bluuebunny/crossref_metadata_2025 huggingface dataset:
Type IV‐pili dependent motility is co‐regulated by PilSR and PilS2R2 two‐component systems via distinct pathways in Myxococcus xanthus
Authors: Bretl Daniel J. , Müller Susanne , Ladd Kayla M. , Atkinson Samantha N. , Kirby John R.
Published: July 2016

Myxococcus xanthus is an environmental bacterium with two forms of motility. One type, known as social motility, is dependent on extension and retraction of Type‐IV pili (T4P) and production of extracellular polysaccharides (EPS). Several signaling systems have been linked to regulation of T4P‐dependent motility. In particular, expression of the pilin subunit pilA requires the PilSR two‐component signaling system (TCS). A second TCS, PilS2R2, encoded within the same locus that encodes PilSR, has also been linked to M. xanthus T4P‐dependent motility. We demonstrate that PilSR and PilS2R2 regulate M. xanthus T4P‐dependent motility through distinct pathways. Consistent with known roles of PilSR, our results indicate that the primary function of PilSR is to regulate expression of pilA. In contrast, PilS2 and PilR2 have little to no affect on PilA protein levels. However, deletion of pilR2 resulted in a reduction of assembled pili, significant decreases in EPS production and loss of T4P‐dependent motility. Furthermore, the pilR2 mutation led to increased production of outer membrane vesicles (OMV). Collectively, we propose that PilS2R2 is required for proper assembly of T4P and regulation of OMV production, and hypothesize that production of these vesicles is related to M. xanthus motility.
The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS‐box RlmA transcription factors
Authors: Valiante Vito , Baldin Clara , Hortschansky Peter , Jain Radhika , Thywißen Andreas , Straßburger Maria , Shelest Ekaterina , Heinekamp Thorsten , Brakhage Axel A.
Published: July 2016

Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)‐melanin. DHN‐melanin forms the gray‐green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN‐melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross‐species promoter analysis identified specific DNA binding sites in the DHN‐melanin biosynthesis genes pksP‐arp1 intergenic region that can be recognized by bHLH and MADS‐box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS‐box) interfered with sporulation and reduced the expression of the DHN‐melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region.
Apyrase inhibitors enhance the ability of diverse fungicides to inhibit the growth of different plant‐pathogenic fungi
Authors: Kumar Tripathy Manas , Weeraratne Gayani , Clark Greg , Roux Stanley J.
Published: July 2016

A previous study has demonstrated that the treatment of Arabidopsis plants with chemical inhibitors of apyrase enzymes increases their sensitivity to herbicides. In this study, we found that the addition of the same or related apyrase inhibitors could potentiate the ability of different fungicides to inhibit the growth of five different pathogenic fungi in plate growth assays. The growth of all five fungi was partially inhibited by three commonly used fungicides: copper octanoate, myclobutanil and propiconazole. However, when these fungicides were individually tested in combination with any one of four different apyrase inhibitors (AI.1, AI.10, AI.13 or AI.15), their potency to inhibit the growth of five fungal pathogens was increased significantly relative to their application alone. The apyrase inhibitors were most effective in potentiating the ability of copper octanoate to inhibit fungal growth, and least effective in combination with propiconazole. Among the five pathogens assayed, that most sensitive to the fungicide‐potentiating effects of the inhibitors was Sclerotinia sclerotiorum. Overall, among the 60 treatment combinations tested (five pathogens, four apyrase inhibitors, three fungicides), the addition of apyrase inhibitors increased significantly the sensitivity of fungi to the fungicide treatments in 53 of the combinations. Consistent with their predicted mode of action, inhibitors AI.1, AI.10 and AI.13 each increased the level of propiconazole retained in one of the fungi, suggesting that they could partially block the ability of efflux transporters to remove propiconazole from these fungi.
Ss‐Rhs1, a secretory Rhs repeat‐containing protein, is required for the virulence of Sclerotinia sclerotiorum
Authors: Yu Yang , Xiao Jifen , Zhu Wenjun , Yang Yuheng , Mei Jiaqin , Bi Chaowei , Qian Wei , Qing Ling , Tan Wanzhong
Published: July 2016

