Nisshesha rechaka pranayama offers benefits through brief intermittent hypoxia.
Hypoxia has been a frightening term for doctors and medical students because of the possibility of damage to cells, tissues and organs. However, we now know that brief, episodic hypoxia gives rise to several adaptive responses. These responses in general prepare the body for better tolerating such hypoxic episodes, and also offer protection against several other types of insults. Indeed, scientists at the erstwhile U.S.S.R. have developed what is known as 'hypoxia therapy' and reaped the benefits of brief intermittent hypoxia for the last several decades. In India, yogic treatment of various diseases is common. A lesser known but important variety of Pranayama is 'nisshesha rechaka', which may be described as breath holding at residual volume. Studies done at our centre have demonstrated that Nisshesha rechaka is the easiest way to produce brief, intermittent hypoxia. There is therefore reason to believe that Nisshesha rechaka pranayama may offer benefits through this mechanism.


The use of radiofrequency ablation in the treatment of musculoskeletal tumors.
Musculoskeletal tumors, both primary neoplasms and metastatic lesions, present a therapeutic challenge for the physician who wishes to provide palliative pain relief using the least invasive approach. The increasing sophistication of imaging modalities such as CT in precisely localizing neoplasm, coupled with the widespread use of radiofrequency ablation (RFA) for treatment of other types of tumor, has generated interest in using RFA to treat musculoskeletal tumors. Primary bone tumors (eg, osteoid osteoma) and metastatic bone tumors have been successfully treated with RFA. Success rates with RFA are equal to those with standard surgical curettage, but RFA has the advantage of decreased surgical morbidity. The procedure is relatively safe, is well-tolerated by the patient, and typically can be performed on an outpatient basis. The most common serious complication reported is localized skin necrosis, which occurs rarely. RFA appears to be a viable minimally invasive approach for palliative treatment of selected bone tumors.


Acromegaly and thyroid cancer: analysis of evolution in a series of patients.
Acromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution. This is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0. Median age of patients at diagnosis of acromegaly was 49.5 years (range 12-69). The median delay in diagnosis of acromegaly was 3 years (range 0.5-23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18-69). At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5-7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb. Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months. When comparing RFU between acromegalics and controls no statistically significant differences were found. Patients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.


Development of the Veterans Crisis Line Caring Letters Suicide Prevention Intervention.
To describe the design, implementation, and plans to evaluate the Veterans Crisis Line (VCL) Caring Letters intervention. Veterans with VCL contact and VHA service utilization. Caring Letters is an evidence-based post-acute care suicide prevention intervention in which brief messages are mailed to individuals at high risk of suicide repeatedly over time to communicate that people care about them and are concerned for their well-being. An effectiveness-implementation hybrid type 1 trial using the RE-AIM evaluation framework is underway to examine the use of Caring Letters with veterans who contact the VCL. A team of suicide prevention subject matter experts, researchers, and operational partners from the VCL will evaluate the effects of Caring Letters on clinical outcomes and Department of Veterans Affairs - Veterans Health Administration (VHA) clinical utilization rates and examine facilitators and barriers to implementing the Caring Letters campaign. Veterans who contact the VCL are linked with national administrative VHA data. Semi-structured interviews were conducted as part of a qualitative formative evaluation. In the first 12 months of the intervention, Caring Letters have been sent to over 100,000 veterans with VCL contact (over 500,000 letters mailed). A formative qualitative evaluation early in implementation revealed a variety of positive veteran perspectives on the intervention. Partnered program design and evaluation with a high level of stakeholder engagement and participant feedback can result in a rigorous and feasible evaluation plan that improves implementation processes and produces actionable results. The initial results of this evaluation will be used to better inform care in the VHA and, specifically, the VCL.


Mother-to-child transmission of HIV infection and its prevention.
An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usually in highly active combinations), elective caesarean section and avoidance of breastfeeding, and where infected women are identified before or in pregnancy and have access to these interventions, risk of MTCT is now below 1-2%. However, prompt identification of pregnant women with HIV infection remains pressing in many developed countries; additionally, concerns have arisen regarding adherence to complex treatment regimens in pregnancy and the potential impact of HIV drug resistance. More disturbingly, most HIV-infected women live in developing countries where many pregnant women even when tested do not return for their HIV results for a variety of reasons including stigma, and where most, if not all, strategies for prevention of MTCT have been of limited accessibility and/or feasibility. However, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and other initiatives including pharmaceutical companies' donation programmes and generic antiretroviral drug production have made prevention of MTCT in resource-poor settings an increasingly realistic goal, coupled with new evidence from clinical trials on the efficacy of abbreviated regimens of antiretroviral prophylaxis, including combination therapy, to prevent MTCT. Research is additionally focussing on reducing the risk of postnatal transmission through breastfeeding, with exclusive breastfeeding, early cessation and antiretroviral prophylaxis to breastfeeding women or breastfed infants under investigation. However, the key to prevention of paediatric HIV infections is adequate prevention of infection in women of reproductive age.


Biochemical basis of the effect of chondroitin sulphate on osteoarthritis articular tissues.
Osteoarthritis is a chronic disease characterised by irreversible damage to joint structures, including loss of articular cartilage, osteophyte formation, alterations in the subchondral bone and synovial inflammation. Pain, functional disability and impairment of health-related quality of life are major complaints in patients with osteoarthritis. Several compounds have been investigated for their positive effects on the relief of clinical symptoms and improvement of structural changes in osteoarthritis. It has been shown that chondroitin sulphate interferes with the progression of structural changes in joint tissues and is used in the management of patients with osteoarthritis. This review summarises data from relevant reports describing the mechanisms of action of chondroitin sulphate involved in the beneficial effects of the drug.


The membrane-associated monooxygenase in the butane-oxidizing Gram-positive bacterium Nocardioides sp. strain CF8 is a novel member of the AMO/PMO family.
The Gram-positive bacterium Nocardioides sp. strain CF8 uses a membrane-associated monooxygenase (pBMO) to grow on butane. The nucleotide sequences of the genes encoding this novel monooxygenase were revealed through analysis of a de novo assembled draft genome sequence determined by high-throughput sequencing of the whole genome. The pBMO genes were in a similar arrangement to the genes for ammonia monooxygenase (AMO) from the ammonia-oxidizing bacteria and for particulate methane monooxygenase (pMMO) from the methane-oxidizing bacteria. The pBMO genes likely constitute an operon in the order bmoC, bmoA and bmoB. The nucleotide sequence was less than 50% similar to the genes for AMO and pMMO. The operon for pBMO was confirmed to be a single copy in the genome by Southern and computational analyses. In an incubation on butane the increase of transcriptional activity of the pBmoA gene was congruent with the increase of pBMO activity and suggested correspondence between gene expression and the utilization of butane. Phylogenetic comparison revealed distant but significant similarity of all three pBMO subunits to homologous members of the AMO/pMMO family and indicated that the pBMO represents a deeply branching third lineage of this group of particulate monooxygenases. No other bmoCAB-like genes were found to cluster with pBMO lineage in phylogenetic analysis by database searches including genomic and metagenomic sequence databases. pBMO is the first example of the AMO/pMMO-like monooxygenase from Gram-positive bacteria showing similarities to proteobacterial pMMO and AMO sequences.


[Acute and chronic injuries to the knee in the doctor's office].
In the diagnostic work-up of acute and chronic injuries to the knee, the patient's history together with the clinical findings are of decisive importance. Injuries to the cruciate and lateral ligaments, or to the menisci, as well as osteochondritis dissecans or chronic recurrent dislocation of the patella can usually be reliably diagnosed on the basis of information provided by the patient, and diagnostic manipulations. In this connection, Lachman's test, various drawer phenomena, the pivot shift test, and tests of the internal menisci described by McMurray, Payr, Steinmann, and Cabot as well as Apley's grinding test have all been described. The Wilson test can indicate osteochondritis dissicans; in chronic recurrent dislocation of the patella, Fairbank's apprehension test is positive.


Chemical composition of Ocimum sanctum by LC-ESI-MS/MS analysis and its protective effects against smoke induced lung and neuronal tissue damage in rats.
Smoke induced oxidative stress is known to cause various cancers and associated health problems including lung cancer. Herbal extracts have been reported as antioxidant supplements which attenuate free radical induced oxidative damage of tissues, among which Ocimum sanctum has been reported as the elixir of life due to its innumerable health benefits. In the present study, we investigated the protective effect of O. sanctum against cracker smoke induced lung and brain tissue damage. The results of the study demonstrate that O. sanctum regulates the hematological and serum biochemical parameters such as RBC, WBC, blood urea nitrogen and creatinine kinase. O. sanctum supplementation inhibited oxidative stress as analyzed by SOD, CAT enzyme levels and i-NOS, HSP-70 protein expression. O. sanctum administration also regulated neurotransmitter levels, such as serotonin, dopamine, and regulated acetylcholine esterase levels which play a vital role in neuronal function. Further O. sanctum treatment also preserved the morphology of lung and brain tissues of smoke stress induced rats as observed by histopathology and transmission electron microscope analysis. The biodistribution of O. sanctum was showed its accumulation in key tissues such as kidney, liver, lungs and heart. The LC-ESI-MS/MS analysis of O. sanctum showed the presence of polyphenols, flavonoids and fatty acids which might be responsible for the observed anti-stress effects.


