultrasound (IPUS) is an adjunctive tool used to assist in resuscitation and management of critically ill patients. It allows clinicians real-time information through noninvasive methods. We aimed to evaluate the types of IPUS performed and the methods surgical critical care (SCC) fellows are trained along with challenges in training. One hundred SCC fellowship directors were successfully sent an email inviting them to participate in a short Web-based survey. We inquired about program characteristics including hospital type, fellowship size, faculty size and training, dedicated surgical critical care beds, and ultrasound equipment availability. The survey contained questions regarding the program directors' perception on importance on cost effectiveness of IPUS, types of IPUS examinations performed, fellows experience with IPUS, challenges to training, and presence and methods of quality assurance (QA) programs. A total of 38 (38.0%) program directors completed the survey. Using a 100-point Likert scale, the majority of the respondents indicated that IPUS is important to patient care in the SICU and is cost-effective (mean score 85.5 and 84.6, respectively). Most (34, 89.5%) utilize IPUS and conduct a mean of 5.1 different examination types with FAST being the most prevalent examination (33, 86.8%). Thirty-three (86.8%) programs include IPUS in their SCC training with varying amounts of time spent training. Of these programs, 19 (57.6%) have a specific curriculum. The most frequently used modalities for training fellows were informal bedside teaching (28, 84.8%), hands-on lectures (20, 60.6%) and formal lectures (19, 57.6%). The top three challenges program directors cited for IPUS education was time (23, 69.7%), followed by concerns for ongoing QA (19, 57.6%) and lack of faculty trained in IPUS (18, 53.9%). Only 20 (60.6%) programs review images as a part of QA/quality improvement. Utilization and training of IPUS is common in SCC fellowships. There is varied education type and training time devoted to IPUS which could lead to gaps in knowledge and care. Development of a standard curriculum for SCC fellowships could assist surgical intensivists in achieving a base of knowledge in IPUS to create a more homogenously trained workforce and standards of care.


Enhancement of static magnetic field on biological hydrogen production via photo-fermentation of giant reed.
The effect of static magnetic field (SMF) on the system of photo-fermentation biological hydrogen production remains dimness. The goal of this study was to clarify the correlation between external SMF addition and hydrogen production via photo-fermentation from giant reed. SMF with 20 mT improved the cumulative H2 yield by 26.1% and reduced the lag time of hydrogen production by 56.7% compared with that of without external magnetic field. Moreover, 20 mT of SMF not only enhanced the activity of nitrogenase by 94.52%, but also obtained the maximum energy conversion efficiency of 27.27%. The distribution of volatile fatty acids proved that the concentration of acetic acid and butyric acid were 137% and 81% higher than that of without SMF, respectively. The results would help to trigger the positive interaction between SMF and microorganism and to avoid the possible negative interaction.


Effects of gestational age, birth weight, and hypoxemia on pharmacokinetics of amikacin in serum of infants.
The serum pharmacokinetics of amikacin were studied in 36 infants treated for suspected bacterial infection. A prolonged serum half-life was associated with the related variables of birth at an early gestational age, low birth weight, and hypoxemia. A postnatal age effect was not apparent when hypoxemic infants were excluded.


Interplay of Oral, Mandibular, and Facial Disorders and Migraine.
Migraine and other primary headache disorders can be localized in the face resembling facial or dental pain, indicating the influence of the trigeminovascular system in the structures innervated by the maxillary (V2) and mandibulary (V3) branches of the trigeminal nerve. Disorders of oral and craniofacial structures may influence primary headache disorders. In the current article, we review the potential links of this interplay. This interplay may be related to anatomy, with the trigeminal pathway and the involvement of both peripheral and central mechanisms, and the presence of calcitonin gene-related peptide (CGRP), a key mediator in migraine pathophysiology. CGRP is also involved in the pathophysiology of temporomandibular disorders (TMD) and their comorbidity with migraine and is also implicated in dental and periodontal pathology. Inflammatory and pathological processes of these structures and their trigeminal nociceptive pathways may influence the trigeminovascular system and consequently may exacerbate or even potentially trigger migraine.


Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional serotonin synthesis in the rat brain: an autoradiographic study.
The effects of acute and repeat administration of the serotonin (5-HT)(1) agonists TFMPP [N -(3-trifluoromethyl)phenylpiperazine hydrochloride] and CGS12066B [7-trifluoromethyl-4- (4-methyl-1-piperazinyl)pyrrolo[1,2-a ]-quinoxaline dimaleate] were evaluated on 5-HT synthesis rates using the alpha-[(14) C]methyl-l-tryptophan (alpha-MTrp) autoradiographic method. In the acute treatment study, TFMPP (10 mg/kg) and CGS12066B (5 mg/kg) were injected intraperitoneally 30 min before an alpha-MTrp injection. In an acute study TFMPP reduced overall brain 5-HT synthesis, in the dorsal and median raphe, and in almost all of their projection areas, with the exception of the parietal, sensory-motor, and frontal cortices, the accumbens nucleus, and the caudate. Acute CGS12066B treatment did not have overall significant effect, but the rates did decrease in the cell body areas of 5-HT neurons. In a 7-day treatment with TFMPP (10 mg/kg/day) or CGS12066B (5 mg/kg/day), the 5-HT synthesis rates (24 h after last dose) decrease, with both compounds, in almost all of the nerve terminal structures. TFMPP reduced the synthesis in the dorsal and median raphe, while CGS12066B reduced it only in the dorsal raphe. This data suggests that after a 7-day treatment with TFMPP and CGS12066B, the rate of 5-HT synthesis in the dorsal raphe is restored and is reduced in many projection areas. The observed effects in the 7-day treatment could also be related to actions through the postsynaptic 5-HT(1B) sites and/or other 5-HT receptors since this compounds have limited selectivity.


Guiding restoration of riparian ecosystems degraded by plant invasions: Insights from a complex social-ecological system in the Global South.
Restoring riparian ecosystems in human-dominated landscapes requires attention to complexity, and consideration of diverse drivers, social actors, and contexts. Addressing a Global North bias, this case study uses a mixed-method approach, integrating historical data, remote sensing techniques and stakeholder perceptions to guide restoration of a river in the Western Cape, South Africa. An analysis of aerial photographs of the riparian zone from 1953 to 2016 revealed that although anthropogenic land conversion happened primarily before the 1950s, several land use and land cover classes showed marked increases in area, including: waterbodies (+ 1074%), urban areas (+ 316%), alien weeds (+ 311%) and terrestrial alien trees (+ 79%). These changes have likely been driven by land fragmentation, disturbance, and agricultural intensification. Stakeholder interviews revealed that despite the clear need for restoration, several barriers exist to successful implementation; these stem from inadequate financial resources, inappropriate funding models, institutional challenges, and a lack of techno-scientific knowledge. We give several recommendations to overcome these barriers.


Health-related quality of life and associated factors in people with diabetes at high risk of foot ulceration.
The health-related quality of life (HRQoL) of people with diabetes-related foot complications has been increasingly reported, mostly from studies of people with a foot ulcer. The aim of this study was to assess HRQoL and determine factors associated with HRQoL in people with diabetes at high risk of foot ulceration. In all, 304 participants enrolled in the Diabetic Foot Temperature Trial (DIATEMP) were included in the cross-sectional analysis. HRQoL was measured by the RAND® 36-Item Short Form Health Survey (SF-36) at baseline. Potential factors associated with HRQoL were analysed using multiple linear regression analyses for the eight domains of the SF-36. Participants were predominantly male (72%), mean age 64.6 (±10.5) years, 77% type 2 diabetes and mean duration of diabetes 20 (±14) years. Mean SF-36 domain scores for the General Health (49.2 ± 20.1), Role Physical (50.9 ± 44.7), Physical Function (58.5 ± 27.9) and Vitality domains (59.8 ± 21.6) were lower compared to the Mental Health (78.4 ± 18.0), Social Functioning (75.3 ± 24.2), Role Emotional (73.5 ± 38.9) and Bodily Pain (67.0 ± 27.0) domains. HRQoL was lower than Dutch population-based and general diabetes samples, but higher than in samples with an ulcer. Use of a walking aid was associated with lower HRQoL across all 8 SF-36 domains (β range - 0.20 to - 0.50), non-Caucasian descent was associated with lower HRQoL in 5 domains (β range - 0.13 to - 0.17). Not working, higher BMI and younger age were associated with lower HRQoL in 3 domains. People at high risk of diabetes-related foot ulceration have reduced HRQoL that varies across domains, with the physical domains most affected. Assessing mobility, ethnicity, BMI and job status may be useful in daily practice to screen for people who might benefit from interventions targeting HRQoL. Netherlands Trial Registration: NTR5403. Registered on 8 September 2015.


