Treatment of multiple sclerosis fatigue with the synthetic psychoactive drug modafinil.
Multiple sclerosis (MS) is a complex disorder characterized by a broad spectrum of symptoms that evolve throughout the disease. Symptoms can be categorized as visible and invisible based on external sight recognition. However, although others poorly recognize it, invisible symptoms such as mood dysfunction, neuropathic pain, or fatigue can significantly affect activities of daily living and the quality of life of people with MS (PwMS). PwMS frequently complain of fatigue, which has physical or cognitive manifestations. Fatigue in MS does not improve or resolve with rest, and it is disproportionate with respect to the exerted effort. Fatigue management in MS is challenging, and a few pharmacological approaches have been successfully proposed. Among them, the drug modafinil has attracted attention because of its properties as a synthetic psychoactive drug. In this review, we focus on the evidence available to date, supporting the use of modafinil in MS fatigue. However, despite the availability of some trials evaluating the effects of modafinil on fatigue, their contrasting results failed to support its usefulness in fatigue management in MS.


Suppression of histamine-induced pruritus by three antihistaminic drugs.
A double-blind crossover study of inhibition of histamine-induced pruritus by three commonly prescribed antihistamines was conducted on 28 normal subjects. Drugs used included diphenhydramine HCl (Benadryl), cyproheptadine (Periactin), hydroxyzine HCl (Atarax), and a lactose placebo in identical capsules. Intradermal histamine dose-response thresholds of pruritus were obtained before and after pretreatment with the three antihistamines and placebo in each subject. Analysis of data revealed a fivefold increase above baseline of the histamine dose required to produce pruritus following both cyproheptadine and placebo. This compared to a tenfold increase following diphenhydramine and a 750-fold increase following hydroxyzine HCl. The most common side effect was drowsiness, which occurred with all three drugs.


The role of pulmonary corticosteroid 11-reductase activity in lung maturation in the fetal rat.
Injection of 11-ketoprogesterone into fetal rats at day 17 of gestation reduced the pulmonary C-11 activation index (an indicator of net gain or loss of glucocorticoid activity) as measured at day 21 (P less than 0.001) and resulted in elevated levels of the inactive hormone 11-dehydrocorticosterone (P less than 0.001), but unchanged corticosterone levels. Adrenal weight was significantly increased (P less than 0.001). 11-Ketoprogesterone-injected fetuses had considerably larger lungs (P less than 0.001) with reduced saturated phosphatidylcholine content (P less than 0.001).


Modeling the predictors of mobile health adoption by Rohingya Refugees in Bangladesh: An extension of UTAUT2 using combined SEM-Neural network approach.
While the healthcare facilities for the people is questionable in Bangladesh, Rohingya refugees is a burning issue for both Bangladesh and global community. Integrating Rohingya refugees into the framework of mHealth could be beneficial for both Bangladesh and Rohingya refugees in general, and in specific situation like COVID-19 outbreak. However, no research has been found on what motivates Rohingya refugees to accept mHealth in Bangladesh. Drawing on the UTAUT2 model, this study investigates the predictors of acceptance of mHealth services technologies among Rohingya refugees. The study also seeks to clarify the roles of mHealth developers, the Bangladesh government, and non-governmental organizations working with the 1.1 million Rohingya refugees in Bangladesh. Quantitative data were collected from refugee camps with the permission of the Refugee Relief and Repatriation Commissioner (RRRC). The data were analyzed in two stages using a mixed approach that combines PLS-SEM and Artificial Neural Network (ANN). This study revealed that Effort expectancy (EE, with t = 5.629, β = 0.313) and facilitating conditions (FC with t = 4.442, β = 0.269) in PLS-SEM, and FC (with 100 percent importance) and Health consciousness (HC, with 94.88 percent importance) in ANN analysis were found to be the most substantial predictors of mHealth adoption. The study also revealed that EE and FC are more important for low education group, while PE and Situational Constraint (SC) are more important for the high education group of refugees. In addition to providing insights for mHealth developers, this study particularly focuses on the role of government institutions and non-governmental social workers in working with the subjects to increase FC and HC among Rohingya refugees and bring them under mHealth services.


Blockade of adrenergic β-receptor activation through local delivery of propranolol from a 3D collagen/polyvinyl alcohol/hydroxyapatite scaffold promotes bone repair in vivo.
Activation of the sympathetic system and adrenergic β-receptors following traumatic bone defects negatively impairs bone regeneration. Whether preventing β-receptor activation could potentially improve bone defect repair is unknown. In this study, we investigated the effect of systematic administration and local delivery of propranolol through composite scaffolds on bone healing. Collagen/PVA/propranolol/hydroxyapatite(CPPH)composite scaffolds were fabricated with 3D printing technique and characterized by scanning electron microscope (SEM). Micro-CT analysis and bone formation histology were performed to detect new bone formation. Osteogenic differentiation of bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow monocytes cultured with scaffolds extract were performed for further verification. Intraperitoneal injection of propranolol did not significantly improve bone repair, as indicated by micro-CT analysis and bone formation histology. However, CPPH scaffolds exhibited sustained release of propranolol in vitro and significantly enhanced bone regeneration compared with vehicle collagen/PVA/hydroxyapatite (CPH) scaffolds in vivo. Moreover, in vitro experiments indicated the scaffolds containing propranolol promoted the osteogenic differentiation and migration of rat BMSCs and inhibited osteoclastogenesis by preventing β-receptor activation. This study demonstrates that local adrenergic β-receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.


Isotopic and hydrochemical analyses reveal nitrogen source variation and enhanced nitrification in a managed peri-urban watershed.
Watershed management practices (WMPs) alter the sources and transformation of reactive nitrogen (N) in peri-urban watersheds, but a precise description of how WMPs impact N cycling is still lacking. In this study, four sampling campaigns were conducted in the wet and dry seasons of 2019 (before WMPs) and 2020 (after WMPs) to determine the spatiotemporal variations in nitrate isotopes (15N-NO3- and 18O-NO3-) and hydrochemical compositions in the Muli River watershed. The results showed that the WMPs could significantly reduce the N load in the middle and lower reaches, but substantial improvements were not observed in 2020. Manure and sewage (M&S, 36.2 ± 15.8-55.0 ± 19.4%) was the major source of nitrate (NO3-) in the stream water, followed by smaller-scale wastewater treatment plants (WWTPs, 14.0 ± 10.9-25.6 ± 11.5%). The WMPs were effective in controlling M&S, resulting in an approximately 16.7% (p < 0.01) lower M&S contribution during the dry season in 2020 compared to that in 2019. However, the smaller-scale WWTP input increased by approximately 5.4% (p < 0.01) after the WMPs. During the study period, the assimilation of NO3- by phytoplankton was important for NO3- loss, but the WMPs promoted nitrification in the watershed because of the elevated redox potential (Eh). Overall, the present study provides a better estimate of the variations in nitrogen sources and transformation in a peri-urban watershed after WMPs and provides an approach for developing timely nitrogen management solutions.


Surgical aspects of pineal region tumors in children.
The use of the operating microscope and specialized anesthesiologic techniques make it possible to operate safely on tumors in the pineal region. A survey is presented of the main surgical and anesthesiologic techniques used: the supracerebellar infratentorial approach in the sitting position and the occipital transtentorial approach in the semi-sitting position. For selecting the optimal approach a CT scan with sagittal sections is very important to localize the tumor in relation to the tentorium cerebelli, the straight sinus and the great vein of Galen. Based upon the comparison of the two techniques the author concludes that nearly all tumors in the pineal region in children can be operated by the infratentorial supracerebellar route and that the transtentorial route offers relatively little advantage.


Yerba Maté (Ilex paraguariensis) aqueous extract decreases intestinal SGLT1 gene expression but does not affect other biochemical parameters in alloxan-diabetic Wistar rats.
Yerba maté (Ilex paraguariensis) is rich in polyphenols, especially chlorogenic acids. Evidence suggests that dietary polyphenols could play a role in glucose absorption and metabolism. The aim of this study was to evaluate the antidiabetic properties of yerba maté extract in alloxan-induced diabetic Wistar rats. Animals (n = 41) were divided in four groups: nondiabetic control (NDC, n = 10), nondiabetic yerba maté (NDY, n = 10), diabetic control (DC, n = 11), and diabetic yerba maté (DY, n = 10). The intervention consisted in the administration of yerba maté extract in a 1 g extract/kg body weight dose for 28 days; controls received saline solution only. There were no significant differences in serum glucose, insulin, and hepatic glucose-6-phosphatase activity between the groups that ingested yerba maté extract (NDY and DY) and the controls (NDC and DC). However, the intestinal SGLT1 gene expression was significantly lower in animals that received yerba maté both in upper (p = 0.007) and middle (p < 0.001) small intestine. These results indicate that bioactive compounds present in yerba maté might be capable of interfering in glucose absorption, by decreasing SGLT1 expression.


Fabrication of CAD-CAM custom-made bar clip for implant-supported overdentures using an intraoral scanner: A dental technique.
This article describes a digital technique for fabricating individually designed overdenture bar clips. The patient was scanned intraorally using a Medit i700 scanner; the custom clip was designed using the Blender software program and milled from polyoxymethylene blocks. This low-cost technique offers more available options compared with traditional clips, improving the management of retention loss.