[Normothermic total hepatic vascular exclusion for hepatectomy].
Experience of normothermic total hepatic vascular exclusion for hepatectomy in two patients with hepatocarcinoma in the second porta hepatis area are reported. The combined method of stepwise exclusion of porta hepatis, total hepatic vascular exclusion, total hepatic vascular exclusion without abdominal aorta and manipulative exclusion of inferior vena cava above liver are described. Biochemical studies before, during and after the operation showed that they are similar to these of routine hepatectomy. This modification, being safer and easier, may increase the resectability and reduce the mortality rate.


The Vascular Endothelium in Patients with Dengue Haemorrhagic Fever.
Dengue fever is the most serious consequence of mosquito-borne infection worldwide. The pathophysiology of DHF in human is complex, which involve endothelial cell activation and impaired endothelial barrier leading to plasma leakage triggering the activation of the haemostatic system. The increased vascular permeability may lead to hypovolemia, hypotension and shock, which is life-threatening. The objective of the study was to determine the effects of dengue haemorrhagic fever on the vascular endothelium. Fifty patients (males 34, females 16), were recruited, Grade 1 (n = 41), Grade 2 (n = 6), Grade 3 (n = 2) and Grade 4 (n = 1) DHF. Blood sampling was performed at the febrile, defervescence and convalescent phases for the determination of haemoglobin, haematocrit, platelets, prothrombin fragment F1 + 2, Von Willebrand Factor (VWF), vascular endothelial growth factor (VEGF) and D-dimer levels. Fifteen normal subjects were recruited to serve as normal controls. The patients aged between 4 and 54 years old. Grades 1 & 2 DHF showed no significant differences in the parameters studied. However, thrombocytopenia, elevated F1 + 2, VWF, VEGF and D-dimer levels were evident in febrile, defervescence and convalescent phases suggesting endothelial activation and plasma leakage. Pleural effusion was observed only in severe DHF. The three patients with Grades 3 and 4 DHF had similar study results. No mortality was recorded in the study. In dengue haemorrhagic fever, the vascular endothelium is activated, causing plasma leakage triggering the activation of the haemostatic system creating a hypercoagulable and enhanced fibrinolytic state evident by marked fibrinolysis.


Early experiences of radiographers in Ireland during the COVID-19 crisis.
Imaging is crucial for assessing the severity and progression of COVID-19. Radiographers are amongst the first-line health professionals that may be exposed to infected persons. This work describes the early experience of radiographers in Ireland to the impact of COVID-19 using two electronic surveys distributed 6 weeks apart. Results were analysed using descriptive statistics and thematic analysis. A total of 370 responded to the first survey and 276 the second, with all six Irish health regions represented. Three quarters of radiographers (77%) reported having adequate personal protective equipment (PPE) available to them. However, almost half of the radiographers were inadvertently exposed to COVID-19-positive patients without appropriate PPE, largely attributed to poor communication and testing. Anxiety levels while initially high, reduced substantially 6 weeks into the crisis period. However, obvious distress was noted amongst some respondents. Forty percent of radiographers reported burnout symptoms due to the COVID-19 crisis and 30% reported considering changing jobs or retiring since the COVID-19 outbreak. Clear communication regarding changing protocols and importantly patients' infectious status are essential to safeguard healthcare workers and to minimise unnecessary anxiety and distress. Attention is required to staff mental health including the identification of burnout symptoms to prevent long-term negative consequences of the pandemic on radiography services.


Thermodynamic and kinetic studies of the gating behavior of a K+-selective channel from the sarcoplasmic reticulum membrane.
A voltage-dependent, K+-selective ionic channel from sarcoplasmic reticulum of rabbit skeletal muscle has been studied in a planar phospholipid bilayer membrane. The purpose [corrected] of this work is to study the mechanism by which the channel undergoes transitions between its conducting and nonconducting states. Thermodynamic studies show that the "open" and "closed" states of the channel exist in a voltage-dependent equilibrium, and that the channel displays only a single open state; the channel conductance is 120 pmho in 0.1 M K+. The channel's gating process follows single exponential kinetics at all voltages tested, and the individual opening and closing rate constants are exponentially dependent on voltage. The individual rate constants may also be determined from a stochastic analysis of channel fluctuations among multiple conductance levels. Neither the thermodynamic nor the kinetic parameters of gating depend on the absolute concentration of channels in the bilayer. The results are taken as evidence that the channel gates by an unusually simple two-state conformational mechanism in which the equivalent of 1.1 net charges are moved across the membrane during the formation of the open channel.


Phylogenetic relationships of the Physciaceae inferred from rDNA sequence data and selected phenotypic characters.
The monophyletic origin of the ascomycete family Physciaceae, its position within the Lecanorales and the phylogenetic structure within the family were investigated using nuclear rDNA sequence analyses. The common origin of the Caliciaceae and Physciaceae as previously shown (Wedin et al 2000) was confirmed. Further it could be shown that the Caliciaceae are nested within the Physciaceae. A unique region in loop 37 of the SSU rRNA secondary structure model was identified, which characterizes the Physciaceae/Caliciaceae. The SSU rDNA sequence data did not support a particular relationship with any other Lecanoralean family. Analyses of ITS rDNA sequences revealed a bifurcation of the Physciaceae/Caliciaceae clade, which was found to be congruent with the distribution of certain morphological characters. The congruence with the ITS phylogeny demonstrated the phylogenetic significance of ascus type, hypothecium pigmentation, ascospore characters and excipulum type. Fine-structure details of ascospores and the structure of excipula were found to be important in the recognition of convergences in these traits. Other previously used characters, i.e., growth habit, certain ascospore types or structure of the upper cortex, were found to be of multiple origins within the Physciaceae. All monophyletic lineages of noncrustose growth habit exhibit uniform ascospore types, indicating a higher evolutionary age of ascospore types than foliose growth habit. The taxonomic segregation of the Physciaceae into the Physciaceae and Caliciaceae is proposed here.


Association between urbanisation and type 2 diabetes: an ecological study.
Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide.


Beneficial effects of GABA-producing potential probiotic Limosilactobacillus fermentum L18 of human origin on intestinal permeability and human gut microbiota.
Gamma-aminobutyric acid (GABA) is a non-protein amino acid with neuroinhibitory, antidiabetic, and antihypertensive properties and is used as a drug for treating anxiety and depression. Some strains of lactobacilli are known to produce GABA and strengthen the gut barrier function which play an important role in ameliorating the effects caused by the pathogen on the gut barrier. The probiotic bacteria are also known to modulate the human fecal microbiota, however, the role of GABA-producing strains on the gut epithelium permeability and gut microbiota is not known. In this study, we report the production of high levels of GABA by potential probiotic bacterium Limosilactobacillus fermentum L18 for the first time. The kinetics of the production of GABA by L18 showed that the maximum production of GABA in the culture supernatant (CS) occurred at 24 h, whereas in fermented milk it took 48 h of fermentation. The effect of L18 on the restoration of lipopolysaccharide (LPS)-disrupted intestinal cell membrane permeability in Caco-2 monolayers showed that it significantly restored the transepithelial electrical resistance (TEER) values, by significantly increasing the levels of junction proteins, occludin and E-cadherin in L18 and LPS-treated Caco-2 cells as compared to only LPS-treated cells. The effect of GABA-secreting L18 on the metataxonome of human stool samples from healthy individuals was investigated by a batch fermentor that mimics the conditions of the human colon. Although, no differences were observed in the α and β diversities of the L18-treated and untreated samples at 24 h, the relative abundances of bacterial families Lactobacillaceae and Bifidobacteriaceae increased in the L18-treated group, but both decreased in the untreated groups. On the other hand, the relative abundance of Enterobacteriaceae decreased in the L18 samples but it increased in the untreated samples. These results indicate that Li. fermentum L18 is a promising GABA-secreting strain that strengthens the gut epithelial barrier by increasing junction protein concentrations and positively modulating the gut microbiota. It has the potential to be used as a psychobiotic or for the production of functional foods for the management of anxiety-related illnesses.


Improving health professionals' management and the organisation of care for overweight and obese people.
Obesity is increasing throughout the industrialised world. If left unchecked it will have major implications for both population health and costs to health services. Health professionals have a key role to play in tackling the obesity problem, but little is known about how they may be encouraged to work more effectively with overweight and obese people. The main objective was to determine whether health professionals' management or the organisation of care for overweight and obese people could be improved. We searched the specialised registers of the Cochrane Effective Practice and Organisation of Care Group (May 1997), the Cochrane Depression, Anxiety and Neurosis Group (August 1997), the Cochrane Diabetes Group (August 1997), the Cochrane Controlled Trials Register (September 1997), MEDLINE to January 1998, EMBASE to December 1997, Cinahl (1982 to November 1997), PsycLit (1974 to December 1997), Sigle (1980 to November 1997), Sociofile (1974 to October 1997), Dissertation Abstracts (1861 to January 1998), Conference Papers Index (1973 to January 1998), Resource Database in Continuing Medical Education. We also hand searched seven key journals and contacted experts in the field. Randomised trials, controlled before-and-after studies and interrupted time series analyses of providers' management of obesity or the organisation of care to improve provider practice or patient outcomes. We addressed three a priori comparisons and a fourth post hoc comparison. 1. Interventions aimed at improving health professionals' management or the delivery of health care for overweight/obese patients are more effective than usual care. 2. Interventions aimed at redressing negative attitudes and related practices towards overweight/obese patients are more effective than usual care. 3. Organisational interventions designed to change the structure of services for overweight/obese people are more effective than educational or behavioural interventions for health professionals. 4. Comparisons of different organisational interventions. Two reviewers independently extracted data and assessed study quality. Twelve studies were included involving more than 393 providers and 3392 patients. Four studies were identified for comparison 1. Three were professional-oriented interventions (the use of reminders and training) and the fourth was a study of professional and organisational interventions of shared care. No studies were identified for comparisons 2 or 3. Eight studies were identified for post hoc comparison 4. These compared either the deliverer of weight loss interventions or the setting of interventions. The included studies were heterogeneous and of generally poor quality. At present, decisions about improving provision of services must be based on the evidence of patient interventions and good clinical judgement. Further research is needed to identify cost effective strategies for improving the management of obesity.