Structural heterogeneity of the Fe(2+)-N epsilon (HisF8) bond in various hemoglobin and myoglobin derivatives probed by the Raman-active iron histidine stretching mode.
We have examined the Fe(2+)-N epsilon (HisF8) complex in hemoglobin A (HbA) by measuring the band profile of its Raman-active nu Fe-His stretching mode at pH 6.4, 7.0, and 8.0 using the 441-nm line of a HeCd laser. A line shape analysis revealed that the band can be decomposed into five different sublines at omega 1 = 195 cm-1, omega 2 = 203 cm-1, omega 3 = 212 cm-1, omega 4 = 218 cm-1, and omega 5 = 226 cm-1. To identify these to the contributions from the different subunits we have reanalyzed the nu Fe-His band of the HbA hybrids alpha(Fe)2 beta(Co)2 and alpha(Co)2 beta(Fe)2 reported earlier by Rousseau and Friedman (D. Rousseau and J. M. Friedman. 1988. In Biological Application on Raman Spectroscopy. T. G. Spiro, editor, 133-216). Moreover we have reanalyzed other Raman bands from the literature, namely the nu Fe-His band of the isolated hemoglobin subunits alpha SH- and beta SH-HbA, various hemoglobin mutants (i.e., Hb(TyrC7 alpha-->Phe), Hb(TyrC7 alpha-->His), Hb M-Boston and Hb M-Iwate), N-ethylmaleimide-des(Arg141 alpha) hemoglobin (NES-des(Arg141 alpha)HbA) and photolyzed carbonmonoxide hemoglobin (Hb*CO) measured 25 ps and 10 ns after photolysis. These molecules are known to exist in different quaternary states. All bands can be decomposed into a set of sublines exhibiting frequencies which are nearly identical to those found for deoxyhemoglobin A. Additional sublines were found to contribute to the nu Fe-His band of NES-des(Arg141 alpha) HbA and the Hb*CO species. The peak frequencies of the bands are determined by the most intensive sublines. Moreover we have measured the nu Fe-His band of deoxyHbA at 10 K in an aqueous solution and in a 80% glycerol/water mixture. Its subline composition at this temperature depends on the solvent and parallels that of more R-like hemoglobin derivatives. We have also measured the optical charge transfer band III of deoxyHbA at room temperature and found, that at least three subbands are required to fit its asymmetric band shape. This corroborates the findings on the nu Fe-His band in that it is indicative of a heterogeneity of the Fe(2+)-N epsilon(HisF8) bond. Finally we measured the nu Fe-His band of horse heart deoxyMb at different temperatures and decomposed it into three different sublines. In accordance with what was obtained for HbA their intensities rather than their frequencies are temperature-dependent. By comparison with VFe-His bands of some Mb mutants (i.e., Mb(His E7.->Gly) and Mb(HisE7__*Met) we suggest that these sublines may be attributed to different conformations of the heme pocket. Our data show, that the V Fe-His band is governed by at least two different coordinates x and y determining its frequency and intensity, respectively. While the former can be assigned to the tilt angle theta between the Fe2+-NJ(HisF8) bond and the heme normal and/or to the displacement delta of the iron from the heme plane, variations in the intensity may be caused by changes of the azimuthal angle phi formed by the projection of the proximal imidazole and the N(l)-Fe2+-N(III) line of the heme. The sublines are therefore interpreted as resulting from different conformational substates of the Fe2+-N(HisFa) complex which differ in terms of x (theta and/or delta). Each of them may further be subdivided in sub-substates with respect to the coordinate y (theta). Quaternary and tertiary transitions of the protein alter the population of these substates thus giving rise to a redistribution of the VFe-HiS sublines which shifts the corresponding peak frequency to higher values.