Endothelin ETA receptor-subtype specific antagonism does not mitigate the acute systemic or renal effects of exogenous angiotensin II in humans.
Angiotensin II (Ang II) is assumed to play a pathophysiological role in a variety of vascular diseases. Animal studies indicate that these effects are partly attributed to stimulation of endothelin-1 (ET-1) release. The aim of the present study was to investigate whether the acute effects of Ang II on systemic and renal haemodynamics in healthy subjects can be influenced by endothelin ET(A)-receptor blockade. The study design was balanced, randomized, placebo-controlled, double blind, two-way cross-over, in 10 healthy male subjects. Subjects received stepwise increasing intravenous doses of Ang II (0.65, 1.25, 2.5, 5 ng kg(-1) min(-1) for 15 min per dose level) in the presence or absence of BQ-123 (60 microg min(-1)), a specific ETA-receptor antagonist. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate and inulin plasma clearance method, respectively. Renal vascular resistance (RVR) was calculated from mean arterial pressure (MAP) and renal plasma flow. Ang II decreased RPF by 34% and GFR by 9% and increased RVR by 94% and MAP by 27% (ANOVA, P < 0.001 vs. baseline, for all parameters). BQ-123 did not alter these renal and systemic haemodynamic responses to a significant degree. In addition, BQ-123 had no significant haemodynamic effect under baseline conditions. Short-term increase of circulating Ang II levels causes systemic and renal pressor effects, which are not mitigated by endothelin ETA-receptor blockade. This suggests that the pressor response to Ang II cannot be accounted for by the acute release of vasoactive ET-1.


Determination of 11 minerals in children using inductively coupled plasma mass spectrometry.
Minerals play an important role in children's growth and cognition. In this study, our aim was to establish reference intervals of mineral level in Children of Liaoning province (China) and provide a reliable basis for future preventive healthcare guidelines. Random samples of 2217 healthy children aged 0-15 years who were referred for routine hospital laboratory examinations in the cities of Shenyang, Fushun, Fuxin, Benxi, Chaoyang and Lingyuan were invited to participate in the study. Serum levels of Calcium (Ca), Iron (Fe), Zinc (Zn), Magnesium (Mg), Copper (Cu), Manganese (Mn), Selenium (Se), Mercury (Hg), Nickel (Ni), Cobalt (Co), and Lithium (Li) were determined by inductively coupled plasma mass spectrometer(ICP-MS). Sex-related significant differences in the serum concentrations of the Mg and Cu (P < 0.05). Age-related significant differences were found in serum levels of Ca, Fe, Zn, Mg, Cu and Mn (P < 0.05) and the concentrations of 9 minerals (Ca, Mg, Cu, Mn,Se,Hg,Ni,Co and Li in serum varied from season to season (P < 0.05). The Spearman correlation matrix of 11 minerals was shown as a heat map, the correlations between Ca-Zn, Ca-Mg, Fe-Zn, Fe-Se, Mn-Ni, Se-Hg, Se-Ni, Hg-Ni, and Ni-Co, Ni-Li were the strongest compared with others. The reference intervals of serum 11 minerals for children should considering the sex, age and season, which may be useful for decisive diagnoses of abnormality of the 11minerals and the related diseases.


A phased array ultrasound system with a robotic arm for neuromodulation.
Ultrasonic neuromodulation (UNMOD) provides a non-invasive brain stimulation. However, the high-resolution region-specificity of UNMOD with a single element transducer combined with a mechanical positioning system could have limits due to the intrinsic positioning error from mechanical systems. A phased array system could lead to highly selective neuromodulation with electronic control. A specialized phased-array system with a robotic arm is implemented for a rhesus monkey model. Various primary motor cortex areas related to tail, hand, and mouth were stimulated with a 200 μm step size. The ultrasonic parameters were ISPTA of 840 mW/cm2, pulse repetition frequency of 100 Hz, and a 5% duty factor at 600 kHz. The induced movement were recorded and analyzed. Separate digits, mouth, and tongue motions were successfully induced by electronically controlling the focus. The identical body part movement could be induced when the focus was moved back to the identical primary motor cortex with electronic control. Accordingly, the reproducibility of UNMOD could be partially validated with rhesus monkey model. A phased-array system appears to have a potential for the non-invasive and region-selective neuromodulation method.


[Histopathology of perforating eye injuries].
Perforating eye injuries endanger the eye due to the loss of internal structures; hypertonia; the proliferation of vascular tissue, glia, and epithelium; hemorrhages, and inflammations. This is illustrated with histologic pictures.


Organizational Safety Climate and Job Enjoyment in Hospital Surgical Teams With and Without Crew Resource Management Training.
The association between organizational safety climate (OSC) and job enjoyment (JE) for team members in surgical units in 2 hospitals was investigated. The treatment hospital received airline industry-based crew resource management (CRM) training, and the comparison hospital did not. Strong OSC has been positively associated with healthy hospital work environments and was expected to also be associated with employee job enjoyment. Two hundred sixty-two surgical personnel responded to surveys about OSC and JE. The effects of OSC on JE did not depend on having CRM training. However, OSC and JE scores were higher in the treatment hospital, and the main effect of OSC and JE scores in the treatment hospital was highly significant (P < 0.001), with higher safety climate scores associated with higher JE. A strong OSC is important to employee job enjoyment. Nurse leaders should promote measures to strengthen the OSC in their surgical services departments.


Plasmapheresis in Goodpasture's syndrome with renal failure.
Four patients who presented with severe proliferative glomerulonephritis associated with linear deposition of IgG on the basement membrane have been treated by intermittent massive plasmapheresis. Two patients had all the features of Goodpasture's syndrome. In the other two cases, the characteristic renal lesion was present but there was no pulmonary involvement. In all cases, renal function improved after plasmapheresis while in two, renal function deteriorated after plasmapheresis was stopped. On of these patients responded to a second course of plasmapheresis but failed to respond to a third. This study supports previous reports of the value of plasmapheresis in patients with Goodpasture's syndrome and renal failure in whom recovery without plasmapheresis has not been recorded. The present study emphasizes the importance of continuing treatment for a period of weeks to permit prolonged remission. If treatment is withdrawn too early, rapid deterioration in renal function may result, and unless plasmapheresis is recommenced at once the renal failure may then prove irreversible.


Convergent synthesis of moslosooflavone, isowogonin and norwogonin from chrysin.
A convergent synthesis route of moslooflavone, isowogonin and norwogoninis reported,starting from chrysin, an easily available flavone, by methylation, bromination, methoxylation and demethylation procedures. This synthetic route is convenient and can give the three rare flavones in good yield.


Microarray analysis of host gene-expression during intracellular nests formation of Trypanosoma cruzi amastigotes.
The intracellular pathogens utilize numerous cellular components of host cells to advance the infection as well as to enter the host cell. Analyzing the host cellular response enables us to get a better understanding of the pathogenesis, and subsequently indicate possible therapeutic targets. We therefore analyzed gene-expression profile of NIH3T3 fibroblast cells infected by Trypanosoma, a representative intracellular pathogen similar to Leishmania, using custom-designed cDNA microarray consisting of 1,701 mKIAA cDNAs. Focusing on intracellular nest formation of Trypanosoma cruzi amastigotes, we profiled the host gene-expression at 8 days post-infection and found several degrees of change in 16 mKIAA genes. Among these genes, 10 were up-regulated and 6 were down-regulated. Assuming that these genes had important roles in the infection's progression, we performed semi-quantitative RT-PCR analysis and con-firmed the gene expression change of 4 genes. Furthermore, 5 genes were mapped on cadherin signaling pathway using pathway analysis software. These results indicate significance of the host cellular pathway in the proliferative stage of Trypanosoma cruzi amastigotes.


Noradrenaline induces supersensitivity of adenylyl cyclase in NG108-15 and HT29-18 cells but not in the beta-cell RINm5F.
In some cells a supersensitive adenylyl cyclase response follows hormonal inhibition of the enzyme. We have compared the effect of pre-treatment with noradrenaline in RINm5F cells to that in cells known to demonstrate supersensitivity. In NG108-15 cells, 12 or 24 hours pre-treatment with 1-10 microM noradrenaline markedly enhanced forskolin (1 microM) stimulated cAMP accumulation compared to that in untreated cells (12 h, 429 +/- 123 vs 72 +/- 8 pmol/mg protein; 24 h 190 +/- 32 vs 82 +/- 10 for treated and untreated cells, respectively). In a second cell, HT29-18, 30 min pre-treatment with 10 microM noradrenaline enhanced forskolin (10 microM) stimulated cAMP accumulation from 47 +/- 13 pmol/mg protein to 405 +/- 109 pmol/mg protein. In contrast, pre-treatment of RINm5F cells with noradrenaline under the same conditions did not enhance the forskolin response. These data indicate that noradrenaline which induces a supersensitive adenylyl cyclase response in NG108-15 and HT29-18 cells does not induce the response in the insulin secreting cell RINm5F.


[Blood level values of rectally applied theophylline and its derivative proxyphylline and diprophylline in aqueous enema (author's transl)].
Serum levels of theophylline and two of its oxypropylic derivatives were determined in repetitive blood samples after instillation of a mixture of the three substances by means of an aqueous enema. From the time course of serum levels a rapid onset of bronchodilation and rather a long-lasting bronchodilatory effect of about 8 h may be expected. Side effects are rare. The pharmacological characteristics of the three compounds are discussed.


Brain endurance training improves shot speed and accuracy in grassroots padel players.
Evidence that mental fatigue impairs sport performance has created a demand for countermeasures. We examined the effects of brain endurance training, a form of fatigue-inoculation, on shot performance in grassroots padel players. A pre-, mid- and post-test design, with participants randomized to brain endurance training (n = 30) or control (n = 31) groups. During testing, participants completed a Padel Stroke Performance Test, before and after a demanding 30-min cognitive task (Stroop). Training comprised 3 sessions/week for 6 weeks. In each training session, participants completed 10-min warm-up, 15-min technical drills, 15-min tactical drills, and 20-min simulated games. These physical activities were intermixed with short 4-min periods of Stroop (brain endurance training group) or rest (control group) totaling 20-min. Performance was measured by shot speed and accuracy of padel strokes. Mental fatigue indices were measured before and after the Stroop task using a visual analog scale rating, a psychomotor vigilance task, and a go/no-go task. During testing, the 30-min Stroop task elicited a state of mental fatigue, confirmed by higher subjective ratings, slower responses during the psychomotor vigilance task, and slower saccade latencies during the go/no go task. Compared to pre-testing, in mid- and post-testing, the brain endurance training group hit progressively faster and more accurate padel shots after the Stroop task compared to controls. Brain endurance training enhanced skill-based psychomotor performance when fatigued compared to standard padel training. Brain endurance training is a countermeasure that promotes mental fatigue durability.