Sclerotinia sclerotiorum is a devastating necrotrophic plant pathogen with a worldwide distribution. Cell wall‐degrading enzymes and oxalic acid are important to the virulence of this pathogen. Here, we report a novel secretory protein, Ss‐Rhs1, which is essential for the virulence of S. sclerotiorum. Ss‐Rhs1 is believed to contain a typical signal peptide at the N‐terminal and eight rearrangement hotspot (Rhs) repeats. Ss‐Rhs1 exhibited a high level of expression at the initial stage of sclerotial development, as well as during the hyphal infection process. Targeted silencing of Ss‐Rhs1 resulted in abnormal colony morphology and reduced virulence on host plants. Microscopic observations indicated that Ss‐Rhs1‐silenced strains exhibited reduced efficiency in compound appressoria formation.
Synergism of thymol, carvacrol and eugenol in larvae of the cattle tick,Rhipicephalus microplus, and brown dog tick,Rhipicephalus sanguineus
Authors: ARAÚJO L. X. , NOVATO T. P. L. , ZERINGOTA V. , MATURANO R. , MELO D. , DA SILVA B. C. , DAEMON E. , DE CARVALHO M. G. , MONTEIRO C. M. O.
Published: July 2016

The effects of combinations of the monoterpenes thymol and carvacrol and the phenylpropanoid eugenol in larvae ofRhipicephalus microplus(Canestrini, 1888) (Acari: Ixodidae) andRhipicephalus sanguineussensu lato (s.l.) (Acari: Ixodidae) were assessed by the larval packet test. The CompuSyn program was used to make qualitative assessments of the effects (synergistic, additive and antagonistic) of the associations. The effects of all combinations tested againstR. micropluslarvae were synergistic, with combination indices (CIs) <0.70. When tested againstR. sanguineus, eight of the mixtures showed a synergistic effect (CI < 0.70); only the carvacrol + thymol mixture at LC50presented a moderate synergistic effect, with CIs between 0.70–0.90. This study is the first to determine the effects of the interactions of these substances in the control of these two tick species. The combinations of carvacrol + thymol, carvacrol + eugenol and thymol + eugenol have synergistic effects inR. microplusandR. sanguineuss.l. larvae.
Identification of three yeast species using the conventional and internal transcribed spacer region sequencing methods as first or second global record from human superficial infections
Authors: Abdel‐Sater Mohamed Ahmed , Moubasher Abdel‐Aal Hassan , Soliman Zeinab
Published: July 2016

During the mycological analysis of skin and nail samples taken from patients with onychomycosis and tineas in Assiut city, it is interesting to report that yeast fungi were the main causal agents being cultured from 45.79% of total cases. In general, 21 species of yeast were isolated. Some of these are reported for the first time from clinical specimens. From the literature available up‐to‐date around the world, this study reports for the first time Saccharomycopsis fibuligera as the causal agent of four clinical cases: two onychomycoses, one tinea capitis and one tinea amiantacea. Also, it is reported here the second record for Trichosporon dohaense from a case of onychomycosis of a 40‐year‐old woman (after its original description in 2009 by Taj‐Aldeen et al. J Clin Microbiol 47: 1791). Candida galli was also reported for the first time from clinical specimen (tinea unguium) in 2014 by Galán‐Sánchez et al. Mycopathol 178: 303, and this study reports the second case of onychomycosis by C. galli. These strains were identified on the basis of their phenotypic, biochemical, physiological and genotypic features. Strains and internal transcribed spacer (ITS) gene sequences of these species are deposited at Assiut University Mycological Center Culture Collection (AUMC) and National Center for Biotechnological Information (NCBI) respectively.
Utilization of posaconazole oral suspension or delayed‐released tablet salvage treatment for invasive fungal infection
Authors: Kim Jong Hun , Benefield Russell J. , Ditolla Kali
Published: July 2016

Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed‐released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL−1) compared to posaconazole SUS (median 1.0 μg mL−1). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.
Mathematics, Morality, and Self‐Effacement
Authors: Woods Jack
Published: July 2016

I argue that certain species of belief, such as mathematical, logical, and normative beliefs, are insulated from a form of Harman‐style debunking argument whereas moral beliefs, the primary target of such arguments, are not. Harman‐style arguments have been misunderstood as attempts to directly undermine our moral beliefs. They are rather best given as burden‐shifting arguments, concluding that we need additional reasons to maintain our moral beliefs. If we understand them this way, then we can see why moral beliefs are vulnerable to such arguments while mathematical, logical, and normative beliefs are not—the very construction of Harman‐style skeptical arguments requires the truth of significant fragments of our mathematical, logical, and normative beliefs, but requires no such thing of our moral beliefs. Given this property, Harman‐style skeptical arguments against logical, mathematical, and normative beliefs are self‐effacing; doubting these beliefs on the basis of such arguments results in the loss of our reasons for doubt. But we can cleanly doubt the truth of morality.
Living donor liver transplantation for inborn errors of metabolism – An underutilized resource in the United States
Authors: Pham Thomas A. , Enns Gregory M. , Esquivel Carlos O.
Published: July 2016

