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Surface attachment, promoted by the actomyosin system of Toxoplasma gondii is important for efficient gliding motility and invasion
No full textAbstract
Background
Apicomplexan parasites employ a unique form of movement, termed gliding motility, in order to invade the host cell. This movement depends on the parasite\u2019s actomyosin system, which is thought to generate the force during gliding. However, recent evidence questions the exact molecular role of this system, since mutants for core components of the gliding machinery, such as parasite actin or subunits of the MyoA-motor complex (the glideosome), remain motile and invasive, albeit at significantly reduced efficiencies. While compensatory mechanisms and unusual polymerisation kinetics of parasite actin have been evoked to explain these findings, the actomyosin system could also play a role distinct from force production during parasite movement.
Results
In this study, we compared the phenotypes of different mutants for core components of the actomyosin system in Toxoplasma gondii to decipher their exact role during gliding motility and invasion. We found that, while some phenotypes (apicoplast segregation, host cell egress, dense granule motility) appeared early after induction of the act1 knockout and went to completion, a small percentage of the parasites remained capable of motility and invasion well past the point at which actin levels were undetectable. Those act1 conditional knockout (cKO) and mlc1 cKO that continue to move in 3D do so at speeds similar to wildtype parasites. However, these mutants are virtually unable to attach to a collagen-coated substrate under flow conditions, indicating an important role for the actomyosin system of T. gondii in the formation of attachment sites.
Conclusion
We demonstrate that parasite actin is essential during the lytic cycle and cannot be compensated by other molecules. Our data suggest a conventional polymerisation mechanism in vivo that depends on a critical concentration of G-actin. Importantly, we demonstrate that the actomyosin system of the parasite functions in attachment to the surface substrate, and not necessarily as force generator
Meeting report: the 5th International expert symposium in Fukushima on radiation and health
No full textAbstract
Background
The symposium entitled \u201cChernobyl +30, Fukushima +5: Lessons and Solutions for Fukushima\u2019s Thyroid Question\u201d was held in September, 2016 in Fukushima. The aim of the Symposium was to revisit and recapitulate evidence from the studies in Chernobyl in order to share multidisciplinary opinions and views on the likely reason for the high rate of thyroid cancer detected by the Thyroid Ultrasound Examination program in Fukushima Prefecture.
Participants and matters discussed
The high prevalence of thyroid cancer in young individuals causes concerns among Fukushima residents and the general public that it might be due to putative radiation exposure from the Fukushima Daiichi Nuclear Power Plant accident. Twenty-six experts from Japan and abroad, including participants affiliated with international organizations, reviewed the results of radiation epidemiology investigations in Chernobyl, presented clinical experience of diagnosis, treatment and follow-up of patients with radiation-related thyroid cancer, and scrutinized the findings on thyroid cancer in Fukushima.
Conclusion
Conclusions drawn at the symposium included understanding that in contrast to Chernobyl, doses to the public from the accident in Fukushima were too low to give rise to a discernible excess risk for thyroid cancer. The high detection rate of thyroid cancer and benign abnormalities resulted from the use of highly sensitive ultrasound equipment and sophisticated protocol of examination used in the Thyroid Ultrasound Examination, and therefore not attributable to radiation. Coordinated efforts will be necessary to avoid overdiagnosis and overtreatment, which may carry its own health disbenefits. Clear communication to the screening participants and their families is recommended in regard to why the examination is being conducted and to explain the likely outcomes and risks, including the means and options for treatment if a thyroid disorder is detected
The influence of marketing on the sports betting attitudes and consumption behaviours of young men: implications for harm reduction and prevention strategies
No full textAbstract
Background
Gambling can cause significant health and social harms for individuals, their families, and communities. While many studies have explored the individual factors that may lead to and minimise harmful gambling, there is still limited knowledge about the broader range of factors that may contribute to gambling harm. There are significant regulations to prevent the marketing of some forms of gambling but comparatively limited regulations relating to the marketing of newer forms of online gambling such as sports betting. There is a need for better information about how marketing strategies may be shaping betting attitudes and behaviours and the range of policy and regulatory responses that may help to prevent the risky or harmful consumption of these products.