[A new case of Rowell's syndrome].
This article introduces a new case of Rowell's syndrome, a controversial entity defined by the association of lupus erythematosus and erythema multiforme. A 43-year-old woman was diagnosed with lupus erythematosus induced by esomeprazole. Because her eruption did not improve after withdrawal of the drug, hydroxychloroquine was administered. Two weeks later, the patient described new annular lesions on her chest and arms, both erosive and crusted, and some had a target-like appearance. The oral mucosa was also affected. Histology revealed sub-epidermal blistering with keratinocytic necrosis, strongly suggesting erythema multiforme. Screening for other causes of erythema multiforme proved negative. A positive outcome was achieved with corticosteroids and hydroxychloroquine. One year later, the patient was in complete remission for both lupus erythematosus and erythema multiforme. The association of lupus erythematosus and erythema multiforme first described in 1963 is known as Rowell's syndrome. While diagnostic criteria have been established in the literature, the reality of this entity is still contested. The annular lesions of subacute lupus erythematosus may be confused with the lesions of erythema multiforme. As suggested in the above section, other authors consider Rowell's syndrome to be a singular entity. Indeed, our patient developed lesions distinct from those initially suggesting subacute lupus erythematosus, in particular: the target-like aspect of the elementary lesions, mucosal involvement, a distinct histological aspect, and dissociated outcomes. Ultimately, the definition of Rowell's syndrome remains highly debated.


[Alternate method for closure of oro-antral fistulas. Plastic covering of jaw opening with lyophilized Dura and alcoholic solution of Prolamin].
The operative closure of an oroantral fistula due to tooth extractions by the method of Rehrmann consists of various disadvantages, e.g. postoperative pain, swelling, flattening of the vestibulum and scar-tissue. Two alternative methods to close fresh oroantral fistulas without surgical intervention are described. By the use of prolamin occlusion gel or lyophilized dura these disadvantages can be avoided. Both techniques were successfully attempted on patients. The rate of failure is on both counts under 4%. Some indications limits must be strictly regarded. Both methods are really a good alternative to the usual operative procedure of Rehrmann and can easily be applied even on patients of great risk.


Ecological connectivity of the marine protected area network in the Baltic Sea, Kattegat and Skagerrak: Current knowledge and management needs.
Marine protected areas (MPAs) have become a key component of conservation and fisheries management to alleviate anthropogenic pressures. For MPA networks to efficiently promote persistence and recovery of populations, ecological connectivity, i.e. dispersal and movement of organisms and material across ecosystems, needs to be taken into account. To improve the ecological coherence of MPA networks, there is hence a need to evaluate the connectivity of species spreading through active migration and passive dispersal. We reviewed knowledge on ecological connectivity in the Baltic Sea, Kattegat and Skagerrak in the northeast Atlantic and present available information on species-specific dispersal and migration distances. Studies on genetic connectivity are summarised and discussed in relation to dispersal-based analyses. Threats to ecological connectivity, limiting dispersal of populations and lowering the resilience to environmental change, were examined. Additionally, a review of studies evaluating the ecological coherence of MPA networks in the Baltic Sea, Kattegat and Skagerrak was performed, and suggestions for future evaluations to meet management needs are presented.


[Iatrogenic colon perforation: experiences with early laparoscopy].
Perforation during colonoscopy is a rare but severe complication. Retrospective analysis was done of 15 patients operated on for perforation from colonoscopy between January 2000 and December 2006. Three perforations occurred during diagnostics and 12 during interventional colonoscopy. Two perforations occurred as transmural thermal injury to the colon wall. Peritonitis was found in four cases and correlated significantly with mean time between perforation and operation. Twelve perforations were sutured laparoscopically and three by laparotomy. Hospital stay was significantly shorter after laparoscopic treatment than by laparotomy. One patient had a postoperative wound infection, and mortality was 0%. Early laparoscopic suturing is a safe and effective method in the treatment of perforation from colonoscopy.


Susceptibility to typhoid fever is associated with a polymorphism in the cystic fibrosis transmembrane conductance regulator (CFTR).
The cystic fibrosis transmembrane conductance regulator (CFTR) is the affected protein in cystic fibrosis (CF). The high rate of CF carriers has led to speculation that there must be, similar to the sickle cell haemoglobin advantage in malaria, a selective advantage for heterozygotes. Such a selective advantage may be conferred through reduced attachment of Salmonella typhi to intestinal mucosa, thus providing resistance to typhoid fever. We tested this hypothesis by genotyping patients and controls in a typhoid endemic area in Indonesia for two highly polymorphic markers in CFTR and the most common CF mutation. We found an association between genotypes in CFTR and susceptibility to typhoid fever (OR=2.6). These analyses suggest that the role CFTR plays in vitro in S. typhi infection is also important for infection in the human population.


Population structure and thinning in natural stands of Atlantic White Cedar (Chamaecyparis thyoides (L.) BSP).
Data from forestry yield tables were used to investigate the population structure of natural stands of Atlantic White Cedar (Chamaecyparis thyoides) in the mid-Atlantic states. The proportion of individuals in three size classes, 1-5 inch dbh, 5-8 inch dbh and > 8 inch dbh was shown to depend on both site age since clearcutting and site quality. Site age and site quality also determined the degree to which cedar populations underwent density dependent mortality (self-thinning). On all sites, the smallest individuals were removed by self-thinning. Analyses of this type allow predictions to be made of forest stand dynamics and further an understanding of population processes in natural communities.


Age-dependent immune and lymphatic responses after spinal cord injury.
Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI. Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord. We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury. Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI. Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair.


Using sediment grain size characteristics to assess effectiveness of mechanical sand barriers in reducing erosion.
Wind and sand control features are important tools for limiting desertification. Sand barriers are one of the oldest engineering measures used to reduce wind-sand hazards. Their efficacy and exact mechanism by which they work has remained a topic of scientific debate however. Sediment grain-size distributions can help constrain their utility and function. This research analyzed sediment grain size distributions in samples collected from areas around six different types of sand barriers installed along the southeastern margin of the Tengger Desert. Results were compared with sediment from a bare dune area (no barriers) used as a control. The barrier area samples contained high proportions of coarse sand and relatively low proportions of silty sand and very fine sand. Fine and medium sand were present but clay was not. The lower proportions of fine sand and higher proportions of coarse sand relative to bare dunes documented an effective reduction in aeolian transport by the barriers. Samples from the barrier areas also showed poorer sorting relative to bare dune areas. This appeared as lower kurtosis values and wider frequency distribution curves relative to those measured from bare dunes samples. The wider cumulative frequency curves for samples from the barrier areas likely reflects the higher proportion of coarse-grained material. The Straw/1.5 and PLA/1 barrier types hosted greater sediment accumulation than that observed for the other barrier types (Straw/1, PLA/1.5, Mixed/1 and Mixed/1.5). Sediment grain size distributions showed that the base and middle slope areas of the dune experienced deposition, while the top of the dunes experienced erosion. The Straw/1 barrier (straw installed as a 1 × 1 m grid) performed best in terms of installation costs and protective effects for the study area. This study demonstrates how sediment grain size distributions can be used as quantitative proxies for sand barrier performance in reducing desertification.


Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis.
Hepatic encephalopathy is characterized by disturbances of motor and cognitive functions involving the basal ganglia. So far no standards for assessment of neuropsychiatric abnormalities (disorders of sleep, mood, anxiety and personality) in subclinical hepatic encephalopathy have been defined. Using an animal model of mild (subclinical) hepatic encephalopathy we investigated now striatum-related behaviors and cortico-striatal synaptic plasticity in rats 2 months after introduction of a portacaval shunt and sham-operated matched controls. In a novel open field portacaval shunt rats displayed less locomotor activity; unlike controls they also showed no habituation to the field and no recall of the field environment after 24 h, indicative of cognitive deficit. The elevated-plus maze test indicated no differences in fear/anxiety in the portacaval shunt animals. Tetanic stimulation of cortical afferents in magnesium-free solution evoked an N-methyl-D-aspartate-dependent long-term potentiation in sham-operated animals. In portacaval shunt animals long-term potentiation was significantly impaired. Histamine, a potent modulator of cortico-striatal transmission, induced a larger long-term depression of field potentials in control compared with portacaval shunt rats. In conclusion, a combination of electrophysiological and behavioral approaches has revealed functional changes in cortico-striatal transmission. These data are relevant for understanding the mechanisms of motor and cognitive dysfunctions in hepatic encephalopathy patients and for the development of precise psychometric tests, evaluating cognitive deficits in subclinical hepatic encephalopathy.


Evaluation of an endo-beta-mannanase produced by Streptomyces ipomoea CECT 3341 for the biobleaching of pine kraft pulps.
An endo-beta-mannanase (EC 188.8.131.52) from Streptomyces ipomoea CECT 3341 was purified and applied to the biobleaching of pine kraft pulps. The maximum level of endo-beta-mannanase activity (0.6 units ml(-1)) was achieved after 4 days of growth in a medium containing locust bean gum and yeast extract. Zymograms revealed mannanase bands (Man) with high and low electrophoretic mobility on the second and seventh days of incubation (Man1, Man3) and three bands of high, medium and low mobility from the third to sixth days of growth (Man1, Man2, Man3). Although these exhibited different molecular masses, their amino-terminal sequences were identical. The action of proteases detected in the culture supernatant could be responsible for such events, suggesting that only one endo-beta-mannanase is produced by S. ipomoea. The purified Man3 exhibited a molecular mass of 40 kDa, an isoelectric point of 4.0 and an optimal temperature and pH reaction of 55 degrees C and 7.5, respectively. It was strongly inhibited by Ag+, Hg2+, Al3+ and Fe3+, and was strongly activated by Mn2+. The ability of the purified endo-beta-mannanase to improve the bleachability of pine kraft pulp, when applied with alkaline extraction, was demonstrated by an increase in the pulp brightness (1.7%, using the International Standards Organisation's test) and an absence of variations in the viscosity values. A relationship between the increase in pulp brightness and the presence of manganese in the pulps could be established.