Inborn metabolic diseases of the liver can be life‐threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver.
Successful long‐term outcome of liver transplantation in late‐onset lysosomal acid lipase deficiency
Authors: Sreekantam S. , Nicklaus‐Wollenteit I. , Orr J. , Sharif K. , Vijay S. , McKiernan P. J. , Santra S.
Published: July 2016

Late‐onset LAL deficiency, previously referred to as cholesteryl ester storage disorder, is a rare lysosomal storage disorder characterized by accumulation of cholesteryl esters. It has a heterogeneous clinical phenotype including abdominal pain, poor growth, hyperlipidemia with vascular complications and hepatosplenomegaly. End‐stage liver disease may occur, but there are few reports of successful LT. There are also concerns that systemic manifestations of the disease might persist post‐LT. We report a case with excellent outcome eight yr following LT. The subject was noted to have asymptomatic hepatosplenomegaly during an intercurrent illness, and LAL deficiency was confirmed with compound heterozygosity in the LIPA. Despite dietary fat restriction, he developed signs of progressive liver disease and subsequently developed hepatopulmonary syndrome. He underwent cadaveric LT at the age of nine and a half yr and recovered with prompt resolution of hepatopulmonary syndrome. Eight yr post‐transplant he has normal growth, normal lipid profile, and liver and renal function tests. Liver histology showed no evidence of disease recurrence at this stage. LT in this subject resulted in an excellent functional correction of late‐onset LAL deficiency.
Pediatric hepatocellular carcinoma in a developing country: Is the etiology changing?
Authors: Palaniappan Kumar , Borkar Vibhor V. , Safwan Mohamed , Vij Mukul , Govil Sanjay , Shanmugam Naresh , Rela Mohamed
Published: July 2016

HCC is the second most common malignant liver tumor of childhood. It typically affects children with a median age of 10–14 yr on background hepatitis B‐related liver disease and is often metastatic or locally advanced at diagnosis. Children below the age of five yr typically constitute <10% of all children with HCC. In these children, it occurs on a background of congenital or metabolic liver disease. The records of all children with HCC who presented to our department over a six‐yr study period were reviewed. Twelve patients with a median age of 5.9 yr (range 1.6–15.4) were diagnosed to have HCC. All patients underwent liver transplantation, and none were resected. Eleven patients had background congenital or metabolic liver disease. All five of those with hereditary tyrosinemia type 1 who presented to us were found to have HCC. No patient had hepatitis B‐related liver (HBV) disease. Eight (66.7%) patients had incidentally discovered HCC on examination of the explant. Incidentally discovered HCC were smaller, well differentiated, and did not show microvascular invasion compared to those diagnosed preoperatively. There was no recurrence with a median follow‐up of five months. The patient demographic for pediatric HCC is changing probably as a consequence of successful immunization against HBV. Younger patients with congenital and metabolic liver disease in whom liver transplantation is the ideal treatment are likely to constitute an ever‐increasing proportion of patients with pediatric HCC as HBV disease is controlled or eradicated.
Challenges managing end‐stage renal disease and kidney transplantation in a child with MTFMT mutation and moyamoya disease
Authors: Oates Aris , Brennan Jessica , Slavotinek Anne , Alsadah Adnan , Chow Daniel , Lee Marsha M.
Published: July 2016

Moyamoya disease is a chronic cerebrovascular disorder with progressive stenosis. We describe a four‐yr‐old female with features of moyamoya disease referred to our center for kidney transplant evaluation with ESRD secondary to presumed renal dysplasia along with concern for cerebral vascular anomalies. With her constellation of organ involvement, a genetic workup revealed a homozygous, frameshift mutation in the mitochondrial methionyl‐tRNA formyltransferase gene. Given her vascular anomalies and evidence of prior infarcts seen on cerebral imaging, it was felt that her risk of future stroke events was high and that hypotension or intravascular volume depletion would further exacerbate this risk. In hopes of improving her tenuous cerebral perfusion, she underwent a bilateral temporal craniotomy for superficial temporal artery to middle cerebral artery bypass. We highlight the challenges faced in a child with ESRD and kidney transplantation when cerebral vasculature is compromised. A multidisciplinary approach is critical in determining the need for a revascularization procedure prior to transplant and to help reduce the risk of ischemic or hemorrhagic events in this patient population.
Commentary on Knowledge Creation and Dissemination in Operations and Supply‐Chain Management
Authors: Starr Martin K.
Published: July 2016

