bluuebunny/crossref_metadata_2025 huggingface dataset:
The septin cytoskeleton facilitates membrane retraction during motility and blebbing
Authors: Gilden Julia K. , Peck Sebastian , M. Chen Yi-Chun , Krummel Matthew F.
Published: January 2012

Increasing evidence supports a critical role for the septin cytoskeleton at the plasma membrane during physiological processes including motility, formation of dendritic spines or cilia, and phagocytosis. We sought to determine how septins regulate the plasma membrane, focusing on this cytoskeletal element’s role during effective amoeboid motility. Surprisingly, septins play a reactive rather than proactive role, as demonstrated during the response to increasing hydrostatic pressure and subsequent regulatory volume decrease. In these settings, septins were required for rapid cortical contraction, and SEPT6-GFP was recruited into filaments and circular patches during global cortical contraction and also specifically during actin filament depletion. Recruitment of septins was also evident during excessive blebbing initiated by blocking membrane trafficking with a dynamin inhibitor, providing further evidence that septins are recruited to facilitate retraction of membranes during dynamic shape change. This function of septins in assembling on an unstable cortex and retracting aberrantly protruding membranes explains the excessive blebbing and protrusion observed in septin-deficient T cells.
A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP
Authors: Lanzi Gaetana , Moratto Daniele , Vairo Donatella , Masneri Stefania , Delmonte Ottavia , Paganini Tiziana , Parolini Silvia , Tabellini Giovanna , Mazza Cinzia , Savoldi Gianfranco , Montin Davide , Martino Silvana , Tovo Pierangelo , Pessach Itai M. , Massaad Michel J. , Ramesh Narayanaswamy , Porta Fulvio , Plebani Alessandro , Notarangelo Luigi D. , Geha Raif S. , Giliani Silvia
Published: January 2012

A female offspring of consanguineous parents, showed features of Wiskott-Aldrich syndrome (WAS), including recurrent infections, eczema, thrombocytopenia, defective T cell proliferation and chemotaxis, and impaired natural killer cell function. Cells from this patient had undetectable WAS protein (WASP), but normal WAS sequence and messenger RNA levels. WASP interacting protein (WIP), which stabilizes WASP, was also undetectable. A homozygous c.1301C>G stop codon mutation was found in the WIPF1 gene, which encodes WIP. Introduction of WIP into the patient’s T cells restored WASP expression. These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal.
The global challenge of zoonoses control
Authors: Palmer Stephen
Published: January 2012

Zoonotic diseases are now recognized as a major global threat to human health and sustainable development and a major concern for national and international agencies (Marano et al. 2006). There was a period in the 1960s and 70s when it was widely expected that the antibiotic and vaccine era would relegate infectious diseases to footnotes of history, and in many countries communicable control systems were neglected (Keusch et al. 2009) but the frequent and often dramatic appearance of new infectious agents or the reappearance of well recognized zoonoses has changed perceptions. ‘A wide variety of animal species, domesticated, peri-domesticated and wild, can act as reservoirs for these pathogens, which may be viruses, bacteria, parasites or prions. Considering the wide variety of animal species involved and the often complex natural history of the pathogens concerned, effective surveillance, prevention and control of zoonotic diseases pose a real challenge to public health’ (WHO 2004). No country has been able to anticipate the sudden and sometimes devastating impact of novel agents, and international trade and transport of people, animals and goods have ensured that wherever zoonoses emerge they have to be considered as global issues. The cost of zoonoses can be enormous. The H1N1v pandemic which began in pig herds on the Mexico-US border resulted in major losses to the pork industry amounting to US$25 million per week; fear that transmission could occur from meat led to the banning of importation of pigs and pork products by at least 15 countries (Keusch et al. 2009). And in addition to these ‘natural’ threats, several zoonoses are prime agents for deliberate release by disaffected groups. A more esoteric threat, though nonetheless a real cause of concern, is the possibility of zoonotic emergence from xenotransplantation (Mattiuzzo et al. 2008).
Mycobacterioses
Authors: Zinsstag Jakob , Müller Borna , Pavlik Ivo
Published: January 2012

The Mycobacterium tuberculosis complex MTC is composed of several species of mycobacteria which are M. tuberculosis, the main cause of human tuberculosis, M. canetti, M. africanum, M. microti, M. pinnipedii, M. caprae, and M. bovis. Cattle are the principal host of M. bovis, but a large number of other ruminants and other mammals, particularly wildlife are infected. Human tuberculosis is a global problem of huge proportions. More than 95% of human tuberculosis cases occur in developing and transition countries, of which one third are in Africa but the proportion of cases caused by M. bovis is still not known. Today, bovine tuberculosis (BTB) is re-emerging and threatens the livestock industry in industrialized countries with wildlife reservoirs like the wild tailed deer (Odocoileus virginianus) in the USA or the badger (Meles meles) in the UK. Most developing countries lack the means and capacity for effective control of BTB. A better understanding of its epidemiology is required to identify novel, locally adapted options for control in a given context. BTB in Africa is emphasized here because of the special importance of multiple transmission interfaces between wildlife, livestock and humans.