Different dimensions of social support differentially predict psychological well-being in late life: opposite effects of perceived emotional support and marital status on symptoms of anxiety and of depression in older outpatients in Italy.
Social support is important to psychological well-being in late life. However, findings in the literature regarding its effects are mixed, less information is available for anxiety than for depressive symptoms, and few studies have been carried out in Italy. Therefore, the aim of this study was to investigate the influence of social support on symptoms of anxiety and of depression in a sample of geriatric outpatients in Italy. This cross-sectional study consecutively enrolled 299 outpatients without dementia (age ≥ 65, all neuropsychologically tested). Social support was assessed with the ENRICHD Social Support Instrument and by interview. Symptoms of anxiety and of depression were evaluated with short versions of the State-Trait Personality Inventory Trait Anxiety and Geriatric Depression scales. The relationship between social support and psychological well-being was examined by multiple linear regression models with socio-demographic and clinical variables, including cognitive performance, as potential confounders. Perceived emotional support was a negative predictor of symptoms of anxiety (standardised beta coefficient (β) -0.288, standard error (SE) 0.074, P < 0.001) and symptoms of depression (β -0.196, SE 0.040, P < 0.001). On the contrary, marital status (i.e. being married) was a positive predictor of symptoms of anxiety (β 0.199, SE 0.728, P = 0.003) and symptoms of depression (β 0.142, SE 0.384, P = 0.035). Different dimensions of social support differentially affect psychological well-being. The protective effect of perceived emotional support is consistent with social cognitive models of health. The harmful effect of being married may be capturing the distress of the pre-bereavement period. Alternatively, it may reflect oppression by gender roles within marriage in a predominantly female sample in a traditional society. Our findings provide insight into the relationship between social support and psychological well-being, and identify potential targets for psychosocial interventions promoting mental health in late life.


Pausing on Polyribosomes: Make Way for Elongation in Translational Control.
Among the three phases of mRNA translation-initiation, elongation, and termination-initiation has traditionally been considered to be rate limiting and thus the focus of regulation. Emerging evidence, however, demonstrates that control of ribosome translocation (polypeptide elongation) can also be regulatory and indeed exerts a profound influence on development, neurologic disease, and cell stress. The correspondence of mRNA codon usage and the relative abundance of their cognate tRNAs is equally important for mediating the rate of polypeptide elongation. Here, we discuss recent results showing that ribosome pausing is a widely used mechanism for controlling translation and, as a result, biological transitions in health and disease.


The functional relevance of visuospatial processing speed across the lifespan.
Visuospatial processing speed underlies several cognitive functions critical for successful completion of everyday tasks, including driving and walking. While it is widely accepted that visuospatial processing speed peaks in early adulthood, performance across the lifespan remains incompletely characterized. Additionally, there remains a lack of paradigms available to assess visuospatial processing speed in unsupervised web-based testing environments. To address these gaps, we developed a novel visuospatial processing speed (VIPS) task adapted from two tests sensitive to visuospatial processing speed declines in older adults, the Useful Field of View paradigm and the PERformance CEntered Portable Test. The VIPS task requires participants to make a central orientation discrimination and complete a simultaneous peripheral visual search task. Data were collected from 86 in-lab volunteers (18-30 years) to compare performance to traditional neuropsychological measures. Consistent with previous literature, performance on the novel VIPS task significantly correlated with measures of selective attention, executive functioning, visual speed, and working memory. An additional 4395 volunteers (12-62 years) were recruited on TestMyBrain.org to establish lifespan trajectories of visuospatial processing speed and associations with functional disability. VIPS task performance peaked in the early 20's, and steadily decreased such that thresholds doubled in 60-year-olds relative to 20-year-olds (817 ms vs. 412 ms). VIPS task performance significantly correlated with self-reported cognitive functioning deficits broadly across the lifespan but was specifically related to mobility issues in middle-age. These findings have important implications for early detection of cognitive decline and provide insights into potential early intervention targets for younger and middle-aged adults.


Increased expression of metabotropic glutamate receptor subtype 1 on spinothalamic tract neurons following spinal cord injury in the rat.
Spinal cord injury (SCI) leads to an increase in metabotropic glutamate receptor subtype 1 (mGluR1) immunoreactivity in the peri-lesion area. The increased expression of mGluR1 parallels the development of thermal hyperalgesia and mechanical allodynia and has been suggested to contribute to the development and maintenance of chronic central pain (CCP) syndromes resulting from SCI. However, expression of mGluR1 has not been directly shown to increase on cells in the pain pathway. Therefore, the expression of mGluR1 on spinothalamic tract (STT) neurons was quantified using confocal imaging and densiometric analysis in normal, sham, and SCI rats. Contusion SCI produced an increase in mGluR1 expression on STT cells in both the cervical enlargement and the spinal section just rostral to contusion SCI. These results suggest that mGluR1 is expressed on neurons that modulate pain transmission and expression on these cells increases following injury, supporting the hypothesis that mGluR1 contributes to CCP following SCI.