The title of this paper might have been Knowledge Creation and Dissemination in the POM Domain. Instead, these accomplished authors (who shall be dubbed with honorable intentions as RSST) define the POM domain as Operations and Supply‐Chain Management. Thereby, they leave no doubt that the POM domain spans the entire supply chain from shovels in the mine and seeds in the ground to recycled waste that is remanufactured and sold as new (as well as refurbished) products. RSST declare that sustainability of the ecosystem cycle must be achieved (even in the face of disaster conditions) by all institutions. RSST believe that practitioners can be taught the necessary attitudes and skills by business and engineering schools. It is noteworthy that the ecosystem cycle they describe is accompanied by marketing and financial decision cycles running parallel from inception of ideas to the “end of life” closure that starts a new cycle for closed‐loop product planning. For these coexisting, interdependent, all‐encompassing systems, the RSST team leaves no doubt about the evolution of teaching and research opportunities for young POM scholars. These authors focus on the fact that everything that is not morphing is likely to become counterproductive in the not too far future. This is a critical point of view which is based on the fact that the status quo is highly vulnerable. Also, very special is the RSST warning that changes are required in the status quo which must be made without damaging the existing fabric. This non‐disruptive way of doing POM business has been remarkably successful for the cohesion of the field over the past 25 years. There is agreement that it is great to shake things up without tearing those things apart. All of this leads to the conclusion that the advice of these authors (RSST) is correct and valuable. Debate and disputation of these points is encouraged and expected by the RSST team.
Underprotection of Unpredictable Statistical Lives Compared to Predictable Ones
Authors: Lipsitch Marc , Evans Nicholas G. , Cotton‐Barratt Owen
Published: July 2016

Existing ethical discussion considers the differences in care for identified versus statistical lives. However, there has been little attention to the different degrees of care that are taken for different kinds of statistical lives. Here we argue that for a given number of statistical lives at stake, there will sometimes be different, and usually greater, care taken to protect predictable statistical lives, in which the number of lives that will be lost can be predicted fairly accurately, than for unpredictable statistical lives, where the lives are at stake because of a low‐probability event, such that most likely no one will be affected by the decision but with low probability some lives will be at stake. One reason for this difference is the statistical challenge of estimating low probabilities, and in particular the tendency of common approaches to underestimate these probabilities. Another is the existence of rational incentives to treat unpredictable risks as if the probabilities were lower than they are. Some of these factors apply outside the pure economic context, to institutions, individuals, and governments. We argue that there is no ethical reason to treat unpredictable statistical lives differently from predictable statistical lives. Moreover, lives that are unpredictable from the perspective of an individual agent may become predictable when aggregated to the level of a societal decision. Underprotection of unpredictable statistical lives is a form of market failure that may need to be corrected by altering regulation, introducing compulsory liability insurance, or other social policies.
Assessment of Health Risk from Historical Use of Cosmetic Talcum Powder
Authors: Anderson Elizabeth L. , Sheehan Patrick J. , Kalmes Renee M. , Griffin John R.
Published: July 2016

This study's objective is to assess the risk of asbestos‐related disease being contracted by past users of cosmetic talcum powder.  To our knowledge, no risk assessment studies using exposure data from historical exposures or chamber simulations have been published. We conducted activity‐based sampling with cosmetic talcum powder samples from five opened and previously used containers that are believed to have been first manufactured and sold in the 1960s and 1970s.  These samples had been subject to conflicting claims of asbestos content; samples with the highest claimed asbestos content were tested.  The tests were conducted in simulated‐bathroom controlled chambers with volunteers who were talc users.  Air sampling filters were prepared by direct preparation techniques and analyzed by phase contrast microscopy (PCM), transmission electron microscopy (TEM) with energy‐dispersive x‐ray (EDX) spectra, and selective area diffraction (SAED).  TEM analysis for asbestos resulted in no confirmed asbestos fibers and only a single fiber classified as “ambiguous.”  Hypothetical treatment of this fiber as if it were asbestos yields a risk of 9.6 × 10−7 (under one in one million) for a lifetime user of this cosmetic talcum powder.  The exposure levels associated with these results range from zero to levels far below those identified in the epidemiology literature as posing a risk for asbestos‐related disease, and substantially below published historical environmental background levels.  The approaches used for this study have potential application to exposure evaluations of other talc or asbestos‐containing materials and consumer products.
Shoal‐water deltas in high‐accommodation settings: Insights from the lacustrine Valimi Formation (Gulf of Corinth, Greece)
Authors: Ambrosetti Elisa , Martini Ivan , Sandrelli Fabio
Published: July 2016