Methods
We conducted qualitative, semi-structured interviews with 50 Australian men (aged 20\u201337\ua0years) who gambled on sports. We explored their attitudes and opinions regarding sports betting marketing, the embedding of marketing within sports and other non-gambling community environments, and the implications this had for the normalisation of betting.
Results
Our findings indicate that most of the environments in which participants reported seeing or hearing betting advertisements were not in environments specifically designed for betting. Participants described that the saturation of marketing for betting products, including through sports-based commentary and sports programming, normalised betting. Participants described that the inducements offered by the industry were effective marketing strategies in getting themselves and other young men to bet on sports. Inducements were also linked with feelings of greater control over betting outcomes and stimulated some individuals to sign up with more than one betting provider.
Conclusions
This research suggests that marketing plays a strong role in the normalisation of gambling in sports. This has the potential to increase the risks and subsequent harms associated with these products. Legislators must begin to consider the cultural lag between an evolving gambling landscape, which supports sophisticated marketing strategies, and effective policies and practices which aim to reduce and prevent gambling harm
TPX2 expression is associated with poor survival in gastric cancer
No full textAbstract
Background
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for microtubule formation in human cells. Several studies have demonstrated that TPX2 is overexpressed in multiple tumor types and promotes tumor growth and metastasis. However, there have been few reports regarding its role in gastric cancer. In this study, we evaluated TPX2 expression and investigated its correlations with gastric cancer clinicopathological features and prognosis.
Methods
Tumor samples were obtained from 290 patients with gastric adenocarcinoma who had undergone gastrectomy. The expression of TPX2 protein was examined using immunohistochemical staining. TPX2 messenger RNA (mRNA) levels were evaluated using real-time quantitative reverse transcription PCR in 19 of the gastric cancer tumors and adjacent normal tissues.
Results
The mRNA levels of TPX2 were significantly higher in gastric cancer tissues than in matched adjacent normal tissues ( p \u2009=\u20090.004). In the immunohistochemical analysis, TPX2 overexpression was found in 123 (42.4%) of 290 patients. High TPX2 expression was positively associated with age, type of histology, depth of tumor, lymph node metastasis, stage, and remote metastasis or recurrence. High TPX2 expression was significantly associated with poorer disease-specific survival ( p \u2009=\u20090.004) and relapse-free interval ( p \u2009=\u20090.013).
Conclusions
Our results indicated that high TPX2 expression was associated with tumor progression and poor survival in gastric cancer
Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome
No full textAbstract
Background
Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated.
Methods
We have assayed the concentration of IFN-\u3b1, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay.
Results
The results showed that IFN-\u3b1, tumor necrosis factor (TNF-\u3b1), granulocyte colony-stimulating factor (G-CSF), interferon-\u3b3 (IFN-\u3b3), macrophage inflammatory protein (MIP-1\u3b1), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons ( p \u2009<\u20090.05); the concentrations of IFN-\u3b1, IFN-\u3b3, G-CSF, MIP-1\u3b1, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients ( p \u2009<\u20090.05).
Conclusion
The concentration of IFN-\u3b1 as well as other cytokines (IFN-\u3b3, G-CSF, MIP-1\u3b1, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm
Preventive transarterial embolization in upper nonvariceal gastrointestinal bleeding
No full textAbstract
Background
Transarterial embolization (TAE) is a therapeutic option for patients with a high risk of recurrent bleeding after endoscopic haemostasis. The aim of our prospective study was a preliminary assessment of the safety, efficacy, and clinical outcomes following preventive TAE in patients with non-variceal acute upper gastrointestinal bleeding (NVUGIB) with a high risk of recurrent bleeding after endoscopic haemostasis.
Methods
Preventive visceral angiography and TAE were performed after endoscopic haemostasis on patients with NVUGIB who were at a high risk of recurrent bleeding (PE+ group). The comparison group consisted of similar patients who only underwent endoscopic haemostasis, without preventive TAE (PE\u2212 group). The technical success of preventive TAE, the completeness of haemostasis, the incidence of rebleeding and the need for surgical intervention and the main outcomes were compared between the groups.