In addition to obligatory pathogenic mycobacteria (esp. members of the MTC), potentially pathogenic mycobacteria (PPM) previously designated as ‘mycobacteria other than tubercle bacilli’ (MOTT) are increasingly important causes of mycobacterioses in humans and animals. Most of them are opportunistic in humans and occur mostly in immunocompromised patients. The mycobacteria that cause human disease are both the M. avium complex (MAC) members and other mycobacterial species MAC members have been detected in more than 95% of cases; this chapter will mainly focus on M. avium subsp. avium, M. a. hominissuis, and M. intracellulare.
Campylobacteriosis
Authors: Lawson A. J.
Published: January 2012

Campylobacter jejuni and C. coli are frequent cause of bacterial enteritis in industrialised countries and is a major cause of childhood illness in the developing world. Although deaths due to campylobacteriosis are rare, the morbidity and public health and economic burden is high because of its very high incidence. Campylobacters normally inhabit the intestinal tract of wild birds and domestic animals. Poultry is a major source of campylobacter infection and a large proportion of retail chicken meat is contaminated. Other meats are contaminated to a lesser degree. Human infection is mostly sporadic and outbreaks are uncommon. Infections arise from the consumption of raw or inadequately cooked meat or from other foods contaminated during production or preparation. Contaminated water and raw milk can also act as vehicles of campylobacter infection and have given rise to significant outbreaks. The most effective means of controlling human campylobacteriosis would be the implementation of measures to reduce the contamination of food producing animals during slaughter and processing. Public health education regarding the principles of hygiene and safe food handling are also important.
Other bacterial diseasesRat-bite fevers
Authors: Salmon Roland L.
Published: January 2012

Infection with Streptobacillus moniliformis, gives rise to Rat-Bite fever also known as Streptobacillary Fever, and, when epidemic Epidemic Arthritic Erythema (Haverhill Fever). It occurs worldwide. Only three outbreaks have been described. It is either caused by the bite of, or similar close contact with, a rat or other infected rodent, or, when epidemic, by the ingestion of water or milk contaminated by rats. Control requires limiting human contact with rats, traditionally by prevention of rat infestation although, of recent years, in developed countries, the keeping of rats as pets has played an important role.
Yellow fever
Authors: Monath Thomas P. , Staples J. Erin
Published: January 2012

Yellow fever is an acute mosquito-borne flavivirus infection characterized in its full-blown form by fever, jaundice, albuminuria, and haemorrhage. Two forms are distinguished: urban yellow fever in which the virus is spread from person to person by peridomestic Aedes aegypti mosquitoes and jungle (sylvan) yellow fever transmitted by tree-hole breeding mosquitoes between non-human primates and sometimes humans. Yellow fever is endemic and epidemic in tropical areas of the Americas and Africa but has never appeared in Asia or the Pacific region. Prevention and control are effected principally through yellow fever vaccination.
American trypanosomosis (Chagas disease)
Authors: Schofield C. J.
Published: January 2012

American trypanosomosis is due to infection with Trypanosoma cruzi (Protozoa, Kinetoplastidae). This is a widespread parasite of small mammals and marsupials throughout most of the Americas, roughly from the Great Lakes of North America (approx. 42 ° N) to southern Argentina (approx. 46 ° S). It is mainly transmitted by blood-sucking bugs of the subfamily Triatominae (Hemiptera, Reduviidae) which are widespread in the Americas, but rare in the Old World. Except in some research laboratories, and infected immigrants from Latin America, T.cruzi has not been reported from the Old World, although closely-related trypanosome species are commonly found in Old and New World bats.

Human infection with T.cruzi is generally known as Chagas disease, taking the name of Brasilian clinician Carlos Justiniano das Chagas who first described it from patients in central Brasil (Chagas 1909). Chagas isolated and described the parasite, correctly deduced most of its life-cycle and clinical symptoms associated with the infection, identified the insect vectors and some of the reservoir hosts, and also trialed initial attempts to control it. He was nominated at least twice for the Nobel prize in medicine (Coutinho and Dias 2000; Lewinsohn 2003).

Although difficult to treat, Chagas disease can be controlled by measures to halt transmission, primarily by eliminating domestic populations of the insect vectors, together with serological screening to avoid transmission by blood donation from infected donors. Since 1991, a series of multinational initiatives have used this approach to halt transmission over vast regions of the areas previously endemic for the human infection. Estimated prevalence of the human infection has declined from the 1990 estimate of 16–18 million people infected, to the current estimate of just over 7 million infected (OPS 2006; Schofield & Kabayo 2008). Prevalence is expected to decline further, and control strategies are now being adjusted to develop a sustainable system of disease surveillance, focal vector control, and specific treatment for any new cases (Schofield et al. 2006; WHO 2007). Guidance for diagnosis and treatment is also required for non-endemic countries, where recent years have seen increasing migration from Latin America such that cases of chronic Chagas disease have now been reported from amongst Latin American migrants in Europe, USA and Canada, and Japan, together with some congenital cases and transmission from infected blood donors and by organ transplant.
The Leishmanioses
Authors: Gramiccia Marina
Published: January 2012