Respiratory mechanics and peripheral airway inflammation and dysfunction in asthma.
Clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices. The correlation between respiratory impedance and spirometry has been reported; however, the association with airway inflammation and pulmonary function, in the lung periphery in particular, is unclear. To assess whether respiratory impedance is associated with peripheral airway inflammation and dysfunction in asthma. Subjects included 78 patients with overall controlled asthma. We measured whole-breath or within-breath respiratory system resistance (Rrs) and reactance (Xrs) using a commercially available multi-frequency FOT device (MostGraph-01), and assessed the correlation with the fraction of exhaled nitric oxide (FeNO), alveolar nitric oxide concentration (CANO), maximal NO flux in the conductive airways (J'awNO), and the N2 phase III slope of single breath N2 washout (delta N2 ). The differences between inspiratory and expiratory phases of Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (ALX) were significantly correlated with CANO; however, there was no correlation between respiratory impedance and FeNO or J'awNO. The delta N2 values were significantly correlated with whole-breath, inspiratory, and expiratory Rrs and Xrs, except for R20. We conclude that respiratory impedance reflects peripheral airway inflammation and ventilation inhomogeneity.


A method demonstrating motor endplates for light and electron microscopy.
The cytochemical localization of acetylcholinesterase activity at motor endplates is commonly employed prior to electron microscopic examination. Methods which involve the use of thiocholine esters often lead to a loss of resolution due to the spread to surrounding tissues of an extremely dense reaction product. A method is presented in which esterase positive sites are revealed by incubation with hexazotized pararosaniline and indoxyl acetate. The osmiophilic property of the reaction product which remains localized to the synaptic cleft allows speedy identification and detailed examination of the endplate at the ultrastructural level. An application of the procedure is also described.


Primary clear cell sarcoma (malignant melanoma) in the right radius.
Clear cell sarcoma (malignant melanoma) originating in bone is an extremely rare occurrence, which has been reported twice previously. It is challenging to differentiate this neoplasm from skeletal metastasis of malignant melanoma because it shows no specific imaging, pathological or immunohistochemical features. However, this differentiation is clinically important due to significant differences in patient management. In this article, we present the case of a 55-year-old man with primary clear cell sarcoma arising in the right radius.


Fluoride and nitrate enrichment in coastal aquifers of the Eastern Province, Saudi Arabia: The influencing factors, toxicity, and human health risks.
Fluoride and nitrate contamination of groundwater is a major environmental issue in the world's arid and semiarid regions. This issue is severe in both developed and developing countries. This study aimed at assessing the concentration levels, contamination mechanisms, toxicity, and human health risks of NO3- and F- in the groundwater within the coastal aquifers of the eastern part of Saudi Arabia using a standard integrated approach. Most of the tested physicochemical properties of the groundwater exceeded their standard limits. The water quality index and synthetic pollution index evaluated the suitability of the groundwater and showed that all the samples have poor and unsuitable quality for drinking. The toxicity of F- was estimated to be higher than NO3-. Also, the health risk assessment revealed higher risks due to F- than NO3-. Younger populations had higher risks than elderly populations. For both F- and NO3-, the order of health risk was Infants > Children > Adults. Most of the samples posed medium to high chronic risks due to F- and NO3- ingestion. However, negligible health risks were obtained for potential dermal absorption of NO3-. Na-Cl and Ca-Mg-Cl water types predominate in the area. Pearson's correlation analysis, principal component analysis, regression models, and graphical plots were used to determine the possible sources of the water contaminants and their enrichment mechanisms. Geogenic and geochemical processes had greater impact he groundwater chemistry than anthropogenic activities. For the first time, these findings provide public knowledge on the overall water quality of the coastal aquifers and could help the inhabitants, water management authorities, and researchers to identify the groundwater sources that are most desirable for consumption and the human populations that are vulnerable to non-carcinogenic health risks.