[Experimental-hygienic basis for the preventive nutrition of workers exposed to intense industrial noise].
Provision with vitamins C, P, B6, PP, changes in the blood serum creatine kinase activity, some parameters of carbohydrate metabolism and integral values were studied in rats exposed to the 30-day action of stable "white" noise with the intensity of 100 dB A, in the presence of both usual physiologic and specially developed, pathogenetically validated nutrition. Simultaneously, the above biochemical parameters, acoustic sensitivity and subjective data were comparatively investigated in two groups of workers of "noisy" occupations. It was shown that the proposed prophylactic ration produced a favourable effect on the studied parameters of the body exposed to intensive industrial noise.


Randomized cross-over study of a 21-day versus a 28-day hormone replacement therapy (HRT).
To compare the occurrence of climacteric symptoms at two points in the cycle, identified as minE (phase of minimum estrogen effect) and MaxP (phase of maximum progesterone effect). Prospective randomized cross-over study in postmenopausal women currently on HRT comparing two opposed, sequential formulations: a regimen of 21 tablets containing estradiol valerate (EV) opposed with cyproterone acetate (CPA) in the last 10 tablets, versus a regimen of 28 tablets of conjugated equine estrogens (CEE), the last 12 tablets of which were taken together with norgestrel (NG). Incidence of 24 climacteric complaints assessed at the specified days of the cycle corresponding to minE (day 6 or 7) and MaxP (day 27 or 28) Contrary to the hypothesis that estrogen-dependent symptoms will recur at minE of the 21-day regimen, no significant differences were noted with the regimen containing 28 days of CEE, which served as the control. There were more complaints with the CEE+NG formulation at both minE and MaxP. Of the 38 patients, 63% preferred the EV+CPA regimen, 18.4% the CEE+NG regimen and 18.4% rated both preparations as equal. The 7-day pause in the 21-day formulation containing EV+CPA did not affect efficacy; it was as effective in relieving climacteric symptoms as the regimen containing 28 days of estrogen. Based on the frequency of complaints both at minE and MaxP, the EV+CPA formulation induced a more acceptable symptom and mood profile.


Cytokine Profile and Concentrations of Metabolic Hormones in the Blood of Overweight Men with Coronary Arteriosclerosis.
Plasma concentrations of cytokines and metabolic hormones and their association with vulnerable atherosclerotic plaques were studied in 36 overweight men (age 40-77 years; BMI 25.0-29.9 kg/m2) with coronary atherosclerosis who underwent coronary endarterectomy. According to histological analysis, the patients were divided into two groups: with stable (17 (47.2%) men) and vulnerable (19 (52.8%) men) plaques in the coronary arteries. The plasma levels of cytokines and metabolic hormones were measured by multiplex analysis: C-peptide, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, IL-6, insulin, leptin, monocyte chemoattractant protein-1, and TNFα. In overweight patients with vulnerable plaques, the level of glucagon was lower by 4.17 times, GIP - by 2.47 times, and insulin - by 2.1 times. At the same time, the risk of occurrence of a vulnerable plaque increases by 5.4% with a decrease in GIP concentration by 1 pg/ml irrespectively of age, as well as by 3.1% with an increase in insulin concentration by 10 pg/ml, without achieving statistical significance when included in the age model. Overweight men with coronary atherosclerosis and vulnerable plaques have lower levels of insulin, glucagon, and GIP. The levels of GIP and insulin are inversely associated with the risk of having vulnerable atherosclerotic plaque.


Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections.
Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.


Evaluating the environmental microbiota across four National Health Service hospitals within England.
Hospital surfaces contaminated with microbial soiling, such as dry surface biofilms (DSBs), can act as a reservoir for pathogenic micro-organisms, and inhibit their detection and removal during routine cleaning. Studies have recognized that such increases in bioburden can hinder the impact of disinfectants and mask the detection of potential pathogens. Cleanliness within healthcare settings is often determined through routine culture-based analysis, whereby surfaces that exhibit >2.5 colony-forming units (CFU) per cm2 pose a risk to patient health; therefore, any underestimation could have detrimental effects. This study quantified microbial growth on high-touch surfaces in four hospitals in England over 19 months. This was achieved using environmental swabs to sample a variety of surfaces within close proximity of the patient, and plating these on to non-specific low nutrient detection agar. The presence of DSBs on surfaces physically removed from the environment was confirmed using real-time imaging through episcopic differential interference contrast microscopy combined with epifluorescence. Approximately two-thirds of surfaces tested exceeded the limit for cleanliness (median 2230 CFU/cm2), whilst 83% of surfaces imaged with BacLight LIVE/DEAD staining confirmed traces of biofilm. Differences in infection control methods, such as choice of surface disinfectants and cleaning personnel, were not reflected in the microbial variation observed and resulting risk to patients. This highlights a potential limitation in the effectiveness of the current standards for all hospital cleaning, and further development using representative clinical data is required to overcome this limitation.


A spectrum of skeletal anomalies associated with pulmonary agenesis: possible neural crest injuries.
Six cases of unilateral pulmonary agenesis with skeletal and other deformities have been diagnosed in our hospitals. The various pulmonary, spinal, rib and limb anomalies with their possible inter-relationships were examined and described in detail and comparison with previously reported cases was made. It became apparent that the limb abnormalities which most constantly involved hypoplasia of the phalanges of a thumb with varying metacarpal and radial anomalies, were ipsilateral to the pulmonary agenesis in all cases. The spinal deformities involved degrees of failure of segementation of T1-T3 with other vertebrae randomly involved. Rib abnormalities also varied and did not necessarily correspond to the same side as the pulmonary agenesis. The concept of the anomalies all being part of a group of neural crest injuries was then explored.


Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma.
ARID2 is the most recurrently mutated SWI/SNF complex member in melanoma; however, its tumor-suppressive mechanisms in the context of the chromatin landscape remain to be elucidated. Here, we model ARID2 deficiency in melanoma cells, which results in defective PBAF complex assembly with a concomitant genomic redistribution of the BAF complex. Upon ARID2 depletion, a subset of PBAF and shared BAF-PBAF-occupied regions displays diminished chromatin accessibility and associated gene expression, while BAF-occupied enhancers gain chromatin accessibility and expression of genes linked to the process of invasion. As a function of altered accessibility, the genomic occupancy of melanoma-relevant transcription factors is affected and significantly correlates with the observed transcriptional changes. We further demonstrate that ARID2-deficient cells acquire the ability to colonize distal organs in multiple animal models. Taken together, our results reveal a role for ARID2 in mediating BAF and PBAF subcomplex chromatin dynamics with consequences for melanoma metastasis.


Brain derived neurotrophic factor circulating levels in patients undergoing IVF.
The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period.


Analysis of genetic variability and relationships among Mentha L. using the limonene synthase gene, LS.
The genus Mentha comprises a group of aromatic plants with worldwide distribution. Because of frequent interspecific hybridization, the genetic relationships within the genus are not clearly understood. Limonene synthase, which catalyses the first committed step in the essential oil monoterpene biosynthetic pathway, is considered to be a possible rate limiting enzyme. With the homology-based cloning method, primers were designed according to cDNA sequence to amplify full-length DNA sequences in 13 Mentha samples from five species, using Perilla as an outgroup. Analyses of gene structure, length variation, GC-content, Ts/Tv ratio and evolutionary diversity were carried out. Consensus phylogenetic trees were obtained using maximum likelihood, neighbor-joining, and maximum parsimony, respectively, based on the full-length genomic DNA sequences, complete ORF coding sequences and predicted amino acid sequences. The results presented here based on the sequence of MhLS provide the first credibly supported genetic relationships for Mentha, which enables a basis for further mint taxonomy, cultivation and breeding.


The symmetry-induced numerosity illusion depends on visual attention.
Symmetry is an important and strong cue we rely on to organize the visual world. Although it is at the basis of objects segmentation in a visual scene, it can sometimes bias our perception. When asked to discriminate numerical quantities between symmetric and asymmetric arrays, individuals tend to underestimate the number of items in the symmetric stimuli. The reason for this underestimation is currently unknown. In this study we investigated whether the symmetry-induced numerosity underestimation depends on perceptual grouping mechanisms by depriving attentional resources. Twenty-six adults judged the numerosity of dot arrays arranged symmetrically or randomly, while ignoring a visual distractor (single task) or while simultaneously judging its color and orientation (dual-task). Diverting attention to the concurrent color-orientation conjunction task halved the symmetry-induced numerosity underestimation. Taken together these results showed that the bias in numerosity perception of symmetric arrays depends-at least partially-on attentional resources and suggested that it might originate from the recruitment of attentional dependent incremental grouping mechanisms.


[Posterior instrumented correction and fusion of adolescent idiopathic scoliosis].
Balanced frontal curve correction with horizontal shoulder levels, restoration of sagittal plane and vertebral derotation with a fusion length as short as possible. Curves larger than 40-50° Cobb angle; furthermore age, location, degree of rotation, and sagittal plane deviation have to be considered. Posteriorly, segmental pedicle screw instrumentation with a high screw density (80%) and both titanium alloy and cobalt chrome rods. Freehand screw placement under consideration of both natural and deformity-induced pedicle morphology. Correction via reduction screws or instruments. Combined correction technique with rod rotation, segmental screw approximation to the generally concave rod and segmental correction of vertebral translation. Moderate concave distraction and convex compression. If needed, final in situ bending of the rods. Schwab type I osteotomies; in rigid curves type II osteotomies. Fusion with local bone, allogenic bone and/or bone substitutes (i.e., tricalcium phosphate). Intraoperative placement of a thoracic epidural catheter for postoperative pain control. Neurological monitoring throughout the procedure. Mobilization on postoperative day 1 with focus on pain management and nutrition. Return to school after 4 weeks. Physiotherapy after 3 months, cycling after 3-6 months, and full sport activities after 1 year. Frontal curve correction of 60-80%, sufficient sagittal plane correction. Correction of rib hump 40%. Patient satisfaction is high at 95% and long-term revision rates of < 10%.


