Soluble interleukin-2 receptor decrease in the sera of HIV-infected patients treated with zidovudine.
Laboratory parameters which are modified following administration of zidovudine are becoming increasingly useful in monitoring the efficacy of treatment of early stages of HIV-1 infection. The serum levels of soluble interleukin (sILR)-2 receptor, which have been reported to increase early in HIV-1 infection, were found to be significantly lower in 24 patients being treated with zidovudine than in 69 patients who were not treated, 28 of whom had CD4+ counts greater than 400 x 10(6)/l, and 41 less than 400 x 10(6)/l, respectively (P less than 0.0001). A prospective study group of 33 subjects treated with zidovudine demonstrated a decrease in sIL-2R during therapy (base values 2113 +/- 1131 versus 1444 +/- 728 after 90 days of therapy; P less than 0.0007). The reduction of sIL-2R was greater in those subjects were p24 antigen became negative during treatment. sIL-2R therefore seems to be a useful tool in the monitoring of therapy with zidovudine.


LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Though miR-205 function has been largely characterized, the nature of its host gene, MIR205HG, is still completely unknown. Here, we show that only lowly expressed alternatively spliced MIR205HG transcripts act as de facto pri-miRNAs, through a process that involves Drosha to prevent unfavorable splicing and directly mediate miR-205 excision. Notably, MIR205HG-specific processed transcripts revealed to be functional per se as nuclear long noncoding RNA capable of regulating differentiation of human prostate basal cells through control of the interferon pathway. At molecular level, MIR205HG directly binds the promoters of its target genes, which have an Alu element in proximity of the Interferon-Regulatory Factor (IRF) binding site, and represses their transcription likely buffering IRF1 activity, with the ultimate effect of preventing luminal differentiation. As MIR205HG functions autonomously from (albeit complementing) miR-205 in preserving the basal identity of prostate epithelial cells, it warrants reannotation as LEADeR (Long Epithelial Alu-interacting Differentiation-related RNA).


Altered glymphatic enhancement of cerebrospinal fluid tracer in individuals with chronic poor sleep quality.
Chronic sleep disturbance is a risk factor for dementia disease, possibly due to impaired sleep-dependent clearance of toxic metabolic by-products. We compared enrichment of a cerebrospinal fluid (CSF) tracer within brain of patients reporting good or poor sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Tracer enrichment in a selection of brain regions was assessed using multiphase magnetic resonance imaging up to 48 hours after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml) serving as tracer. Tracer enrichment differed between patients with good (PSQI ≤5) and poor (PSQI >5) sleep quality in a cohort of non-dementia individuals (n = 44; age 42.3 ± 14.5 years), and in patients with the dementia subtype idiopathic normal pressure hydrocephalus (n = 24; age 71.0 ± 4.9 years). Sleep impairment was associated with increased CSF tracer enrichment in several brain regions. Cortical brain volume as well as entorhinal cortex thickness was reduced in the oldest cohort and was correlated with the severity of sleep disturbance and the degree of cortical tracer enrichment. We suggest chronic sleep disturbance is accompanied by altered glymphatic function along enlarged perivascular spaces.


Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.
Central carbon metabolism (CCM) is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays), the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 18.104.22.168), in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis), the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.


Improving diabetes care at the end of life.
The number of people with diabetes in the UK is increasing. Many are aged over 75 years, and this has resulted in rising numbers of patients for whom diabetes exists comorbidly with other disease processes. Those with life-limiting illness require palliative care services. However, end of life care for patients with diabetes is generally poor. The aim of end of life care for these individuals is to maintain comfort, while minimising the risks of osmotic symptoms. The wishes of patients, carers and families should be taken into consideration when agreeing new glucose control targets, adjusting treatment or changing focus on diet. Patients and carers should feel that the condition is being managed with the support of healthcare professionals. These professionals need the knowledge, skills and confidence to recognise the end of life to tailor diabetes care appropriately.


Nafion as cosurfactant: solubilization of nafion in water in the presence of Pluronics.
Incorporation of Nafion to aqueous solutions of Pluronics adversely impacts micellization due to extensive Nafion/copolymer interactions. Light scattering and zeta potential measurements provide evidence for the formation of sizable and stable Nafion/copolymer complexes, in expense of the neat copolymer micelles. At high copolymer concentrations, the overall interaction diagram of Nafion/copolymer reflects the competitive action of the release of packing constraints due to micellar destabilization induced by Nafion on one hand and the gelator nature of the Nafion on the other. Measurements using a quartz crystal microbalance (QCM-D) show that aqueous solutions of Pluronics (even at very low concentration) can dissolve the Nafion coating on the crystal resonator, while typical low molecular weight ionic surfactants fail to induce similar effects. These studies demonstrate that complexation with this class of copolymers is a facile route to impart dispersibility to Nafion in aqueous environments that otherwise can be achieved through tedious and harsh treatments.


Blood pressure response to out-patient drug treatment of hypertension in 1973-1993 at Korle-Bu Teaching Hospital, Accra, Ghana.
A retrospective audit of the first twelve months of out patient drug treatment of hypertension at the Korle-Bu Teaching Hospital during the period 1973-1993 is reported. A previous study had shown that at least 7 drug regimes were used to treat hypertension at Korle-Bu during the period. The aim of the present study was to compare the effect and efficacy of these antihypertensive drug treatment regimes on blood pressure during the first 12 months of treatment. Result of 155 (47%) case notes, which met the inclusion criteria, are presented. One month of drug treatment of hypertension significantly reduced systolic and diastolic blood pressure by 21.4 +/- 30.5 (p<0.001) and 13.8 +/- 16.5 (p<0.001) mmHg, respectively. This reduction in blood pressure was maintained to the 12th month. At 12 months, systolic and diastolic blood pressures were unchanged in 19% and 28% of patients, respectively, indicating no response to drug treatment. Recommended target blood pressure of < or = 140/90 mm Hg was achieved in only 25.6% of all patients. All drug treatment regimes significantly reduced blood pressure to a similar extent so that any differences were not statistically significant. However, the efficacy of the drug regimes differed significantly (p=0.02). It was greatest in patients treated with monotherapy with either diuretic or reserpine, intermediate with two drug combinations and least with 3 or 4 drugs. The data showed that diuretics were marginally better than reserpine as first line monotherapy. Furthermore, any diuretic based 2-drug regime was equally efficacious although a beta-blocker or methyldopa as second drug seemed favoured by the data. The addition of a third or fourth drug was counter productive as the increased number of drugs did not decrease blood pressure significantly.


Postchemotherapy-related changes in mediastinal mixed germ cell tumor masquerading as a vascular neoplasm.
Florid vascular proliferation in teratoma is rare morphological presentation. We present a case of mediastinal germ cell tumor masquerading as a vascular neoplasm in a 14-year-old male who presented with right hemithoracic mass. The initial histopathology of resected mass was suggestive of vascular neoplasm. Fine needle aspiration cytology (FNAC) of right axillary mass with immunohistochemistry on cell block was consistent with metastatic mixed germ cell tumor. Repeat extensive sectioning of the resected mediastinal mass showed focal viable tumor with mainly teratomatous component. Further enquiry into the history revealed patient having received prior chemotherapy; this he received in another hospital before being admitted to our hospital for surgical resection of the mass. The florid vascular proliferation may represent postchemotherapy change or a rare component of germ cell tumor possibly resistant to preoperative chemotherapy.


Brain vessels in the rats exposed to primary and repeated tail-suspension. Minimization of structural changes after repeated exposure.
The aim of study was histological examination of brain vessels in the rats exposed to repeated tail-suspension (TS). The rats were subjected to 30-day TS, then readapted to horizontal position for 30 days and again exposed to 14-day TS simultaneously with the rats which were underwent to 14-day TS for the first time. 30-day TS induced in brain vessels the adaptive changes hindering the excessive blood inflow to brain--spasm and hypertrophy of muscle-elastic valves in extra- and intracerebral arteries and also the destructive changes--loss of vascular tone in extra- and intracerebral arteries, plethora in extra- and intracerebral veins, intracerebral venules and capillaries, conglutination of erythrocytes in capillaries, plasmatization of veins and capillaries and edema of brain tissue pointing out in total the increase in blood inflow to the brain and difficulty of blood outflow. After 30-day readaptation of TS-rats to horizontal position only adaptive changes in extracerebral arteries and intracerebral capillaries (cell proliferation) and edema of brain tissue were revealed. After repeated, 14-day TS in spite of new redistribution of blood to the head, in contrast to the vessel alterations after primary 14-day TS, the adaptive and destructive changes in brain vessels were lack, excluding only moderate plethora of intracerebral veins, cell proliferation in capillaries and weak signs of edema.


A Novel Regulatory Cascade Involving BluR, YcgZ, and Lon Controls the Expression of Escherichia coli OmpF Porin.
In Escherichia coli, OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin. This pathway involves BluR, a transcriptional regulator repressing the expression of the ycgZ-ymgABC operon. We showed that BluR was responsible for the temperature-dependent regulation of the ycgZ-ymgABC operon. Furthermore, our results showed that independent expression of YcgZ led to a decreased activity of the ompF promoter, while YmgA, YmgB, and YmgC expression had no effect. We also determined that YcgZ accumulates in the absence of the Lon protease. Thus, mutation in bluR leads to de-repression of ycgZ-ymgABC transcription. With a second mutation in lon, YcgZ protein accumulates to reach levels that do not allow increased expression of OmpF under growth conditions that usually would, i.e., low temperature. With BluR responding to blue-light and temperature, this study sheds a new light on novel signals able to regulate OmpF porin.