The stratigraphic architecture of shoal‐water deltaic systems developed in low‐accommodation settings is relatively well‐known. In contrast, the features of shoal‐water deltas developed in high‐accommodation settings remain relatively poorly documented, especially when compared with the available data sets for Gilbert‐type deltaic systems developed in the same settings. The lacustrine Valimi Formation (Gulf of Corinth, Greece) provides an opportunity to investigate the facies assemblage and architectural style of shoal‐water deltaic systems developed in high‐accommodation settings. The studied interval accumulated during the Pliocene and Pleistocene and represents part of the early syn‐rift Gulf of Corinth succession. Six facies associations, each described in terms of depositional processes and geometries, have been identified and interpreted to represent a range of proximal to distal deltaic sub‐environments: delta plain, distributary channel, mouth‐bar, delta front, prodelta and open lake. The facies associations and their architectural elements reveal characteristics which are not common in traditionally described shoal‐water deltas. Of note, different facies arrangements are observed in the distributary channels in different sectors of the delta, passing from thick single‐storey channel fills embedded within delta‐plain fines in landward positions, to thin, amalgamated and multi‐storey channels closer to the river mouth. This study proposes a new depositional model for shoal‐water deltas in high‐accommodation settings documenting, for the first time, that shoal‐water delta deposits can form a substantial part of stratigraphic successions that accumulate in these settings. The proposed depositional model provides new criteria for the recognition and interpretation of these deposits; the results of this study have applied significance for reservoir characterization.
Detection rate of blood group alloimmunization based on real‐world testing practices and kinetics of antibody induction and evanescence
Authors: Stack Gary , Tormey Christopher A.
Published: July 2016

BACKGROUND

Failure to detect non‐ABO blood group alloantibodies places patients at risk for hemolytic reactions. Suboptimal alloantibody detection could result from posttransfusion testing performed too early, too late, or not at all. Testing performed too early may precede antibody induction, while testing performed too late could miss antibodies that have evanesced. Taking these factors into account, our goal was to determine the percentage of alloantibodies detected with real‐world testing practices.

STUDY DESIGN AND METHODS

The alloantibody detection rate in a general hospital setting was determined based on the frequency and timing of antibody testing after red blood cell (RBC) transfusions and rates of antibody induction and evanescence. Intervals to follow up testing after RBC transfusions (n = 561 RBC units in 100 random patients) were determined retrospectively. Best‐fit lines and equations for antibody induction and evanescence were computed on previously published data.

RESULTS

Nearly half (271/561; 48.3%) of RBC infusions had either no follow‐up antibody screen or testing too soon (<30 days) after transfusion to detect alloimmunization. Of the remaining RBC units, 10.3% (58/561) had follow‐up testing 30 to 112 days posttransfusion, 28.7% (161/561) were followed up at more than 112 days, and 12.7% (71/561) were tested at both 30 to 112 days and more than 112 days. By inputting these timing data into best‐fit line equations for antibody induction and evanescence, we calculated an alloantibody detection rate of 31.6%.

CONCLUSION

Posttransfusion antibody testing was inadequately timed for optimal alloantibody detection. Real‐world compatibility testing was predicted to detect less than one‐third of non‐ABO antibodies, thereby exposing patients to risks of mismatched transfusion.
Serotonin controls initiation of locomotion and afferent modulation of coordination via 5‐HT7receptors in adult rats
Authors: Cabaj Anna M. , Majczyński Henryk , Couto Erika , Gardiner Phillip F. , Stecina Katinka , Sławińska Urszula , Jordan Larry M.
Published: July 2016

Key points

Experiments on neonatal rodent spinal cord showed that serotonin (5‐HT), acting via 5‐HT7receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter‐ and intralimb coordination, but the importance of the 5‐HT system in adult locomotion is not clear.

Blockade of spinal 5‐HT7receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5‐HT neurons for production of locomotion.

The direct control of coordinating interneurons by 5‐HT7receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults.

An understanding of the afferents controlled by 5‐HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs.

Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5‐HT7) receptor agonists and antagonists and 5‐HT7receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily fromin vitrostudies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of serotonin (5‐HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5‐HT7receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5‐HT7receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5‐HT7antagonist SB269970 in adult intact rats suppressed locomotion by partial paralysis of hindlimbs. This occurred without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra‐ and interlimb coordination during locomotion in all intact animals but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR). MLR‐evoked fictive locomotion was transiently blocked, then the amplitude and frequency of rhythmic activity were reduced by SB269970, consistent with the notion that the MLR activates 5‐HT neurons, leading to excitation of central pattern generator neurons with 5‐HT7receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5‐HT7receptor‐mediated control of sensory pathways during development.
The transition of smooth muscle cells from a contractile to a migratory, phagocytic phenotype: direct demonstration of phenotypic modulation
Authors: Sandison Mairi E. , Dempster John , McCarron John G.
Published: July 2016

Key points

Smooth muscle cell (SMC) phenotypic conversion from a contractile to a migratory phenotype is proposed to underlie cardiovascular disease but its contribution to vascular remodelling and even its existence have recently been questioned.

Tracking the fate of individual SMCs is difficult as no specific markers of migratory SMCs exist.

This study used a novel, prolonged time‐lapse imaging approach to continuously track the behaviour of unambiguously identified, fully differentiated SMCs.

In response to serum, highly‐elongated, contractile SMCs initially rounded up, before spreading and migrating and these migratory cells displayed clear phagocytic activity.

This study provides a direct demonstration of the transition of fully contractile SMCs to a non‐contractile, migratory phenotype with phagocytic capacity that may act as a macrophage‐like cell.

Atherosclerotic plaques are populated with smooth muscle cells (SMCs) and macrophages. SMCs are thought to accumulate in plaques because fully differentiated, contractile SMCs reprogramme into a ‘synthetic’ migratory phenotype, so‐called phenotypic modulation, whilst plaque macrophages are thought to derive from blood‐borne myeloid cells. Recently, these views have been challenged, with reports that SMC phenotypic modulation may not occur during vascular remodelling and that plaque macrophages may not be of haematopoietic origin. Following the fate of SMCs is complicated by the lack of specific markers for the migratory phenotype and direct demonstrations of phenotypic modulation are lacking. Therefore, we employed long‐term, high‐resolution, time‐lapse microscopy to track the fate of unambiguously identified, fully‐differentiated, contractile SMCs in response to the growth factors present in serum. Phenotypic modulation was clearly observed. The highly elongated, contractile SMCs initially rounded up, for 1–3 days, before spreading outwards. Once spread, the SMCs became motile and displayed dynamic cell‐cell communication behaviours. Significantly, they also displayed clear evidence of phagocytic activity. This macrophage‐like behaviour was confirmed by their internalisation of 1 μm fluorescent latex beads. However, migratory SMCs did not uptake acetylated low‐density lipoprotein or express the classic macrophage marker CD68. These results directly demonstrate that SMCs may rapidly undergo phenotypic modulation and develop phagocytic capabilities. Resident SMCs may provide a potential source of macrophages in vascular remodelling.
Prevalence of HPV high and low risk types in cervical samples from the Italian general population: a population based study
Authors: Giorgi Rossi Paolo , Bisanzi Simonetta , Paganini Irene , Di Iasi Angela , Angeloni Claudio , Scalisi Aurora , Macis Rosalba , Pini Maria Teresa , Chini Francesco , Carozzi Francesca Maria ,   HPV Prevalence Italian Working Group
Published: July 2016

Background

This multicenter study describes the type-specific prevalence of HPV infection in the general population from central and southern Italy, comparing the data with previously published Italian studies.

Methods

Women aged from 25 to 65 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11.

Results

3817 women had a valid HCII test: 350 of them (9.2%) were positive for HR probes, 160 (4.2%) for LR probes, while 57 women were positive for both. Multiple infections were detected in 97 HR HPV positive women. The most common types were HPV 16 (3%), 31 (1.2%), 51 (1%). HPV6 ranked fifth (0.6%), HPV18 ranked tenth (0.5%) and HPV11 sixteenth (0.3%).

In Sardinia the prevalence of high-risk infection was 13%, significantly higher than the mean value (p < 0.00005).

The distribution of the most frequent types did not significantly differ by centre (p = 0.187) and age (p = 0.085).