Results
The PE+ group consisted of 25 patients, and the PE\u2212 group of 50 patients, similar in age (median age 66 vs. 63\ua0years), gender and comorbid conditions. The ulcer size at endoscopy was not significantly different (median of 152\ua0mm vs. 127\ua0mm). The most frequent were Forest II type ulcers, 44% in both groups. The distribution of the Forest grade was even. The median haemoglobin on admission was 8, 2\ua0g/dl vs. 8,7\ua0g/dl, p \u2009=\u20090,482, erythrocyte count was 2,7\u2009\ud7\u200910
12
/L vs. 2,9\u2009\ud7\u200910
12
/L, p \u2009=\u20090,727. The shock index and Rockall scores were similar, as well as and transfusion \u2013 on average, four units of packed red blood cells for the majority of patients in both groups, however, significantly more fresh frozen plasma was transfused in the PE\u2212 group, p \u2009=\u20090,013. The rebleeding rate was similar, while surgical treatment was needed notably more often in the PE- group, 8% vs. 35% accordingly, p \u2009=\u20090,012. The median ICU stay was 3\ua0days, hospital stay \u2013 6\ua0days vs. 9\ua0days, p \u2009=\u20090.079. The overall mortality reached 20%; in the PE+ group it was 4%, not reaching a statistically significant difference.
Conclusion
Preventive TAE is a feasible, safe and effective minimally invasive type of ..
Electroacupuncture for the prevention of postoperative gastrointestinal dysfunction in participants undergoing vascular laparotomy under general anesthesia: a randomized controlled trial
No full textAbstract
Background
Postoperative gastrointestinal dysfunction (PGD) is a common complication following laparotomy under general anesthesia (GA). Abdominal distension occurs in 8\u201328% of surgeries within 24\ua0h postoperatively. The present study aimed to analyze the efficacy of electroacupuncture (EA) for the prevention of PGD by applying preoperative EA stimulation of PC6 ( Neiguan ), ST36 ( Zusanli ), and ST37 ( Shangjuxv ) bilaterally twice within 24\ua0h prior to surgery, compared with no acupuncture treatment.
Methods
The study participants were assessed and selected from participants undergoing vascular laparotomy under GA at the Liver and Vascular Surgery Unit in West China Hospital of Sichuan University. The selected participants were randomly allocated to two groups: routine-treatment (RT) and EA group receiving EA at PC6, ST36, and ST37. A computer-generated list of random numbers was used to determine the allocation of the participants, with numbered opaque sealed envelopes containing the randomization schedule. Eligible participants were all adults aged 18\ua0years or above who were scheduled to undergo vascular laparotomy under GA within 24\ua0h and had no history of EA treatment. The exclusion criteria included participants with serious systemic disease and history of EA treatment. While the RT group received standard treatments, the EA group received additional EA treatments. During each treatment session, EA stimulation was performed for a duration of 20\ua0min at a frequency of 15\ua0Hz with a continuous wave. All such participants received two EA treatments within 24\ua0h before surgery. The outcomes were measured in three metrics: incidence and degree of abdominal distension; first times of flatus and defecation; and duration of hospitalization.
Results
Forty-three participants were recruited, of whom 42 participants successfully completed the study. Each group contained 21 participants. The incidence of abdominal distension (42.8, 76.2%) and degree of abdominal distension were significantly reduced in the EA group ( P \ua0=\ua00.03 and P \ua0=\ua00.03, respectively). In comparisons of the first times of flatus (3.05\ua0\ub1\ua00.58, 3.29\ua0\ub1\ua00.42\ua0days) and defecation (2.81\ua0\ub1\ua00.51, 3.20\ua0\ub1\ua00.55\ua0days) and duration of hospitalization (5.33\ua0\ub1\ua00.68, 5.75\ua0\ub1\ua00.66\ua0days), the EA group was superior to the RT group to some extent ( P \ua0=\ua00.13, P \ua0=\ua00.02, and P \ua0=\ua00.04, respectively).
Conclusions
Preoperative EA at PC6, ST36, and ST37 might be useful for preventing PGD, thereby improving gastrointestinal function ..