[The role of laparoscopy in the management of the right iliac fossa syndrome].
Many cases of nonspecific right-sided lower abdominal pain syndromes are still difficult to diagnose regarding the accuracy of identifying which organ is suffering, in spite of the continuous development of various investigations. The aim of our study is to establish the limits of noninvasive explorations and to evaluate the benefits of laparoscopy approach of such cases. 45 patients, admitted and treated for right lower quadrant abdominal pain along 5 years in the Surgical Department of University Hospital "Caritas" Bucharest, were followed up. For all those patients, diagnostic uncertainty indicated laparoscopic exploration. Analyzing the cases, we noticed that the diagnosis was correctly established on the basis of non-invasive preoperative explorations in 13,33% of cases. In 11,11% of cases the diagnosis was completed by laparoscopy approach and in most cases (75,55%) was established by this procedure. The laparoscopic approach allowed diminishing the number of unnecessary appendectomies, detecting and resolving concomitant lesions with minimal parietal trauma and, essentially, avoiding "exploratory laparotomy".


Enhancing the performance of motor imagery EEG classification using phase features.
An electroencephalogram recognition system considering phase features is proposed to enhance the performance of motor imagery classification in this study. It mainly consists of feature extraction, feature selection and classification. Surface Laplacian filter is used for background removal. Several potential features, including phase features, are then extracted to enhance the classification accuracy. Next, genetic algorithm is used to select sub-features from feature combination. Finally, selected features are classified by extreme learning machine. Compared with "without phase features" and linear discriminant analysis on motor imagery data from 2 data sets, the results denote that the proposed system achieves enhanced performance, which is suitable for the brain-computer interface applications.


How and when to use erythropoietin.
Recombinant human erythropoietin is used in clinical practice mainly for treatment of anemia of renal failure. In the past years, however, its use has been approved for other indications, including prevention of anemia in surgical patients or in patients undergoing platinum-based chemotherapy, treatment of anemia of prematurity, of anemia induced by zidovudine therapy in HIV-infected patients, and of anemia induced by chemotherapy of nonmyeloid malignancies. Erythropoietin should routinely be given subcutaneously to maximize its effects. Most patients undergoing rHuEpo treatment develop functional iron deficiency, a situation in which iron supply to the erythroid marrow is inadequate for the erythrocyte precursor demand. Iron supplementation should, therefore, be given to all individuals receiving rHuEpo except for those patients with increased serum iron and transferrin saturation. Outside the setting of uremia, only a portion of patients can clearly benefit from erythropoietin therapy; therefore, the use of rHuEpo should be individualized in nonrenal applications.


Evaluation of different cryoprotectant solutions for the cryopreservation of somatic tissues of Dasyprocta leporina (Linnaeus, 1758).
Somatic tissue banks represent important tools for the conservation of wild mammals, aiming at the immediate maintenance and safeguarding of biological samples. For agouti, Dasyprocta leporina, studies on the formation of these banks are still scarce, especially regarding protocols of the best cryoprotectant solution employed. To optimize the cryoprotectant solution [ethylene glycol (EG), dimethyl sulfoxide (DMSO), sucrose (SUC)] used for the cryopreservation of agouti somatic tissues. We treated ear tissues with various cryoprotectant solutions: 3.0 M EG (EG group), 3.0 M EG and 0.25 M SUC (EG-SUC group), 3.0 M DMSO (DMSO group), 3.0 M DMSO and 0.25 M SUC (DMSO-SUC group), 1.5 M EG and 1.5 M DMSO (EG-DMSO group) and 1.5 M EG, 1.5 M DMSO and 0.25 M SUC (EG-DMSO-SUC group). Non-cryopreserved tissues were used as controls. All tissues were analyzed for their ultrastructural and morphometric characteristics by scanning electron microscopy and conventional histology. EG-DMSO-SUC was found to be the optimal cryoprotectant solution in terms of the evaluated parameters, such as thickness of the dermis and skin, number of perinuclear halos, proliferative potential, number of empty lacunas and degenerated chondrocytes. Agouti somatic tissue cryopreservation may serve for its conservation and as an experimental model for the development of preservation methods for species of the same genus that are either vulnerable or critically endangered.


In vitro antibody response to influenza virus. II. Specificity of helper T cell recognizing hemagglutinin.
Intraperitoneal immunization of mice with liver influenza virus was shown to induce helper T (TH) cells with specificity for the hemagglutinin (HA). The interaction of virus-primed TH cells with purified HA was studied independently of B cell reactivity to the same antigen by using the generation of nonspecific help as an index of activation of HA-specific TH cells. TH cells from mice primed with any of the H3 viruses A/Aichi/68 X A/Bel/42 (H3N1), A/Memphis/102/72 X A/Bel/42 (H3N1) or A/Port Chalmers/73 (H3N2) were strongly cross-reactive towards HA of other strains within the H3 subtype. In addition, several examples of cross-reactivity towards HA of a different subtype were observed, usually of a lower magnitude. TH cells from mice primed to any of the H3 viruses above or to A/Bel/42 (H1N1) virus cross-reacted with the HA of A/Japan/305/57 (H2); furthermore, priming with A/Bel/42 or with A/Jap/305/57 X A/Bel/42 (h2N1) virus yielded TH cells that cross-reacted with certain of the H3 HA preparations. The cross-reactivity observed between subtypes was not due to the common chicken host carbohydrate component of HA, since no response to the purified type A HA preparations was obtained with T cells from mice primed with egg-grown influenza B/Hong-Kong/8/73 virus. The results indicate that HA of different subtypes may share cross-reactive antigenic determinants recognized by TH cells. Within a subtype, HA are highly cross-reactive with respect to tH cell recognition.


Discovery of AB680: A Potent and Selective Inhibitor of CD73.
Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure-activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (Ki = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclinical species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clinical trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human.


Fatty acid synthesis by explant cultures from the mammary glands of goats on days 60 and 120 of pregnancy.
Explants of mammary glands from 60-day pregnant goats showed a mean fourfold increase in fatty acid synthesis from acetate when cultured with insulin+ cortisol. Epithelial cells increased their area by 60% but no secretory activity was induced. In 120-day pregnant goats, fatty acid synthesis and epithelial cell area were greater than at day 60 of pregnancy and were unaffected by hypophysectomy or by daily treatment with bromocriptine from day 60. Neither increased further on culture of mammary explants in insulin + cortisol. Ovine prolactin increased fatty acid synthesis two-fold when added to insulin + cortisol in cultures of mammary tissue from goats on day 60 of pregnancy and secretory activity was induced. On day 120 of pregnancy insulin + cortisol + prolactin sustained or slightly stimulated both fatty acid synthesis and the extensive secretion present in the tissue at the start of culture. Synthesis of medium-chain fatty acids of milk-fat was also sustained by prolactin in one goat. An atmosphere of air was found to maintain normal histological structure of the mammary gland. By contrast, in 95% oxygen, explants from goats which were 60 days pregnant showed epithelial cells filling the lumina of ducts and alveoli in 60% of explants and a poor response to prolactin.


Salivary Cortisol, Perceived Stress, and Metabolic Syndrome: A Matched Case-Control Study in Female Shift Workers.
Although the pathogenesis of metabolic syndrome (MetS) is complex and multifactorial, there is limited information if psychological factors, such as stress exposure, are involved in the etiology of MetS. Therefore, this study investigated the associations between MetS and cortisol levels and perceived stress levels among women shift workers in Southern Brazil. A matched case-control study was conducted, including 50 cases of MetS and 200 age-matched controls (±3 years, 4 for each case). Salivary cortisol levels were evaluated immediately after waking and one upon returning home from work. Perceived stress levels were measured by the Perceived Stress Scale with 10 items (PSS-10). Multivariate-adjusted associations between MetS and salivary cortisol levels and perceived stress levels were assessed by conditional logistic regression. Means±standard deviations of salivary cortisol levels were not significantly different between cases and controls either immediately after waking (5.37±4.10 vs. 6.03±5.39 nmol/l; p = 0.53) or after work (2.74±2.87 vs. 2.78±2.85 nmol/l; p = 0.93). There was no significant difference in perceived stress level between cases and controls (14.2±5.9 vs. 15.5±5.6; p = 0.15). No independent association was observed in the multivariate model between MetS and salivary cortisol level or perceived stress level after these exposures were stratified into tertiles. Overall, there was no difference between women with or without MetS in regard to the free salivary cortisol and perceived stress. Our results do not support an association between stress exposure and MetS among women shift workers.


Prioritizing material recovery for end-of-life printed circuit boards.
The increasing growth in generation of electronic waste (e-waste) motivates a variety of waste reduction research. Printed circuit boards (PCBs) are an important sub-set of the overall e-waste stream due to the high value of the materials contained within them and potential toxicity. This work explores several environmental and economic metrics for prioritizing the recovery of materials from end-of-life PCBs. A weighted sum model is used to investigate the trade-offs among economic value, energy saving potentials, and eco-toxicity. Results show that given equal weights for these three sustainability criteria gold has the highest recovery priority, followed by copper, palladium, aluminum, tin, lead, platinum, nickel, zinc, and silver. However, recovery priority will change significantly due to variation in the composition of PCBs, choice of ranking metrics, and weighting factors when scoring multiple metrics. These results can be used by waste management decision-makers to quantify the value and environmental savings potential for recycling technology development and infrastructure. They can also be extended by policy-makers to inform possible penalties for land-filling PCBs or exporting to the informal recycling sector. The importance of weighting factors when examining recovery trade-offs, particularly for policies regarding PCB collection and recycling are explored further.