A causal relationship between irritability and cardiovascular diseases: a Mendelian randomization study.
Observational studies have suggested that irritability is associated with a higher risk of cardiovascular disease (CVD). However, the potential causal association is not clear. Therefore, we used Mendelian randomization (MR) analysis to assess the causal association of irritability with CVD risk. A two-sample MR analysis was performed to confirm the causal association of irritability with the risk of several common CVDs. The exposure data were derived from the UK biobank involving 90,282 cases and 232,386 controls, and outcome data were collected from the published genome-wide association studies (GWAS) and FinnGen database. Inverse-variance weighted (IVW), MR-Egger, and weighted median methods were performed to assess the causal association. Furthermore, the mediating effect of smoking, insomnia, and depressed affect was explored by using a two-step MR. The MR analysis indicated that genetically predicted irritability increased the risk of CVD, including coronary artery disease (CAD) (Odds ratio, OR: 2.989; 95% confidence interval, CI: 1.521-5.874, p = 0.001), myocardial infarction (MI) (OR: 2.329, 95% CI: 1.145-4.737, p = 0.020), coronary angioplasty (OR: 5.989, 95% CI: 1.696-21.153, p = 0.005), atrial fibrillation (AF) (OR: 4.646, 95% CI: 1.268-17.026, p = 0.02), hypertensive heart disease (HHD) (OR: 8.203; 95% CI: 1.614-41.698, p = 0.011), non-ischemic cardiomyopathy (NIC) (OR: 5.186; 95% CI: 1.994-13.487, p = 0.001), heart failure (HF) (OR: 2.253; 95% CI: 1.327-3.828, p = 0.003), stroke (OR: 2.334; 95% CI: 1.270-4.292, p = 0.006), ischemic stroke (IS) (OR: 2.249; 95% CI: 1.156-4.374, p = 0.017), and ischemic stroke of large-artery atherosclerosis ISla (OR: 14.326; 95% CI: 2.750-74.540, p = 0.002). The analysis also indicated that smoking, insomnia, and depressed affect play an important role in the process of irritability leading to cardiovascular disease. Our findings support the first genetic evidence of the causality of genetically predicted irritability with the risk of developing into CVDs. Our results deliver a viewpoint that more early active interventions to manage an individual's anger and related unhealthy lifestyle habits are needed to prevent the occurrence of adverse cardiovascular events.


Impact of ischemia and scar on therapeutic benefit of myocardial revascularization.
The question of how to optimally manage coronary artery disease (CAD) has been a challenge for the cardiology community. The results of early, large randomized clinical trials (RCTs) comparing strategies of medical therapy alone versus revascularization plus medical therapy in patients with stable CAD suggested a survival advantage for a revascularization strategy in the setting of more advanced, higher-risk CAD (left main, three-vessel CAD), but a superiority of medical therapy in patients with more limited, relatively lower-risk CAD (one vessel, limited two-vessel CAD). The results of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) and Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trials redefined the management of CAD, supporting the concept that the impact of aggressively applied modern "medical therapy" on patient survival and patient-reported outcomes is not further improved by the addition of percutaneous intervention. On the other hand, RCTs incorporating fractional flow reserve have shown that this physiologic metric can help identify which patients will benefit from a revascularization strategy. This paradigm has been extended to the use of myocardial perfusion imaging-identified ischemia to determine which patients may have enhanced survival with early revascularization versus medical therapy. Although data from a series of observational studies suggest that inducible ischemia on myocardial perfusion scintigraphy can identify revascularization candidates, several studies, including substudies from major RCTs, do not support this idea. Until RCTs comparing revascularization with medical therapy strategies are performed, many questions remain open. The correct thresholds for treatment, the metric to guide treatment, and how revascularization should be performed are as yet undefined.


Interaction of lncRNA-CR33942 with Dif/Dorsal Facilitates Antimicrobial Peptide Transcriptions and Enhances Drosophila Toll Immune Responses.
The Drosophila Toll signaling pathway mainly responds to Gram-positive (G+) bacteria or fungal infection, which is highly conserved with mammalian TLR signaling pathway. Although many positive and negative regulators involved in the immune response of the Toll pathway have been identified in Drosophila, the roles of long noncoding RNAs (lncRNAs) in Drosophila Toll immune responses are poorly understood to date. In this study, our results demonstrate that lncRNA-CR33942 is mainly expressed in the nucleus and upregulated after Micrococcus luteus infection. Especially, lncRNA-CR33942 not only modulates differential expressions of multiple antimicrobial peptide genes but also affects the Drosophila survival rate during response to G+ bacterial infection based on the transiently overexpressing and the knockdown lncRNA-CR33942 assays in vivo. Mechanically, lncRNA-CR33942 interacts with the NF-κB transcription factors Dorsal-related immunity factor/Dorsal to promote the transcriptions of antimicrobial peptides drosomycin and metchnikowin, thus enhancing Drosophila Toll immune responses. Taken together, this study identifies lncRNA-CR33942 as a positive regulator of Drosophila innate immune response to G+ bacterial infection to facilitate Toll signaling via interacting with Dorsal-related immunity factor/Dorsal. It would be helpful to reveal the roles of lncRNAs in Toll immune response in Drosophila and provide insights into animal innate immunity.


Protein adsorption at the interface between charged polymer substrata and migrating osteoblasts.
The in vitro migratory morphology of neonate rat calvarial osteoblasts on positively or negatively-charged polymer substrata was observed using scanning (SEM) and transmission electron microscopy (TEM). Proteins adsorbed from the culture medium onto these charged substrata were desorbed using 2% SDS and separated using polyacrylamide gel electrophoresis (PAGE). The charge sign of the substrata affected both protein adsorption and osteoblast migratory morphology. Cells flattened and adapted so closely to positively-charged substrata that the ventral cell membrane could not be distinguished at TEM. On negatively-charged substrata the ventral cell membrane was readily visible, with only focal areas of close contact with the substratum. The depth of the ventral extracellular space varied with the surface charge-carrier species on the negative substrata. Two desorbed protein fractions (MW 220 and 30 kDaltons, respectively) were correlated with osteoblast spreading on positive and negatively-charged surfaces respectively. Another protein fraction was uniquely present on PAGE profiles desorbed from negatively-charged substrata. It was concluded that the migratory morphology of osteoblasts was influenced via the intermediary of specifically adsorbed proteins.


Influence of the character of NOM on the ozonation of MIB and geosmin.
Tastes and odours (T&Os) are a major concern in drinking water as they are not efficiently removed by conventional water treatment. Ozonation has been effective for their destruction in some studies. However, the natural organic matter (NOM) in waters can affect the ozonation process and subsequently affect the destruction of T&Os. Five NOM fractions were isolated and ozonated in synthetic waters. The fraction containing the more highly coloured, higher molecular weight compounds exhibited the highest ozone (O3) demand, whereas the low aromatic fraction exhibited the lowest O3 demand. The character of the NOM fractions influenced the ozonation of MIB and geosmin. The destruction of MIB and geosmin was significantly higher in the fraction with the highest colour and UV/visible absorbance at all O3 doses. The destruction of the compounds in the other fractions showed the same trends, increasing MIB and geosmin destruction with increasing UV/visible absorbing character of the NOM. MIB was also ozonated in two real waters. with results showing a competing effect between NOM concentration and NOM character. The O3 reaction time was shown to be important for the destruction of both compounds.


Evaluation of an HMGA2 variant contribution to height and basal insulin concentrations in ponies.
The HMGA2:c.83G>A variant was identified in Welsh ponies having pleiotropic effects on height and insulin concentration. Determine whether the HMGA2:c.83G>A variant is associated with decreased height and higher basal insulin concentrations across pony breeds. Two hundred thirty-six ponies across 6 breeds. Cross-sectional study. Ponies were genotyped for the HMGA2:c.83G>A variant and phenotyped for height and basal insulin concentrations. Stepwise regression was performed for model analysis using a linear regression model for height and mixed linear model for insulin with farm as a random effect. Coefficient of determination, pairwise comparison of the estimated marginal means and partial correlation coefficients (parcor) were calculated to assess the relationship between HMGA2 genotype and height or insulin. Breed and genotype accounted for 90.5% of the variation in height across breeds, and genotype explained 21% to 44% of the variation within breeds. Breed, genotype, cresty neck score, sex, age, and farm accounted for 45.5% of the variation in insulin, with genotype accounting for 7.1%. The HMGA2 A allele frequency was 62% and correlated with both height (parcor = -0.39; P < .001) and insulin (parcor = 0.22; P = .02). Pairwise comparisons found A/A ponies were >10 cm shorter than other genotypes. Compared with G/G individuals, A/A and G/A individuals had 4.3 μIU/mL (95% confidence interval [CI]: 1.8-10.5) and 2.7 μIU/mL (95% CI: 1.4-5.3) higher basal insulin concentrations, respectively. These data demonstrate the pleiotropic effects of the HMGA2:c.83G>A variant and its role in identifying ponies at increased risk for insulin dysregulation.


Central and near peripheral retinal contributions to the depth-of-focus using naturalistic stimulation.
Although the depth-of-focus (DOF) has been investigated separately in the central retina and in the near retinal periphery, knowledge about their combined relative contribution to overall blur perception has remained unknown. In the present study, the DOF was measured psychophysically with a naturalistic pictorial stimulus as a function of spatial extent across the near retinal periphery under monocular Badal viewing conditions with accommodation paralyzed. The group mean total DOF progressively increased linearly with target size. Based on the individual DOF responses, the group was categorized into two subgroups: a predominantly centrally-driven and a centrally plus peripherally-driven subgroup. The results implicated partial cone pooling of blur information, as well as influence from perceptual, attentional, and optical aspects. However, the subgroup response profiles suggested individual differences in the weighting of the near peripheral blur information at the retinal level, and perhaps at higher-level areas of the visual system, involving spatial integration and global attentional processing.