Acute MDMA and Nicotine Co-administration: Behavioral Effects and Oxidative Stress Processes in Mice.
3,4-Methylenedioxy-methylamphetamine (MDMA), a synthetic substance commonly known as ecstasy, is a worldwide recreational drug of abuse. As MDMA and nicotine activate the same neuronal pathways, we examined the influence of co-administration of nicotine (0.05 mg/kg) and MDMA (1 mg/kg) on cognitive processes, nicotine-induced behavioral sensitization and on processes linked with oxidative stress and α7 nicotinic acetylcholine receptors (nAChRs) expression in the brain of male Swiss mice. For behavioral study the passive avoidance (PA) test and locomotor sensitization paradigm were used. Also, the oxidative stress parameters as well as expression levels of α7 nAChRs in prefrontal cortex and hippocampus of mice treated with MDMA alone or in combination with nicotine were assessed. The results revealed that MDMA injections as well as co-administrations of MDMA and nicotine improved memory consolidation in male Swiss mice tested in PA task. Furthermore, one of the main findings of the present study is that MDMA increased locomotor activity in nicotine-sensitized mice. Our study showed for the first time strong behavioral and biochemical interactions between nicotine and MDMA. Both drugs are very often used in combination, especially by young people, thus these results may help explaining why psychoactive substances are being co-abused and why this polydrug administration is still a social problem.


Modelling flock heterogeneity in the transmission of peste des petits ruminants virus and its impact on the effectiveness of vaccination for eradication.
Peste des petits ruminants (PPR) is an acute infectious disease of small ruminants targeted for global eradication by 2030. The Global Strategy for Control and Eradication (GSCE) recommends mass vaccination targeting 70% coverage of small ruminant populations in PPR-endemic regions. These small ruminant populations are diverse with heterogeneous mixing patterns that may influence PPR virus (PPRV) transmission dynamics. This paper evaluates the impact of heterogeneous mixing on (i) PPRV transmission and (ii) the likelihood of different vaccination strategies achieving PPRV elimination, including the GSCE recommended strategy. We develop models simulating heterogeneous transmission between hosts, including a metapopulation model of PPRV transmission between villages in lowland Ethiopia fitted to serological data. Our results demonstrate that although heterogeneous mixing of small ruminant populations increases the instability of PPRV transmission-increasing the chance of fadeout in the absence of intervention-a vaccination coverage of 70% may be insufficient to achieve elimination if high-risk populations are not targeted. Transmission may persist despite very high vaccination coverage (>90% small ruminants) if vaccination is biased towards more accessible but lower-risk populations such as sedentary small ruminant flocks. These results highlight the importance of characterizing small ruminant mobility patterns and identifying high-risk populations for vaccination and support a move towards targeted, risk-based vaccination programmes in the next phase of the PPRV eradication programme. Our modelling approach also illustrates a general framework for incorporating heterogeneous mixing patterns into models of directly transmitted infectious diseases where detailed contact data are limited. This study improves understanding of PPRV transmission and elimination in heterogeneous small ruminant populations and should be used to inform and optimize the design of PPRV vaccination programmes.


Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations.
Prion propagation involves the conversion of cellular prion protein (PrPC) into a disease-specific isomer, PrPSc, shifting from a predominantly alpha-helical to beta-sheet structure. Here, conditions were established in which recombinant human PrP could switch between the native alpha conformation, characteristic of PrPC, and a compact, highly soluble, monomeric form rich in beta structure. The soluble beta form (beta-PrP) exhibited partial resistance to proteinase K digestion, characteristic of PrPSc, and was a direct precursor of fibrillar structures closely similar to those isolated from diseased brains. The conversion of PrPC to beta-PrP in suitable cellular compartments, and its subsequent stabilization by intermolecular association, provide a molecular mechanism for prion propagation.


Time lapse photography of clouds.
The equipment and procedures used in preparing more than 15,240 m of 16-mm time lapse movies of atmospheric clouds is described. Such photographic records are of great value in establishing a dynamic cloud census of a specific area. Operational techniques, the support diagrams, and the optimum time intervals in use for different types of records are presented.


Inhibition of in vitro macrophage digestion capacity by infection with Leishmania donovani (Protozoa: Kinetoplastida).
Promastigotes of Leishmania donovani transformed into amastigotes and survived in cultured macrophages. Promastigotes of Leptomonas costoris, a kinetoplastid parasite of water striders, transformed into amastigotes but did not survive in cultured macrophages. A significant difference in size between the two species of parasitic protozoa allowed development of a bioassay in which the in vitro digestion rate of L. costoris was taken as a measure of macrophage digestive capacity following preinfection with L. donovani. In a 12- to 24-hr period, macrophage cultures infected with the 2S strain of L. donovani retained 50% more L. costoris than did control macrophages infected with L. costoris alone. The 2S strain has been in culture since 1967 and has retained its infectivity for hamsters, although its virulence is attenuated. In similar experiments with promastigotes of the Khartoum strain of L. donovani, a strain but evidently has lots its infectivity for hamsters, no such suppression of macrophage ability to digest L. costoris was observed. The results suggests that infective strains of Leishmania donovani suppress macrophage function beyond the time at which initial lysosomal fusion with the parasitophorous vacoule occurs.


Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.
The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.


Selective serotonin re-uptake inhibitors potentiate gene blunting induced by repeated methylphenidate treatment: Zif268 versus Homer1a.
There is a growing use of psychostimulants, such as methylphenidate (Ritalin; dopamine re-uptake inhibitor), for medical treatments and as cognitive enhancers in the healthy. Methylphenidate is known to produce some addiction-related gene regulation. Recent findings in animal models show that selective serotonin re-uptake inhibitors (SSRIs), including fluoxetine, can potentiate acute induction of gene expression by methylphenidate, thus indicating an acute facilitatory role for serotonin in dopamine-induced gene regulation. We investigated whether repeated exposure to fluoxetine, in conjunction with methylphenidate, in adolescent rats facilitated a gene regulation effect well established for repeated exposure to illicit psychostimulants such as cocaine-blunting (repression) of gene inducibility. We measured, by in situ hybridization histochemistry, the effects of a 5-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or a combination on the inducibility (by cocaine) of neuroplasticity-related genes (Zif268, Homer1a) in the striatum. Repeated methylphenidate treatment alone produced minimal gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine added to methylphenidate robustly potentiated methylphenidate-induced blunting for both genes. This potentiation was widespread throughout the striatum, but was most robust in the lateral, sensorimotor striatum, thus mimicking cocaine effects. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs, such as fluoxetine, may increase the addiction liability of methylphenidate.


Sickle cell disease up-regulates vasopressin, aquaporin 2, urea transporter A1, Na-K-Cl cotransporter 2, and epithelial Na channels in the mouse kidney medulla despite compromising urinary concentration ability.
Sickle cell disease (SCD)-induced urinary concentration defect has been proposed as caused by impaired ability of the occluded vasa recta due to red blood cell sickling to serve as countercurrent exchangers and renal tubules to absorb water and solutes. However, the exact molecular mechanisms remain largely unknown. The present studies were undertaken to determine the effects of SCD on vasopressin, aquaporin2 (AQP2), urea transporter A1 (UTA1), Na-K-Cl co-transporter 2 (NKCC2), epithelial Na channels (ENaC), aquaporin1 (AQP1), nuclear factor of activated T cells 5 (NFAT5) and Src homology region-2 domain-containing phosphatase-1 (SHP-1), an important regulator of NFAT5, in the Berkeley SCD mouse kidney medulla. Under water repletion, SCD only induced a minor urinary concentration defect associated with increased urinary vasopressin level alone with the well-known effects of vasopressin: protein abundance of AQP2, UTA1 and ENaC-β and apical targeting of AQP2 as compared with non-SCD. SCD did not significantly affect AQP1 protein level. Water restriction had no further significant effect on SCD urinary vasopressin. NFAT5 is also critical to urinary concentration. Instead, water restriction-activated NFAT5 associated with inhibition of SHP-1 in the SCD mice. Yet, water restriction only elevated urinary osmolality by 28% in these mice as opposed to 104% in non-SCD mice despite similar degree increases of protein abundance of AQP2, NKCC2 and AQP2-S256-P. Water-restriction had no significant effect on protein abundance of ENaC or AQP1 in either strain. In conclusion, under water repletion SCD, only induces a minor defect in urinary concentration because of compensation from the up-regulated vasopressin system. However, under water restriction, SCD mice struggle to concentrate urine despite activating NFAT5. SCD-induced urinary concentration defect appears to be resulted from the poor blood flow in vasa recta rather than the renal tubules' ability to absorb water and solutes.