Effect of culture duration on chondrogenic preconditioning of equine bone marrow mesenchymal stem cells in self-assembling peptide hydrogel.
Ex vivo induction of chondrogenesis is a promising approach to improve upon the use of bone marrow mesenchymal stem cells (MSCs) for cartilage tissue engineering. This study evaluated the potential to induce chondrogenesis with days of culture in chondrogenic medium for MSCs encapsulated in self-assembling peptide hydrogel. To simulate the transition from preconditioning culture to implantation, MSCs were isolated from self-assembling peptide hydrogel into an individual cell suspension. Commitment to chondrogenesis was evaluated by seeding preconditioned MSCs into agarose and culturing in the absence of the chondrogenic cytokine transforming growth factor beta (TGFβ). Positive controls consisted of undifferentiated MSCs seeded into agarose and cultured in medium containing TGFβ. Three days of preconditioning was sufficient to produce chondrogenic MSCs that accumulated ∼75% more cartilaginous extracellular matrix than positive controls by day 17. However, gene expression of type X collagen was ∼65-fold higher than positive controls, which was attributed to the absence of TGFβ. Potential induction of immunogenicity with preconditioning culture was indicated by expression of major histocompatibility complex class II (MHCII), which was nearly absence in undifferentiated MSCs, and ∼7% positive for preconditioned cells. These data demonstrate the potential to generate chondrogenic MSCs with days of self-assembling peptide hydrogel, and the ability to readily recover an individual cell suspension that is suited for injectable therapies. However, continued exposure to TGFβ may be necessary to prevent hypertrophy indicated by type X collagen expression, while immunogenicity may be a concern for allogeneic applications. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1368-1375, 2019.


[Dilated cardiomyopathy: role of clinical and instrumental evaluation of the neuromuscular system].
There are a number of cardiomyopathies secondary to a more widespread striated muscle involvement. While in some conditions the heart is affected as part of a severe myopathy (such as the dilated cardiomyopathy found in Duchenne and Becker muscular dystrophies), there are examples in which the skeletal muscle involvement is subtle. From a classification point of view, some of these cardiomyopathies are secondary to muscular dystrophies, or to metabolic disorders, or to other myopathies. From a practical diagnostic point of view, metabolic conditions predominate in infancy, whereas the dystrophic forms are more frequently found from the third decade onwards. Useful clinical clues to suggest a skeletal muscle involvement are muscle hypertrophy or wasting and contractures, in addition to weakness. Serum creatine kinase should always be studied when suspecting a form secondary to a muscular dystrophy, although a normal serum creatine kinase does not exclude a muscular dystrophy. Electromyography and muscle imaging are additional useful investigations in these patients. This article is focused on practical clinical suggestions on when to suspect and how to investigate patients with a cardiomyopathy secondary to neuromuscular disorders.


Increase in number of myocardial [3H]BAY K 8644 binding sites during adult maturation of rat.
In the present study we investigated the binding properties of [3H]BAY K 8644 to the purified sarcolemmal membrane, isolated from 2- and 12-month old Sprague-Dawley rats. Specific binding of [3H]BAY K 8644 was saturable and the Scatchard plot analysis revealed a single class of binding sites in purified sarcolemmal membrane. The estimated maximum number of binding sites in the membrane of 12-month-old rat was 2.4 +/- 0.1 pmol/mg protein, which was significantly greater than the maximum number of binding sites in 2-month-old rats (1.7 +/- 0.2 pmol/mg protein). The affinity to bind [3H]BAY K 8644 was, however, reduced in older rats (KD, 14.5 +/- 0.8 vs. 4.8 +/- 0.3 nM). Measurement of activities of sarcolemmal and subcellular marker enzymes showed that the purification of membrane was virtually identical in two age groups. This would suggest that membrane purity was not a contributing factor to the observed increase in [3H]BAY K 8644 receptor density. Since dihydropyridine receptor sites are very likely to represent voltage-gated calcium channels of sarcolemma, it is concluded that the density of myocardial voltage-gated calcium channels increases during adult maturation.


TNF-alpha induces the late-phase airway hyperresponsiveness and airway inflammation through cytosolic phospholipase A(2) activation.
Late-phase airway hyperresponsiveness (AHR) in asthma is considered the event leading to persistent inflammation in the lungs, but the molecular mechanisms involved in this process are poorly understood. To examine the role of TNF-alpha in the development of a late AHR and airway inflammation in asthma. We established a murine model of asthma with not only biphasic AHR to methacholine but also airway eosinophilia. The effect of TNF-alpha blockade was determined by using anti-TNF-alpha antibody and TNF-alpha knockout mice. Cytosolic phospholipase A(2) (cPLA(2)) mRNA expression and activity were assessed by using RT-PCR and 1-stearoyl-2-[1-(14)C] arachidonyl-sn-glycero-3-phosphocholine as the substrate, respectively. TNF-alpha blockade resulted in significant inhibition of the late AHR without affecting the early AHR, and reduction in airway eosinophilia and inflammation. cPLA(2) activity was increased in asthmatic lungs in a TNF-alpha-dependent way, and cPLA(2) inhibitor blocked late AHR and airway eosinophilia. TNF-alpha also stimulated the synthesis of cPLA(2) metabolites such as leukotriene B(4) and platelet-activating factor in the airway. Specific inhibitors of cPLA(2) metabolites inhibited the late AHR and airway eosinophilia. TNF-alpha is the proximal key cytokine capable of developing late-phase AHR and subsequent airway inflammation through expression/activation of cPLA(2).


Artificial Intelligence and Multiple Sclerosis: Up-to-Date Review.
Multiple sclerosis (MS) remains a challenging neurological disorder for the clinician in terms of diagnosis and management. The growing integration of AI-based algorithms in healthcare offers a golden opportunity for clinicians and patients with MS. AI models are based on statistical analyses of large quantities of data from patients including "demographics, genetics, clinical and radiological presentation." These approaches are promising in the quest for greater diagnostic accuracy, tailored management plans, and better prognostication of disease. The use of AI in multiple sclerosis represents a paradigm shift in disease management. With ongoing advancements in AI technologies and the increasing availability of large-scale datasets, the potential for further innovation is immense. As AI continues to evolve, its integration into clinical practice will play a vital role in improving diagnostics, optimizing treatment strategies, and enhancing patient outcomes for MS. This review is about conducting a literature review to identify relevant studies on AI applications in MS. Only peer-reviewed studies published in the last four years have been selected. Data related to AI techniques, advancements, and implications are extracted. Through data analysis, key themes and tendencies are identified. The review presents a cohesive synthesis of the current state of AI and MS, highlighting potential implications and new advancements.


[Epidemiology of Campylobacteriosis in Castile and Leon, Spain,during the period 2008-2015].
Campylobacter is considered the most frequent agent of gastroenteritis in humans all around the world. The aim of this study was to know the incidence, trend and seasonality of notified campylobacteriosis cases in Castile and Leon, Spain, from 2008 to 2015. In addition, to describe the type of case and source of notification, and study the influence of age, sex and Campylobacter species on the hospitalization of cases. Retrospective cross-sectional study with a time series analysis. Data on notified campylobacteriosis cases were collected from the Epidemiological Surveillance System of Castile and Leon (2008-2015). Incidence rates and incidence rate ratios by age, sex and year of notification were calculated. In order to estimate trend and seasonality, a time series analysis was performed using a multiplicative method and adjusted to a linear and exponential model. From 4,330 cases analyzed, 49.4% of children aged under 5 were affected. The ratio of men to women was 1.43 and 61.8% of cases were notified from secondary care. C. jejuni was isolated from 72.3% of samples (n=2,593). Incidence rate ranged from 11.42 cases per 100,000 inhabitants in 2008 to 33.53 in 2015. The seasonality range was from 71.97% (13th four-week period) to 125.54% (9th four-week period). Hospitalization reached 62.5% for people aged 60 or over. A growing trend of notified campylobacteriosis cases is observed in Castile and Leon (2008-2015), mainly in children aged under 5, with a peak in summer months. Males are more affected than females and hospitalization increases with age.


Acupuncture and burning mouth syndrome: a pilot study.
Burning mouth syndrome (BMS) is a chronic condition most common in middle-aged and elderly women, with prevalence rates in the general population ranging from 0.5% to 5%. Defined by the International Headache Society as "an intraoral burning sensation for which no medical or dental cause can be found," BMS is considered a form of neuropathic pain. The management of BMS remains unsatisfactory. In this pilot study, we investigated the use of acupuncture in a small group of BMS patients. The study group, after 4 refusals, was composed of 10 BMS patients (9 females and 1 male; mean age, 65.2 years; range, from 48 to 80 years; mean duration of BMS, 2.6 years; SD ± 0.8 years). Oral pain/burning sensation (primary outcome) was measured using a visual analogue scale (VAS). Health-related quality of life (secondary outcome) was measured using the 36-item Short-Form Health Survey (SF-36). Acupuncture treatment lasted 8 weeks and consisted of 20 sessions. Patients reported a mean reduction in pain of 0.99 points on the VAS (max 2.1-min 0.1), which, although slight, was statistically significant (Wilcoxon test P < 0.009). No significant improvement in the overall score for quality of life was observed, although subjects receiving acupuncture treatment seemed better able cope with their oral symptoms.


Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure.
Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid-specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products.


Three-dimensional High-resolution Anorectal Manometry in Children With Non-retentive Fecal Incontinence.
Three-dimensional high-resolution anorectal manometry (3D-HRAM) is a precise tool to assess the function of the anorectum. Our aim is to evaluate children diagnosed with non-retentive fecal incontinence (NRFI) using 3D-HRAM. In all children diagnosed with NRFI, manometric parameters and 3-dimensional reconstructions of the anal canal subdivided into 8 segments were recorded. All data were compared to raw data that were obtained from asymptomatic children, collected in our laboratory and published previously (C group). Forty children (31 male; median age, 8 years; range, 5-17) were prospectively included in the study. Comparison of the NRFI group and C group revealed lower values of mean resting pressure (74.4 mmHg vs 89.2 mmHg, P > 0.001) and maximum squeeze pressure (182 mmHg vs 208.5 mmHg, P = 0.018) in the NRFI group. In the NRFI group, the thresholds of sensation, urge and discomfort (40 cm3, 70 cm3, and 140 cm3, respectively) were significantly higher than those in the C group (20 cm3, 30 cm3, and 85 cm3, respectively; P > 0.001). In the NRFI group, 62.5% presented a mean resting pressure above the fifth percentile, and 82.5% of patients presented a maximum squeeze pressure above the fifth percentile. The comparisons between segments obtained from these patients and those obtained from the C group revealed several segments with significantly decreased pressure values in the NRFI group. Our study demonstrated lower pressure parameters in children with NRFI. In patients with normal resting pressures, 3D-HRAM may reveal segments with decreased pressures, which may play a potential role in the pathomechanism of incontinence.