Rawal's catalyst as an effective stimulant for the highly asymmetric Michael addition of β-keto esters to functionally rich nitro-olefins.
A general approach to asymmetric synthesis of highly substituted dihydroquinolines was achieved through neighboring ortho-amino group engaged sequential Michael/amination/dehydration reactions on (E)-2-(2-nitrovinyl)anilines with cyclic and acyclic β-keto esters in the presence of a catalytic amount of Rawal's quinidine-NH-benzyl squaramide followed by TFA.


The feasibility of debranching aortic arch and visceral arteries with sutureless telescoping anastomoses during open aortic aneurysm repair.
Open repair of aortic aneurysms frequently requires reimplantation of major aortic vessels. Traditional techniques can be time consuming, require meticulous hemostasis, and risk aneurysmal patch degeneration, which can require a challenging reoperation. We describe our experience using a stent graft to create a sutureless anastomosis that obviates these drawbacks. Between April 2018 and March 2021, all consecutive adult patients who underwent open repair of the aorta with at least one supra-aortic trunk or visceral vessel reimplanted using the sutureless anastomotic technique were included. Anastomoses were constructed by bridging a branch graft and the target artery with a Viabahn self-expanding stent (W.L. Gore & Associates, Flagstaff, AZ). Clinical information and perioperative outcomes for the patients were collected and analyzed. Among 26 patients, 50 individual aortic vessels were debranched using sutureless self-expanding stent anastomoses, including 42 visceral vessels and 8 supra-aortic trunk vessels. Technical success was 100%. The median time to complete the anastomosis was 3 minutes, 12 seconds (range, 2-6 minutes). Perioperative mortality was 15% (n = 4). No stent-related complications, such as occlusion, bleeding, stroke, renal failure requiring hemodialysis, bowel ischemia, or the need for anastomotic reintervention, occurred. Follow-up imaging at 1 year revealed a 100% patency rate and no anastomotic stenosis, misalignment, or kinking. The sutureless anastomosis technique to debranch the aorta during open aortic aneurysm repair is technically feasible and reliably hemostatic and does not require early reintervention. The operative outcomes have been acceptable, and the short-term follow-up imaging findings demonstrated excellent patency without anastomotic kinking. In select cases, sutureless anastomoses are a possible alternative to traditional sutured anastomoses during aortic debranching. Further research is needed to compare the operative times and long-term patency of sutureless anastomosis to those of traditional sutured techniques.


Accuracy of Various Forms of Contrast-Enhanced MRI for Diagnosing Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
Contrast-enhanced MRI can be used to identify patients with hepatocellular carcinoma (HCC). However, studies around the world have found differing diagnostic accuracies for the technique. Hence, we designed this meta-analysis to assess the accuracy of contrast-enhanced MRI for HCC diagnosis. We conducted a systematic search for all studies reporting the diagnostic accuracy of contrast-enhanced MRI for HCC in the databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, ScienceDirect, and Google Scholar from inception until January 2021. We used the "Midas" package from the STATA software to perform the meta-analysis. Our study was based on 21 publications with 5,361 patients. The pooled HCC diagnosis sensitivity and specificity were 75% (95% CI, 70%-80%) and 90% (95% CI, 88%-92%), respectively, for gadoxetic acid-enhanced MRI; and they were 70% (95% CI, 57%-81%) and 94% (95% CI, 85%-97%), respectively, for MRI with extracellular contrast agents (ECA-MRI). We found significant heterogeneity with a significant chi-square test and an I 2 statistic >75%. We also found significant publication bias as per Deeks' test results and funnel plot. We found that both types of contrast-enhanced MRI are accurate diagnostic and surveillance tools for HCC and offer high sensitivity and specificity. Further studies on different ethnic populations are required to strengthen our findings.


[Septicemia, bilateral community acquired pneumonia and empyema due to Burkholderia pseudomallei (mellioidosis) with a favorable outcome following prolonged specific antibiotic therapy].
Melioidosis is an infectious disease due to Burkholderia pseudomallei (Bp). It is regarded as endemic in southeast Asia and northern Australia. The septicaemic form is a severe illness with a high mortality. The tsunami in 2004 has renewed its current importance. A 57 year old man was admitted to hospital with a 2 week history of fever, productive cough and progressive weight loss. On admission he was in septic shock and respiratory failures secondary to a left lower lobe community acquired pneumonia. This progressed to a left sided empyema. Bp was isolated from blood cultures and the pleural pus. Initial intensive therapy with ceftazidime and cotrimoxazole for 4 weeks, followed by cotrimoxazole alone for 20 weeks, led to complete recovery with little residual radiological abnormality. Follow up gave no evidence of relapse but revealed an operable, squamous cell, bronchial carcinoma. Melliodosis seems to be an emerging disease in New Caledonia with 10 cases identified since 1999. A favourable climate and possibly an animal reservoir might explain sporadic cases in this region. It is important for the medical profession to be aware of this disease in order to ensure the rapid and correct management of patients whose life is at risk.


Accelerated fibrin clot degradation is associated with arterial thromboembolism in patients following venous thrombosis: a cohort study.
Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3-4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31-68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59-1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univariable Cox proportional hazards analysis showed that age, diabetes, and D-Drate were risk factors for subsequent ATE. Increased D-Drate (by 0.001 mg/L/min; hazard ratio, 1.08; 95% CI 1.02-1.14) was an independent predictor of ATE after adjustment for potential confounders. Faster fibrin clot degradation at 3 months since VTE may increase the risk of ATE among VTE patients during follow-up.


Poly(ethylene glycol)-poly(ε-caprolactone) iodinated nanocapsules as contrast agents for X-ray imaging.
Synthesis and formulation of iodinated PCL-mPEG nanocapsules as new original blood pool contrast agents for computed tomography. PCL-mPEG was synthesized and formulated following the emulsion-solvent diffusion process, in the form of iodinated nanocapsules. Physico-chemical characterization of such nano-materials was performed by DLS and transmission electron microscopy. A stability study of the nanocapsules suspension was followed-up to 3 month. Blood biocompatibility was performed. Finally, the nanocapsules suspension radiopacity was evaluated in vitro then in vivo in mice as micro-CT contrast agent. In this study, the iodine concentration in nanocapsules suspension was about 70 mgI/mL. Besides, these nanocarriers appeared non-toxic, and stable in suspension. In vivo, i.v. administration of 10 μL/g of mouse body weight of theses nano-particles induced a vascular contrast enhancement of 168 HU and a half-life in blood of 4.2 +/- 0.5 h. Elimination route of these particles appears mainly performed by the liver, without sequestration in spleen and lymph nodes confirming their stealth properties. This study proposes the first example of iodinated biodegradable polymeric blood pool contrast agent, able to induce an exploitable contrast enhancement. The main advantage of polymeric system compared to lipid ones, lies in their stability and handling, e.g. towards drying for storage.


Relationship between nitrapyrin and varying nitrogen application rates with nitrous oxide emissions and nitrogen use efficiency in a maize filed.
Reducing nitrogen losses can be accomplished by mixing fertilizers with nitrification inhibitors (NI). In some agricultural systems, increasing soil N supply capacity by the use of NI could lead to improved N use efficiency (NUE) and increased crop yields. This study examined the effect of different N rates and NI in maize in the north of Iran. The maize was fertilized with urea at three levels (69, 115 and 161 kg N.ha-1) alone or with nitrapyrin as NI. Increasing the N application rate resulted in a considerable rise in growing-season N2O emissions. When nitrapyrin was used, N2O emissions were dramatically reduced. NI treatment reduced N2O emissions in the growth season by 88%, 88%, and 69% in 69, 115, and 161 kg of N.ha-1, respectively. NI treatment reduced yield-scaled N2O emissions; the lowest quantity of yield-scaled N2O was found in 69 N + NI (0.09 g N2O-N kg-1 N uptake). Additionally, grain yield increased by 19%, 31% and 18.4% after applying NI to 69 N, 115 N, and N69, N115 and N161. Results showed that 115 N + NI and N69 treatments showed the highest (65%) and lowest (29%) NUEs, respectively. Finally, our findings show that NI can reduce N2O emissions while increasing NUE and yield, but that the application method and rate of nitrapyrin application need to be improved in order to maximize its mitigation potential.


Short hydrogen-bond network confined on COF surfaces enables ultrahigh proton conductivity.
The idea of spatial confinement has gained widespread interest in myriad applications. Especially, the confined short hydrogen-bond (SHB) network could afford an attractive opportunity to enable proton transfer in a nearly barrierless manner, but its practical implementation has been challenging. Herein, we report a SHB network confined on the surface of ionic covalent organic framework (COF) membranes decorated by densely and uniformly distributed hydrophilic ligands. Combined experimental and theoretical evidences have pointed to the confinement of water molecules allocated to each ligand, achieving the local enrichment of hydronium ions and the concomitant formation of SHBs in water-hydronium domains. These overlapped water-hydronium domains create an interconnected SHB network, which yields an unprecedented ultrahigh proton conductivity of 1389 mS cm-1 at 90 °C, 100% relative humidity.


Structure of triosephosphate isomerase from Cryptosporidium parvum.
Cryptosporidium parvum is one of several Cryptosporidium spp. that cause the parasitic infection cryptosporidiosis. Cryptosporidiosis is a diarrheal infection that is spread via the fecal-oral route and is commonly caused by contaminated drinking water. Triosephosphate isomerase is an enzyme that is ubiquitous to all organisms that perform glycolysis. Triosephosphate isomerase catalyzes the formation of glyceraldehyde 3-phosphate from dihydroxyacetone phosphate, which is a critical step to ensure the maximum ATP production per glucose molecule. In this paper, the 1.55 Å resolution crystal structure of the open-loop form of triosephosphate isomerase from C. parvum Iowa II is presented. An unidentified electron density was found in the active site.


Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium.
Our previous electron microscopic study of the prefrontal cortex (PFC) demonstrated ultrastructural signs of apoptosis and necrosis of oligodendroglial cells in schizophrenia (SCH) and bipolar disorder (BPD). Using optical dissector methodology, we have now conducted a morphometric study of numerical density (Nv) of oligodendroglial cells in layer VI and in adjacent white matter of Brodmann area 9 (BA 9) of the Stanley Foundation Neuropathology Consortium (SFNC). The SFNC consists of 15 cases in each of four groups: schizophrenia, bipolar disorder, major depression (MDD) and unaffected controls. A significant reduction in Nv of oligodendroglial cells was found in layer VI of subjects with schizophrenia (-25%), bipolar disorder (-29%) and major depression (-19%) as compared to controls. In adjacent white matter, there were no significant differences between groups. The data suggest that lowered density of oligodendroglial cells that occurs in schizophrenia and mood disorders could contribute to the atrophy of neurones that has been described in the prefrontal cortex of subjects with severe mental illness.


Some reflections on the evolution of meta-analysis.
I reflect on the evolution of meta-analysis in clinical research over 35 years since I first encountered the key ideas in the late 1970s.


G Protein-regulated inducer of neurite outgrowth (GRIN) modulates Sprouty protein repression of mitogen-activated protein kinase (MAPK) activation by growth factor stimulation.
Gα(o/i) interacts directly with GRIN (G protein-regulated inducer of neurite outgrowth). Using the yeast two-hybrid system, we identified Sprouty2 as an interacting partner of GRIN. Gα(o) and Sprouty2 bind to overlapping regions of GRIN, thus competing for GRIN binding. Imaging experiments demonstrated that Gα(o) expression promoted GRIN translocation to the plasma membrane, whereas Sprouty2 expression failed to do so. Given the role of Sprouty2 in the regulation of growth factor-mediated MAPK activation, we examined the contribution of the GRIN-Sprouty2 interaction to CB1 cannabinoid receptor regulation of FGF receptor signaling. In Neuro-2A cells, a system that expresses all of the components endogenously, modulation of GRIN levels led to regulation of MAPK activation. Overexpression of GRIN potentiated FGF activation of MAPK and decreased tyrosine phosphorylation of Sprouty2. Pretreatment with G(o/i)-coupled CB1 receptor agonist attenuated subsequent FGF activation of MAPK. Decreased expression of GRIN both diminished FGF activation of MAPK and blocked CB1R attenuation of MAPK activation. These observations indicate that Gα(o) interacts with GRIN and outcompetes GRIN from bound Sprouty. Free Sprouty then in turn inhibits growth factor signaling. Thus, here we present a novel mechanism of how G(o/i)-coupled receptors can inhibit growth factor signaling to MAPK.


Time-resolved X-ray diffraction reveals movement of F helix of D96N bacteriorhodopsin during M-MN transition at neutral pH.
D96N bacteriorhodopsin has two photointermediates with the deprotonated Schiff base: the M and MN intermediates. We measure the time-resolved x-ray diffraction of the D96N purple membrane after flash photoexcitation (pH 7.0, 25 degrees C). The data clearly show the M-MN transition during the D96N photocycle. Low-resolution projection maps of these states show that the F helix of the MN intermediate shifts from its original position and this shift is much larger than that of the M intermediate. This indicates that the F helix moves in the M-MN transition of the D96N bacteriorhodopsin photocycle. Moreover, the existence of the MN intermediate in the D96N photocycle under neutral pH indicates that the MN intermediate is not peculiar to the alkaline condition. It is notable that the structural transition of M-MN is independent of the protonation state of the Schiff base. Therefore, the F helix movement precedes reprotonation of the Schiff base in the bacteriorhodopsin photocycle. Our previous study showed that the M-MN transition is hydration-dependent and that the MN intermediate is more hydrated than the M intermediate. Considering this together with the present results, we conclude that the movement of the F helix causes hydration of the cytoplasmic side, which promotes the reprotonation of the Schiff base.


Infrared laser light further improves bone healing when associated with bone morphogenetic proteins and guided bone regeneration: an in vivo study in a rodent model.
This study assessed histologically the effect of laser photobiomodulation on the repair of surgical defects created in the femurs of Wistar rats treated or not treated with bone morphogenetic proteins (BMPs) and organic bovine bone graft. This paper is part of an ongoing series of works in which biomaterials and/or guided bone regeneration (GBR) are used in association with laser photobiomodulation. Several previous reports from our group have shown that the use of laser photobiomodulation improves the treatment of bone defects. Forty-eight adult male Wistar rats were divided into four randomized groups: group 1 (controls, n = 12); group 2 (laser photobiomodulation, n = 12); group 3 (BMPs + organic bovine bone graft + GBR, n = 12); and group 4 (BMPs + organic bovine bone graft + GBR + laser photobiomodulation, n = 12). The irradiated groups received seven irradiations every 48 h, the first immediately after the surgical procedure. Laser photobiomodulation (830 nm, 40 mW, CW, phi approximately 0.6 mm) consisted of a total of 16 J/cm2 per session at four points (4 J/cm2 each) equally spaced around the periphery of the defect. The animals were sacrificed after 15, 21, and 30 d, and the specimens were routinely embedded in wax and stained with hematoxylin and eosin and Sirius red stains and analyzed under light microscopy. The results showed histological evidence of increased deposition of collagen fibers (at 15 and 21 d), as well as an increased amount of well-organized bone trabeculi at the end of the experimental period (30 d) in irradiated animals compared to non-irradiated controls. We concluded that the use of laser photobiomodulation in association with BMPs, organic bovine bone grafts, and GBR increases the positive biomodulating effects of laser energy.


Electron crystallography and dedicated electron-diffraction instrumentation.
Electron diffraction (known also as ED, 3D ED or microED) is gaining momentum in science and industry. The application of electron diffraction in performing nano-crystallography on crystals smaller than 1 µm is a disruptive technology that is opening up fascinating new perspectives for a wide variety of compounds required in the fields of chemical, pharmaceutical and advanced materials research. Electron diffraction enables the characterization of solid compounds complementary to neutron, powder X-ray and single-crystal X-ray diffraction, as it has the unique capability to measure nanometre-sized crystals. The recent introduction of dedicated instrumentation to perform ED experiments is a key aspect of the continued growth and success of this technology. In addition to the ultra-high-speed hybrid-pixel detectors enabling ED data collection in continuous rotation mode, a high-precision goniometer and horizontal layout have been determined as essential features of an electron diffractometer, both of which are embodied in the Eldico ED-1. Four examples of data collected on an Eldico ED-1 are showcased to demonstrate the potential and advantages of a dedicated electron diffractometer, covering selected applications and challenges of electron diffraction: (i) multiple reciprocal lattices, (ii) absolute structure of a chiral compound, and (iii) R-values achieved by kinematic refinement comparable to X-ray data.


Facile synthesis, characterization, antioxidant activity, and antibacterial activity of carboxymethyl inulin salt derivatives.
A series of novel carboxymethyl inulin derivatives bearing thiosemicarbazide salts, aminoguanidine salts, and aniline salts were prepared via a facile method and employed to evaluate in vitro antioxidant activity and antibacterial activity. Their structures were characterized by Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). The characterization results confirmed the successful synthesis of carboxymethyl inulin salt derivatives. The in vitro antioxidant activity evaluation results presented a significant improved superoxide radical scavenging ability, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, and reducing ability of carboxymethyl inulin salt derivatives as compared to inulin and carboxymethyl inulin. In particular, the series of carboxymethyl inulin derivatives containing thiosemicarbazide salts and aminoguanidine salts showed remarkable free radical scavenging ability and reducing ability. Moreover, the carboxymethyl inulin derivatives containing thiosemicarbazide salts and aniline salts displayed potential antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria. The cytotoxicity assay was also carried out on L929 cells by CCK-8 method, and all samples showed weak cytotoxicity. Furthermore, hemolysis results showed no hemolytic activity of most prepared inulin derivatives. In summary, the inulin derivatives containing thiosemicarbazide salts exhibited outstanding antioxidant activity, antibacterial activity, and biocompatibility, and the all-inclusive properties highlighted their potential use in food and medical applications.


Strategic self-limiting production of infectious HIV particles by CRISPR in permissive cells.
Post-translational glycosylation of the HIV-1 envelope protein involving precursor glycan trimming by mannosyl oligosaccharide glucosidase (MOGS) is critically important for morphogenesis of virions and viral entry. Strategic editing of the MOGS gene in T lymphocytes and myeloid origin cells harboring latent proviral DNA results in the production of non-infectious particles upon treatment of cells with latency reversal agents. Controlled activation of CRISPR-MOGS by rebound HIV-1 mitigates production of infectious particles that exhibit poor ability of the virus to penetrate uninfected cells. Moreover, exclusive activation of CRISPR in cells infected with HIV-1 alleviates concern for broad off-target impact of MOGS gene ablation in uninfected cells. Combination CRISPR treatment of peripheral blood lymphocytes prepared from blood of people with HIV-1 (PWH) tailored for editing the MOGS gene (CRISPR-MOGS) and proviral HIV-1 DNA (CRISPR-HIV) revealed a cooperative impact of CRISPR treatment in inhibiting the production of infectious HIV-1 particles. Our design for genetic inactivation of MOGS by CRISPR exhibits no detectable off-target effects on host cells or any deleterious impact on cell survival and proliferation. Our findings offer the development of a new combined gene editing-based cure strategy for the diminution of HIV-1 spread after cessation of antiretroviral therapy (ART) and its elimination.


CaMKII activation state underlies synaptic labile phase of LTP and short-term memory formation.
The labile state of short-term memory has been known for more than a century. It has been frequently reported that immediate postlearning intervention can readily disrupt newly formed memories. However, the molecular and cellular mechanisms underlying the labile state of new memory are not understood. Using a bump-and-hole-based chemical-genetic method, we have rapidly and selectively manipulated alpha CaMKII activity levels in the mouse forebrain during various stages of the short-term memory processes. We find that a rapid shift in the alpha CaMKII activation status within the immediate 10 min after learning severely disrupts short-term memory formation. The same manipulation beyond the 15 min after learning has no effect, suggesting a critical time window for CaMKII action. We further show that during this same 10 min time window only, shifting in CaMKII activation state is capable of altering newly established synaptic weights and/or patterns. The initial 10 min of memory formation and long-term potentiation are sensitive to inducible genetic upregulation of alphaCaMKII activity. Our results suggest that molecular dynamics of CaMKII play an important role in underlying synaptic labile state and representation of short-term memory during this critical time window.