Four-year treatment outcomes of adult patients enrolled in Mozambique's rapidly expanding antiretroviral therapy program.
In Mozambique during 2004-2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported. In a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004-2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4(+) T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3-1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6-2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3-2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0-1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2-1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively. ART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed.


Continuing professional development in nursing in Australia: current awareness, practice and future directions.
Australian nurses and midwives are expected to compile a professional development portfolio during their annual registration process. This study aimed to ascertain the current understanding, practice and future continuing professional development (CPD) needs of nurses and midwives employed in a regional area of Queensland, Australia. Perceived barriers and incentives for CPD were also measured. 289 public and private hospital nurses and midwives responded to the survey. Results showed that participants understood the new requirements, valued ongoing learning, preferred education to occur within work hours, and considered their workplaces as accepting of change. Approximately two-thirds of participants believed CPD should be shared between them and their employers. Barriers to undertaking CPD included understaffing, and the concern that CPD would interfere with time outside work. Organisational support positively influenced attitudes to CPD. This study highlights the importance of supportive management in encouraging their workforce to embrace ongoing learning and change.


Which obesity index best explains the link between adipokines, coronary heart disease risk and metabolic abnormalities in type 2 diabetes mellitus?
The aim of this study was to determine, which of: body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist circumference (WC) correlates best with adipokines and is, therefore, the most suitable for the assessment of insulin resistance (IR), metabolic syndrome (MS), type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) risk. We studied 248 T2DM patients classified by gender, IR, MS and CHD. Fasting adiponectin, leptin, resistin, high-sensitivity C-reactive protein (CRP), insulin, glucose, IR (HOMA), and lipid profile were measured. Univariate and multivariate regression analyses were used to find the associations of these variables with each other and with IR, MS and CHD. Receiver operating characteristic (ROC) analyses were used to find the best markers of IR, MS and CHD. There were gender differences in the correlations and associations of BMI, WHR, WHtR and WC with IR, MS and CHD; e.g. in males, WHR showed significant correlation with only resistin (r = 0.30) and leptin (r = 0.39) whereas in females, it showed significant correlations with only adiponectin (r = -0.33). In males and females WHR showed the weakest correlations with CRP and the adipokines and BMI showed the highest correlations. ROC analysis showed that the BMI had the highest diagnostic values for detection of IR, MS and CHD; WHR had the worst diagnostic value. Anthropometric indices show differences in performance and associations with adipokines, CRP, IR, MS and CHD. In patients with T2DM, BMI should be the preferred marker for risk assessment on account of its association with adipokines and diagnostic performance characteristics.


Effect of aggregation state of hard segment in segmented poly(urethaneureas) on their fatigue behavior after interaction with blood components.
Characterization of microphase separated structure, interaction with blood components, such as lipids, and fatigue behavior after immersion in blood components were carried out for segmented poly(urethaneureas). The materials studied were Biomer and segmented poly(urethaneurea) (TU-Mn) composed of hard segment with 4,4'-diphenylmethane diisocyanate (MDI)-ethylenediamine (EDA) or 4,4'-diaminodiphenylmethane (DAM) and soft segment with MDI-polytetramethylene glycol (PTMG) [Mn of 856, 1350, and 2000]. Small-angle x-ray scattering, wide-angle x-ray diffraction, and dynamic viscoelastic measurements revealed that these materials showed the state of microphase separation. TU-Mn with PtMG of Mn = 856 shows the partial phase mixing between hard and soft segments, and phase separation was improved with an increase of Mn of PTMG. Biomer has the characteristics of stronger aggregation of hard segment than that of TU-Mn. All the specimen showed lipid absorption, but the amount of absorption decreased remarkably after precoating on the specimen surface with serum albumin. Lipid absorption of the specimen was confirmed by dynamic viscoelastic and IR measurements. In the case of segmented poly(urethaneurea) which did not immersed in lipids solution, their fatigue strength are sufficient for application to artificial heart systems. However, fatigue strength of the TU-Mn series was decreased drastically after absorption of lipids. On the other hand, Biomer did not show a decrease of fatigue strength after lipid absorption. The reduction of fatigue strength in the TU-Mn series after lipid absorption will be attributed to the weak aggregation of hard segment domain. This reduction of fatigue strength in the TU-Mn series is characterized by formation of microcrack and mirror zone in fatigue fractured specimen. As the precoating of the specimen surface with serum albumin inhibits the absorption of lipids, the reduction of fatigue strength was not observed for the specimen precoated with serum albumin even after immersing the TU-Mn series in lipids solution for 96 days.


Distribution and content of nuclear and cellular RNA among cell populations of acute lymphoblastic and nonlymphoblastic leukemia.
The RNA content of intact cells and isolated nuclei of normal human lymphocytes and mononuclear cell populations (containing at least 50% blasts) from patients with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL) was measured by flow cytometry based on metachromatic red luminescence of acridine orange-stained cells. Relative nuclear RNA (n-RNA) and cellular RNA (c-RNA) content was estimated in relation to luminescence of RNase-treated nuclei, which served as a standard. The mean values (+/- SE) of n-RNA were 22.6 +/- 3.2, 25.8 +/- 3.2, and 51.5 +/- 6.1 arbitrary units for normal lymphocytes, ALL, and ANLL cell populations, respectively. The mean values for c-RNA were 51.3 +/- 5.2, 71.9 +/- 11.3, and 128 +/- 13.4 for the same cell populations, respectively. The differences between normal lymphocytes or ALL and ANLL cell populations were statistically significant (t-test, with respect to both n- and c-RNA), while differences between normal and ALL populations were not. The proportions of n-RNA versus c-RNA were similar within all three types of cell populations. The intercellular variabilities with respect to n- and c-RNA among the G0/1 cell populations of all three types of cells were characterized by the coefficient of variation (CV) of the mean RNA and the third moment about the mean (MOM3). CV and MOM3 of c-RNA were significantly different between all three types of cell populations, whereas CV and MOM3 of n-RNA showed significant differences between control and leukemic cells. Thus, mean RNA, CV, and MOM3 of RNA on the cellular and nuclear levels of G0/1 cells discriminate normal lymphocytes, ALL lymphoblasts, and ANLL blast cells from each other fully on statistically significant levels.


Non-covalent interactions in electrochemical reactions and implications in clean energy applications.
Understanding and controlling non-covalent interactions associated with solvent molecules and redox-inactive ions provide new opportunities to enhance the reaction entropy changes and reaction kinetics of metal redox centers, which can increase the thermodynamic efficiency of energy conversion and storage devices. Here, we report systematic changes in the redox entropy of one-electron transfer reactions including [Fe(CN)6]3-/4-, [Fe(H2O)6]3+/2+ and [Ag(H2O)4]+/0 induced by the addition of redox inactive ions, where approximately twenty different known structure making/breaking ions were employed. The measured reaction entropy changes of these redox couples were found to increase linearly with higher concentration and greater structural entropy (having greater structure breaking tendency) for inactive ions with opposite charge to the redox centers. The trend could be attributed to the altered solvation shells of oxidized and reduced redox active species due to non-covalent interactions among redox centers, inactive ions and water molecules, which was supported by Raman spectroscopy. Not only were these non-covalent interactions shown to increase reaction entropy, but they were also found to systematically alter the redox kinetics, where increasing redox reaction energy changes associated with the presence of water structure breaking cations were correlated linearly with the greater exchange current density of [Fe(CN)6]3-/4-.


Participation and program outcomes in a church-based cancer prevention program for Hispanic women.
This study examined program attendance and related outcomes for Compañeros en la Salud, a church-based culturally focused health promotion program specifically designed for low-acculturated, low-income Hispanic women. In this church-based study, the cancer prevention intervention was the major intervention group, and its effects were compared with a noncancer-oriented family mental health group. The goal of the present study was to identity predictors of program attendance and increases in cancer prevention knowledge and behaviors. Lower levels of acculturation level and greater overall church attendance were predictive of program attendance for Hispanic women in the cancer prevention component. Also, attendance in the cancer intervention component of the Compañeros en la Salud program was predictive of posttest cancer prevention knowledge. By contrast, higher acculturation level was a significant predictor of having had a clinical breast exam at posttest. Similarly, younger age and lower fear of cancer were predictive of having had a pap smear at posttest. Finally, pretest cancer prevention knowledge was a significant predictor of mammography screening for women ages 40 and over. These results offer implications for the development of culturally tailored cancer prevention programs for Hispanic women.


[Redo Valve Replacement of Wada-Cutter Prosthetic Valve at Tricuspid Valve Position 47 Years After Implantation;Report of a Case].
We experienced an explantation of Wada-Cutter prosthetic tilting disk valve of 47 years after implantation. The patient was 53 years old female who underwent the 1st operation for Ebstein's anomaly, which included tricuspid valve replacement (TVR), closure of atrial septal defect (ASD) and posterior annulorrhaphy when she was 6 years old. She was doing well after the 1st operation without symptom,but dyspnea and systemic edema worsened recently though increased admission of diuretics. Echocardiography revealed severe tricuspid valve stenosis, severe tricuspid valve insufficiency, and increased right atrium volume. The tilting disk of the valve was almost fixed. The patient underwent repeat TVR. The explanted Wada-Cutter valve was covered by pannus the whole casing and disk. The structure of the valve was preserved but the occlusion disk was almost fixed by pannus formation, not distorted or dislodged.