Leishmanioses are a large group of parasitic diseases range over the intertropical zones of America and Africa, and extend into temperate regions of South America, Southern Europe and Asia. The clinical aspect of the diseases is wide ranging from a simple, self-resolving cutaneous lesion to the potentially fatal visceral leishmaniosis, known as kala-azar. In numerous underdeveloped countries leishmanioses remain a major public health problem representing one of the most neglected diseases. Among 15 well-recognized Leishmania species known to infect humans, 13 have definite zoonotic nature, which include agents of visceral, cutaneous and mucocutaneous forms of the disease in both the Old and New Worlds. Mammal reservoir hosts belong to the marsupalia, edentata, carnivora, hyracoidea, and rodentia, maintaining sylvatic zoonotic foci in the deserts of Africa and Asia, the forests of South and Central America, as well as synanthropic foci in the Mediterranean basin and much of South America. Although the known vectors are all phlebotomine sandflies, these have a wide range of specific habits and habitats. The complexity of this group of infections has only recently been appreciated and is still being worked out. Currently, leishmanioses show a wider geographical distribution than previously known, with increased global incidence of human disease. Environmental, demographic and human behavioural factors contribute to the changing leishmaniosis landscape, which basically include increasing risk factors for zoonotic cutaneous leishmanioses, and new scenarios associated with the zoonotic entity of visceral leishmaniosis. In comparison with the anthroponotic entities of leishmaniosis, limited progresses were made for the control of the zoonotic ones, consisting mainly in new tools developed for the control of L. infantum in the canine reservoir.
Toxoplasmosis, sarcocystosis, isosporosis, and cyclosporosis
Authors: Dubey J. P.
Published: January 2012

Toxoplasmosis is a protozoan disease caused by Toxoplasma gondii. It is widely prevalent in humans and animals throughout the world, especially in the western hemisphere. Virtually all warm-blooded animals can act as intermediate hosts but the life cycle is completed only in cats, the definitive host. Cats excrete the resistant stage of T. gondii (oocysts) in faeces, and oocysts can survive in the environment for months. Humans become infected congenitally, by ingesting undercooked infected meat, or by ingesting food and water contaminated with oocysts from cat faeces. It can cause mental retardation and loss of vision in congenitally infected children and deaths in immunosuppressed patients, especially those with AIDS. There is no vaccine to control toxoplasmosis in humans at the present time but one is available for reduction of fetal losses in sheep.
Anisakiosis (Anisakidosis)
Authors: Sohn Woon-Mok , Chai Jong-Yil
Published: January 2012

The term ‘anisakiosis (anisakidosis)’ or ‘anisakiasis’ collectively defines human infections caused by larval anisakids belonging to the nematode family Anisakidae or Raphidascarididae. Anisakis simplex, Anisakis physeteris, and Pseudoteranova decipiens are the three major species causing human anisakiosis. Various kinds of marine fish and cephalopods serve as the second intermediate hosts and the infection source. Ingestion of viable anisakid larvae in the fillet or viscera of these hosts is the primary cause of infection. The parasite does not develop further in humans as they are an accidental host. Clinical anisakiosis develops after the penetration of anisakid larvae into the mucosal wall of the alimentary tract, most frequently the stomach and the small intestine. The affected sites undergo erosion, ulceration, swelling, inflammation, and granuloma formation around the worm. The patients may suffer from acute abdominal pain, indigestion, nausea, vomiting, and in some instances, allergic hypersensitive reactions. Symptoms in gastric anisakiosis often resemble those seen in peptic ulcer or gastric cancer, and symptoms in intestinal anisakiosis resemble those of appendicitis or peritonitis. Treatments include removal of larval worms using a gastroendoscopic clipper or surgical resection of the mucosal tissue surrounding the worm. No confirmed effective anthelmintic drug has been introduced, though albendazole and ivermectin have been tried in vivo and in vitro. Prevention of human anisakiosis can be achieved by careful examination of fish fillet followed by removal of the worms in the restaurant or household kitchen. Immediate freezing of fish and cephalopods just after catching them on fishing boats was reported helpful for prevention of anisakiosis. It is noteworthy that anisakiosis is often associated with strong allergic and hypersensitivity reactions, with symptoms ranging from isolated angioedema to urticaria and life threatening anaphylactic shock.
Occasional, miscellaneous, and opportunistic parasites and fungi
Authors: Lloyd Sheelagh
Published: January 2012

A variety of organisms are mentioned, these either not closely related to groups in earlier chapters or free-living to opportunistically infect man. The parasites are presented usually under their most important clinical presentation, the fungi separately as a group. As usually rare these infections do not often generate suspicion among health providers, often are difficult to differentiate from more common infections, yet some can be fatal if misdiagnosed.
Fasciolosis
Authors: Parkinson Michael , Dalton John P. , O’Neill Sandra M.
Published: January 2012

Liver fluke disease, or fasciolosis, of livestock and humans is caused by endoparasitic trematodes of the genus Fasciola. Fasciola hepatica is responsible for the disease in temperate climates whereas F. gigantica is found in tropical zones. Recently, hybrids between F. hepatica and F. gigantica have been described (Le et al. 2008, Periago et al. 2008). Fasciolosis is a true zoonoses as it is predominantly a disease of animals that can be transmitted to humans at a specific stage of the parasite’s complex life cycle. There are a number of definitive hosts which includes sheep, cattle, and humans but this parasite has evolved to infect many other mammalian hosts including pigs, dogs, alpacas, llamas, rats, and goats (Apt et al. 1993; Chen and Mott 1990; Esteban et al. 1998). While prevalence of infection in humans may be relatively low in relation to animals, in specific geographic locations, for example in Bolivia, the prevalence of fasciolosis is so high in the human populations (hyperendemic) that it contributes to the spread of disease in animals (Esteban et al. 1999; Mas-Coma et al. 1999).