Upper-airway dysbiosis related to frequent sweets consumption increases the risk of asthma in children with chronic rhinosinusitis.
Innate immunity response to local dysbiosis seems to be one of the most important immunologic backgrounds of chronic rhinosinusitis (CRS) and concomitant asthma. We aimed to assess clinical determinants of upper-airway dysbiosis and its effect on nasal inflammatory profile and asthma risk in young children with CRS. We recruited one hundred and thirty-three children, aged 4-8 years with doctor-diagnosed CRS with or without asthma. The following procedures were performed in all participants: face-to-face standardized Sinus and Nasal Quality of Life questionnaire, skin prick test, taste perception testing, nasopharynx swab, and sampling of the nasal mucosa. Upper-airway dysbiosis was defined separately by asthma-specific microbiome composition and reduced biodiversity. Multivariate methods were used to define the risk factors for asthma and upper-airway dysbiosis and their specific inflammatory profile of nasal mucosa. The asthma-specific upper-airway microbiome composition reflected by the decreased ratio of Patescibacteria/Actinobacteria independently of atopy increased the risk of asthma (OR:8.32; 95%CI: 2.93-23.6). This asthma-specific microbiome composition was associated with ≥ 7/week sweet consumption (OR:2.64; 95%C:1.11-6.28), reduced biodiversity (OR:3.83; 95%CI:1.65-8.87), the presence of Staphylococcus strains in the nasopharynx (OR:4.25; 95%CI:1.12-16.1), and lower expression of beta-defensin 2, IL-5, and IL-13 in the nasal mucosa. The reduced biodiversity was associated with frequent antibiotic use and with a higher nasal expression of IL-17 and T1R3 (sweet taste receptor). In asthmatic children, reduced sweet taste perception was observed. Specific upper-airway dysbiosis related to frequent sweet consumption, frequent antibiotic courses, and altered nasal immune function increases the risk of asthma in young children with CRS.


Nondeletional ABO*O alleles frequently cause blood donor typing problems.
Difficulties in the demonstration of expected isoagglutinins is a common problem in ABO reverse typing. Some nondeletional ABO*O alleles have been shown to encode for the expression of minimal amounts of A antigen, resulting in very weak anti-A activity in some cases. It is unknown whether minor problems with ABO reverse typing are related to specific ABO*O alleles. Among 2196 blood group O red cell (RBC) donations, the ABO alleles of those donations in which the isoagglutinins were incorrectly identified were analyzed with an autoanalyzer. The presence of nondeletional ABO alleles was determined by sequence-specific priming and sequencing. Fifty (2.3%) of the group O RBC donations tested had to be typed manually because of isoagglutinin detection problems in automated typing: reduced anti-A activity was observed in 45 cases, reduced anti-B activity in 4 cases, and variably reduced isoagglutinin activity in 1 case. The nondeletional ABO*O alleles ABO*O03 and ABO*Aw08 were implicated in 38 of these 50 cases (1.7% of all blood group O donors). The remaining samples, including those with reduced anti-B activities, were homozygous for deletional ABO*O alleles. Nondeletional ABO*O alleles are the most frequent cause of isoagglutinin detection problems in blood group O donors.


Brain Necrosis in Adult Patients After Proton Therapy: Is There Evidence for Dependency on Linear Energy Transfer?
To investigate if radiographic imaging changes defined as necrosis correlate with regions in the brain with elevated linear energy transfer (LET) for proton radiation therapy treatments with partial brain involvement in central nervous system and patients with head and neck cancer. Fifty patients with head and neck, skull base, or intracranial tumors who underwent proton therapy between 2004 to 2016 with a minimum prescription dose of 59.4 Gy (relative biological effectiveness) and with magnetic resonance imaging changes indicative of brain necrosis after radiation therapy were retrospectively reviewed. Each treatment plan was recalculated using Monte Carlo simulations to provide accurate dose distributions as well as 3-dimensional distributions of LET. To assess the effect of LET on radiographic imaging changes several voxel-based analyses were performed. In this patient cohort, LET adjusted for dose was not found to be associated with risk of brain necrosis. A voxel-based analysis of brain necrosis as an endpoint is difficult owing to uncertainties in the origin of necrosis, timing of imaging, variability in patient specific radiosensitivity, and the simultaneous effect of dose and LET. Even though it is expected that the LET and thus relative biological effectiveness increases at the end of range, effects in patients might be small compared with interpatient variability of radiosensitivity and might be obscured by other confounding factors.


Effects of cervical sympathetic ganglionectomy on cyclic-AMP and prostaglandins in brain and eye tissues and fluids.
Studies were conducted confirming supersensitivity to catecholamines on intraocular pressure and pupil size following bilateral superior cervical ganglionectomy in rabbits. At the termination of these studies we examined changes in cyclic adenylic acid and prostaglandin content in jugular vein effluent and various brain and ocular tissues and fluids of the sympathectomized versus control animals. In the blood effluent we found significant elevation of cyclic adenylic acid and significant lowering of prostaglandin F1alpha in the sympathectomized animals. Although we found elevation of prostaglandin in certain tissues of the sympathectomized animals, there were no significant changes in cyclic adenylic acid levels between sympathectomized and control animals in the tissues examined. The findings of prostaglandin (blood and tissue) and cyclic adenylic acid (blood) changes in sympathectomized animals, associated with known changes in intraocular pressure and pupil size (due to catecholamine supersensitivity) must elicit further interest in the correlation and interpretation of various other central physiological and metabolic events in cervical sympathectomized animals.


Synthetic studies directed toward the assembly of the C-glycoside fragment of the telomerase inhibitor D8646-2-6.
[reaction: see text] Construction and characterization of the C-glycosidic moiety of telomerase inhibitor D8646-2-6 (1) are described. This is the first example of the C-glycosylation using electron-poor aromatics, 4-hydroxypyrone, as a glycosyl acceptor. The glycosylation reaction and base-promoted isomerization affords desired beta-C-glycoside in a 61% overall yield.


Renal function during hospitalization and outcome in Chinese patients with acute decompensated heart failure: A retrospective study and literature review.
The heart and kidneys had demonstrated a bidirectional interaction that dysfunction of the heart or kidneys can induce dysfunction in the other organ. Renal function and its decline during hospitalization may have impact on cardiovascular outcomes in patients with acute decompensated heart failure (ADHF). A total of 119 consecutive Chinese patients admitted for ADHF were prospectively enrolled. The course of renal function was presented with estimated glomerular filtration rate (eGFR), calculated by the four-variable equation proposed by the Modification of Diet in Renal Disease (MDRD) Study. Worsening renal function (WRF) was defined as eGFR decline between admission (eGFRadmission ) and predischarge (eGFRpredischarge ). Clinical outcomes were defined as 4P-major adverse cardiovascular events (4P-MACE), including the composition of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal HF hospitalization. During an average 2.6 ± 3.2 years follow-up, 66 patients (55%) experienced 4P-MACE. Patients with impaired eGFRpredischarge (<60 ml/min/1.73 m2 ) had more 4P-MACE than those with preserved eGFRpredischarge (64.7% vs. 43.1%, p = .019). The Kaplan-Meier survival curves showed significantly higher incidence of 4P-MACE in patients with impaired eGFRpredischarge than those with preserved eGFRpredischarge (p = .002). Cox regression analysis revealed that impaired eGFRpredischarge was significantly correlated with the development of 4P-MACE (hazard ratio, 2.003; 95% confidence interval, 1.072-3.744; p = .029). In contrast, outcomes would be similar with regard to eGFR on admission and eGFR decline during hospitalization. Impaired renal function before discharge, but not impaired renal function on admission or WRF, is a significant risk factor for poor outcomes in patients with ADHF.


Development of silver nanoparticles and aptamer conjugated biosensor for rapid detection of E. coli in a water sample.
A simple, rapid, and sensitive electrochemical biosensor based on a screen-printed carbon electrode (SPCE) was developed for onsite detection of E. coli in real time. This work analyzed the effect of aptamer conjugation and PBS buffer solution on the colloidal stability of the silver nanoparticles (AgNPs). Aggregations of the AgNPs after aptamer conjugation in PBS buffer were observed from the particle size distribution analysis. The AgNP-aptamer conjugation and its affinity towards E. coli (DH5α) were confirmed by UV-visible spectrophotometry, which showed a linear increment in the absorption with increasing E.coli concentration. The screen-printed carbon electrodes were modified by drop-casting of AgNPs, which were used as an effective immobilization platform for E. coli-specific aptamers. The modified electrode's surface modification and redox behavior were characterized using cyclic voltammetry. Finally, E. coli was detected using differential pulse voltammetry with an optimized incubation time of 15 min. The developed biosensors showed a linear decrease in current intensity with an increase in the concentration of E. coli. The biosensor had a relative standard deviation (RSD) of 6.91% (n = 3), which showed good reproducibility. The developed biosensors are highly sensitive and have a limit of detection (LOD) as low as 150 CFU/ml. The biosensor showed good selectivity for E.coli coli when comparing the signal response obtained for bacteria other than E.coli. Also, the biosensor was found stable for four weeks at room temperature and showed high recoveries from 95.27% to 107% during the tap water sensitivity validation.


Cyclic 3',5'-AMP phosphodiesterase in Physarum polycephalum. I. Chemotaxis toward inhibitors and cyclic nucleotides.
The effect of several inhibitors of the enzyme cyclic 3',5'-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3',5'-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3',5'-AMP at concentrations as high as 1 . 10(-2) M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3',5'-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3',5'-AMP in the directional movement in P. polycephalum is discussed.