Heterogeneity of nucleoside transport in mammalian cells. Two types of transport activity in L1210 and other cultured neoplastic cells.
The characteristics of nucleoside transport were examined in L1210 murine leukemia cells and five other cultured neoplastic cells. The initial rates of uridine, adenosine, and thymidine transport in L1210 cells were only partially inhibited by 1 microM nitrobenzylthioinosine (NBMPR), a potent inhibitor of nucleoside transport in other cells. The IC50 for NBMPR inhibition of uridine transport was 5 nM, but 20% of the activity remained insensitive to concentrations as high as 3 microM. Uridine uptake in the presence of 1 microM NBMPR was saturable and was inhibited by other nucleosides, suggesting the participation of an NBMPR-insensitive transport mechanism. There appeared to be little difference in the specificity of NBMPR-sensitive and -insensitive transport for the physiological nucleosides. Uridine, adenosine, and thymidine were all substrates for both mechanisms, and the Km values for total and NBMPR-insensitive uridine transport were the same (250 microM). Furthermore, little difference was found in the ability of several other nucleosides to inhibit total or NBMPR-insensitive uridine transport. In both cases, adenosine was the most effective inhibitor while cytidine and deoxycytidine were the least effective. The two transport processes did, however, differ from each other in their sensitivity to p-mercuribenzenesulfonate (pMBS). NBMPR-insensitive uridine transport was inhibited by pMBS with an IC50 less than 25 microM, while the IC50 for NBMPR-sensitive transport was greater than 400 microM. Cloning of the parent L1210 cell line indicated that both NBMPR-sensitive and -insensitive transport occurred in the same cell. Both types of uridine transport activity were also observed in three other cell lines (RPMI 6410, L5178Y, and P388), while two lines, S49 and Walker 256, exhibited only NBMPR-sensitive and -insensitive transport, respectively. The level of NBMPR-insensitive transport was an important determinant in the ability of NBMPR to inhibit uridine uptake over prolonged periods (10 min), with as little as 20% NBMPR-insensitive transport sufficient to render uptake over 10 min virtually insensitive to NBMPR. The existence of these two types of nucleoside transport activity in mammalian cells may have important implications in the chemotherapeutic use of transport inhibitors in combination with cytotoxic nucleosides or with inhibitors of pyrimidine and purine biosynthesis.


Nurses' responses to suicide and suicidal patients: a critical interpretive synthesis.
To provide an inclusive understanding of nurses' responses to suicide and suicidal patients that can benefit nursing practice and guide research. The question was 'What is a critical interpretive synthesis of accumulated nursing research on nurses' responses to suicide and suicidal patients?' Various studies address nurses' responses to suicide and suicidal patients. An understanding of accumulated research-based literature about nurses' responses to suicide and suicidal patients may guide nurses to care for suicidal patients in ways that facilitate suicide prevention and recovery. The design is reflexive and iterative. A Critical Interpretive Synthesis was conducted, which comprised of six phases: formulating the review question, searching the literature, sampling, determining quality, extracting data and conducting an interpretive synthesis. Qualitative content analysis and systematic review of literature was included in these phases. The results report the review question, literature review strategies, purposive sample (26 full-text studies published in peer reviewed journals, 1988-July 2009, conducted mostly in Europe and North American), quality determinants, data extraction into themes and an interpretive synthesis of four key concepts, i.e. critical reflection, attitudes, complex knowledge/professional role responsibilities, desire for support services/resources. This understanding of accumulated research-based literature enhances contextual, conceptual and methodological perspectives. Contextually, gaps exist in international research. Conceptually, the four key concepts can serve as a useful guide for nurses to understand their own and other nurses' responses to caring for suicidal patients in various settings. Methodologically, the Critical Interpretive Synthesis approach moved a small body of knowledge that varied in quality measures beyond an aggregate understanding. Understanding nurses' responses to suicide and suicidal patients may guide nurses to care for suicidal patients in ways that facilitate suicide prevention and recovery, thus addressing the urgent work of suicide prevention in the world.


Product quality risk perceptions and decisions: contaminated pet food and lead-painted toys.
In the context of the recent recalls of contaminated pet food and lead-painted toys in the United States, we examine patterns of risk perceptions and decisions when facing consumer product-caused quality risks. Two approaches were used to explore risk perceptions of the product recalls. In the first approach, we elicited judged probabilities and found that people appear to have greatly overestimated the actual risks for both product scenarios. In the second approach, we applied the psychometric paradigm to examine risk perception dimensions concerning these two specific products through factor analysis. There was a similar risk perception pattern for both products: they are seen as unknown risks and are relatively not dread risks. This pattern was also similar to what prior research found for lead paint. Further, we studied people's potential actions to deal with the recalls of these two products. Several factors were found to be significant predictors of respondents' cautious actions for both product scenarios. Policy considerations regarding product quality risks are discussed. For example, risk communicators could reframe information messages to prompt people to consider total risks packed together from different causes, even when the risk message has been initiated due to a specific recall event.


Gazing at Cell Wall Expansion under a Golden Light.
In plants, cell growth is constrained by a stiff cell wall, at least this is the way textbooks usually present it. Accordingly, many studies have focused on the elasticity and plasticity of the cell wall as prerequisites for expansion during growth. With their specific evolutionary history, cell wall composition, and environment, brown algae present a unique configuration offering a new perspective on the involvement of the cell wall, viewed as an inert material yet with intrinsic mechanical properties, in growth. In light of recent findings, we explore here how much of the functional relationship between cell wall chemistry and intrinsic mechanics on the one hand, and growth on the other hand, has been uncovered in brown algae.


Shock wave sensors: I. Requirements and design.
In the last 9 years, extracorporeal shock wave lithotripsy has become one of the preferred procedures for the treatment of urinary and gallbladder calculi. While there is still uncertainty as to the mechanisms of stone fragmentation, current hypotheses suggest that acoustical shock wave parameters such as rise time, peak compressional and rarefactional pressure, and frequency content may all influence the treatment's efficiency. Thus, optimization of lithotripsy treatment needs pressure sensors that can adequately characterize the shock wave field. This article presents and discusses the design of reliable, wideband, quantitative shock wave sensors made of piezoelectric material. The development, design, and performance characteristics of the sensors are presented. Sensor construction details are described, as are the methods used to characterize the sensor's acoustical performance. The key acoustical parameters of the sensor, its frequency response, and directivity pattern are presented; theory indicates that the probes feature uniform sensitivity over the frequency range up to 100 MHz. Preliminary experimental results indicate that piezoelectric polymer sensors made of polyvinylidene fluoride (PVDF) with a low acoustical impedance backing are suitable for lithotripter field measurements. The applicability of sensors based on fiber optics to shock wave measurements is also briefly discussed. In a companion article, shock wave measurement techniques are outlined and selected lithotripter test data are presented.


Consequences of the instar stage for behavior in a pit-building antlion.
Pit-building antlion larvae are opportunistic predators that dig conical pits in loose soils, and prey on small arthropods that fall into their traps. We investigated different behavioral traits of second and third instar larvae selected for similar body masses, while also exploring the behavioral consistency and personalities of the third instar stage. Second instar larvae constructed smaller pits than third instar larvae. The former also responded more slowly to prey and exploited prey less efficiently. Notably, all these instar-based differences disappeared after molting into the third instar stage. In addition, third instar larvae exhibited consistent behavior in their pit size, response times to prey and to less extent in relocation distances. We detected two axes of behavior. The first axis included a correlation between pit size, response time and prey exploitation efficiency, thus reflecting investment in foraging activity. The second axis seemed to represent a trade-off between response time and relocation distance, implying that individuals that responded more slowly to prey, relocated over larger distances. These results point to coordinated behavior reflecting different levels of investment in foraging, while also emphasizing the importance of instar stage, in addition to body mass, when studying the behavior of such organisms characterized by a complex life cycle.


Multi-locus genome-wide association study and genomic prediction for flowering time in chrysanthemum.
Multi-locus GWAS detected several known and candidate genes responsible for flowering time in chrysanthemum. The associations could greatly increase the predictive ability of genome selection that accelerates the possible application of GS in chrysanthemum breeding. Timely flowering is critical for successful reproduction and determines the economic value for ornamental plants. To investigate the genetic architecture of flowering time in chrysanthemum, a multi-locus genome-wide association study (GWAS) was performed using a collection of 200 accessions and 330,710 single-nucleotide polymorphisms (SNPs) via 3VmrMLM method. Five flowering time traits including budding (FBD), visible colouring (VC), early opening (EO), full-bloom (OF) and senescing (SF) stages, plus five derived conditional traits were recorded in two environments. Extensive phenotypic variations were observed for these flowering time traits with coefficients of variation ranging from 6.42 to 38.27%, and their broad-sense heritability ranged from 71.47 to 96.78%. GWAS revealed 88 stable quantitative trait nucleotides (QTNs) and 93 QTN-by-environment interactions (QEIs) associated with flowering time traits, accounting for 0.50-8.01% and 0.30-10.42% of the phenotypic variation, respectively. Amongst the genes around these stable QTNs and QEIs, 21 and 10 were homologous to known flowering genes in Arabidopsis; 20 and 11 candidate genes were mined by combining the functional annotation and transcriptomics data, respectively, such as MYB55, FRIGIDA-like, WRKY75 and ANT. Furthermore, genomic selection (GS) was assessed using three models and seven unique marker datasets. We found the prediction accuracy (PA) using significant SNPs identified by GWAS under SVM model exhibited the best performance with PA ranging from 0.90 to 0.95. Our findings provide new insights into the dynamic genetic architecture of flowering time and the identified significant SNPs and candidate genes will accelerate the future molecular improvement of chrysanthemum.