Performance of the ARX-derived auditory evoked potential index as an indicator of anesthetic depth: a comparison with bispectral index and hemodynamic measures during propofol administration.
Autoregressive modeling with exogenous input of middle-latency auditory evoked potential (A-Line autoregressive index [AAI]) has been proposed for monitoring anesthetic depth. The aim of the current study was to compare the accuracy of this new index with the Bispectral Index (BIS), predicted effect-site concentration of propofol, and hemodynamic measures. Twenty female patients scheduled for ambulatory gynecologic surgery received effect compartment controlled infusion of propofol. Target effect-site concentration was started at 1.5 microg/ml and increased every 4 min by 0.5 microg/ml. At every step, sedation level was compared with monitoring values using different clinical scoring systems and reaction to noxious stimulus. Bispectral Index, AAI, and predicted propofol effect-site concentration were accurate indicators for the level of sedation and loss of consciousness. Hemodynamic variables were poor indicators of the hypnotic-anesthetic status of the patient. BIS correlated best with propofol effect-site concentration, followed by AAI. Hemodynamic measurements did not correlate well. No indicators predicted reaction to noxious stimulus. Poststimulus, BIS and AAI showed an increase as a result of arousal. This reaction occurred more rapidly with the AAI than with BIS. Bispectral Index, AAI, and predicted propofol effect-site concentration revealed information on the level of sedation and loss of consciousness but did not predict response to noxious stimulus.


ADAM function in embryogenesis.
Cleavage of proteins inserted into the plasma membrane (shedding) is an essential process controlling many biological functions including cell signaling, cell adhesion and migration as well as proliferation and differentiation. ADAM surface metalloproteases have been shown to play an essential role in these processes. Gene inactivation during embryonic development have provided evidence of the central role of ADAM proteins in nematodes, flies, frogs, birds and mammals. The relative contribution of four subfamilies of ADAM proteins to developmental processes is the focus of this review.


Functional outcome of bone marrow stem cells (CD45(+)/CD34(-)) after cell therapy in chronic spinal cord injury in Wistar rats.
Therapy with diverse cell types has been proposed to regenerate spinal cord injuries seeking to minimize the consequences for the lives of chronic patients. The types considered are: mononuclear and mesenchymal adult stem cells, embryonic stem cells, and Schwann cells. Ninety male Wistar rats that underwent spinal cord contusion injury (NYU Impactor) were followed with the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale for 14 days. Animals with scores < or = 16 were randomly divided into 2 groups: control (vehicle) versus cell therapy group. The mononuclear fraction (CD45(+)/CD34(-)) obtained by puncture-aspiration of the bone marrow was isolated by a density gradient (d = 1.077). The parenchymal cell infusion was performed using a syringe (100 U/1 mL) with a 30G1/2 needle. The animals were followed for 10 days before euthanasia. Statistical analyses comparing groups were performed by the Mann-Whitney test and group comparisons by the Wilcoxon test. Among 90 injured rats, 65 (72.2%) survived, including 44 whose scores were < or = 16. Eleven animals finished the study in the control group (64.7%) and 17 in the therapy group (80.9%). The statistical analyses did not demonstrate significance (P > .05) for either test. Mononuclear adult stem cell therapy was not demonstrated to be functionally effective for chronic spinal cord injury.


Using network analysis to explore the key bridge symptoms between posttraumatic stress symptoms and posttraumatic growth among survivors 10 years after the Wenchuan earthquake in China.
Despite previous research has illustrated there is high-coexistence between posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) in the aftermath of traumatic events, few studies have conceptualized the coexistence mechanism of the two psychological phenomena. Using the network analysis, this study aimed to identify the key bridge symptoms and compare sex differences between PTSD symptoms and PTG elements in survivors 10 years after the Wenchuan earthquake in China. A total of 744 survivors 10 years after the Wenchuan earthquake in China completed self-reported questionnaires on demographics, PTSD symptoms (4-item of Posttraumatic Stress Disorder Checklist), and PTG (10-item of Posttraumatic Growth Inventory). Network analysis was used to identify the network structure of PTSD symptoms and elements of PTG, along with bridge symptoms. Additionally, sex differences in the network structure were compared by the Network Comparison Test. Results revealed that the network of PTSD symptoms and elements of PTG was robust to stability and accuracy tests. The key bridge symptoms in the network were "Stronger religious faith", "Changed priorities", and "Easily startled". There were significant differences in network global strength across sex, and network structure across the severity of property loss other than house damage. Future interventions targeting the three key bridge symptoms are expected to relieve the severity of PTSD and promote growth following exposure to traumatic events.