Molecular and electronic properties transferred to Silicon via wet-chemistry surface nanofunctionalization: ethynylferrocene on Si(100).
In the frame of our research activity on covalent anchoring of functional molecules on Si oriented surfaces, we report here on the hybrid species resulting from the reaction of ethynylferrocene with H-Si(100) either in a single, direct step, or after production of a self-assembled alpha,omega-bifunctional alkyl monolayer. In the former approach, a short Si-C covalent bond is established through visible-light activation of the unsaturated side arm of ethynylferrocene via an extra-mild approach. In the latter case, an azide-alkyne Huisgen cycloaddition reaction ("click" chemistry) is induced between the C[triple bond]C group of the molecule and the -N3 terminations of undecyl hydrocarbon chains pre-assembled onto H-Si(100). These two routes lead to electroactive monolayers wherein the ferrocene head groups are respectively located close to or far from the Si surface. This allows for a fine tuning of the properties of the resulting hybrids on Si, in terms of distinct redox potentials, electron transfer rate constants, oxidation resistance. The different reaction steps have been monitored with X-ray Photoelectron Spectroscopy (XPS), in order to evaluate the presence and the chemical nature of the anchored species, while electrochemical measurements have evidenced reversible redox responses of the resulting SAMs.


Sjögren's syndrome--a plethora of clinical and immunological phenotypes with a complex genetic background.
Primary Sjögren's syndrome is a complex autoimmune disorder, considered to represent an ideal disease with which to study the mechanisms underlying autoimmunity because its manifestations are both organ specific and systemic in nature. The characteristic histologic finding in target organs is a progressive focal infiltration of mononuclear lymphoid cells, replacing glandular epithelium (lymphoepithelial lesion). This involvement has been re-emphasized in the 2002 revised EU criteria for Sjögren's syndrome. Moreover, ectopic secondary lymphoid follicles in Sjögren's syndrome contain all elements of relevance for driving an autoimmune response. A number of cytokines and chemokines are involved and particularly B cell activating factor seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation. The recent discovery of clinical benefit after B cell depletion also highlights the pivotal role of B cells in Sjögren's syndrome. A major challenge in Sjögren's syndrome will be to stratify the disease process including genetic and environmental triggers. Identification of novel genetic and molecular markers may lead to the development of better diagnostic and prognostic tools in Sjögren's syndrome including its systemic complications. This minor review will cover the current knowledge on classification, pathogenesis, multiplex findings, potential candidate genes, gene profiling results, and novel therapy approaches. New hypotheses behind the complexity of Sjögren's syndrome are expected to follow.


[Application of liquid-based cytology and high-risk human papillomavirus DNA detection in cervical lesion screening].
To explore the application of liquid-based cytology test (LCT) and high-risk human papillomavirus (HR-HPV) DNA test in cervical lesion screening. A retrospective analysis was conducted in 4264 patients with LCT, among whom 621 patients had colposcopic biopsy and HR-HPV test for atypical squamous cells of undetermined significance (ASCUS and over). Of the 621 patients, 388 were identified to have ASCUS, 147 had low-grade squamous intraepithelial lesions (LSIL), 75 had high-grade squamous intraepithelial lesions (HSIL) and 11 had squamous cell carcinomas (SCC). Comparison of the diagnostic results of LCT and histopathology diagnosis suggested a rate of agreement of 72.41% (147/203) for LSIL, 92.60% (75/81) for HSIL, and 100% (11/11) for SCC. The infection rate of HR-HPV was 43.32%(269/621) in the 621 patients, 100.00% (11/11) in SCC patients, 84.85% (28/33) in CIN III patients, 70.83% (34/48) in CIN II patients, 84.073 (172/203) in CIN I patients, 7.32% (24/326) in patients with normal cervix/cervicitis, indicating increased rate of HR- HPV infection with aggravation of cervical lesion. The sensitivity and specificity of LCT test were 81.04% and 91.64% respectively, and those of HR-HPV were 90.47% and 93.14 respectively. The combination of LCT and HR-HPV DNA test increases the sensitivity and specificity of diagnosis in cervical dysplasia, and may help in better prophylaxis and treatment of cervical carcinoma.


Hypoglycemia in pediatric renal allograft recipients.
Symptomatic hypoglycemia developed 5 to 45 months after transplantation in nine children who had renal transplants before 6 years of age. During hypoglycemia, serum glucose levels ranged from 14 to 39 mg/dl (0.8 to 2.1 mmol/L). Hypoglycemic episodes occurred between 1.7 and 7.5 years of age. Six patients had generalized seizures; the remaining three had diaphoresis with stupor or lethargy. None of the children had serious infections, diabetes, congenital defects of glucose metabolism, or a history of treatment with insulin or oral hypoglycemic agents. Six patients had hypoglycemic symptoms after a prolonged fast, and at least four had ketosis. Eight of the nine patients were receiving propranolol when hypoglycemia occurred. No differences in the daily prednisone dose, the number of transplant rejection episodes, or the frequency of treatment with medications other than propranolol were noted between hypoglycemic patients and 56 normoglycemic age-matched renal transplant recipients. All hypoglycemic patients were subsequently treated with frequent feedings and discontinuation of propranolol. No further hypoglycemic episodes have occurred in eight of nine patients. Symptomatic hypoglycemia should be recognized as a potentially devastating complication of pediatric renal transplantation.


Silk-Derived 2D Porous Carbon Nanosheets with Atomically-Dispersed Fe-Nx -C Sites for Highly Efficient Oxygen Reaction Catalysts.
Controlled synthesis of highly efficient, stable, and cost-effective oxygen reaction electrocatalysts with atomically-dispersed Me-Nx -C active sites through an effective strategy is highly desired for high-performance energy devices. Herein, based on regenerated silk fibroin dissolved in ferric chloride and zinc chloride aqueous solution, 2D porous carbon nanosheets with atomically-dispersed Fe-Nx -C active sites and very large specific surface area (≈2105 m2 g-1 ) are prepared through a simple thermal treatment process. Owing to the 2D porous structure with large surface area and atomic dispersion of Fe-Nx -C active sites, the as-prepared silk-derived carbon nanosheets show superior electrochemical activity toward the oxygen reduction reaction with a half-wave potential (E1/2 ) of 0.853 V, remarkable stability with only 11 mV loss in E1/2 after 30 000 cycles, as well as good catalytic activity toward the oxygen evolution reaction. This work provides a practical and effective approach for the synthesis of high-performance oxygen reaction catalysts towards advanced energy materials.


[Evolution and prognosis in patients with primary liver cancer. I. The effect of individual factors on the survival of patients with primary liver cancer].
The data of the frequency, evolution and prognosis of 63 patients with primary liver carcinoma which had developed on the basis of liver cirrhosis are presented. An attempt is made to assess the importance of the etiologic factors, type of liver cirrhosis, macroscopic type of the tumor, histologic pattern of the cancer, sex and age for the evolution and prognosis of the disease. The patients with primary liver carcinoma without cirrhosis have a better prognosis. As high risk factors may be accepted: male sex, age over 50 years, toxic factors, hepatitis B virus infection and chronic alcoholism. The macroscopic type of the tumor also affects the prognosis. The histologic pattern of the cancer does not influence the survival of the patients with primary liver carcinoma.


Using ToxCast™ Data to Reconstruct Dynamic Cell State Trajectories and Estimate Toxicological Points of Departure.
High-content imaging (HCI) allows simultaneous measurement of multiple cellular phenotypic changes and is an important tool for evaluating the biological activity of chemicals. Our goal was to analyze dynamic cellular changes using HCI to identify the "tipping point" at which the cells did not show recovery towards a normal phenotypic state. HCI was used to evaluate the effects of 967 chemicals (in concentrations ranging from 0.4 to 200 μM) on HepG2 cells over a 72-hr exposure period. The HCI end points included p53, c-Jun, histone H2A.x, α-tubulin, histone H3, alpha tubulin, mitochondrial membrane potential, mitochondrial mass, cell cycle arrest, nuclear size, and cell number. A computational model was developed to interpret HCI responses as cell-state trajectories. Analysis of cell-state trajectories showed that 336 chemicals produced tipping points and that HepG2 cells were resilient to the effects of 334 chemicals up to the highest concentration (200 μM) and duration (72 hr) tested. Tipping points were identified as concentration-dependent transitions in system recovery, and the corresponding critical concentrations were generally between 5 and 15 times (25th and 75th percentiles, respectively) lower than the concentration that produced any significant effect on HepG2 cells. The remaining 297 chemicals require more data before they can be placed in either of these categories. These findings show the utility of HCI data for reconstructing cell state trajectories and provide insight into the adaptation and resilience of in vitro cellular systems based on tipping points. Cellular tipping points could be used to define a point of departure for risk-based prioritization of environmental chemicals. Shah I, Setzer RW, Jack J, Houck KA, Judson RS, Knudsen TB, Liu J, Martin MT, Reif DM, Richard AM, Thomas RS, Crofton KM, Dix DJ, Kavlock RJ. 2016. Using ToxCast™ data to reconstruct dynamic cell state trajectories and estimate toxicological points of departure. Environ Health Perspect 124:910-919; http://dx.doi.org/10.1289/ehp.1409029.