Overdiagnosis of mental disorders in children and adolescents (in developed countries)
No full textAbstract
During the past 50\ua0years, health insurance providers and national registers of mental health regularly report significant increases in the number of mental disorder diagnoses in children and adolescents. However, epidemiological studies show mixed effects of time trends of prevalence of mental disorders. Overdiagnosis in clinical practice rather than an actual increase is assumed to be the cause for this situation. We conducted a systematic literature search on the topic of overdiagnosis of mental disorders in children and adolescents. Most reviewed studies suggest that misdiagnosis does occur; however, only one study was able to examine overdiagnosis in child and adolescent mental disorders from a methodological point-of-view. This study found significant evidence of overdiagnosis of attention-deficit/hyperactivity disorder. In the second part of this paper, we summarize findings concerning diagnostician, informant and child/adolescent characteristics, as well as factors concerning diagnostic criteria and the health care system that can lead to mistakes in the routine diagnostic process resulting in misdiagnoses. These include the use of heuristics instead of data-based decisions by diagnosticians, misleading information by caregivers, ambiguity in symptom description relating to classification systems, as well as constraints in most health systems to assign a diagnosis in order to approve and reimburse treatment. To avoid misdiagnosis, standardized procedures as well as continued education of diagnosticians working with children and adolescents suffering from a mental disorder are needed
Efficacy of fluralaner against Otodectes cynotis infestations in dogs and cats
No full textAbstract
Background
The efficacy of fluralaner for the treatment of Otodectes cynotis infestations in dogs and cats was evaluated after oral (dogs) or topical administration (dogs and cats).
Twenty-four dogs and sixteen cats were experimentally infested with O. cynotis and randomly allocated to equal sized groups ( n \u2009=\u20098/group). Dog groups were treated once, either orally with fluralaner at a minimum dose of 25\ua0mg/kg body weight, topically with fluralaner at a dose of 25\ua0mg/kg body weight or topically with saline solution (control). Cat groups were treated once, either topically with fluralaner at a dose of 40\ua0mg/kg body weight or topically with saline solution. Ears of all animals were examined otoscopically for live visible mites and the amount of debris and cerumen before, and 14 and 28\ua0days after treatment. Twenty-eight days after treatment, animals were sedated and both ears were flushed to obtain the total number of live mites per animal. The efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner treated groups versus the saline solution treated group.
Results
A single topical treatment of cats with fluralaner reduced the mean mite counts by 100% ( P \u2009<\u20090.001) at 28\ua0days after treatment. Similarly, a single oral or topical treatment of dogs with fluralaner reduced the mean mite counts by 99.8% ( P \u2009<\u20090.001) at 28\ua0days after treatment. Cats treated topically with fluralaner had no mites visible during otoscopic examination at either 14 or 28\ua0days after treatment. All dogs treated orally or topically with fluralaner had no mites visible during otoscopic examination at 28\ua0days after treatment. At 14\ua0days after treatment, only 1\u20132 mites were visible in three dogs (oral treatment: 2 dogs, topical treatment: 1 dog). All fluralaner-treated animals showed improvement in the amount of cerumen exudation compared with observations performed before treatment. No treatment related adverse events were observed in any dogs or cats enrolled in these studies.
Conclusions
In this study, fluralaner administered topically to cats and orally or topically to dogs was highly effective against Otodectes cynotis mite infestations
Genetic diagnosis and treatment of a Chinese ketosis-prone MODY 3 family with depression
No full textAbstract
Background
To analyze the gene mutation and mental disorder of a Chinese ketosis-prone diabetes (KPD) family, and to make a precise diagnosis and give a treatment for them.
Methods
We studied a Chinese family with a clinical diagnosis of maturity-onset diabetes of the young (MODY). The clinical data and the blood samples were collected. The promotor and coding regions inclusive intron exon boundaries of the HNF1A, HNF4A were detected by polymerase chain reaction (PCR) and direct sequencing. The missense mutation was also analyzed by bioinformatics. Genetic counseling was performed twice a month to relieve the mental disorder of the persons.
Results
The missense mutation c.779 C>T (p.T260M) in exon4 of HNF1A gene was detected, and the symptom heterogenicity among persons in this family were found. All the members were retreated with Gliclazide and stopped to use other medicine, the blood glucose of them were well controlled. We also performed an active genetic counseling to them and the mental disorder of the proband\u2019s sister was relieved.
Conclusions
A missense mutation of HNF1A gene was first found in Chinese ketosis-prone MODY family with manifestations heterogenicity among the persons. Sulphonylureas medicine and genetic counseling are efficiency ways to treat MODY 3 and its\u2019 mental disorder respectively