Archeological studies showing Fasciola eggs in ancient mummies in Egypt demonstrate that fasciolosis is an ancient human disease (David 1997). Sporadic cases of fasciolosis were reported in Egypt in 1958 (Kuntz et al. 1958). The first to carry out an extensive review on human fasciolosis were Chen and Mott (1990). They reported 2,595 cases in over 40 countries in Europe, the Americas, Asia, Africa and the western Pacifi c from 1970 – 1990. This review raised awareness of fasciolosis in humans and triggered a growth in epidemiological studies and a consequential dramatic increase in reporting of cases in the literature. Now human fasciolosis is recognized by the World Health Organization (WHO) as an important disease in humans with an estimated 2.4 million people infected annually and 180 million at risk to infection in over 61 countries (Haseeb et al. 2002). There have been several cases of large scale epidemics in France (Dauchy et al. 2007), Egypt (Curtale et al. 2007) and Iran (Rokni et al. 2002).

However, the only extensive epidemiological studies to determine the rate of infection have been carried out in Egypt and Bolivia (Curtale et al. 2003, 2007; Esteban et al. 2002; Parkinson et al. 2007). These studies have shown that co-infection with other diseases is a common occurrence and this may lead to under-reporting of the incidence of fasciolosis (Esteban et al. 2003; Maiga et al. 1991). In many countries, the overall rates of infection are extrapolated from sporadic reports of the disease and, consequently, worldwide disease prevalence is uncertain. In this chapter we will review the cause and effect of human fasciolosis, and particularly highlight important considerations in designing control strategies to reduce infection in at-risk communities.
Psychoanalytic theories of suicide
Authors: Ronningstam Elsa , Weinberg Igor , Maltsberger John T
Published: January 2012

Psychoanalytic theories and studies have influenced the explorations of suicide over the past hundred years. Freud’s first observations of self-objectification in melancholic depression were followed by contributions from object relation theorists and self-psychologists, highlighting foremost the role of narcissistic rage and structural vulnerability. Several of the central clinical concepts that unfolded have more recently been subject to empirical testing. This chapter provides an overview and discussion of the different psychoanalytic formulations applied to suicide. Empirical studies of several assumptions and constructs related to emotions, defences, and structural deficits and vulnerabilities verify their association to or explanation of chronic and acute suicidality. Further conceptualizations and research, especially on subtypes of suicide and individual experiences leading up to and dominating suicidal states, are called for.
Major psychiatric disorders in suicide and suicide attempters
Authors: Lönnqvist Jouko
Published: January 2012

Suicidal behaviour is closely connected with mental disorders. Virtually all mental disorders carry an increased risk of suicidal ideation, suicide attempt, and suicide. Psychiatric disorder may be an almost necessary, yet insufficient, risk factor for suicide. About 90 per cent of individuals who attempt or commit suicide meet diagnostic criteria for a psychiatric disorder, most often mood disorder, substance use disorders, psychoses, and personality disorders. The risk of suicidal behaviour in anxiety disorders and eating disorders, both having strong comorbidity with depression, is often underestimated. Under-treatment, comorbidity, treatment non-compliance and poor adherence, as well as a high frequency of non-responders are common problems and challenges in the treatment of suicidal persons. On the other hand, there is growing evidence of lower risk of suicidal behaviour during closely monitored long-term treatment of suicidal patients, indicating that treatment adherence is an important factor in medical suicide prevention.
Suicide prevention in Sweden
Authors: Wasserman Danuta , Nordenskiöld Ana , Ramberg Inga-Lill , Wasserman Camilla
Published: January 2012

Suicide and attempted suicide are still surrounded by feelings of guilt, shame, fear and unease. These acts are often incorrectly perceived as being predestined and impossible to prevent. Suicide among men in the 15–44 age group is the most common cause of death in Sweden. For females in the same age group, suicide is the second most common cause of death after tumours.

A suicidal act is not only a drastic example of difficulties in coping with the hardships of life and mental problems, but it is also a frequent indicator of how the health care and public health systems and ordinary fellow human beings fail to respond in an adequate manner to suicidal people. The responses encountered by suicidal individuals seeking care are a measure of quality, not only of medical and psychological care services, but also of the psychosocial conditions in society.

Ambiguous attitudes towards preventive measures and the persistent taboo surrounding suicide, as well as the attitude that suicide is a human right, make suicide-preventive activities necessary. In 1993, the Riksdag (the Swedish Parliament) stated that a country wishing to embark on active efforts to prevent suicide needs to have a national programme, as well as an institution for activities of this kind.
Megacycles of atmospheric carbon dioxide concentration correlate with fossil plant genome size
Authors: Franks Peter J. , Freckleton Rob P. , Beaulieu Jeremy M. , Leitch Ilia J. , Beerling David J.
Published: January 2012