Are prosthodontics a vital part of dentistry?
Prosthodontics in all of its various subspecialties is in high demand in the United States. It represents a major portion of a typical dentist's income. On the basis of data recently obtained about the projected increase in the physiological need for prosthodontic services and the extensive involvement of U.S. dentists in all areas of prosthodontics, one cannot deny the need for continued and increased predoctoral, doctoral and postgraduate education in prosthodontics.


Structure and dynamics of calmodulin in solution.
To characterize the dynamic behavior of calmodulin in solution, we have carried out molecular dynamics (MD) simulations of the Ca2+-loaded structure. The crystal structure of calmodulin was placed in a solvent sphere of radius 44 A, and 6 Cl- and 22 Na+ ions were included to neutralize the system and to model a 150 mM salt concentration. The total number of atoms was 32,867. During the 3-ns simulation, the structure exhibits large conformational changes on the nanosecond time scale. The central alpha-helix, which has been shown to unwind locally upon binding of calmodulin to target proteins, bends and unwinds near residue Arg74. We interpret this result as a preparative step in the more extensive structural transition observed in the "flexible linker" region 74-82 of the central helix upon complex formation. The major structural change is a reorientation of the two Ca2+-binding domains with respect to each other and a rearrangement of alpha-helices in the N-terminus domain that makes the hydrophobic target peptide binding site more accessible. This structural rearrangement brings the domains to a more favorable position for target binding, poised to achieve the orientation observed in the complex of calmodulin with myosin light-chain kinase. Analysis of solvent structure reveals an inhomogeneity in the mobility of water in the vicinity of the protein, which is attributable to the hydrophobic effect exerted by calmodulin's binding sites for target peptides.


How Useful Is Endoscopic Ultrasound in Differentiating T3/T4a T Stage of Colorectal Cancer: A Prospective Study.
Endoscopic ultrasound (EUS) is an established method for staging of colorectal cancer. Nevertheless, prior assessments of its T stage accuracy have been limited, particularly ambiguity in assessed T3 and T4a stage. This study was to characterize the EUS image features and pay attention to distinguish T3 from T4a T stage. A total of 638 patients who prospectively underwent colorectal EUS were recorded. The final diagnoses were compared with the concurrent or follow-up histopathology. Univariate and multivariate logistic regressions were used to assess variation in diagnostic performance with case attributes. The accuracies of EUS in classifying colorectal cancer for overall, T1, T2, T3, and T4a stages are 73.04, 62.32, 67.46, 71.26, and 83.52%, respectively. With attention to EUS image features, the lesion penetrates the entire wall and locates below the seminal vesicles or cervix is T3 stage. If the lesion locates above clearly-defined space between the anterior rectal wall and the posterior surface of the seminal vesicles or cervix, we identify as T4a stage; However, when located above seminal vesicles or cervix but on the posterior wall of the rectum, the lesion still considers as T3 stage. The tumor location and histological type are associated with inaccuracy T stage. EUS provides reliable diagnostic accuracy in the colorectal cancer stage. The seminal vesicles and cervix are the important markers to predict infiltration depth for T3/T4a stage. Furthermore, the tumor location, histological type, and EUS image features for each tumor T stage should warrant attention.


How and when melanic coloration is an advantage for lizards: the case of three closely-related species of Liolaemus.
Body temperature affects various aspects of ectotherm biology. Reptiles, as ectotherms, gain and control their temperature mainly through behavioural adjustments, although some body traits may also be advantageous. According to the thermal melanism hypothesis (TMH) dark colour may be thermally advantageous in cold environments. Additionally, differences in thermoregulatory capacity may also affect performance. We analysed the role of melanism in the thermoregulation and sprint speed performance of three species of Liolaemus lizards from Argentinean Patagonia. Liolaemus shitan, L. elongatus and L. gununakuna are phylogenetically close, with similar body sizes and life history traits, but differ in their melanic colouration, L. shitan being the darkest and L. gununakuna the lightest species. We estimated sprint speed performance curves and heating rates, and recorded final body temperature and sprint speed achieved after a fixed heating time, from two different initial body temperatures, and with and without movement restriction. Performance curves were similar for all the species, but for L. gununakuna the curve was more flattened. Darker species showed faster heating rates, ran faster after fixed heating trials at the lowest temperature, and reached higher body temperatures than L. gununakuna, but this was compensated for by behavioural adjustments of the lighter lizards. Similarity of sprint speed performance may be due to the conservative nature of this character in these species, while variation in heating ability, particularly when starting from low temperatures, may reflect plasticity in this trait. The latter provides support for the TMH in these lizards, as melanism helps them increase their body temperature. This may be especially advantageous at the beginning of the day or on cloudy days, when temperatures are lower.


Comparison of toric intraocular lens alignment between femtosecond laser-assisted capsular marking and digital marking.
To compare the accuracy of toric intraocular lens (IOL) alignment between femtosecond laser-assisted capsular marking and digital marking. Ruhr University Eye Clinic, Bochum, Germany. Prospective clinical trial. In this study 28 eyes (23 patients), who underwent femtosecond laser-assisted cataract surgery with implantation of a toric intraocular lens were included. Intraoperatively, both femtosecond laser-assisted capsular marking and digital marking were applied simultaneously and compared in every case. The toric IOL was aligned to the capsular markings. Postoperatively, the axis of the capsular markings and toric IOL alignment were examined. Visual acuity and refractive outcomes were evaluated. Both alignment methods were performed without intraoperative complications in all cases. 25 eyes were included in the final analysis. Misalignment was significantly lower with femtosecond laser-assisted capsular marking than with digital marking (1.71° ± 1.25° versus 2.64° ± 1.70°, p = 0.016). Deviation from the target axis of the toric IOL was 1.62° ± 1.24° 4 - 6 weeks postoperatively. Postoperative uncorrected distance visual acuity was 0.14 ± 0.13 logMAR and residual astigmatism was 0.3 ± 0.23 D with an astigmatism ≤ 0.5 D in 93% of eyes. Both methods showed excellent results for alignment of toric IOLs. However, femtosecond laser-assisted capsular marking was significantly more precise than digital marking and showed good refractive results. In addition, capsular marking offers the possibility to avoid parallax error and evaluating postoperative IOL rotation.


A statistical model for FEV1 response to arbitrary dynamic ozone exposure conditions.
Lung function response to inhaled ozone at ambient air pollution levels is known to be a function of ozone concentration, exposure duration, and minute ventilation. Most data-driven exposure-response models address exposures under static condition (i.e., with a constant ozone concentration and exercise pattern). Such models are simplifications, as both ambient ozone concentrations and normal human activity patterns change with time. The purpose of this study was to develop a dynamic model of response with the advantages of a statistical model (a relatively simple structure with few parameters). A previously proposed mechanistic model for changes in specific airways resistance was adapted to describe the percent change in forced expiratory volume in one second (FEV1). This model was then reduced using the fit to three existing exposure-response data sets as criterion. The resulting model consists of a single linear differential equation together with an algebraic logistic equation. Under restricted static conditions the model reduces to a logistic model presented earlier by the authors.


Sub-7 fs radially-polarized pulses by post-compression in thin fused silica plates.
We experimentally demonstrate the post-compression of radially polarized 25 fs pulses at 800 nm central wavelength in a multiple thin plate arrangement for the first time, to the best of our knowledge. Sub-7 fs pulses with 90 µJ energy were obtained after dispersion compensation, corresponding to a compression factor of more than 3.5. Preservation of radial polarization state was confirmed by polarized intensity distribution measurements. Linear projections of the radially polarized pulses were also fully characterized in the temporal domain.


Estimating base cation weathering rates in the United States: challenges of uncertain soil mineralogy and specific surface area with applications of the PROFILE model.
The weathering release rate of base cations (BCw) from soil minerals is fundamentally important for terrestrial ecosystem growth, function, and sensitivity to acid deposition. Understanding BCw is necessary to reduce or prevent damage to acid-sensitive natural systems, in that this information is needed to both evaluate the effectiveness of existing policies, and guide establishment of further policies in the event they are required. Yet BCw is challenging to estimate. In this study, major sources of uncertainty associated with a process-based model (PROFILE) commonly used to estimate weathering rates were quantified in the context of efforts to quantify BCw for upland forest sites across the continental U.S. These include uncertainty associated with parameterization of mineral content where horizon data are not available, stoichiometry of individual minerals, and specific surface area of soil and individual soil minerals. Mineral stoichiometry was not an important influence on BCw estimates (uncertainty < 1%). Characterizing B horizon mineralogy by averaging A and C horizons was found to be a minor (< 5%) contributor to uncertainty in some areas, but where mineralogy is known to vary with depth the uncertainty can be large. Estimating mineral-specific surface areas had a strong influence on estimated BCw, with rates increasing by as much as 250%. The greatest uncertainty in BCw estimates, however, was attributed to the particle size class-based method used to estimate the total specific surface area upon which weathering reactions can take place. The resulting uncertainty in BCw spanned multiple orders of magnitude at individual sites, highlighting this as the greatest challenge to ongoing efforts to produce robust BCw estimates across large spatial scales in the U.S. Recommendations for improving estimates of BCw to support robust decision making for protection against terrestrial acidification are provided.