Conclusions

Because cervical cancer incidence and Pap test coverage is lower in southern than in northern Italy, a lower prevalence of high-risk infections in the general population was expected in the south. However, prevalence detected in this study for the south of the country is slightly but significantly higher than the rest of Italy. The consequence may be an epidemic of cervical cancer in the next decades if adequate screening programs are not implemented there.
Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk factors for hospital mortality
Authors: Xi Xiuming , Xu Yuan , Jiang Li , Li Ang , Duan Jie , Du Bin ,   the Chinese Critical Care Clinical Trial Group (CCCCTG)
Published: July 2016

Background

In April 2009, the pandemic influenza A(H1N1) virus emerged and spread globally. The objective of this study was to describe the independent risk factors for hospital mortality and the treatment effect of corticosteroids among patients with 2009 influenza A(H1N1) infection.

Methods

We retrospectively obtained clinical data of 155 adult patients with confirmed infection of 2009 influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December 23, 2009. Risk factors for hospital mortality were identified with multivariate logistic regression analysis.

Results

Among the 155 patients, 90 (58.1%) were male, and mean age was 43.0 ± 18.6 years, and comorbidities were present in 81 (52.3%) patients. The most common organ dysfunctions included acute respiratory failure, altered mental status, septic shock, and acute renal failure. Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%) were treated with systemic corticosteroids, with a median daily dose of 80 mg. Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were independent risk factors of hospital death, as were septic shock and altered mental status. Corticosteroids use was associated with a trend toward higher hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052).

Conclusions

Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The risk factors at hospitalization may help clinicians to identify the high-risk patients. In addition, corticosteroids use should not be regarded as routine pharmacologic therapy.
Loss of balancing selection in the βS globin locus
Authors: Salih Niven A , Hussain Ayman A , Almugtaba Ibrahim A , Elzein Abeir M , Elhassan Ibrahim M , Khalil Eltahir AG , Ishag Hani B , Mohammed Hiba S , Kwiatkowski Dominic , Ibrahim Muntaser E
Published: July 2016

Background

Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations.

Methods

We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in future generations.

Results

Genotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa.

Conclusions

Such loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy.
Identifying and managing malnutrition in the community
Authors: McEvilly Aimee
Published: July 2016

Malnutrition affects more than 3 million people in the UK, most of whom live in the community. Malnutrition is both a cause and consequence of disease and can lead to increased mortality and morbidity, delayed recovery from illness and impaired body function which can make carrying out activities of daily living difficult. Managing malnutrition in the community involves identifying malnutrition using a universally validated screening tool and implementing appropriate care plans according to the degree of malnutrition. Regional and local guidance can be used to assist healthcare professionals to prescribe appropriate oral nutritional supplements and monitor nutritional aims and goals.
Nasogastric tube feeding: a safe option for patients?
Authors: Williams Trish
Published: July 2016

This article will show that fine-bore nasogastric tube feeding can be facilitated for patients when long term percutaneous endoscopic gastrostomy (PEG) or radiologically inserted gastrostomy (RIG) options are not suitable. How the safe replacement of these tubes is facilitated, and what instructions the patient and the nursing home are given to support patient care and safety are also discussed. The decision to support this type of feeding must be completely individualised, considering home and external support agencies available to each patient. The risk assessment completed to facilitate this has been based on the patients' individual circumstances, and a nasogastric tube home passport developed to help in the assessment and decision-making process. For fine-bore nasogastric tube feeding to be safe, it does have to be supported once the patient is discharged from the hospital. A good knowledge of the home support and carer support agencies, and what is available, should be discussed. Multidisciplinary team support is essential in ensuring a safe discharge can be planned and managed. Good patient risk assessment and nursing considerations are discussed to show how the challenges that may prevent a patient discharge with this type of feed are managed. This article will show how two very different patients discharges were facilitated by safe fine-bore nasogastric tube feeding in the community. Patient assessment and nursing considerations are discussed, as well as the importance of a multidisciplinary approach to show how this was successfully achieved in a local district hospital.
Diabetes care: prevalence and types
Authors: Nazarko Linda
Published: July 2016

Diabetes is a global and national health emergency. Globally, it affects 422 million people and leads to 3.7 million deaths annually ( World Health Organisation (WHO), 2016a:6 ). Nationally, it affects 3.5 million people, or one person in 16 ( Diabetes UK, 2015:2 ). The incidence of diabetes in UK has increased by 250% in the past 16 years. Most people have type 2 diabetes mellitus (DMT2). This was once a condition of middle age, but is now being seen in children ( WHO, 2016a:2 ).

Type 2 diabetes is often considered to be ‘mild’, but it can affect the entire body, increase the risk of dementia and stroke and affect vision. It also increases the risk of heart attack and can lead to incontinence, impotence, renal failure and amputation. Diabetes reduces life expectancy by 6-11 years and affects quality of life ( Livingstone et al, 2015 ; Seshasai et al, 2011 ).