Tectonic processes drive megacycles of atmospheric carbon dioxide (CO
2
) concentration,
c
a
, that force large fluctuations in global climate. With a period of several hundred million years, these megacycles have been linked to the evolution of vascular plants, but adaptation at the subcellular scale has been difficult to determine because fossils typically do not preserve this information. Here we show, after accounting for evolutionary relatedness using phylogenetic comparative methods, that plant nuclear genome size (measured as the haploid DNA amount) and the size of stomatal guard cells are correlated across a broad taxonomic range of extant species. This phylogenetic regression was used to estimate the mean genome size of fossil plants from the size of fossil stomata. For the last 400 Myr, spanning almost the full evolutionary history of vascular plants, we found a significant correlation between fossil plant genome size and
c
a
, modelled independently using geochemical data. The correlation is consistent with selection for stomatal size and genome size by
c
a
as plants adapted towards optimal leaf gas exchange under a changing CO
2
regime. Our findings point to the possibility that major episodes of change in
c
a
throughout Earth history might have selected for changes in genome size, influencing plant diversification.
WUSCHEL-RELATED HOMEOBOX5Gene Expression and Interaction of CLE Peptides with Components of the Systemic Control Add Two Pieces to the Puzzle of Autoregulation of Nodulation
Authors: Osipova Maria A. , Mortier Virginie , Demchenko Kirill N. , Tsyganov Victor E. , Tikhonovich Igor A. , Lutova Ludmila A. , Dolgikh Elena A. , Goormachtig Sofie
Published: January 2012

In legumes, the symbiotic nodules are formed as a result of dedifferentiation and reactivation of cortical root cells. A shoot-acting receptor complex, similar to the Arabidopsis (Arabidopsis thaliana) CLAVATA1 (CLV1)/CLV2 receptor, regulating development of the shoot apical meristem, is involved in autoregulation of nodulation (AON), a mechanism that systemically controls nodule number. The targets of CLV1/CLV2 in the shoot apical meristem, the WUSCHEL (WUS)-RELATED HOMEOBOX (WOX) family transcription factors, have been proposed to be important regulators of apical meristem maintenance and to be expressed in apical meristem “organizers.” Here, we focus on the role of the WOX5 transcription factor upon nodulation in Medicago truncatula and pea (Pisum sativum) that form indeterminate nodules. Analysis of temporal WOX5 expression during nodulation with quantitative reverse transcription-polymerase chain reaction and promoter-reporter fusion revealed that the WOX5 gene was expressed during nodule organogenesis, suggesting that WOX genes are common regulators of cell proliferation in different systems. Furthermore, in nodules of supernodulating mutants, defective in AON, WOX5 expression was higher than that in wild-type nodules. Hence, a conserved WUS/WOX-CLV regulatory system might control cell proliferation and differentiation not only in the root and shoot apical meristems but also in nodule meristems. In addition, the link between nodule-derived CLE peptides activating AON in different legumes and components of the AON system was investigated. We demonstrate that the identified AON component, NODULATION3 of pea, might act downstream from or beside the CLE peptides during AON.
Clinical laboratory assessment of the abuse liability of an electronic cigarette
Authors: Vansickel Andrea R. , Weaver Michael F. , Eissenberg Thomas
Published: January 2012

Aims  To provide an initial abuse liability assessment of an electronic cigarette (EC) in current tobacco cigarette smokers.

Design  The first of four within‐subject sessions was an EC sampling session that involved six, 10‐puff bouts (30 seconds inter‐puff interval), each bout separated by 30 minutes. In the remaining three sessions participants made choices between 10 EC puffs and varying amounts of money, 10 EC puffs and a varying number of own brand cigarette (OB) puffs, or 10 OB puffs and varying amounts of money using the multiple‐choice procedure (MCP). The MCP was completed six times at 30‐minute intervals, and one choice was reinforced randomly at each trial.

Setting  Clinical laboratory.

Participants  Twenty current tobacco cigarette smokers.

Measurements  Sampling session outcome measures included plasma nicotine, cardiovascular response and subjective effects. Choice session outcome was the cross‐over value on the MCP.

Findings  EC use resulted in significant nicotine delivery, tobacco abstinence symptom suppression and increased product acceptability ratings. On the MCP, participants chose to receive 10 EC puffs over an average of $1.06 or three OB puffs and chose 10 OB puffs over an average of $1.50 (P < 0.003).

Conclusions   Electronic cigarettes can deliver clinically significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes, at least under certain laboratory conditions.
The effects of sildenafil on rectal sensitivity and tone in patients with the irritable bowel syndrome
Authors: Gonçalves de Medeiros M. T. , de Oliveira R. B. , dos Santos A. A. , de Leopoldino D. M. , Oliveira Lima M. C. , Arrais Nobre R. , Nobre e Souza M. Â.
Published: January 2012

Background

Visceral tone supposedly affects gut sensitivity in irritable bowel syndrome (IBS). Sildenafil increases nitric oxide and influences visceral compliance.

Aim

To evaluate the effects of sildenafil tone inhibition on rectal sensitivity.

Methods

Eight controls and 21 IBS patients (Rome II) were enrolled in a double‐blind study, after dosing with placebo or sildenafil (50 mg p.o.). Thresholds for first sensation, first desire to defecate, pain and supraliminar pain were the sensory endpoints, measured with a barostat and 600‐mL rectal bag. Pain (100‐mm VAS) and depression‐anxiety (Hamilton questionnaire) were scored.