De Novo Synthesis of Phosphorylated Triblock Copolymers with Pathogen Virulence-Suppressing Properties That Prevent Infection-Related Mortality.
Phosphate is a key and universal "cue" in response to which bacteria either enhance their virulence when local phosphate is scarce or downregulate it when phosphate is adundant. Phosphate becomes depleted in the mammalian gut following physiologic stress and serves as a major trigger for colonizing bacteria to express virulence. This process cannot be reversed with oral supplementation of inorganic phosphate because it is nearly completely absorbed in the proximal small intestine. In the present study, we describe the de novo synthesis of phosphorylated polyethylene glycol compounds with three defined ABA (hydrophilic/-phobic/-philic) structures, ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k-Pi20, and linear polymer PEG20k-Pi20 absent of the hydrophobic block. The 10k, 16k, and 20k demonstrate the molecular weights of the poly(ethylene glycol) block, and Pi10, Pi14, and Pi20 represent the repeating units of phosphate. Polymers were tested for their efficacy against Pseudomonas aeruginosa virulence in vitro and in vivo by assessing the expression of the phosphate sensing protein PstS, the production of key virulence factor pyocyanin, and Caenorhabditis elegans killing assays. Results indicate that all phosphorylated polymers suppressed phosphate sensing, virulence expression, and lethality in P. aeruginosa. Among all of the phosphorylated polymers, ABA-PEG20k-Pi20 displayed the greatest degree of protection against P. aeruginosa. To define the role of the hydrophobic core in ABA-PEG20k-Pi20 in the above response, we synthesized PEG20k-Pi20 in which the hydrophobic core is absent. Results indicate that the hypdrophobic core of ABA-PEG20k-Pi20 is a key structure in its protective effect against P. aeruginosa, in part due to its ability to coat the surface of bacteria. Taken together, the synthesis of novel polymers with defined structures and levels of phosphorylation may elucidate their antivirulence action against clinically important and lethal pathogens such as P. aeruginosa.


Blunt and non-blunt cannabis use associated with cigarette, e-cigarette, and cigar initiation: Findings from the population assessment of tobacco and health (PATH) study.
Smoking cannabis using a tobacco-derived cigar shell or wrap, called blunt smoking, exposes individuals to non-trivial amounts of nicotine. The extent smoking blunts impact the risk of initiating other tobacco products is not well understood. We investigated if past-year blunt smoking is related to the risk of initiating cigarettes, e-cigarettes, and cigars. We obtained data on a nationally representative, non-institutionalized, civilian cohort of US residents aged 12 years and older who had never used cigarettes, e-cigarettes, or any cigar at baseline and surveyed annually for three years from the Population Assessment of Tobacco and Health Study. We estimated the proportional hazard (odds) of initiating these tobacco products associated with past-year blunt smoking, non-blunt cannabis use, or neither using discrete-time survival analyses. Smoking blunts increased the risk of starting cigarettes (OR = 4.5), e-cigarettes (OR = 3.7), and cigars (OR = 6.7) compared to using neither blunts nor cannabis. Non-blunt cannabis use also increased the risk of starting cigarettes (OR = 4.0) but moderately for e-cigarettes (OR = 2.8) and any cigar (OR = 2.2). Blunt use was strongly related to starting combustible tobacco (cigarettes or cigars; OR = 9.0) and any three tobacco products (OR = 10.9). Exploratory findings showed that cigarillos drove cigar results and effect modification by age, race/ethnicity, and sex. People who smoke blunts risk starting cigarettes, e-cigarettes, and cigars more than those who abstain from cannabis. Blunts may contribute to tobacco initiation above cannabis alone.


Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects.
Shared epidemiological risks have resulted in HIV-infected populations having a high prevalence of hepatitis B virus (HBV) co-infection. Several prospective studies have investigated the impact of HBV co-infection on HIV disease progression; most of them were negative. On the contrary, there is evidence that HIV may modify the natural history of HBV infection. HIV positive subjects have higher rates of HBV chronification, higher HBV replication, lower ALT levels and lower rates of seroconversion to anti-HBe and anti-HBs. The impact of HIV co-infection on the outcome of HBV infection is still controversial, even if some studies have shown an accelerated progression towards decompensated cirrhosis in HIV co-infected subjects. HBV co-infection is a risk factor for severe hepatotoxicity during HAART. Vaccination for HBV is mandatory in nonimmune HIV subjects, however its efficacy in immunosuppressed patients is still controversial. HIV co-infection decreases the effectiveness of Interferon in the treatment of HBV infection. Because of its activity against both HBV and HIV, lamivudine is used in HIV-HBV co-infected patients at doses of 300 mg/daily and as part of an antiretroviral regimen, but the rate of sustained response is poor and HBV strains with mutations associated with lamivudine resistance occur at a rate of 20% per year. Trials of new drugs with activity against HBV, some of them with activity also against HIV, and some of them without cross-resistance with lamivudine, are now underway. Highly Active Anti-Hepatitis B Therapy will probably soon come of age.


Efficient Electrochemical and Photoelectrochemical H2 Production from Water by a Cobalt Dithiolene One-Dimensional Metal-Organic Surface.
Solar-driven hydrogen evolution from water has emerged as an important methodology for the storage of renewable energy in chemical bonds. Efficient and practical clean-energy devices for electrochemical or photoelectrochemical splitting of water require the immobilization of stable and active hydrogen-evolving catalysts onto electrode or photocathode materials, which remains a significant challenge. Here we show that cobalt(II) reacts with benzene-1,2,4,5-tetrathiol in the presence of base to form a cobalt dithiolene polymer 1. The generated polymer is immobilized onto glassy carbon electrodes (GCE) to generate a metal-organic surface (MOS 1|GCE), which displays efficient H2-evolving activity and stability in acidic aqueous solutions. Moreover, the generated polymer is integrated with planar p-type Si to generate very efficient photocathode materials (MOS 1|Si) for solar-driven hydrogen production from water. Photocurrents up to 3.8 mA/cm(2) at 0 V vs RHE were achieved under simulated 1 Sun illumination. MOS 1|Si photocathodes operate at potentials 550 mV more positive than MOS 1|GCE cathodes to reach the same activity for H2 evolution from water (1 mA/cm(2)).


Newcastle disease virus in West Africa: new virulent strains identified in non-commercial farms.
Forty-four Newcastle disease virus (NDV) strains, obtained between 2002 and 2007 from different poultry species in Nigeria, Niger, Burkina Faso and Cameroon, were phylogenetically analysed based on partial F sequences. Lineage 2 viruses were genetically identical or similar to the locally used LaSota vaccine strain and were mostly detected in commercial farms. Lineage 1, 3 and 4 strains were only sporadically found, and their origin was less clear. Twenty-one strains from backyard farms and live bird markets formed three new clusters within lineage 5, tentatively named 5f, 5g and 5h. All of these strains were predicted to be virulent based on their F protein cleavage site sequence. Minimal genetic distances between new and previously established sublineages ranged from 9.4 to 15.9%, and minimal distances between the new sublineages were 11.5 to 17.3%. Their high genetic diversity and their presence in three different Sub-Saharan countries suggest that these new sublineages represent the NDV variants indigenous to West Africa.


Visual Evoked Potential Recordings in Mice Using a Dry Non-invasive Multi-channel Scalp EEG Sensor.
For scalp EEG research environments with laboratory mice, we designed a dry-type 16 channel EEG sensor which is non-invasive, deformable, and re-usable because of the plunger-spring-barrel structural facet and mechanical strengths resulting from metal materials. The whole process for acquiring the VEP responses in vivo from a mouse consists of four steps: (1) sensor assembly, (2) animal preparation, (3) VEP measurement, and (4) signal processing. This paper presents representative measurements of VEP responses from multiple mice with a submicro-voltage signal resolution and sub-hundred millisecond temporal resolution. Although the proposed method is safer and more convenient compared to other previously reported animal EEG acquiring methods, there are remaining issues including how to enhance the signal-to-noise ratio and how to apply this technique with freely moving animals. The proposed method utilizes easily available resources and shows a repetitive VEP response with a satisfactory signal quality. Therefore, this method could be utilized for longitudinal experimental studies and reliable translational research exploiting non-invasive paradigms.


Engineering the Macrocyclic Donor Structures towards Deep-Blue Thermally Activated Delayed Fluorescence Emitters.
Deep-blue thermally activated delayed fluorescence (TADF) molecules present promising potential in organic light-emitting diodes (OLEDs), especially for display applications. Here, an efficient molecular engineering approach to modifying the donor or acceptor features of the D-π-A-configured TADF molecules for deep-blue emission is reported. By introducing oxygen and sulfone as a bridge unit onto the macrocyclic donor, two emitters, c-ON-MeTRZ and c-NS-MeTRZ, are synthesized and characterized, respectively. The reduced donor strength of c-ON-MeTRZ and c-NS-MeTRZ as compared to that of the model molecule c-NN-MeTRZ leads to blue-shifted emissions with high photoluminescence quantum yields (PLQYs) and retains TADF characters, while the new emitter c-NN-MePym with the most blue-shifted emission only exhibits a pure fluorescent nature because of the electron-accepting feature of pyrimidine that is insufficient for inducing the TADF property. In the presence of macrocyclic donors, these new emitters show high horizontal dipole ratios (Θ// = 85-89%), which are beneficial for improving the light out-coupling efficiency. Deep-blue TADF OLEDs incorporating c-ON-MeTRZ as an emitter doped in the mCPCN host achieves a high maximum external quantum efficiency (EQEmax) of 30.2% together with 1931 Commission Internationale de I'Eclairage (CIE) coordinates of (0.14, 0.13), while the counter device employing c-NS-MeTRZ as a dopant gives EQEmax of 15.4% and CIE coordinates of (0.14, 0.09). The EQEmax of c-ON-MeTRZ- and c-NS-MeTRZ-based devices can be significantly improved to 34.4 and 29.3%, respectively, with a polar host DPEPO, which stabilizes the charge transfer (CT) S1 state to give lower ΔEST for improving the reverse intersystem crossing process. The efficient TADF character, high PLQYs, and high anisotropic emission dipole ratios work together to render the superior electroluminescence (EL) efficiencies. Based on the detailed characterizations of physical properties, theoretical analyses, and comprehensive study on the corresponding devices, a clear structure-property-performance relationship has been successfully established to verify the effective molecular design strategy of modulating the macrocyclic donor characters for efficient deep-blue TADF emitters.