Endocrine responses to the oral ingestion of a physiological dose of essential amino acids in humans.
The response of insulin, human growth hormone (hGH), cortisol, leptin and ghrelin, in addition to various metabolic parameters, was measured at 10 minute intervals following the oral ingestion of a standardised physiological dose of essential amino acids (AA). Twenty-eight healthy male, fasted volunteers (aged 18-40 yrs, BMI 18.0-24.5 kg/m(2)) took part in the study; 13 volunteers in the AA group, nine subjects in an iso-caloric control group, and a further six subjects served as fasting controls. Twenty minutes after ingestion, insulin reached peak concentrations that were up to 500% higher than basal values (P<0.0001). The AA group and iso-caloric control group showed a similar insulin response. AA ingestion led to an increase in hGH secretion with maximum concentrations being 2100+/-1013% higher than the basal values (P<0.0001). In contrast, no changes in hGH concentrations were observed in the iso-caloric controls; in the fasting controls only a slight increase in hGH was found towards the end of the fasting period. While cortisol decreased significantly (P<0.01) during the study in the AA group, neither control group showed a significant change in this parameter. Changes in leptin levels remained insignificant in all three groups, whereas ghrelin showed a different profile in each of the three groups, i.e. a continuous rise towards the end of the study period (P<0.001) in the AA group, a less significant effect for the fasting group, and no effect at all in the iso-caloric control group. There was no significant correlation between the concentrations or the area under curve of the hormones measured in any of the groups. The endocrine data provided in this study indicate that a single bolus of essential AA in fasted individuals is associated with both anabolic and catabolic hormonal responses.


Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 in melanoma cells through Egr-1.
The hepatocyte growth factor/scatter factor (HGF/SF) receptor c-Met and variants of the CD44 family of surface adhesion molecules, including CD44v6, have been implicated in cancer progression and metastasis. CD44 isoforms bearing heparin sulfate chains can bind to HGF/SF and facilitate its presentation to c-Met. Here, we demonstrate that HGF/SF-Met binding up-regulates the expression of CD44v6 in murine melanoma cells, serving to compensate for loss by internalization. c-Met-mediated CD44v6 up-regulation was achieved through transcriptional activation of the immediate early gene egr-1. Enhanced egr-1 expression was apparent at the level of RNA 40 min after exposure to HGF/SF, and Egr-1 protein was detectable between 1 and 2 h post-treatment. CD44v6 RNA levels were correspondingly elevated 2 h after HGF/SF exposure. HGF/SF induced egr-1 activation via the Ras>Erk1/2 pathway but not through either phosphatidylinositol 3'-kinase or protein kinase C. Binding of NK2, a naturally occurring splice variant of HGF/SF, to c-Met failed to induce either Egr-1 or CD44v6, accounting at least in part for its antagonistic behavior. We also identified an Egr-1-binding site in the mouse CD44 gene promoter that accounts for its responsiveness to HGF/SF in melanoma cells. The compensatory up-regulation of both c-Met and CD44v6 in response to HGF/SF has important implications with respect to strategies used by cancer cells to sustain stimulation of growth- and metastasis-promoting pathways associated with tumor progression.


Beta-lactam allergy in patients: an antibiotic stewardship challenge.
Patients are commonly reported as being allergic to beta-lactam (BL) antibiotics. However, many patients with this reported allergy are able to receive BL treatments because they do not have true allergies. In many cases these are simply intolerances due to side effects reported as an allergy. Delabelling these patients leads to better clinical outcomes, optimal antibiotic usage, decreased bacterial resistance and reduced healthcare costs. Therefore, the aims of this study were to identify incorrectly labelled BL allergies in hospitalised patients and to assess antibiotic use in delabelled patients in order to establish a quality indicator to optimise antimicrobial treatments. A prospective study was conducted in which hospitalised patients treated with antimicrobial drugs and labelled as 'BL-allergic' were identified by clinical pharmacists. An allergist assessed whether patients were suitable candidates for a skin test or oral challenge. The Allergy Service removed 'BL-allergic' labels if negative results were obtained. Delabelled patients were followed up by clinical pharmacists to study the use of BL antibiotics as a result of the delabelling programme. A total of 176 suspected allergic patients were identified and 91 (51.7%) were tested either by a skin test or oral challenge based on the patient indicators. Seven (16.4%) patients tested were allergic to BL antibiotics, 76 (83.5%) were totally delabelled and eight (0.1%) were partially delabelled. Thirty-two (38.1%) delabelled patients required antibiotic treatment in another inpatient or outpatient setting, of whom 27 (84.3%) patients with a new infectious episode received BL treatments while five (15.7%) continued to receive antimicrobial treatments without BL. After the implementation of a protocol to detect incorrect BL allergy labels, 83.5% of the patients in this cohort were completely delabelled. This shows that there is a clear opportunity to optimise the use of antibiotics by delabelling 'BL-allergic' patients.


New biocomposites based on bioplastic flax fibers and biodegradable polymers.
A new generation of entirely biodegradable and bioactive composites with polylactic acid (PLA) or poly-ε-caprolactone (PCL) as the matrix and bioplastic flax fibers as reinforcement were analyzed. Bioplastic fibers contain polyhydroxybutyrate and were obtained from transgenic flax. Biochemical analysis of fibers revealed presence of several antioxidative compounds of hydrophilic (phenolics) and hydrophobic [cannabidiol (CBD), lutein] nature, indicating their high antioxidant potential. The presence of CBD and lutein in flax fibers is reported for the first time. FTIR analysis showed intermolecular hydrogen bonds between the constituents in composite PLA+flax fibers which were not detected in PCL-based composite. Mechanical analysis of prepared composites revealed improved stiffness and a decrease in tensile strength. The viability of human dermal fibroblasts on the surface of composites made of PLA and transgenic flax fibers was the same as for cells cultured without composites and only slightly lower (to 9%) for PCL-based composites. The amount of platelets and Escherichia coli cells aggregated on the surface of the PLA based composites was significantly lower than for pure polymer. Thus, composites made of PLA and transgenic flax fibers seem to have bacteriostatic, platelet anti-aggregated, and non-cytotoxic effect.


[Treatment of renal artery stenosis with intra-arterial stents].
In some patients with hypertension or renal insufficiency, renal artery stenosis can play a causative part. If fibromuscular dysplasia is the pathology of the stenosis, treatment of the stenosis by transluminal percutaneous renal angioplasty (TPRA) results in improvement of the concomitant hypertension in 80-90% of the patients. In case of atherosclerotic lesions 50% of the patients benefit by such treatment. In renal insufficiency TPRA of atherosclerotic lesions results in improvement of renal function in only one third of the patients. As restenosis and elastic recoil are seen as the prime determinants of this lack of success in atherosclerosis, intravascular stents were developed with the aim to accomplish a permanent dilation of the arterial lumen. In recent studies stent placement resulted in cure of high blood pressure in 0-16% of the patients and in improvement in 35-70%. The percentage of improvement must be viewed with caution because of the open design of these studies. Improvement of renal function was reported in 7-36% of the patients and worsening in 8-18%. Based on these outcomes stent placement in stenosed renal arteries should not be regarded as a routine clinical treatment.


Surface versus untargeted intramuscular EMG based classification of simultaneous and dynamically changing movements.
The pattern recognition-based myoelectric control scheme is in the process of being implemented in clinical settings, but it has been mainly tested on sequential and steady state data. This paper investigates the ability of pattern recognition to resolve movements that are simultaneous and dynamically changing and compares the use of surface and untargeted intramuscular EMG signals for this purpose. Ten able-bodied subjects participated in the study. Both EMG types were recorded concurrently from the right forearm. The subjects were instructed to track dynamic contraction profiles using single and combined degrees of freedom in three trials. During trials one and two, the amplitude and the frequency of the profile were kept constant (nonmodulated data), and during trial three, the two parameters were modulated (modulated data). The results showed that the performance was up to 93% for nonmodulated tasks, but highly depended on the nature of the data used. Surface and untargeted intramuscular EMG had equal performance for data of similar nature (nonmodulated), but the performance of intramuscular EMG decreased, compared to surface, when tested on modulated data. However, the results of intramuscular recordings obtained in this study are promising for future use of implantable electrodes, because, besides the value added in terms of potential chronic implantation, the performance is theoretically the same as for surface EMG provided that enough information is captured in the recordings. Nevertheless, care should be taken when training the system since data obtained from selective recordings probably need more training data to generalize to new signals.