Results

Irritable bowel syndrome rectal compliance and sensory‐endpoint thresholds were similar to controls. Five IBS patients had pain threshold lower than controls 95% confidence interval (hypersensitive). Depression score was greater in IBS than controls (11.9 ± 1.3 vs. 6.3 ± 2.5, P = 0.036). In IBS, pain intensity was nonsignificantly higher (37.6 ± 5.3 mm vs. 23.4 ± 8.5 mm, P = 0.064) and supraliminar pain intensity was greater (45.6 ± 5.4 mm vs. 25.9 ± 5.1 mm, P = 0.044) than controls. IBS rectal relaxation increased volume (155.4 ± 41.3 mL vs. 118.8 ± 47.7 mL, P = 0.004) and tension (193.1 ± 118.6 mmHg mL−1 vs. 133.2 ± 98.1 mmHg mL−1, P = 0.019) for triggering first desire to defecate but not for other perceptions. Sildenafil increased volume for both first desire to defecate and pain in the hypersensitive IBS patients. Sildenafil increased rectal compliance only in diarrhoea‐IBS. Mixed‐IBS obtained higher anxiety (12.9 ± 1.3 vs. 5.9 ± 3.1, P < 0.05) and depression scores (13.9 ± 1.9 vs. 6.3 ± 2.5, P < 0.05) and reported more intense supraliminar pain (53.6 ± 9.8 mm vs. 25.9 ± 5.1 mm, P < 0.05) than controls.

Conclusions

Rectal relaxation following dosing with sildenafil 50 mg increased the first desire to defecate threshold in IBS as a whole, but decreased pain only in the hypersensitive subset. Mixed‐IBS presented higher supraliminar pain and anxiety‐depression scores.
Organization and expression of the Australian sheep blowfly (Lucilia cuprina) hsp23, hsp24, hsp70 and hsp83 genes
Authors: Concha C. , Edman R. M. , Belikoff E. J. , Schiemann A. H. , Carey B. , Scott M. J.
Published: January 2012

In this study we report the isolation and characterization of a heat shock protein 70 (hsp70) gene, the hsp83 gene and two genes that encode small Hsps (Lchsp23 and Lchsp24) from the Australian sheep blowfly, Lucilia cuprina, a major agricultural pest. Phylogenetic analyses indicate that the LcHsp23 protein is the orthologue of Drosophila melanogaster Hsp23 and LcHsp24 is the orthologue of Sarcophaga crassipalpis Hsp23. Quantitative reverse‐transcriptase PCR analysis showed that the basal level of Lchsp83 RNA is relatively high at all developmental stages and only moderately induced by heat shock. In contrast, Lchsp70 transcripts are present at low levels and strongly induced by heat shock at all stages. The basal levels of expression and degrees of heat induction of the Lchsp23 and Lchsp24 transcripts were more variable across the different developmental stages. Putative heat shock factor binding sites were identified in the Lchsp24, Lchsp70 and Lchsp83 gene promoters. The isolation of these hsp gene promoters will facilitate constitutive or conditional expression of a gene of interest in transgenic Lucilia.
Monitoring the effective population size of a brown bear (Ursus arctos) population using new single‐sample approaches
Authors: SKRBINŠEK TOMAŽ , JELENČIČ MAJA , WAITS LISETTE , KOS IVAN , JERINA KLEMEN , TRONTELJ PETER
Published: January 2012

The effective population size (Ne) could be the ideal parameter for monitoring populations of conservation concern as it conveniently summarizes both the evolutionary potential of the population and its sensitivity to genetic stochasticity. However, tracing its change through time is difficult in natural populations. We applied four new methods for estimating Ne from a single sample of genotypes to trace temporal change in Ne for bears in the Northern Dinaric Mountains. We genotyped 510 bears using 20 microsatellite loci and determined their age. The samples were organized into cohorts with regard to the year when the animals were born and yearly samples with age categories for every year when they were alive. We used the Estimator by Parentage Assignment (EPA) to directly estimate both Ne and generation interval for each yearly sample. For cohorts, we estimated the effective number of breeders (Nb) using linkage disequilibrium, sibship assignment and approximate Bayesian computation methods and extrapolated these estimates to Ne using the generation interval. The Ne estimate by EPA is 276 (183–350 95% CI), meeting the inbreeding‐avoidance criterion of Ne > 50 but short of the long‐term minimum viable population goal of Ne > 500. The results obtained by the other methods are highly consistent with this result, and all indicate a rapid increase in Ne probably in the late 1990s and early 2000s. The new single‐sample approaches to the estimation of Ne provide efficient means for including Ne in monitoring frameworks and will be of great importance for future management and conservation.
Induction of systemic resistance againstCucumber mosaic virusbyPenicillium simplicissimumGP17‐2 inArabidopsisand tobacco
Authors: Elsharkawy M. M. , Shimizu M. , Takahashi H. , Hyakumachi M.
Published: January 2012