Serum trypsin-like immunoreactivity after endoscopic retrograde cholangiopancreatography.
Serum trypsin-like immunoreactivity (TLI) was studied in 31 patients before and after endoscopic retrograde cholangiopancreatography. None of the patients developed clinical acute pancreatitis. Generally, the serum TLI peak was observed within the first 6 hours after the examination. Most patients (73%) showed a pathologically high TLI but very high values were not frequent (19%). Successful pancreatic opacification was followed by a significant increase in serum TLI which was pathologically high in nearly all cases (18/20). On the contrary, after cholangiography alone abnormal values were less frequent (4/8) and the increase was not significant. In most patients TLI and amylase responses were in agreement. A significant, though poor, linear relation was found between serum TLI and serum amylase 3, 6 and 12 hours after the examination.


Failed percutaneous kyphoplasty in treatment of stage 3 Kummell disease: A case report and literature review.
Albeit it is rare, the authors report a stage 3 Kummell disease case. It is diagnosed by dynamic thoracic magnetic resonance imaging (MRI). Because there is no established strategy on stage 3 Kummell disease, we performed percutaneous kyphoplasty at first, but unfortunately made a revision surgery to remove the polymethylmethacrylate (PMMA) cement after the failure of percutaneous kyphoplasty. A 73-year-old lady with severe back pain due to osteoporosis vertebral fracture was admitted to our hospital on June 23, 2016. She underwent percutaneous kyphoplasty with the back pain improved shortly. Unfortunately, she went back to our hospital due to aggravated back pain and partial paralysis on July 25, 2016. Kummell disease, lumbar stenosis, lacunar infarction. Specially, the compression of spinal cord was obvious in the hyperflexion position on dynamic MRI. Even though there was no improvement in muscle strength, the patient was satisfied with the back pain relief after percutaneous kyphoplasty. But, the same back pain reappeared after about 1 month. Then, we took out the PMMA cement and performed posterior vertebral column resection. At last, the back pain was relieved again but the muscle strength was improved not obviously after operation. At the same time, the kyphosis was corrected and the intravertebral stability was achieved. Dynamic MRI is helpful in Kummell disease with neurologic symptoms, even if there is no obvious compression in the neutral position. Furthermore, the intravertebral instability is probably the main reason of the neurologic symptoms in this case. Percutaneous kyphoplasty could not reconstruct the intravertebral stability. Stage 3 Kummell disease with obvious intravertebral instability should be treated by open surgery.


A critical appraisal of mucormycosis in COVID- 19 patients in a tertiary care centre in India.
Morbidity and mortality of opportunistic fungal infections in COVID-19 patients are less studied and defined. The patients receiving immunosuppressive therapy, broad-spectrum antibiotics, corticosteroids, and invasive and non-invasive ventilation are the high-risk groups. The demographic profile as well as clinical and radiological findings of all the patients with COVID-19 suspected of Mucormycosis (MM) were recorded. The tissue samples from all the patients were sent for microbiological (KOH mount and culture) and histopathological analysis for confirmation of MM. In total, 45 COVID-19 patients suspected of MM were included in the study and MM was confirmed in 42 patients. The mean age of the patients was 50.30±14.17 years with a female: male ratio of 1.1:1. The most common symptom was headache (52.38%) followed by purulent nasal discharge (38.09%) and facial pain in 33.33% of the cases. The ocular symptoms included a diminution of vision (33.33%) and redness of the eye (2.38%). The most common site of involvement was rhino-orbital (42.85%) followed by sinonasal (23.80%) and rhino cerebral (19.04%). Majority (38.09%) of the patients were diagnosed with stage II of Rhino-orbital-cerebral Mucormycosis (ROCM) based on radiology. A history of diabetes mellitus and steroids was present in 97.61% and 85.71% of the cases, respectively. Moreover, KOH was positive for MM in 97.61% of the cases while the culture was positive in only 35.71% of the cases. In addition, on histopathology, MM was confirmed in 64.28 % of the cases. Mixed growth with Aspergillus species and Rhizopus species was observed in 14.28% of the cases in culture and 11.90% of the cases in histopathology test. Furthermore, angioinvasion was found in 23.80% of the cases according to the histopathology test. Based on the results, the most common conditions associated with MM in COVID-19 patients were diabetes mellitus and steroid therapy. A high level of clinical suspicion aided with diagnostic tests, including KOH mount, culture, histopathology, and radiology which helped the early detection of opportunistic fungal infection in COVID-19 patients to ensure timely treatment.


Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.
To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase (BtChoEase; EC 126.96.36.199) and Torpedo electric organ "true" acetylcholinesterase (AcChoEase; EC 22.214.171.124). Using these probes, we isolated several cDNA clones from lambda gt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A)+ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These findings demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species.


[Mandibular odontogenic carcinosarcoma: a case report].
The last W.H.O classification of odontogenic tumors (1992) individualized a new entity called odontogenic carcinosarcoma. We report a case in which we encountered some difficulties to establish the diagnosis. The patient J.Z., a 26 year-old woman was operated on for a left mandibular tumor corresponding, histologically, to an ameloblastic fibrosarcoma. One year later, we noted a submandibular swelling considered as a local recurrence. After resection, the pathologic examination diagnosed a lymph node metastasis from the same tumor. We decided to observe the patient. Three years post operatively, metastatic lymph nodes appeared, involving a double-component tumor: ameloblastic fibrosarcoma and malignant ameloblastoma. These features allowed the diagnosis of odontogenic carcinosarcoma. We insist on difficulties of the diagnosis and the necessity of radical resection of the tumor with neck dissection.


The types and effects of feedback received by emergency ambulance staff: a systematic mixed studies review with narrative synthesis.
The phenomenon of feedback is well-researched within the wider healthcare context, where it is suggested that feedback can improve patient care and patient safety by enhancing clinical performance and staff mental health (Ivers et al., 2012). Within a pre-hospital context, systematic reviews have been conducted for automated feedback from defibrillators and debrief after simulation, but not on the wider concept of feedback. The aim of this systematic review was to identify, describe and synthesise the published literature on the types and effects of feedback received by emergency ambulance staff. This study is a systematic mixed studies review including empirical primary research of qualitative, quantitative and mixed-methods methodology published in peer-reviewed journals in English. Studies were included if they explored the concept of feedback as defined in this review, i.e. the systematised provision of information to emergency ambulance staff regarding their performance within pre-hospital practice and/or patient outcomes. The search strategy consisted of three facets: ambulance staff synonyms, feedback synonyms and feedback content. Databases searched on 11 June 2020 from inception were MEDLINE, EMBASE, AMED, PsycInfo, HMIC, CINAHL and Web of Science. Study quality was appraised using the Mixed Methods Appraisal Tool (Hong et al., 2018), and data were analysed using narrative synthesis guided by Popay et al. (2006) following a parallel-results convergent synthesis design. The search strategy yielded 2424 articles, excluding duplicates. Seventy-eight studies met the inclusion criteria after full-text review, of which 37 only mentioned feedback as a solution to improving specific circumstances (e.g. decision-making, burnout). The remaining 41 studies consisted of: 34 interventional pre-hospital feedback studies; four non-interventional feedback studies; and three preparatory studies. The source, content and mode of pre-hospital feedback represented in the studies varied greatly and encompassed feedback on behaviour and/or feedback on outcomes of behaviour (Michie et al., 2013). The main outcome measure of included studies was quality of care (e.g. quality of CPR, adherence to guidelines) but softer measures such as staff wellbeing, professional development and clinical decision-making were also represented. It is anticipated that the review findings will be useful to guide the development of future pre-hospital feedback interventions, for which there is growing interest in the national and international pre-hospital setting. Further empirical research is required to explore whether the published literature reflects current pre-hospital practice.


Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients.
Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.


Responsiveness to stimuli of bispectral index, middle latency auditory evoked potentials and clinical scales in critically ill children.
We performed simultaneous recordings of Bispectral Index (BIS) and middle latency auditory evoked potentials. We also recorded two clinical scales, the Modified Ramsay scale and the COMFORT scale. Heart rate and blood pressure were measured once a day, for a maximum of 5 days, in 81 critically ill children. Changes with tactile, auditory, and painful stimuli were analysed. All the stimuli significantly increased the BIS value, the painful stimulus having the greatest effect. The painful stimulus was the only one that altered the middle latency auditory evoked potentials. Although the responses of the clinical scales to stimuli were statistically significant, they were of little clinical relevance. None of the stimuli used significantly altered the heart rate or blood pressure. We conclude that tactile, auditory and painful stimuli produced changes of little relevance in the clinical scales, BIS or middle latency auditory evoked potentials. We found the BIS was the most sensitive method and the painful stimulus had the greatest effect.


Erythema nodosum after golimumab treatment in ankylosing spondylitis patients: a case report and literature review.
Erythema nodosum (EN) is a self-limited septal panniculitis that presents with fever, arthralgia, and arthritis. Tumor necrosis factor alpha (TNF-α) inhibitor such as golimumab has been found to treat EN in inflammatory bowel diseases (IBD). We herein report the paradoxical occurrence of EN following golimumab for ankylosing spondylitis. A 34-year-old female presented in June 2022 with a complaint of 'sores' on her feet that intermittently presented for approximately 5 months but that had worsened dramatically in the last 24 h. The patient had an 8-year history of ankylosing spondylitis for 7 years. Subcutaneous golimumab was administered every 4 weeks as she had not responded to other treatments. Twenty-four hours after the fifth subcutaneous injection, painful, erythematous nodules appeared, histologically compatible with EN. Despite this side effect, we continue therapy due to the good response and efficacy. Skin reactions were associated with the treatment with golimumab, including warm tender skin around the injection site, eruptions, itchiness, and sometimes a full-body rash. Golimumab was successfully used in treating EN in Crohn's disease. Because our patient continued on golimumab, the temporal association of EN flares with therapeutic injection and the lack of any etiology support a direct causal relationship between EN and golimumab treatment. TNF-α inhibitors are useful in treating Crohn's disease patients with EN, although it may present as an adverse effect of this treatment. Further work is needed.