This article, the first in a series, examines the causes, consequences, prevalence, types and clinical features of diabetes.
Communication, ethics and healthcare assistants
Authors: Barber Chris
Published: July 2016

Effective communication is key to the delivery of safe, person-centred services for patients, service users, carers and their families, regardless of where this care is delivered. This can be confirmed through its inclusion as one of the ‘6Cs’ created by the Chief Nursing Officer for England in 2013. This article will explore the meaning of communication and its use in a number of clinical settings.
A distance-learning journey from healthcare assistant to registered nurse
Authors: Lear Karen
Published: July 2016

This article discusses the findings from a naturalistic case study that explored the views of final year, distance learning university, practice-based student nurses on their preparation for the role of registered nurse. The students were all healthcare assistants (HCAs), who were sponsored by their employers on the DipHE Adult Nursing Pre Registration Nursing Programme (PRNP).

The findings and themes that evolved from this study show the significant areas that informed these student nurses' journeys and their preparation to become registered nurses. The practice areas had a vested interest in preparing these sponsored students to be competent, skilled practitioners, as they were ‘growing’ their own workforce. The study reported that all of the students obtained posts as Newly Qualified (NQ) nurses, 80% in the practice areas where they were dual-role HCA/students, thereby demonstrating the effectiveness of the PRNP working in partnership with employers to support workforce development.
Providing high-quality care: trans people
Authors: Peate Ian
Published: July 2016

The provision of care for trans people can be very rewarding. A knowledgeable healthcare assistant or assistant practitioner (HCA and AP) can ensure that the care that trans people receive is of a high quality. This article provides a definition of key terms and encourages those who provide care and support to trans people to be trans-inclusive, ensuring trans equality, regardless of a person's ethnicity, disability, age, social class and other aspects of their identity. Trans people face discrimination and prejudice on a daily basis and when this occurs in the provision of health services, it is unacceptable. This article calls for HCAs and APs to offer a fair and equitable service for all.
CPD: A shift in approach
Authors: Weston David
Published: July 2016

Ahead of the publication of the government's new CPD standards, David Weston looks at shifting our thinking on professional development to ensure a more appropriate approach for schools in 2016
Narrowing the gaps
Authors: Corrigan Jo
Published: July 2016

The recent Pupil Premium Awards saw a range of schools from across the country recognised for their work in closing the gap for disadvantaged pupils. Jo Corrigan looks at the approaches of two finalists
A whole-school guided reading programme
Authors: Twomey Auveen
Published: July 2016

Deputy headteacher Auveen Twomey describes her work to introduce a whole-school guided reading programme to raise standards of literacy, boost reading for pleasure and raise pupil outcomes
The Learning Superheroes!
Authors: Madsen Heather
Published: July 2016

Learning behaviours are something we are all familiar with, but to children they can seem abstract concepts. Headteacher Heather Madsen explains how they overcame this challenge at Red Oak Primary
SMSC and British Values
Authors: Frostick Helen
Published: July 2016

Social, moral, spiritual and cultural education and development is a crucial duty for schools, especially in light of requirements to teach ‘British Values’. Headteacher Helen Frostick looks at key definitions to help you evaluate your school's provision and offers some ideas for SMSC activities
Assessment chaos: From Baseline to SATs
Authors: O'Connell Suzanne
Published: July 2016

It has been quite a year for assessment. With a backdrop of parent protests, leaks and anxiety over changing standards, the SATs have been particularly chaotic. On top of this, the long planned introduction of the Reception Baseline was suddenly axed after ministers admitted it couldn't work. Suzanne O'Connell looks at how schools have handled this assessment chaos
Research roundup: July 2016
Authors: Greener Mark
Published: July 2016

In brief

Following guidance from the National Institute for Health and Care Excellence about reviewing and stepping down patients taking proton-pump inhibitors could reduce costs and prevent side effects Statins are associated with a small increased risk of developing diabetes, particularly with more intensive therapy. The lack of an association between drugs that the summary of product characteristics suggests could disturb sleep, and problems reported by patients, raise questions over the generalisability of prescribing information Most antidepressants do not seem to offer benefits for children and adolescents, while venlafaxine seems to increase suicidal behaviour or ideation
Managing diabetes in people with mental health problems
Authors: Nazarko Linda
Published: July 2016

People with serious mental illness experience poorer health outcomes than the general population and die around 15 years earlier. This article uses a case history approach to illustrate the relationship between mental and physical health care, and the challenges of providing quality care to an individual with diabetes and mental health problems.