The plant growth‐promoting fungus,Penicillium simplicissimumGP17‐2, was evaluated for its ability to induce resistance againstCucumber mosaic virus(CMV) inArabidopsis thalianaand tobacco plants. Treatment with barley grain inoculum (BGI) of GP17‐2 significantly enhanced fresh weight, dry weight and leaf number ofA. thalianaand tobacco plants 6 weeks after planting. Two weeks after CMV inoculation, all plants treated with BGI of GP17‐2 or its culture filtrate (CF) showed a significant reduction in disease severity compared with non‐treated control plants, which exhibited severe mosaic symptoms by the end of the experiment. The enzyme‐linked immunosorbent assay (ELISA) demonstrated that CMV accumulation was significantly reduced in plants treated with GP17‐2 or its CF relative to control plants. Based on RT‐PCR, plants treated with GP17‐2 (BGI or CF) also exhibited increased expression of regulatory and defence genes involved in the SA and JA/ET signalling pathways. These results suggested that multiple defence pathways inA. thalianaand tobacco were involved in GP17‐2‐mediated resistance to CMV, although neither the transgenicNahGline, nor thenpr1,jar1orein3mutants disrupted the response inA. thaliana. This is the first report to demonstrate the induction of systemic resistance against CMV by GP17‐2 or its CF.
A novel HLA‐B*51:01:29 allele identified by sequence‐based typing
Authors: Barbuti S. , Fornaciari S. , Mariotti M. L. , Curcio M. , Scatena F.
Published: January 2012

A novel HLA‐B*51:01:29 allele differs from B*51:01:01 at one nucleotidic position in the exon 3.
Lack of effect of central nervous system‐active doses of nabilone on capsaicin‐induced pain and hyperalgesia
Authors: Kalliomäki Jarkko , Philipp Andrew , Baxendale Jane , Annas Peter , Karlsten Rolf , Segerdahl Märta
Published: January 2012

The aim of the present study was to investigate the effects of nabilone on capsaicin‐induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) effects.

A randomized, double‐blind, placebo‐controlled, crossover study was conducted in 30 healthy male volunteers receiving single doses of nabilone (1, 2 or 3 mg). Pain intensity after intradermal capsaicin injections in the forearm was assessed by continuous visual analogue scale (0–100 mm). Capsaicin cream was applied to the calf to induce hyperalgesia. Primary hyperalgesia was assessed by measuring heat pain thresholds, whereas secondary hyperalgesia was assessed by measuring the area where light tactile stimulation was felt to be painful. Pain and hyperalgesia were measured at baseline and 2–3.5 h after dosing. The CNS effects were assessed at baseline and up to 24 h after dosing using visual analogue mood scales for feeling ‘stimulated’, ‘anxious’, ‘sedated’ and ‘down’. Plasma samples for pharmacokinetic analysis were obtained up to 24 h after drug administration.

Nabilone did not significantly attenuate either ongoing pain or primary or secondary hyperalgesia, whereas dose‐dependent CNS effects were observed from 1.5 to 6 h after dosing, being maximal at 4–6 h. Plasma concentrations of nabilone and its metabolite carbinol were maximal 1–2 h after dosing. Adverse events (AE) were common on nabilone treatment. Four subjects withdrew due to pronounced CNS AE (anxiety, agitation, altered perception, impaired consciousness).

Although nabilone had marked CNS effects, no analgesic or antihyperalgesic effects were observed.
Perianal abscess in children: aiming for optimal management
Authors: Buddicom Emily , Jamieson Amy , Beasley Spencer , King Sebastian
Published: January 2012

Background:  Perianal abscess is common in infants and children, yet the optimal surgical management is argued: incision and drainage alone is a simple procedure but is associated with a much higher recurrence rate than incision and drainage with simultaneous laying open of the associated fistula. This retrospective review established the institutional recurrence rate and its close association with how the fistula was managed at the initial operation.

Methods:  A retrospective review of all children requiring an operation for a perianal abscess over a 13‐year period from 1996 to 2009 was performed. Data were compared with published series.

Results:  A fistula was sought in 89 of 91 (98%) patients, and identified in 66 (73%). Recurrence occurred in 5/66 (8%) in whom a fistula was identified at the initial operation, compared with 6/25 (24%) (P = 0.06) in whom a fistula was not identified.

Conclusion:  Recurrence of perianal infection is influenced by whether a fistula was identified and laid open at the initial operation. The recurrence rate is higher when the abscess is treated with incision and drainage alone. Given the ease with which most fistulae may be identified, and laid open without morbidity, optimal treatment involves drainage of the abscess and laying open of the fistulous tract.
Lost opportunity cost of surgical training in the Australian private sector
Authors: Aitken R. James
Published: January 2012

Background:  To meet Australia's future demands, surgical training in the private sector will be required. The aim of this study was to estimate the time and lost opportunity cost of training in the private sector.

Methods:  A literature search identified studies that compared the operation time required by a supervised trainee with a consultant. This time was costed using a business model.

Results:  In 22 studies (34 operations), the median operation duration of a supervised trainee was 34% longer than the consultant. To complete a private training list in the same time as a consultant list, one major case would have to be dropped. A consultant's average lost opportunity cost was $1186 per list ($106 698 per year). Training in rooms and administration requirements increased this to $155 618 per year. To train 400 trainees in the private sector to college standards would require 54 000 training lists per year. The consultants' national lost opportunity cost would be $137 million per year. The average lost hospital case payment was $5894 per list, or $330 million per year nationally. The total lost opportunity cost of surgical training in the private sector would be about $467 million per year. When trainee salaries, other specialties and indirect expenses are included, the total cost will be substantially greater.