The synapsins: beyond the regulation of neurotransmitter release.
The synapsins are a family of five closely related neuron-specific phosphoproteins associated with the membranes of synaptic vesicles. The synapsins have been implicated in the regulation of neurotransmitter release. They tether synaptic vesicles to actin filaments in a phosphorylation-dependent manner, controlling the number of vesicles available for release at the nerve terminus. A growing body of evidence suggests that the synapsins play a broad role during neuronal development. They participate in the formation and maintenance of synaptic contacts among central neurons. In addition, each synapsin has a specific role during the elongation of undifferentiated processes and their posterior differentiation into axons and dendrites. In this review, we focus on these novel roles of synapsins during the early stages of development.


Femtosecond pulse generation from a Ti3+:sapphire laser near 800 nm with voltage reconfigurable graphene saturable absorbers.
We experimentally show that a voltage-controlled graphene-gold supercapacitor saturable absorber (VCG-gold-SA) can be operated as a fast saturable absorber with adjustable linear absorption at wavelengths as low as 795 nm. This was made possible by the use of a novel supercapacitor architecture, consisting of a high-dielectric electrolyte sandwiched between a graphene and a gold electrode. The high-dielectric electrolyte allowed continuous, reversible adjustment of the Fermi level and, hence, the optical loss of the VCG-gold-SA up to the visible wavelengths at low bias voltages of the order of a few volts (0-2 V). The fast saturable absorber action of the VCG-gold-SA and the bias-dependent reduction of its loss were successfully demonstrated inside a femtosecond Ti3+:sapphire laser operating near 800 nm. Dispersion compensation was employed by using dispersion control mirrors and a prism pair. At a bias voltage of 1.2 V, the laser operated with improved power performance in comparison with that at zero bias, and the VCG-gold-SA initiated the generation of nearly transform-limited pulses as short as 48 fs at a pulse repetition rate of 131.7 MHz near 830 nm. To the best of our knowledge, this represents the shortest wavelength where a VCG-gold-SA has been employed as a mode locker with adjustable loss.


Blast injuries: mechanics and wounding patterns.
Blast and fragment injuries are the most frequently encountered wounds in modern warfare. Explosive devices have become the preferred weapon of domestic and foreign terrorists because they are relatively inexpensive to manufacture and can cause substantial casualties. Although blast injuries have traditionally been associated with the battlefield, this type of trauma is being seen more commonly today among noncombatants due to increasing worldwide terrorism.


Do Smokers' Perceptions of the Harmfulness of Nicotine Replacement Therapy and Nicotine Vaping Products as Compared to Cigarettes Influence Their Use as an Aid for Smoking Cessation? Findings from the ITC Four Country Smoking and Vaping Surveys.
This study examined whether smokers' harm perceptions of nicotine replacement therapy (NRT) and nicotine vaping products (NVPs) relative to cigarettes predicted their subsequent use as smoking cessation aids during their last quit attempt (LQA). We analyzed data from 1,315 current daily smokers (10+ cigarettes per day) who were recruited at Wave 1 (2016), and who reported making a quit attempt by Wave 2 (2018) of the International Tobacco Control Four Country Smoking and Vaping Surveys in Australia, Canada, England, and the United States. We used multinomial logistic regression models to examine prospective associations between harm perceptions of (a) NRT and (b) NVPs and their use at LQA, controlling for socio-demographic and other potential confounders. Smokers who perceive that (a) NRT and (b) NVPs are much less harmful than cigarettes were more likely to subsequently use the respective product as an aid than using no aid or other aids during LQA (adjusted relative risk ratio [aRRR] = 3.79, 95%CI = 2.16-6.66; and aRRR = 2.11, 95%CI = 1.29-3.45, respectively) compared to smokers who perceive these products as equally or more harmful. Additionally, those who perceive NVPs as much less harmful than cigarettes were less likely to use NRT as a quit aid (aRRR = 0.34, 95%CI = 0.20-0.60). No country variations for these associations were found. This study found that smokers' perceptions of the harmfulness of (a) NRT and (b) NVPs relative to cigarettes predicted the respective product use when trying to quit smoking. Corrective education targeting misperceptions of nicotine products' relative harmfulness may facilitate their use for smoking cessation. Nicotine replacement therapy and nicotine vaping products are two commonly used smoking cessation aids. This study demonstrates that misperceptions of the harms of nicotine products relative to cigarettes influence their use for smoking cessation. Believing that nicotine vaping products are much less harmful than cigarette smoking may lead some smokers to prefer these products over nicotine replacement therapy to aid smoking cessation. Education targeting misperceptions of nicotine products' harmfulness relative to cigarettes may enable smokers to make informed choices about which are appropriate to aid smoking cessation.


Acute IgA-Dominant Glomerulonephritis Associated with Syphilis Infection in a Pregnant Teenager: A New Disease Association.
Chronic kidney disease (CKD) is increasingly recognized as a risk factor in pregnancy; the differential diagnosis between CKD and preeclampsia (PE) may be of pivotal importance for pregnancy management and for early treatment of CKD. Acknowledging this connection may be useful also in a wider context, such as in the case reported in this paper, which for the first time describes an association between syphilis infection and IgA-dominant glomerulonephritis. A 16-year-old woman, referred to a general hospital due to a seizure, was found to be unknowingly pregnant. Based on hypertension and nephrotic proteinuria, she was initially diagnosed with PE. Immunological tests, as well as hepatitis and HIV tests showed negative results. However, secondary syphilis was diagnosed. In discordance with the PE diagnosis, urinalysis showed glomerular microhematuria with cellular casts. Proteinuria and hypertension did not remit after delivery, which was made via caesarean section, due to uncontrolled hypertension, at an estimated gestational age of 29 weeks. A male baby, weighing 1.1 kg (6.5 centile) was born. The baby was hospitalized in the neonatal intensive care unit, where he developed subependymal hemorrhage and thrombocytopenia, and neonatal syphilis was diagnosed. The mother underwent a kidney biopsy one week after delivery, leading to the diagnosis of IgA-dominant postinfectious glomerulonephritis. Mother and child were treated with support and antibiotic therapy, and were discharged in good clinical conditions four weeks later. Four months after delivery, the mother was normotensive without therapy, with normal kidney function and without hematuria or proteinuria. In conclusion, this case suggests that IgA-dominant postinfectious glomerulonephritis should be added to the spectrum of syphilis-associated glomerulonephritides, and underlines the need for a careful differential diagnosis with CKD in all cases of presumed PE. While diagnosis relies on kidney biopsy, urinary sediment, a simple and inexpensive test, can be the first step in distinguishing PE from other nephropathies.


Potential regulatory relationship between the nested gene DDC8 and its host gene tissue inhibitor of metalloproteinase-2.
Nested genes are fairly common within the mammalian nervous system, yet few studies have examined whether the guest and host genes might be coordinately regulated. Tissue inhibitors of metalloproteinase (TIMPs) inhibit extracellular matrix proteolysis mediated by metzincin proteases. TIMP-2 is the only TIMP not nested within a synapsin gene. It does, however, serve as a host for differential display clone 8 (DDC8), a testis-specific gene whose expression is upregulated during spermatogenesis. Here, we demonstrate that DDC8 is not testis specific. Furthermore, DDC8 expression in nonneural and neural tissues mimics that of TIMP-2, including its upregulation in response to traumatic brain injury, suggesting a potential regulatory relationship. The most striking observation is that the TIMP-2 knockout mouse brain contains TIMP-2 mRNA encoding exons 2-5, which are downstream of DDC8, but not exon 1, which contains the signal sequence and cysteine residue required for MMP inhibition, indicating a functional knockout. That TIMP-2 transcripts in wild-type brain contain DDC8 sequence suggests alternative splicing between the two genes.


The relationship between life satisfaction, risk-taking behaviors, and youth violence.
This study builds on existing criminological theories and examines the role of life satisfaction and self-control in explaining youth violence. Using data from a stratified cluster sample of 5,414 public high school students who responded to the South Carolina Youth Risk Behavior Survey, the study examines the relationship between adolescents'perceptions of life satisfaction, behavioral risky acts, and self-reported acts of violence. Analyses indicate that higher levels of life satisfaction are associated with lower violence. Participation in work and involvement in health-related risk-taking behaviors pertaining to sex, drugs, and alcohol are also associated with increased violence. The implications of these findings for criminological theory and for school-based violence prevention programs are discussed.


Atypical Manifestation of Cutaneous Fowlpox in Broiler Chickens Associated with High Condemnation at a Processing Plant.
The present case is an unusual report of cutaneous fowlpox with an atypical appearance and incidence in broilers. Gross skin lesions were noticed in 41-day-old commercial broilers during the veterinary inspection at a processing plant in the north of Iran. The skin lesions were only observed on feathered skin areas of the broilers and remained unnoticed until slaughter. Round, nodular or coalescent, elongated, reddish-brown proliferative lesions were mainly located on the back, thighs, and proximal areas of the neck of broilers. Nonfeathered skin, including the wattle, comb, eyelids, and legs, were not affected. This condition incurred high losses due to a 5.3% condemnation and trimming of carcasses. Cutaneous lesions were sampled for histopathology and molecular virology for further investigations. Histopathology revealed multifocal necrotic dermatitis with epidermal eosinophilic cytoplasmic inclusion bodies in the skin lesions. Molecular investigations confirmed the presence of fowlpox virus (FWPV) in the proliferative lesions, with further investigations identifying two FWPV genome populations, one carrying a portion of the reticuloendotheliosis virus (REV) and the other a nearly complete REV provirus. Furthermore, the 4b core protein gene-based molecular analysis clustered the field virus into clade A of the genus Avipoxvirus.