Amphiphobic Polytetrafluoroethylene Membranes for Efficient Organic Aerosol Removal.
Polytetrafluoroethylene (PTFE) membrane is an extensively used air filter, but its oleophilicity leads to severe fouling of the membrane surface due to organic aerosol deposition. Herein, we report the fabrication of a new amphiphobic 1H,1H,2H,2H-perfluorodecyl acrylate (PFDAE)-grafted ZnO@PTFE membrane with enhanced antifouling functionality and high removal efficiency. We use atomic-layer deposition (ALD) to uniformly coat a layer of nanosized ZnO particles onto porous PTFE matrix to increase surface area and then subsequently graft PFDAE with plasma. Consequently, the membrane surface showed both superhydrophobicity and oleophobicity with a water contact angle (WCA) and an oil contact angle (OCA) of 150° and 125°, respectively. The membrane air permeation rate of 513 (m(3) m(-2) h(-1) kPa(-1)) was lower than the pristine membrane rate of 550 (m(3) m(-2) h(-1) kPa(-1)), which indicates the surface modification slightly decreased the membrane air permeation. Significantly, the filtration resistance of this amphiphobic membrane to the oil aerosol system was much lower than the initial one. Moreover, the filter exhibited exceptional organic aerosol removal efficiencies that were greater than 99.5%. These results make the amphiphobic PTFE membranes very promising for organic aerosol-laden air-filtration applications.


[Fatal pneumonitis due to oseltamivir-resistant new influenza A(H1N1) in the case of an intensive care patient].
A 58-year-old man was submitted to our intensive care ward with respiratory failure due to pneumonitis. He had previously been treated for non-Hodgkin lymphoma by autologous stem cell transplantation, as a result of which bone marrow function was reduced. Further analysis showed infection with new influenza A(H1N1); typing revealed an oseltamivir-resistant subpopulation (H275Y). The patient was treated with oseltamivir and intravenously with zanamivir, but died of respiratory disease progression. This is the first published case of oseltamivir-resistant new influenza A(H1N1) infection in the Netherlands.


Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking.


The cycle of distrust in health policy and behavior: Lessons learned from the Negev Bedouin.
Over the last decades, health systems worldwide have faced a decline in public trust. For marginalized minority populations, who generally suffer from poverty and political exclusion, the roots of this trend go much deeper, establishing a state of bi-directional distrust between them and health institutions. Although studied to a lesser extent compared to trust, distrust does impede health initiatives, such as infectious diseases prevention programs, mostly of so-called Neglected Zoonotic Diseases (NZDs). Where distrust prevails, even trust building actions such as defining rights and obligations, prioritizing "the greater good" and increasing transparency, are prone to failure. In this study, we deepen the understanding of the concept of distrust through a unique case study of Brucellosis, a prevalent bacterial zoonotic disease endemic to disadvantaged Bedouin communities in southern Israel. In the years 2015-2019, we qualitatively studied socio-political aspects in a governmental Brucellosis control campaign in southern Israel. We used in-depth interviews with 38 governmental and private health workers, agriculture and nature preservation workers, livestock owners and community leaders. Further, we conducted participant observation in 10 livestock pens and in policymaking meetings, and collected policy and media documents in order to triangulate the results. We conceptualize three different types of distrust between authorities and marginalized communities-"intention-based distrust", "values-based distrust" and "circular distrust"-to better explain how distrust originates and reinforces itself, reproducing the endemicity of NZDs. Based on that, we portray a practical framework to reduce distrust in health policies, by reframing local discourses, reshaping disease monitoring schemes from enforcement-based to participation-based, and promoting political inclusion of disadvantaged communities. The suggested analysis and framework redirect health policy objectives to not only acknowledge, contain and reduce the consequences of distrust, but also to strive for societal justice as a tool for health promotion.


Characterization of a new human multiple myeloma cell line, UMJF-2, which suppresses antibody production by B-lymphocytes in vitro.
A new human plasma cell line, UMJF-2, has been derived from the bone marrow of a patient with multiple myeloma. Morphological studies disclosed large nucleoli, moderate numbers of mitochondria, and scant endoplasmic reticulum consistent with a plasmablastic morphology. The cells have immunologic characteristics of early plasma cells, including intense expression of cytoplasmic IgG-lambda and weaker, but discernible, expression of surface IgG-lambda. Cell surface antigens defined by the monoclonal antibodies OKT10 (CD38) and PCA-1, characteristic of mature plasma cells, and B1 (CD20), B4 (CD19), and I-2 (HLA-DR), characteristic of earlier stages of B-lymphocyte differentiation, are present on UMJF-2 cells. Cytogenetic studies reveal the presence of trisomy 12. UMJF-2 does not contain the Epstein-Barr virus by Southern blot analysis. Tissue culture media conditioned by these cells contains a soluble immunosuppressive factor, capable of inhibiting pokeweed mitogen induced IgM secretion by normal human B-lymphocytes. UMJF-2 provides a model for the study of the pathogenesis of polyclonal hypogammaglobulinemia in human multiple myeloma.


Electrocardiogram changes in Thyrotoxic Periodic Paralysis.
Thyrotoxic periodic paralysis (TPP) attacks are characterized as recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. Episodes of weakness are accompanied by hypokalemia, which left untreated can lead to life-threatening arrhythmias (6). In this case study, we followed a patient's potassium levels analyzing how they correlate with electrocardiogram changes seen while treating his hypokalemia and ultimately his paralysis.


Mitochondrial inner membrane bound Pet1402 protein is rapidly imported into mitochondria and affects the integrity of the cytochrome oxidase and ubiquinol-cytochrome c oxidoreductase complexes.
In vitro synthesized Pet1402 precursor protein is very rapidly and efficiently imported into isolated mitochondria. The import depends on a membrane potential and functional mtHsp70. The mitochondrial targeting sequence of the Pet1402 precursor protein is removed by the matrix processing peptidase MPP and the mature protein is firmly embedded in the inner mitochondrial membrane. The Pet1402 protein is required for the integrity of the cytochrome oxidase and ubiquinol-cytochrome c oxidoreductase complexes.


BH3-only activator proteins Bid and Bim are dispensable for Bak/Bax-dependent thrombocyte apoptosis induced by Bcl-xL deficiency: molecular requisites for the mitochondrial pathway to apoptosis in platelets.
A pivotal step in the mitochondrial pathway of apoptosis is activation of Bak and Bax, although the molecular mechanism remains controversial. To examine whether mitochondrial apoptosis can be induced by just a lack of antiapoptotic Bcl-2-like proteins or requires direct activators of the BH3-only proteins including Bid and Bim, we studied the molecular requisites for platelet apoptosis induced by Bcl-xL deficiency. Severe thrombocytopenia induced by thrombocyte-specific Bcl-xL knock-out was fully rescued in a Bak and Bax double knock-out background but not with single knock-out of either one. In sharp contrast, deficiency of either Bid, Bim, or both did not alleviate thrombocytopenia in Bcl-xL knock-out mice. An in vitro study revealed that ABT-737, a Bad mimetic, induced platelet apoptosis in association with a conformational change of the amino terminus, translocation from the cytosol to mitochondria, and homo-oligomerization of Bax. ABT-737-induced Bax activation and apoptosis were also observed in Bid/Bim-deficient platelets. Human platelets, upon storage, underwent spontaneous apoptosis with a gradual decline of Bcl-xL expression despite a decrease in Bid and Bim expression. Apoptosis was attenuated in Bak/Bax-deficient or Bcl-xL-overexpressing platelets but not in Bid/Bim-deficient platelets upon storage. In conclusion, platelet lifespan is regulated by a fine balance between anti- and proapoptotic multidomain Bcl-2 family proteins. Despite residing in platelets, BH3-only activator proteins Bid and Bim are dispensable for Bax activation and mitochondrial apoptosis.


The photocatalytic properties of ultrathin bismuth oxychloride nanosheets: a first principles study.
Two-dimensional (2D) nanosheet structures have obvious advantages with respect to their bulk counterparts in photocatalytic reaction due to their extraordinary electronic and optical properties. So do the 2D BiOCl nanosheets with significant improvement of photocatalytic activity in the degradation of dyes shown by recent studies. In the present work, the surface energies, electronic structure and photocatalytic properties of ultrathin BiOCl nanosheets are examined by means of density functional theory to investigate the origin of their high photocatalytic performance. The results show that the Cl atom terminated BiOCl(001) surface possesses lower surface energy than others and is very likely to be introduced in the ultrathin nanosheet. Moreover, our proposed model accounts well for the origin of band edge upshift of the ultrathin BiOCl nanosheets with respect to BiOCl nanoplates observed in experiments. In addition, the presence of Bi vacancies on the surfaces of nanosheets can enhance the built-in electric field and further promote the separation of photo-generated carriers, which is extremely advantageous for the photocatalytic process. Our results provide a new insight into the high photocatalytic performance of BiOCl(001) nanosheets.


Multilocalization and the van Cittert-Zernike theorem. 2. Application to the Wollaston prism
The van Cittert-Zernike theorem can be used to evaluate visibility at the exit of an amplitude-division interferometer with two-beam interferences. If the source illuminating the interferometer is a periodic array of slits, at the exit there is a sequence of localization surfaces. The formulas for the position and fringe spacing of the principal localization surfaces are applied to a Wollaston quartz prism, and there is good agreement between theoretical and experimental results. Moreover, the fringe localization depth and the intermediate localization surfaces obtained experimentally coincide with those predicted by theory.


Anti-HIV diphyllin glycosides from Justicia gendarussa.
In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B. The compounds are identified as new arylnaphthalide lignans (ANL) glycosides. We further determined that the ANL glycosides are the chemical constituents that contribute to the anti-HIV activity of this plant. Justiprocumin B displayed potent activity against a broad spectrum of HIV strains with IC50 values in the range of 15-21 nM (AZT, IC50 77-95 nM). The compound also displayed potent inhibitory activity against the NRTI (nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-11617-1) of the analogue (AZT) as well as the NNRTI (non-nucleoside reverse transcriptase inhibitor)-resistant isolate (HIV-1N119) of the analogue (nevaripine).


Brachial artery cross-sectional area and distensibility before and after arteriolar vasodilatation in men with sustained essential hypertension.
Blood pressure, volume distensibility (VD), and cross-sectional area (CSA) of the brachial artery were studied using pulsed Doppler systems in 51 patients with sustained essential hypertension in comparison with 21 normotensive controls of the same age. In hypertensive patients, in baseline conditions, CSA was significantly increased and VD decreased--the two parameters strongly and negatively correlated independent of the blood pressure level. Arteriolar vasodilatation was produced by three pharmacological agents--cadralazine, a dihydralazine-like compound; nicorandil, a nicotinamide derivative; and nitrendipine, a calcium entry blocker. For the same blood pressure reduction, cadralazine significantly reduced CSA, while nicorandil and nitrendipine increased it. Nitrendipine significantly increased VD, which was not modified by cadralazine and nicorandil. For cadralazine and nicorandil, a significant negative correlation was observed between VD and CSA. The relationship was the same as in baseline conditions. With nitrendipine, no significant correlation was observed between the two parameters. At any given CSA, distensibility was higher with nitrendipine than with cadralazine or nicorandil. The study provided evidence that, in men with essential hypertension, in basal conditions, the negative relationship between VD and CSA reflected intrinsic alterations of the arterial wall, while cadralazine, nicorandil, and nitrendipine caused a similar degree of arteriolar dilatation, nicorandil and nitrendipine caused active arterial dilatation as well, and changes in distensibility after drug administration were not directly related to blood pressure level and were mediated either by predominant geometrical modifications (cadralazine, nicorandil) or by the predominant relaxing effect of the drug on arterial smooth muscle tone (nitrendipine), or both.


A Fully Protective Congenital CMV Vaccine Requires Neutralizing Antibodies to Viral Pentamer and gB Glycoprotein Complexes but a pp65 T-Cell Response Is Not Necessary.
A vaccine against congenital cytomegalovirus infection is a high priority. Guinea pig cytomegalovirus (GPCMV) is the only congenital CMV small animal model. GPCMV encodes essential glycoprotein complexes for virus entry (gB, gH/gL/gO, gM/gN) including a pentamer complex (gH/gL/GP129/GP131/GP133 or PC) for endocytic cell entry. The cohorts for protection against congenital CMV are poorly defined. Neutralizing antibodies to the viral glycoprotein complexes are potentially more important than an immunodominant T-cell response to the pp65 protein. In GPCMV, GP83 (pp65 homolog) is an evasion factor, and the GP83 mutant GPCMV has increased sensitivity to type I interferon. Although GP83 induces a cell-mediated response, a GP83-only-based vaccine strategy has limited efficacy. GPCMV attenuation via GP83 null deletion mutant in glycoprotein PC positive or negative virus was evaluated as live-attenuated vaccine strains (GP83dPC+/PC-). Vaccinated animals induced antibodies to viral glycoprotein complexes, and PC+ vaccinated animals had sterilizing immunity against wtGPCMV challenge. In a pre-conception vaccine (GP83dPC+) study, dams challenged mid-2nd trimester with wtGPCMV had complete protection against congenital CMV infection without detectable virus in pups. An unvaccinated control group had 80% pup transmission rate. Overall, gB and PC antibodies are key for protection against congenital CMV infection, but a response to pp65 is not strictly necessary.


Packaging of brome mosaic virus RNA3 is mediated through a bipartite signal.
The three genomic and a single subgenomic RNA of brome mosaic virus (BMV), an RNA virus infecting plants, are packaged by a single-coat protein (CP) into three morphologically indistinguishable icosahedral virions with T = 3 quasi-symmetry. Genomic RNAs 1 and 2 are packaged individually into separate particles whereas genomic RNA3 and subgenomic RNA4 (coat protein mRNA) are copackaged into a single particle. We report here that packaging of dicistronic RNA3 requires a bipartite signal. A highly conserved 3' tRNA-like structure postulated to function as a nucleating element (NE) for CP subunits (Y. G. Choi, T. W. Dreher, and A. L. N. Rao, Proc. Natl. Acad. Sci. USA 99:655-660, 2002) and a cis-acting, position-dependent packaging element (PE) of 187 nt present in the nonstructural movement protein gene are the integral components of the packaging core. Efficient incorporation into BMV virions of nonviral RNA chimeras containing NE and the PE provides confirmatory evidence that these two elements are sufficient to direct packaging. Analysis of virion RNA profiles obtained from barley protoplasts transfected with a RNA3 variant lacking the PE provides the first genetic evidence that de novo synthesized RNA4 is incompetent for autonomous assembly whereas prior packaging of RNA3 is a prerequisite for RNA4 to copackage.


[Autoimmune/infl ammatory syndrome induced by adjuvants, ASIA].
There have been many cases of the appearance of autoantibodies and symptoms of disease after exposure to adjuvants, not only after breast augmentation with silicone implants, but also as a very rare vaccination side effect, such as Gulf war syndrome or macrophagic myofasciitis syndrome. Diseases whose symptoms developed after such adjuvant exposure are called autoimmune/ in􀏐lammatory syndrome induced by adjuvants (ASIA). The group of adjuvants includes not only silicone implants, silica, squalen and aluminium, but also ink components used for making tattoos. Analyzing the available reports on the in􀏐luence of adjuvants on the development of autoimmune diseases, the conclusion is that apart from long -term silicone exposure, the coexistence of other factors such as genetic or environmental is also necessary. Metaanalyses clearly do not con􀏐irm an increased risk of developing autoimmune disease after breast augmentation with silicone implants, or tattooing, but it seems that among these patients there is a group that is more predestined to develop disease symptoms. In the general population the bene􀏐its of vaccination are obvious, and the risk of severe adverse events following immunisation is incomparably lower than the risk of developing a speci􀏐ic disease and its complications, also for patients with diagnosed autoimmune diseases. Because of data heterogeneity in previous studies and dif􀏐iculties in diagnosing ASIA it seems necessary to conduct further analyses of adjuvants' in􀏐luence on autoimmune disease development, and to re􀏐ine ASIA diagnostic criteria, which now allow too easy a diagnosis of this syndrome.


The activity of cAMP-dependent protein kinase is required at a posttranslational level for induction of voltage-dependent sodium channels by peptide growth factors in PC12 cells.
The synthesis and expression of voltage-dependent sodium (Na) channels is a crucial aspect of neuronal differentiation because of the central role these ion channels play in the generation of action potentials and the transfer of information in the nervous system. We have used rat pheochromocytoma (PC12) cell lines deficient in cAMP-dependent protein kinase (PKA) activity to examine the role of PKA in the induction of Na channel expression by nerve growth factor (NGF) and basic FGF (bFGF). In the parental PC12 cell line both NGF and bFGF elicit an increase in the density of functional Na channels, as determined from whole-cell patch clamp recordings. This increase does not occur in two PC12 cell lines deficient in both isozymes of PKA (PKAI and PKAII), and is strongly reduced in a third line deficient in PKAII, but not PKAI. Despite the inability of the neurotrophic factors to induce functional Na channel expression in the PKA-deficient cells, Northern blot hybridization studies and saxitoxin binding assays of intact cells indicate that NGF and bFGF are still capable of eliciting increases in both Na channel mRNA and Na channel protein in the membrane. Thus, PKA activity appears to be necessary at a posttranslational step in the synthesis and expression of functional Na channels, and thereby plays an important role in determining neuronal excitability.


Management of anesthesia in pregnant women with pulmonary hypertension.
Pulmonary hypertension (PH) is a rare heart disease associated with high maternal and fetal mortality. This study aims to discuss anesthesia management and the fetal and maternal outcomes of patients with PH followed-up at our clinic. This study includes a retrospective analysis of 105 pregnant women with PH. The patients were classified according to the mean pulmonary artery pressure (mPAP) values measured at rest by transthoracic echocardiography. The first group included patients with an mPAP value between 25 and 49 mmHg, considered to have a mild PH, whereas patients with an mPAB value ≥50 mmHg were considered to have severe PH and were included in the second group. When the patients were examined for etiology, the majority (n=84, 70.5%) were found to have type 2 PH. It was found that in pregnant women with severe PH, the diameters of the left atrium, right atrium, and right ventricle were significantly larger (p=0.008, p=0.04, and p=0.013, respectively), and the ejection fraction was also significantly lower (p=0.04). Although there has been a partial decrease in mortality for PH in recent years, it is still a serious condition that requires a multidisciplinary approach and well-planned obstetric treatment.