Conclusion:  It is unlikely that surgeons or hospitals will be prepared to absorb these costs. There needs to be a public debate about the funding implications of surgical training in the private sector.
Anal duplex fails to show changes in vascular anatomy after the haemorrhoidal artery ligation procedure
Authors: Schuurman J.‐P. , Go P. M. N. Y. H.
Published: January 2012

Aim  The aim of this prospective study was to evaluate whether the beneficial effect of haemorrhoidal artery ligation/transanal haemorrhoidal dearterialization (HAL/THD) is attributable to a change in the vascular anatomy at the level of the corpus cavernosum recti.

Method  Patients treated by HAL/THD for Grade II or Grade III haemorrhoids were scanned by anal colour Doppler endosonography before treatment and 6 weeks postoperatively. As part of a randomized controlled trial, patients were treated either with or without the Doppler scan. The number and diameter of vascular structures were measured at the distal, mid and proximal levels in the anal canal.

Results  There were 30 patients in the non‐Doppler group and 34 in the Doppler group. The postoperative measurements of the anal colour Doppler endosonography did not show any significant differences in vascular anatomy compared with the preoperative measurements, regardless of whether the Doppler probe was used (P > 0.05).

Conclusion  This study failed to show that the effect of HAL/THD is caused by alteration of the macroscopic vascular anatomy in the corpus cavernosum recti.
Ginsenoside‐Rd improves outcome of acute ischaemic stroke – a randomized, double‐blind, placebo‐controlled, multicenter trial
Authors: Liu X. , Wang L. , Wen A. , Yang J. , Yan Y. , Song Y. , Liu X. , Ren H. , Wu Y. , Li Z. , Chen W. , Xu Y. , Li L. , Xia J. , Zhao G.
Published: January 2012

Background and purpose:  Ginsenoside‐Rd is a receptor‐operated calcium channel antagonist and has shown promise as a neuroprotectant in our phase II study. As an extended work, we sought to confirm its efficacy and safety of Ginsenoside‐Rd in patients with acute ischaemic stroke.

Methods:  We conducted a randomized, double‐blind, placebo‐controlled trial involving 390 patients with acute ischaemic stroke in a 3:1 ratio to receive a 14‐day intravenous infusion of Ginsenoside‐Rd or placebo within 72 h after the onset of stroke. Our primary end‐point was the distribution of disability scores on the modified Rankin scale (mRs) at 90 days.

Results:  The efficacy analysis was based on 386 patients (Ginsenoside‐Rd group: 290; placebo group: 96). Ginsenoside‐Rd significantly improved the overall distribution of scores on the mRs, as compared with the placebo (P = 0.02; odds ratios [OR], 1.74; 95% confidence interval [CI], 1.08–2.78). There were significant differences between the two groups when we categorized the scores into 0–1 vs. 2–5 (P = 0.01; OR, 2.32; 95% CI, 1.23–4.38; 66.8% vs. 53.1%). It also improved the National Institutes of Health Stroke Scale (NIHSS) at 15 days [P < 0.01; least squares mean (LSM), −0.77; 95% CI, −1.31 to −0.24]. Mortality and rates of adverse events were similar in the two groups.

Conclusions:  Ginsenoside‐Rd improved the primary outcome of acute ischaemic stroke and had an acceptable adverse‐event profile.
CsRAV1 induces sylleptic branching in hybrid poplar
Authors: Moreno‐Cortés Alicia , Hernández‐Verdeja Tamara , Sánchez‐Jiménez Paloma , González‐Melendi Pablo , Aragoncillo Cipriano , Allona Isabel
Published: January 2012

Featured paper: See also the Commentary by Ellis
A novel µ‐conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors
Authors: Favreau Philippe , Benoit Evelyne , Hocking Henry G , Carlier Ludovic , D' hoedt Dieter , Leipold Enrico , Markgraf René , Schlumberger Sébastien , Córdova Marco A , Gaertner Hubert , Paolini‐Bertrand Marianne , Hartley Oliver , Tytgat Jan , Heinemann Stefan H , Bertrand Daniel , Boelens Rolf , Stöcklin Reto , Molgó Jordi
Published: January 2012

BACKGROUND AND PURPOSE

The µ‐conopeptide family is defined by its ability to block voltage‐gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new µ‐conopeptide (µ‐CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant.

EXPERIMENTAL APPROACH

µ‐CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. µ‐CnIIIC was also studied on HEK‐293 cells expressing various rodent VGSCs and also on voltage‐gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross‐interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data.

KEY RESULTS

Synthetic µ‐CnIIIC decreased twitch tension in mouse hemidiaphragms (IC50= 150 nM), and displayed a higher blocking effect in mouse extensor digitorum longus muscles (IC = 46 nM), compared with µ‐SIIIA, µ‐SmIIIA and µ‐PIIIA. µ‐CnIIIC blocked NaV1.4 (IC50= 1.3 nM) and NaV1.2 channels in a long‐lasting manner. Cardiac NaV1.5 and DRG‐specific NaV1.8 channels were not blocked at 1 µM. µ‐CnIIIC also blocked the α3β2 nAChR subtype (IC50= 450 nM) and, to a lesser extent, on the α7 and α4β2 subtypes. Structure determination of µ‐CnIIIC revealed some similarities to α‐conotoxins acting on nAChRs.

CONCLUSION AND IMPLICATIONS

µ‐CnIIIC potently blocked VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels.