Kinematic simulation of turbulent dispersion of triangles.
As three particles are advected by a turbulent flow, they separate from each other and develop nontrivial geometries, which effectively reflect the structure of the turbulence. We investigate here the geometry, in a statistical sense, of three Lagrangian particles advected, in two dimensions, by kinematic simulation (KS). KS is a Lagrangian model of turbulent diffusion that makes no use of any delta correlation in time at any level. With this approach, situations with a very large range of inertial scales and varying persistence of spatial flow structure can be studied. We first demonstrate that the model flow reproduces recent experimental results at low Reynolds numbers. The statistical properties of the shape distribution at a much higher Reynolds number is then considered. The numerical results support the existence of nontrivial shape statistics, with a high probability of having elongated triangles. Even at the highest available inertial range of scales, corresponding to a ratio between large and small scale L/eta=17,000, a perfect self-similar regime is not found. The effects of the parameters of the synthetic flow, such as the exponent of the spectrum and the effect of the sweeping affect our results, are also discussed. Special attention is given to the effects of persistence of spatial flow structure.


Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models.
Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3D in vitro systems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as μRods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 μm, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Furthermore, RNA sequencing revealed subtle upregulation of certain genes associated with migration and stress, such as induced through mechanical deformation, for spheroids exposed to actuation vs. controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the μRods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.


Nuclear medicine in the era of genomics and proteomics: lessons from annexin V.
In the past decade, genomics and proteomics have begun to develop many new targets for potential diagnostic and therapeutic agents. Among the life sciences, nuclear medicine is also deeply involved in the field of clinical investigation. Experience with radiolabeled annexin V highlights the many steps required to translate a good basic-science concept into the clinical setting. This model also emphasizes the value of synergy between basic and medical specialties in developing and optimizing a clinically useful product initially derived from basic investigation.


Lysine deacetylase inhibition promotes relaxation of arterial tone and C-terminal acetylation of HSPB6 (Hsp20) in vascular smooth muscle cells.
There is increasing interest in establishing the roles that lysine acetylation of non nuclear proteins may exert in modulating cell function. Lysine deacetylase 8 (KDAC8), for example, has been suggested to interact with α-actin and control the differentiation of smooth muscle cells. However, a direct role of smooth muscle non nuclear protein acetylation in regulating tone is unresolved. We sought to define the actions of two separate KDAC inhibitors on arterial tone and identify filament-interacting protein targets of acetylation and association with KDAC8. Compound 2 (a specific KDAC8 inhibitor) or Trichostatin A (TSA, a broad-spectrum KDAC inhibitor) inhibited rat arterial contractions induced by phenylephrine (PE) or high potassium solution. In contrast to the predominantly nuclear localization of KDAC1 and KDAC2, KDAC8 was positioned in extranuclear areas of native vascular smooth muscle cells. Several filament-associated proteins identified as putative acetylation targets colocalized with KDAC8 by immunoprecipitation (IP): cortactin, α-actin, tropomyosin, HSPB1 (Hsp27) and HSPB6 (Hsp20). Use of anti-acetylated lysine antibodies showed that KDAC inhibition increased acetylation of each protein. A custom-made antibody targeting the C-terminal acetylated lysine of human HSPB6 identified this as a novel target of acetylation that was increased by KDAC inhibition. HSPB6 phosphorylation, a known vasodilatory modification, was concomitantly increased. Interrogation of publicly available mass spectrometry data identified 50 other proteins with an acetylated C-terminal lysine. These novel data, in alliance with other recent studies, alert us to the importance of elucidating the mechanistic links between changes in myofilament-associated protein acetylation, in conjunction with other posttranslational modifications, and the regulation of arterial tone.


A novel missense mutation (p.P52R) in amelogenin gene causing X-linked amelogenesis imperfecta.
Amelogenesis imperfecta (AI) is a hereditary disease with abnormal dental enamel formation. Here we report a Japanese family with X-linked AI transmitted over at least four generations. Mutation analysis revealed a novel mutation (p.P52R) in exon 5 of the amelogenin gene. The mutation was detected as heterozygous in affected females and as hemizygous in their affected father. The affected sisters exhibited vertical ridges on the enamel surfaces, whereas the affected father had thin, smooth, yellowish enamel with distinct widening of inter-dental spaces. To study the pathological cause underlying the disease in this family, we synthesized the mutant amelogenin p.P52R protein and evaluated it in vitro. Furthermore, we studied differences in the chemical composition between normal and affected teeth by x-ray diffraction analysis and x-ray fluorescence analysis. We believe that these results will greatly aid our understanding of the pathogenesis of X-linked AI.


Duodenal Diverticulitis Following Biliopancreatic Diversion: A Case Report.
Duodenal diverticulitis is a relatively uncommon finding in patients. Treatment of complications of duodenal diverticulitis may be challenging in patients with altered intestinal anatomy such as those with altered anatomy from weight loss procedures involving intestinal bypass. We present a case report describing the management of duodenal diverticulitis following a biliopancreatic diversion, our decision-making process, and our final treatment strategy.


Ultra-performance liquid chromatography-Quadrupole time-of-flight tandem mass spectrometry-based metabolite profiling, quality evaluation, and marker analysis of Trachyspermum ammi (L.) Sprague by high-performance thin-layer chromatography.
Trachyspermum ammi (L.) Sprague (Apiaceae), commonly known as "Ajwain" is distributed throughout India. Ajwain fruits contain fiber, carbohydrates, phenolic acids, flavonoids, and tannins. The fruits also yield a small amount of essential oil, with Thymol as the principal constituent. Ajwain has various pharmacological activities like anti-leishmanial, antimicrobial, cytotoxic, antispasmodic, nematocidal, and anthelmintic. The fruits are of high therapeutic value; thus, it becomes quite essential to evaluate the quality of Trachyspermum ammi (L.) Sprague to authenticate and ensure its therapeutic and nutritional properties. The ethyl acetate fraction of Trachyspermum ammi (L.) Sprague fruits exhibited the highest total phenolic and flavonoid content values of 149.55 ± 1.19 mg rutin equivalent and 682.85 ± 3.68 mg gallic acid equivalent, respectively. Metabolite profiling of the ethyl acetate fraction using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry analysis resulted in identifying 19 phytomolecules. A validated high-performance thin-layer chromatography method was developed to quantify standard phytomolecules in the ethyl acetate fraction. The highest and lowest percentages of phytomarker were found to be caffeic acid (5.51% ± 0.16% w/w) and gallic acid (1.29% ± 0.09% w/w), respectively. This validated rapid, accurate, and precise method for standardization of Trachyspermum ammi (L.) Sprague will be beneficial for its quality evaluation as well as the derived products.


Low temperature photoacoustic spectroscopy of the purple membrane of Halobacterium halobium.
The photoacoustic spectra of light- and dark-adapted bacteriorhodopsin in aqueous and mixed water-glyc-erol (1:2) suspensions are studied in the 90-300 K temperature range. Photochemical transients are observed and interpreted in terms of the known photocycles of trans- and 13-cis-bacteriorhodopsin. The spectra differ from those obtained by low temperature optical absorption spectroscopy of glassy glycerol-water suspensions.


[The system of information concerning pharmaceuticals and its role in efficient using of medicines: opinion of medical specialists].
The issues of efficient application of pharmaceuticals by national authorities and supranational institutions are considered as important ones. The WHO recommends implementing twelve key propositions enhancing efficient application of pharmaceuticals. The development of independent information system concerning pharmaceuticals. The WHO recognizes that absence of neatly organized information system concerning pharmaceuticals information is usually spreading through different channels by manufacturers of medicines. The WHO determines admissible sources of information concerning pharmaceuticals and also requirements to content of presented information. The article presents results of survey of opinions of medical professionals about information sources concerning pharmaceuticals regulated in the Russian Federation and the WHO and also about actual information system concerning pharmaceuticals in the Russian Federation and its role in efficient application of medicines.


What is the role of global health and sustainable development in Swedish medical education? A qualitative study of key stakeholders' perspectives.
Global health and sustainable development have increasingly been recognised as important parts of medical education, yet education on these issues remains fragmented and scarce. In 2020, a bill to reform the national medical curricula across all Swedish medical schools was introduced, including a greater emphasis on global health and sustainable development. This study aimed to explore the perspectives of key stakeholders in medical education on the role of global health and sustainable development in Swedish medical education. This was a qualitative study based on semi-structured interviews with 11 key stakeholders in medical education, broadly defined as faculty board members (dean and/or vice-deans for medical education) and/or programme chairs representing six universities. Data were analysed using qualitative content analyis (QCA). The study was conducted according to the Consolidated Criteria for Reporting Qualitative research (COREQ) guidelines. Stakeholders discussed the challenges and opportunities associated with the modification of medical education, which was seen as necessary modernisation to fit the changing societal perception of the role of medical doctors. The anchoring process of redesigning the curriculum and integrating global health and sustainable development was discussed, with emphasis on ownership and mandate and the role of teachers and students in the process. Finding a shared understanding of global health and sustainable development was perceived as a challenge, associated with resistance due to fear of curriculum overload. To overcome this, integrating global health and sustainable development with other topics and developing existing components of the curricula were seen as important. Additionally, it was stressed that fostering capacity building and developing infrastructure, including utilization of digital tools and collaborations, were essential to ensure successful implementation. Medical institutions should prepare future doctors to respond to the needs of a globalised world, which include knowledge of global health and sustainable development. However, conceptual uncertainties and questions about ownership remain among key stakeholders in medical education. Yet, key stakeholders also highlight that the inclusion of global health and sustainable development in the new curricula represents multiple overarching educational opportunities that can bring about necessary improvement.


Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion strategy.
Recombinase-mediated unidirectional DNA inversion and transcriptional arrest is a promising strategy for high throughput conditional mutagenesis in the mouse. Banks of mouse embryonic stem cells with defined, transcriptionally silent insertions that can be activated by Cre recombinase would take advantage of existing transgenic Cre lines to rapidly produce hundreds of lineage specific and temporally controlled knockout mice for each gene, thereby introducing significant parallelism to functional gene annotation. However, the extent to which this strategy results in effective gene knockout has not been established. To test the feasibility of this strategy we targeted ErbB3, a member of the ErbB family of tyrosine kinase receptors, using this strategy. Insertion of a reversed "flipflox" vector consisting of a gene inactivation cassette (GI) and an internal ribosome entry site (IRES)-GFP reporter into intron 1 of ErbB3 was transcriptionally silent and did not affect ErbB3 expression. Crosses with ubiquitous and lineage specific Cre recombinase expressing lines permanently inverted the inserted GI cassette and blocked ErbB3 expression. Unidirectional DNA inversion by in vivo recombination is an effective strategy for targeted or ubiquitous gene knockout.


Sentinel Lymph Node Biopsy in Pure DCIS: Is It Necessary?
Introduction. Sentinel lymph node biopsy (SLNB) in patients with pure ductal carcinoma in situ (DCIS) has been a matter of debate due to very low rate of axillary metastases. We therefore aimed to identify factors in a single institutional series to select patients who may benefit from SLNB. Material and Methods. Patients, diagnosed with pure DCIS (n = 63) between July 2000 and March 2011, were reviewed. All the sentinel lymph nodes were examined by serial sectioning (50 μm) of the entire lymph node and H&E staining, and by cytokeratin immunostaining in suspicious cases. Results. Median age was 51 (range, 30-79). Of 63 patients, 40 cases (63.5%) with pure DCIS underwent SLN, and 2 of them had a positive SLN (5%). In both 2 cases with SLN metastases, only one sentinel lymph node was involved with tumor cells. Patients who underwent SLNB were more likely to have a tumor size >30 mm or DCIS with intermediate and high nuclear grade or a mastectomy in univariate and multivariate analyses. Conclusion. In our series, we found a slightly higher rate of SLNB positivity in patients with pure DCIS than the large series reported elsewhere. This may either be due to the meticulous examination of SLNs by serial sectioning technique or due to our patient selection criteria or both.


A ramble through the cell: how can we clear such a complicated trail?
The arrangement of course information in a logical sequence for molecular life science (MLS) courses remains a matter of some controversy, even within a single subdiscipline such as biochemistry. This is due to the explosion of knowledge, the latest bioinformatic revelations, and the observation that new discoveries sometimes reveal specific connections between previously disparate topics. However, the general outlines of biomedical information are in place, at least the knowledge that should be conveyed to undergraduates taking cell and molecular biology and biochemistry. Despite the increasing amount and complexity of the information to be presented, integration and unification are possible because the molecular reactions and interactions that underlie all life processes are coming into view: they are common to all cellular structural rearrangements, nucleic acid functions, and biochemical reactions, whether of plant or animal origin. Also, it is no longer possible to draw clear boundaries between cell biology, biochemistry, and molecular biology that would not violate the fundamental unity of our understanding. Therefore, an arrangement of content is proposed for a two-semester course that aims to present a unified portrait of upper-division undergraduate MLS.


Genetic structure of pig breeds from Korea and China using microsatellite loci analysis.
To understand molecular genetic characteristics of Korean pigs, the genetic relationships of nine pig breeds including two Korean pigs (Korean native pig and Korean wild pig), three Chinese pigs (Min pig, Xiang pig, and Wuzhishan pig), and four European breeds (Berkshire, Duroc, Landrace, and Yorkshire) were characterized from a 16-microsatellite loci analysis. The mean heterozygosity within breeds ranged from 0.494 to 0.703. Across multiple loci, significant deviation from Hardy-Weinberg equilibrium was observed in most pig breeds, except for two Chinese pigs (Min pig and Wuzhishan pig). This deviation was in the direction of heterozygote deficit. Across population loci, 36 of 144 significantly deviated (P < 0.05) from Hardy-Weinberg equilibrium. The mean FST, a measure of genetic divergence among subpopulations, of all loci indicated that 26.1% of total variation could be attributed to the breed difference. Relationship trees based on the Nei's DA genetic distance and scatter diagram from principal component analysis consistently displayed pronounced genetic differentiation among the Korean wild pig, Xiang pig, and Wuzhishan pig. Individual assignment test using a Bayesian method showed 100% success in assigning Korean and Chinese individual pigs into their correct breeds of origin and 100% exclusion success from all alternative reference populations at P < 0.001. These findings indicate that the Korean native pig has been experiencing progressive interbreeding with Western pig breeds after originating from a North China pig breed with a black coat color. Considering the close genetic relationship of Korean pigs to the Western breeds such as Berkshire and Landrace, our findings can be used as valuable genetic information for the preservation and further genetic improvement of the Korean native pig.


Torpedo Maculopathy Associated with NEXMIF Mutation.
Mutations in the neurite extension and migration factor (NEXMIF) gene are associated with X-linked intellectual disability. Thus far, all males reported with NEXMIF mutations have mild to profound intellectual disability with varying combinations of autistic features, poor or absent speech, epilepsy, facial dysmorphism, and strabismus. Affected females tend to have milder intellectual disability but severe, drug-resistant epilepsy. Here, we present a 32-month-old boy with a novel de novo frameshift NEXMIF pathogenic variant (p.Glu375ArgfsX21) who has mild motor delay, language delay, autistic features, and strabismus. In addition to these commonly described findings of NEXMIF mutations, his fundus exam revealed a very rare ophthalmologic abnormality, torpedo maculopathy. This finding has not previously been reported with NEXMIF mutation; however, on literature review, 7/15 males with NEXMIF mutations had other ophthalmologic abnormalities. This patient expands the phenotypic spectrum for males with NEXMIF mutations and suggests that NEXMIF may play an important role in ocular development.


Canadian Treatment Guidelines on Psychosocial Treatment of Schizophrenia in Adults.
It is generally recognised that psychosocial interventions are essential components of the effective treatment of schizophrenia in adults. A considerable body of research is being published regarding the effectiveness of such interventions. In the current article, we derive recommendations reflecting the current state of evidence for their effectiveness. Recommendations were formulated on the basis of a review of relevant guidelines, particularly those formulated by the Scottish Intercollegiate Guideline Network (SIGN) and National Institute for Health and Care Excellence (NICE). There is evidence strongly supporting the use of family interventions, supported employment programs, and cognitive-behavioural therapy. There are also reasons to recommend the use of cognitive remediation, social skills training, and life skills training under specified circumstances. It is important that all patients and families be provided with education about the nature of schizophrenia and its treatment. Several recent innovative psychosocial approaches to treatment are awaiting more thorough evaluation. There continues to be strong evidence for the effectiveness of several psychosocial interventions in improving outcomes for adults with schizophrenia. In the past decade, innovative interventions have been described, several of which are the subject of ongoing evaluative research.


Kondo Destruction in RKKY-Coupled Kondo Lattice and Multi-Impurity Systems.
In a Kondo lattice, the spin exchange coupling between a local spin and the conduction electrons acquires nonlocal contributions due to conduction electron scattering from surrounding local spins and the subsequent RKKY interaction. It leads to a hitherto unrecognized interference of Kondo screening and the RKKY interaction beyond the Doniach scenario. We develop a renormalization group theory for the RKKY-modified Kondo vertex. The Kondo temperature T_{K}(y) is suppressed in a universal way, controlled by the dimensionless RKKY coupling parameter y. Complete spin screening ceases to exist beyond a critical RKKY strength y_{c} even in the absence of magnetic ordering. At this breakdown point, T_{K}(y) remains nonzero and is not defined for larger RKKY couplings y>y_{c}. The results are in quantitative agreement with STM spectroscopy experiments on tunable two-impurity Kondo systems. The possible implications for quantum critical scenarios in heavy-fermion systems are discussed.


Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.
We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.


The glutathione S-transferase P1 341C>T polymorphism and cancer risk: a meta-analysis of 28 case-control studies.
GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted. The relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08-1.81, P(het.) = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08-1.81, P(het.) = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias. This meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.


Amplicon sequencing and improved detection of human rhinovirus in respiratory samples.
Improved knowledge of the genotypic characteristics of human rhinovirus (HRV) is required, as are nucleic detection assays with the capacity to overcome both the similarities between members of the family Picornaviridae and the wide diversity of different HRV serotypes. The goal of the present study was to investigate the variability and the genotypic diversity of clinical strains circulating in the community. Since most reverse transcription (RT)-PCR assays available cannot differentiate HRV from other members of the family Picornaviridae, we also validated an assay specific for HRV detection. The 5' noncoding regions of 87 different HRV serotypes and clinical isolates were sequenced. On the basis of sequence analysis and phylogenetic determination, we first confirmed that all clinical isolates were HRV. We then validated a real-time RT-PCR assay that was able not only to detect all HRV serotypes and all clinical isolates tested but also to accurately discriminate between rhinovirus and other viruses from the family Picornaviridae. This assay was negative with isolates of coxsackievirus (types A and B), echovirus, enterovirus, parechovirus, and poliovirus, as well as nonpicornaviruses. Among a series of bronchoalveolar lavage specimens, 4% (7 of 161) were positive by culture, whereas 13% (21 of 161) were positive by RT-PCR. In the present study we showed that to specifically identify HRV in clinical specimens, diagnostic assays need to overcome both the diversities and the similarities of picornaviruses. By sequencing the 5' noncoding regions of rhinoviruses recovered from clinical specimens, we designed probes that could specifically detect rhinovirus.


[Efficiency of Operation Trombendarterektomy From Pulmonary Artery Branches Depending on the Degree of Pulmonary Hypertension and Duration of Disease].
to assess effect of thromboendarterectomy from pulmonary artery branches on clinical functional state of patients with chronic thromboembolic pulmonary hypertension (CTEPH) in dependence on degree of pulmonary hypertension and disease duration. Patients (n=152) were divided into 3 groups: (1) with systolic pulmonary artery pressure (SPAP) less or equal 50 mm Hg (n=20), (2) with SPAP>50- less or equal 80mm Hg (n=46), (3) with SPAP >80mm Hg (n=86). Examination included registration of dynamics of general clinical state and character of complaints, six-minute walk test, transthoracic echocardiography with measurement of SPAP and right ventricular ejection fraction, pulmonary perfusion scintigraphy with calculation of index of perfusion deficit. Pulmonary thromboendarterectomy from pulmonary artery branches was associated with stable improvement of clinical functional state of patients with CTEPH and regression of symptoms irrespective of preoperative level of pulmonary hypertension.


The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys.
In cardiovascular surveys, the WHO questionnaire on intermittent claudication has traditionally been used as a measure of atherosclerotic peripheral arterial disease of the lower limbs. But the questionnaire is of limited value because atherosclerotic disease is frequently asymptomatic. Research on the validity and reliability of the questionnaire and the simpler non-invasive tests of peripheral arterial disease are reviewed. These tests include measurement of the ankle-brachial systolic pressure ratio, a treadmill exercise test, a reactive hyperaemia test, and assessment of toe-pulse reappearance time. The performance of these non-invasive tests is such that they should be used, in conjunction with the intermittent claudication questionnaire, in epidemiological studies of atherosclerotic peripheral arterial disease of the lower limbs.


Origin of Gliomas.
Malignant glioma is a common type of brain tumor that remains largely incurable. Although a definitive cell of origin of gliomas remains elusive, numerous population studies, sequencing efforts, and genetically engineered mouse models have contributed to our understanding of the early events that may lead to gliomagenesis. Herein we summarize our current knowledge on the population epidemiology of gliomas, heritable genetic risk factors, the somatic events that contribute to tumor evolution, and mouse models that have shed light on the glioma cell of origin. Future studies will increase our understanding of the sequence of early events within susceptible cells and their niche that trigger the path to malignant transformation. Such knowledge will allow us to design more effective treatment options to control tumor growth or screening methods for early detection.


Second Harmonic Correlation Spectroscopy: Theory and Principles for Determining Surface Binding Kinetics.
A novel application of second harmonic correlation spectroscopy (SHCS) for the direct determination of molecular adsorption and desorption kinetics to a surface is discussed in detail. The surface-specific nature of second harmonic generation (SHG) provides an efficient means to determine the kinetic rates of adsorption and desorption of molecular species to an interface without interference from bulk diffusion, which is a significant limitation of fluorescence correlation spectroscopy (FCS). The underlying principles of SHCS for the determination of surface binding kinetics are presented, including the role of optical coherence and optical heterodyne mixing. These properties of SHCS are extremely advantageous and lead to an increase in the signal-to-noise (S/N) of the correlation data, increasing the sensitivity of the technique. The influence of experimental parameters, including the uniformity of the TEM00 laser beam, the overall photon flux, and collection time are also discussed, and are shown to significantly affect the S/N of the correlation data. Second harmonic correlation spectroscopy is a powerful, surface-specific, and label-free alternative to other correlation spectroscopic methods for examining surface binding kinetics.


Increased mean lung density: another independent predictor of lung cancer?
To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n=119) and controls (n=989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1s (FEV1) independently of MLD (OR 5.37, 95% CI: 2.63-10.97 for FEV1<60% vs. FEV1≥90%), and with increasing MLD independently of FEV1 (OR 3.00, 95% CI: 1.60-5.63 for MLD>-823 vs. MLD<-857 Hounsfield units). Emphysema per se was not associated with lung cancer whereas decreased FEV1 was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.


Dopamine D1 receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via both AP-1- and NFATc4-mediated transcriptional processes.
Although our recent report demonstrates the essential involvement of up-regulation of a regulator of intracellular Ca(2+) concentration, type 1 inositol 1,4,5-trisphosphate receptors (IP(3) Rs-1), mediated via dopamine D1-like receptor (D1DR) stimulation in the cocaine-induced psychological dependence, the exact mechanisms of regulation of IP(3) R-1 expression by D1DRs have not yet been clarified. This study attempted to clarify these mechanisms using mouse cerebral cortical neurons. An agonist for phosphatidylinositide-linked D1DRs, SKF83959, induced dose- and time-dependently IP(3) R-1 protein up-regulation following its mRNA increase without cAMP production. U73122 (a phospholipase C inhibitor), BAPTA-AM (an intracellular calcium chelating reagent), W7 (a calmodulin inhibitor), KN-93 (a calmodulin-dependent protein kinases inhibitor), and FK506 (a calcineurin inhibitor), significantly inhibited the SKF83959-induced IP(3) R-1 up-regulation. Furthermore, immunohistochemical examinations showed that SKF83959 increased expression of both cFos and cJun in nucleus as well as enhanced translocation of both calcineurin and NFATc4 complex to nucleus from cytoplasm. In addition, SKF83959 directly recruited binding of both AP-1 and NFATc4 to IP(3) R-1 promoter region. These results indicate that D1DR activation induces IP(3) R-1 up-regulation via increased translocation of AP-1 as well as NFATc4 in Gαq protein-coupled calcium signaling transduction pathway.


Risk for acute confusion on hospital admission.
Elderly individuals are at risk for acute confusion (AC) during hospitalization. Using a prospective design, this study assessed the relationship between admission risk factors and subsequent development of AC in 117 elderly hospitalized patients. AC was ascertained using the NEECHAM Confusion Scale. Other measures included demographic data, cognitive status, physical function, laboratory data, medications, infections, activity, pain, and nursing acuity. The cumulative incidence estimate was 14%. Patients who developed AC were more likely to be admitted to the hospital from somewhere other than home, to have lower admission NEECHAM and MMSE scores, and to have restricted activity levels, an infection, and abnormal lab values. These patients were more cognitively and physically frail and may have been chronically undernourished and dehydrated on admission to the hospital. Nurses can be trained to routinely assess for acute confusion using easily implemented instruments incorporated into a research-based protocol.


Comparison of chain- and plate-loaded bench press training on strength, joint pain, and muscle soreness in Division II baseball players.
The purpose of this study was to investigate the effects of chain- (CBP) and plate-loaded (PBP) bench press training on measures of strength, shoulder pain, and muscle soreness in Division II baseball players. Twenty-eight subjects with previous resistance training experience (4.8 +/- 2.7 years) completed the study while participating in off-season baseball practice. All subjects completed a one-repetition maximum pre- and posttest on the CBP and PBP and reported shoulder pain and muscle soreness on 15 occasions during training. Two treatment groups, CBP and PBP, trained 2 d.wk for 9 weeks during the off-season with a linear periodization strength training program. The CBP group used chains attached to the bar as the entire load, and the PBP group used only traditional plate-loaded resistance. The chains provided a variable resistance, with a reduction in load during the descent as the weight collected on the floor and with the load increasing during ascent as the weight was lifted from the floor. Statistically significant increases were found in strength scores after training for the CBP test (p < 0.001) and the PBP test (p < 0.001). Both groups were able to improve strength on the CBP and PBP, but no significant differences were found in strength gains between the groups on the CBP and PBP tests. Although levels of pain and soreness were not significantly different, a threefold difference was found for perceived levels of shoulder pain (mean totals of 2.15 vs. 6.14), whereas reported soreness was similar (9.38 vs. 10.57) for the CBP and PBP group, respectively. The data indicate that training with chain- and plate-loaded resistance produce similar short-term strength improvement on the chain- and plate-loaded bench press. Baseball players may benefit from CBP training with improved free-weight strength while minimizing shoulder stress.


Implication for transglutaminase 2-mediated activation of β-catenin signaling in neointimal vascular smooth muscle cells in chronic cardiac allograft rejection.
Cardiac allograft vasculopathy (CAV) remains the main cause of long-term transplant rejection. CAV is characterized by hyperproliferation of vascular smooth muscle cells (VSMCs). Canonical β-catenin signaling is a critical regulator of VSMC proliferation in development; however, the role of this pathway and its regulation in CAV progression are obscure. We investigated the activity of β-catenin signaling and the role for a putative activating ligand, transglutaminase 2 (TG2), in chronic cardiac rejection. Hearts from Bm12 mice were transplanted into C57BL/6 mice (class II mismatch), and allografts were harvested 8 weeks after transplantation. Accumulation and sub-cellular distribution of β-catenin protein and expression of several components of β-catenin signaling were analyzed as hallmarks of pathway activation. In vitro, platelet-derived growth factor treatment was used to mimic the inflammatory milieu in VSMC and organotypic heart slice cultures. Activation of β-catenin in allografts compared with isografts or naïve hearts was evidenced by the augmented expression of β-catenin target genes, as well as the accumulation and nuclear localization of the β-catenin protein in VSMCs of the occluded allograft vessels. Expression of TG2, an activator of β-catenin signaling in VSMCs, was dramatically increased in allografts. Further, our ex vivo data demonstrate that TG2 is required for VSMC proliferation and for β-catenin activation by platelet-derived growth factor in cardiac tissue. β-Catenin signaling is activated in occluded vessels in murine cardiac allografts. TG2 is implicated as an endogenous activator of this signaling pathway and may therefore have a role in the pathogenesis of CAV during chronic allograft rejection.


What indigestion means to the malays?
Despite being a large ethnic group within the South-East Asia, there is a paucity of reported literatures on dyspepsia in the Malay population. Recent population-based studies indicate that uninvestigated dyspepsia, based on the Rome II criteria, is reported in 12.8% and 11.6% of Malays in the urban and rural communities respectively. Organic causes of dyspepsia including upper gastrointestinal tract cancers, its precancerous lesions, and erosive diseases are uncommon which is largely due to an exceptionally low prevalence of Helicobacter pylori infection in this population. On the other hand, functional dyspepsia and irritable bowel syndrome are relatively common in the Malays than expected. Within a primary care setting, functional dyspepsia, based on the Rome III criteria, is reported in 11.9% of Malays, of which epigastric pain syndrome is found to be more common. Married Malay females are more likely to have functional dyspepsia and psychosocial alarm symptoms. Also based on the Rome III criteria, irritable bowel syndrome, commonly overlapped with functional dyspepsia, is reported in 10.9% of Malays within a community-based setting. Rather than psychosocial symptoms, red flags are most likely to be reported among the Malays with irritable bowel syndrome despite having a low yield for organic diseases. Based upon the above observations, "proton pump inhibitor test" is probably preferable than the "test and treat H. pylori" strategy in the initial management of dyspepsia among the Malays.


Dietary fructose and risk of metabolic syndrome in adults: Tehran Lipid and Glucose study.
Studies have shown that the excessive fructose intake may induce adverse metabolic effects. There is no direct evidence from epidemiological studies to clarify the association between usual amounts of fructose intake and the metabolic syndrome. The aim this study was to determine the association of fructose intake and prevalence of metabolic syndrome (MetS) and its components in Tehranian adults. This cross-sectional population based study was conducted on 2537 subjects (45% men) aged 19-70 y, participants of the Tehran Lipid and Glucose Study (2006-2008). Dietary data were collected using a validated 168 item semi-quantitative food frequency questionnaire. Dietary fructose intake was calculated by sum of natural fructose (NF) in fruits and vegetables and added fructose (AF) in commercial foods. MetS was defined according to the modified NCEP ATP III for Iranian adults. The mean ages of men and women were 40.5 ± 13.6 and 38.6 ± 12.8 years, respectively. Mean total dietary fructose intakes were 46.5 ± 24.5 (NF: 19.6 ± 10.7 and AF: 26.9 ± 13.9) and 37.3 ± 24.2 g/d (NF: 18.6 ± 10.5 and AF: 18.7 ± 13.6) in men and women, respectively. Compared with those in the lowest quartile of fructose intakes, men and women in the highest quartile, respectively, had 33% (95% CI, 1.15-1.47) and 20% (95% CI, 1.09-1.27) higher risk of the metabolic syndrome; 39% (CI, 1.16-1.63) and 20% (CI, 1.07-1.27) higher risk of abdominal obesity; 11% (CI, 1.02-1.17) and 9% (CI, 1.02-1.14) higher risk of hypertension; and 9% (CI, 1-1.15) and 9% (1.04-1.12) higher risk of impaired fasting glucose. Higher consumption of dietary fructose may have adverse metabolic effects.


Entropy production and time asymmetry in the presence of strong interactions.
It is known that the equilibrium properties of open classical systems that are strongly coupled to a heat bath are described by a set of thermodynamic potentials related to the system's Hamiltonian of mean force. By adapting this framework to a more general class of nonequilibrium states, we show that the equilibrium properties of the bath can be well defined, even when the system is arbitrarily far from equilibrium and correlated with the bath. These states, which retain a notion of temperature, take the form of conditional equilibrium distributions. For out-of-equilibrium processes we show that the average entropy production quantifies the extent to which the system and bath state is driven away from the conditional equilibrium distribution. In addition, we show that the stochastic entropy production satisfies a generalized Crooks relation and can be used to quantify time asymmetry of correlated nonequilibrium processes. These results naturally extend the familiar properties of entropy production in weakly coupled systems to the strong coupling regime. Experimental measurements of the entropy production at strong coupling could be pursued using optomechanics or trapped-ion systems, which allow strong coupling to be engineered.


Non-compliance and associated factors against smoke-free legislation among health care staffs in governmental hospitals in Addis Ababa, Ethiopia: an observational cross-sectional study.
In 2014, the Ethiopian government passed a new smoking legislation that banned smoking in public and workplaces including health care facilities. However, data's on level of non-compliance and associated factors with non-compliance towards smoke-free legislation in hospital settings of the country has not been studied yet. Hospital-based Cross-sectional study design triangulated with observational study was conducted in five hospitals. Data were collected through direct observation and interviews using checklist, structured and pre-tested questionnaires for observational study and survey of hospital employee respectively. Nine data collectors and one supervisor were involved in data collection. Three hundred fifty (350) health care staffs were interviewed. Fifteen (15) buildings were purposively observed for observational non-compliance in the selected hospitals. Data were entered by Epi Info and analyzed using SPSS version 21 software. Logistic regression was used to compute the crude and adjusted odds ratios for the factors affecting employee non-compliance with the legislation. A p-value of < 0.05 at 95% CI was considered to be statistically significant. Anti-smoking signs were absent from a high proportion of hospital areas (97% overall) although visible cigarette butts were generally not observed in most areas of the hospitals. Non-compliance level among health care staffs was 50(10.3%).Associated factors affecting to the non-compliance level of the staff were: being male (AOR = 5.89, p value = 0.001), having poor knowledge (AOR = 2.71, p-value = 0.022) and having Unfavorable attitudes (AOR = 6.15, p-value = 0.000). Non-compliance level was high and needs careful implementation for 100% smoke-free legislation in addressing knowledge and attitudes of health care staffs.


The novel long noncoding RNA RP11-357H14.17 acts as an oncogene by promoting cell proliferation and invasion in diffuse-type gastric cancer.
Current evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in human cancers. The present study aims to assess differentially expressed lncRNAs related to diffuse-type gastric carcinoma (DGC). Next-generation RNA sequencing was carried out to detect aberrantly expressed lncRNAs in DGC. Real-time polymerase chain reaction (RT-PCR) was performed to evaluate RP11-357H14.17 gene expression levels in DGC cell lines/tissues comparatively with normal gastric epithelial cell lines and adjacent normal tissues. The associations of RP11-357H14.17 expression levels with the clinicopathological features were also analyzed. The regulatory effects of RP11-357H14.17 on the biological behaviors of DGC cells were evaluated by MTT, colony formation assays, flow cytometry for apoptosis, wound healing assay, and transwell migration and invasion assays. RP11-357H14.17 expression was remarkably increased in DGC tissues and cell lines compared with normal gastric epithelial cells and adjacent normal tissues. High levels of RP11-357H14.17 were associated with increased tumor size, deeper depth of invasion, lymphatic metastasis, and advanced pathological stage. Further experiments demonstrated that the DGC cells MGC-803 transfected with si-RP11-357H14.17 showed reduced cell proliferation, migration, invasion, enhanced G1 phase arrest and cell apoptosis. These findings suggest that the novel lncRNA RP11-357H14.17 is associated with poor prognosis, and may serve as a potential prognostic biomarker and target for new antineoplastic therapies in human DGC.


Effect of Baicalein on GLUT4 Translocation in Adipocytes of Diet-Induced Obese Mice.
Although baicalein has been shown to increase insulin sensitivity in liver of mice, there is no literature available about the effect of baicalein on glucose transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of diet-induced obese mice. In the present study, the obese model was induced in mice fed a high fat diet (20% carbohydrates, 21% protein and 59% fat) for 16 weeks. The diet-induced obese mice were given 20mg/kg baicalein intraperitoneally (i.p.) once a day for 21 days. The plasma insulin was measured by enzyme-linked immunosorbent assay. Fasting blood glucose and insulin resistance indexes were measured by glucose tolerance test (GTT). The expression levels of PGC-1α, UCP1, GLUT4, PPARγ, pP38MAPK, pERK and pAKT in adipocytes were determined by quantitative real-time polymerase chain reaction and western blotting. The present findings showed that administration of baicalein decreased pP38MAPK, pERK and PPARγ levels, but enhanced pAKT, PGC-1α and UCP1 contents as well as GLUT4 expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalein treatment increased GLUT4 concentration in plasma membranes of adipocytes, i.e. baicalein may prevent insulin resistance through the GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes. These results suggest that baicalein is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/GLUT4 pathway.


Buffer loading for counteracting metal salt-induced signal suppression in electrospray ionization.
The decrease in the sensitivity of electrospray ionization mass spectrometry caused by the presence of metal salts, such as sodium chloride, in the sample matrix is well known and is particularly problematic for biological samples. We report here that addition of high levels of ammonium acetate can improve analyte signal in aqueous electrospray solutions and counteracts the signal suppression caused by sodium chloride. A approximately 3-fold improvement in S/N is obtained by adding 8 M ammonium acetate to aqueous solutions of cytochrome c without added sodium chloride. No organic solvents or acids are added into the electrospray solutions. The signal-to-noise ratios of cytochrome c and ubiquitin (10(-)(5) M) ions formed from aqueous solutions containing 2.0 x 10(-)(2) M sodium chloride are improved by factors of approximately 7 and 11, respectively, by adding 7 M ammonium acetate to the solution. We propose that this effect is a result of the precipitation of Na(+) and Cl(-) from solution within the evaporating electrospray droplets prior to the formation of gas-phase protein ions. This method is potentially useful for improving the abundance of protein ions formed from solutions in which the molecules have a nativelike conformation and is particularly advantageous for such solutions that have high levels of sodium.


A Minimally Invasive Approach for the Treatment of Multiple Adjacent Gingival Recessions with a Volume-Stable Collagen Matrix: A Case Series.
Several soft tissue graft materials have been utilized over the years as alternatives to the autogenous connective tissue graft for reducing patient morbidity. In particular, a novel volume-stable xenogeneic collagen matrix (VXCM) has recently been introduced for soft tissue augmentation at implant sites. The VXCM is porous in nature, and its mechanical properties suggest utilizing a specific flap approach when treating multiple adjacent gingival recessions (MAGRs). Herewith, a minimally invasive surgical technique is described in combination with VXCM for treatment of MAGRs. Five patients with 16 MAGRs were treated with this approach. All sites healed uneventfully, and patients reported minimal discomfort. At 6 months, the technique resulted in a mean root coverage of 94.73%, and complete root coverage was achieved in 13 sites (81.25%). The proposed minimally invasive approach may have potential to enhance flap blood supply and graft vascularization, promoting rapid healing with minimal postoperative discomfort. In addition, this approach can result in satisfactory clinical, esthetic, and patient-reported outcomes. Future adequately powered clinical trials are needed to validate the findings of this preliminary report.


The special location of p-H3 and p-CENP-A on heterochromatin during mitosis in MCF-7.
CENP-A locates at nucleosome as histone H3-like proteins, and is phosphorylated during mitosis. We investigated the dynamic distribution of p-CENP-A to explore the details of its function. We found that p-CENP-A was phosphorylated at late prophase, and the signal of p-CENP-A arranged at equatorial plate along with nucleosomes at metaphase, but moved to midbody at later phase of mitosis. The phosphorylation modification of CENP-A shares some characters of H3, but has different temporal patterns during mitosis. Our results suggested that the CENP-A might have similar functions as H3, but with different patterns for their different binging materials.


[Parenteral replacement of thyroid hormones].
Because of the development in parenteral nutrition, the replacement of thyroid hormones in hypothyroid or athyroid patients under intravenous hyperalimentation has become a new problem to be considered. We tried parenteral replacement of the hormones, intravenously or by enema, in three such patients. Two patients, 54 y-o and 64 y-o females, who underwent laryngo-esophago-thyroidectomy for cervical esophageal cancer or thyroid cancer, had replacement with intravenous l-thyroxine with an initial dose of 100 micrograms/day for 9 and 22 days, respectively. Another patient, a 56 y-o female with dysphagia due to local recurrence of cervical esophageal cancer after laryngo-esophago-thyroidectomy, was given 100 mg of desiccated thyroid by enema for 8 days followed by intravenous l-thyroxine for 104 days. Serum levels of thyroxine, triiodothyronine and TSH before l-thyroxine treatment indicated severe hypothyroidism in all cases. During the first 7 days of the intravenous therapy, serum thyroxine and triiodothyronine levels increased by 0.87 +/- 0.14 microgram/dl/day and 6.7 +/- 4.7 ng/dl/day, respectively, while serum TSH levels decreased by 7.8 +/- 6.4 microU/ml/day. Plasma T4 levels reached the normal level within 7 days, and plasma T3 levels within 11 days, while it took 14 days for plasma TSH levels to decrease to the normal level. The maintenance dose checked by the normal TSH levels in a patient undergoing a long term therapy was 75 micrograms/day or 1.83 micrograms/kg of body weight/day.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of pharmacokinetic-pharmacodynamic modelling in early clinical drug development.
Early clinical pharmacology studies in healthy subjects are often dissociated from patient studies. In this review we encourage the use of modelling and simulation techniques to generate valuable information at an early stage of clinical development. We illustrate these principles by presenting 5 different case studies from a spectrum of therapeutic drug classes. Their application leads to a better understanding of drug characteristics early on, thereby facilitating the design of dose-finding studies in the target patient population and saving resources.


Structural analysis of N-linked glycans in Caenorhabditis elegans.
Caenorhabditis elegans is an excellent model for morphogenetic research. However, little information is available on the structure of cell-surface glycans in C. elegans, although several lines of evidence have suggested a role for these glycans in cell-cell interactions during development. In this study, we analyzed N-glycan structures. Oligosaccharides liberated by hydrazinolysis from a total membrane fraction were labeled by pyridylamination, and around 90% of the N-glycans were detected as neutral oligosaccharides. The most dominant structure was Man(alpha)1-6(Man(alpha)1-3)Man(beta)1-4GlcNAc(beta)1-4GlcNAc, which is commonly found in insects. Branching structures of major oligomannose-type glycans were the same as those found in mammals. Structures that had a core fucose or non-reducing end N-acetylglucosamine were also identified, but ordinary complex-type glycans with N-acetyllactosamine were not detected as major components.


Purification, characterization, and modification of T lymphocyte-stimulating polysaccharide from spores of Ganoderma lucidum.
The hot-water extract of the spores of Ganoderma lucidum was shown to have a stimulating effect on concanavalin A-induced mitogenic activity of T lymphocytes. Bioassay-guided separation led to the isolation of a polysaccharide with potent T lymphocyte-stimulating activity by ethanol fractionation, anion-exchange, and size-exclusion chromatography. Based on the composition and methylation analyses, periodate oxidation, Smith degradation, and NMR spectroscopy, the native polysaccharide was shown to be a beta-D-(1-->3)-glucan with branches of terminal glucosyl residues substituted at C-6 of the glucose residues in the main chain. The branching ratio is approximately 20%. A series of sulfated or carboxymethylated derivatives were prepared and their structural features were elucidated by chemical and spectral analyses. The solution conformation and T lymphocyte proliferation effect of the glucans before and after derivatization were compared and discussed. The data obtained indicate that the introduction of ionic groups would significantly affect the original conformation of the native glucan in aqueous solution and further affect T lymphocyte-stimulating activity. The triple-helical structure of the glucans, the nature of the ionic groups, and the density of negative charge were considered to be closely related to this activity.


Locus of fragility in robust breast cancer system.
Functional heterogeneous redundancy of breast cancer makes this tumor to be robust. Signaling mechanisms which control cancer responses are crucial for controlling robustness. Identification of locus of fragility in cancer represents basic mechanism to target robustness. The goal of this prospect is to present locus of fragility in breast cancer robust system, and how disruption of this locus induces failure of robustness. My recent research show, that locus of fragility in breast cancer cells is suppression of nitric oxide (NO). When it was targeted, dynamics of cancer to generate robustness failed that it blocked cancer cell proliferation dependent on the NO/Rb pathway, blocked cell migration and angiogenesis dependent on the VEGF/PI3K/AKT/NO/ICAM-1 pathway, and induced breast cancer cell apoptosis through the NO/ROCK/FOXO3a signaling pathway. This tiny and trivial perturbation in breast cancer cells such as suppression of NO represents locus of fragility (weakness) and new approach for breast cancer chemotherapy.


Bioaccumulation of ultraviolet sunscreen compounds (mycosporine-like amino acids) by the heterotrophic freshwater ciliate Bursaridium living in alpine lakes.
Ciliates in shallow alpine lakes are exposed to high levels of incident solar ultraviolet radiation (UVR). We observed the presence of specific sunscreen compounds, the mycosporine-like amino acids (MAAs), in several populations of Bursaridium, a relatively large ciliate species found in such lakes. The populations from 3 highly UV transparent lakes revealed the presence of 7 MAAs (MG, SH, PR, PI, AS, US, and PE) in total concentrations of 3.6-52.4 10-5 μg μg-1 dry weight (DW) per individual, whereas in one glacially turbid and less UV transparent lake, no MAAs were detected in the Bursaridium population. The MAAs in the ciliates generally reflected the composition and relative amounts of the lakes' seston MAAs, assuming that the ciliates fed on MAA-rich plankton. We experimentally found that naturally acquired MAAs prevented ciliate mortality under simulated UVR and photosynthetically active radiation (PAR) conditions. We further tested the dietary regulation of the MAAs-content in the ciliates under artificial UVR and PAR exposure and found an increase in MAAs concentrations in all treatments. Our assumption was that several stress factors other than irradiation were involved in the synthesis or up-regulation of MAAs.


Origin of double-line structure in nonsequential double ionization by few-cycle laser pulses.
We investigate nonsequential double ionization (NSDI) of molecules by few-cycle laser pulses at the laser intensity of 1.2-1.5 × 10(14) W/cm(2) using the classical ensemble model. The same double-line structure as the lower intensity (1.0 × 10(14) W/cm(2)) is also observed in the correlated electron momentum spectra for 1.2-1.4 × 10(14) W/cm(2). However, in contrast to the lower intensity where NSDI proceeds only through the recollision-induced double excitation with subsequent ionization (RDESI) mechanism, here, the recollision-induced excitation with subsequent ionization (RESI) mechanism has a more significant contribution to NSDI. This indicates that RDESI is not necessary for the formation of the double-line structure and RESI can give rise to the same type of structure independently. Furthermore, we explore the ultrafast dynamics underlying the formation of the double-line structure in RESI.


Fluorescence lifetime measurement via a radionuclide-scintillation light source and analog cross correlation.
beta-Emitting 90Sr is used with a plastic scintillator to produce excitation-light pulses for fluorescence lifetime analysis. This light source is less expensive, more compact, and much more reliable than traditionally employed excitation sources such as lasers or pulsed flash lamps. The pulse train from this light source varies randomly in amplitude and time. Cross-correlation signal analysis is ideal for such a source because, unlike other time domain techniques, cross correlation takes complete advantage of its random nature. Here we report on the construction of an instrument and the methods employed to make fluorescence lifetime measurements via the new source and an analog correlation processor. Although the light intensity of the scintillator-based excitation source is comparatively low, an adequate signal level can be generated. The fluorescence lifetimes of three fluorophores are measured with a 1-mCi radionuclide to demonstrate a lifetime range from less than 1.5 to 28 ns. Long-lifetime measurements require an extra calibration step in order to compensate for delay cable energy loss. The light collection efficiency of the current instrument was found to be undesirably low; improvements in the instrument optics are suggested that will increase the collection efficiency and enhance the detection capability.


Examining the Structural and External Validity of the Adult Concentration Inventory for Assessing Sluggish Cognitive Tempo in Adults.
The Adult Concentration Inventory (ACI) is an adult self-report measure of sluggish cognitive tempo (SCT) developed following a meta-analysis identifying items distinguishing SCT from attention-deficit/hyperactivity disorder (ADHD) inattention. To date, only one study conducted in college students has examined the structural and external validity of the ACI. The current study evaluated the convergent and discriminative validity of the ACI in a community sample of adults, in addition to testing unique associations with internalizing symptoms, daily life executive functions, and sleep. Adults (N = 286; Mage = 44.45; 83.6% female) completed ratings of SCT, ADHD symptom dimensions, and external correlates. An a priori two-factor model with cross-loadings found 10 of the 16 SCT items to have high loadings on the SCT factor and low loadings on the ADHD inattention factor. SCT was uniquely associated with higher internalizing symptoms, time management and self-organization difficulties, poorer sleep quality, shorter sleep duration, lower sleep efficiency, and more daytime sleepiness. These findings replicate and extend support for the ACI in assessing SCT in adults.


Closing the Opportunity Gap in Early Childhood Education.
(1) Nineteen percent of low-income families enroll in high-quality early childhood education, while 29 percent of high income families do. (2) African-American, Hispanic/Latino and low-income children enter kindergarten, on average, significantly behind in reading and math skills. (3) Gaps in math and reading achievement generally persist in fourth grade and are even larger by eighth grade.


Recommendations for dealing with waste contaminated with Ebola virus: a Hazard Analysis of Critical Control Points approach.
To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks. A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point. The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste. The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease.


Determination of cardiac output with multislice spiral computed tomography: a validation study.
To validate and to determine the reproducibility of cardiac output (CO) measurements based on a test-bolus examination in multislice spiral computed tomography (MSCT) in comparison with invasively measured CO using the thermal dilution technique. In 8 swine, CO was determined by invasive thermal dilution technique and by analysis of enhancement data from dynamic MSCT test-bolus examinations. To assess reproducibility, all MSCT examinations were performed twice. Results were compared using Pearson's correlation coefficient and Bland-Altman plots. Measure by thermal dilution technique CO was 3.71 +/- 1.12 L/min, whereas CO was 3.67 +/- 1.30 L/min using MSCT. Pearson's correlation coefficient was 0.89. The average deviation between MSCT and thermal dilution technique was 0.04 L/min with a standard deviation of 0.59 L/min. There was a good agreement between both MSCT measurements with a mean deviation of -0.03 L/min and a standard deviation of 0.51 L/min. CO can reliably be determined from MSCT by means of indicator dilution technique. Measurements are reproducible and provide valuable information on the overall cardiovascular performance without application of additional contrast material or radiation. As this technique does not require time-consuming postprocessing it can be added to routine reporting.


Biodiversity conservation in an anthropized landscape: Trees, not patch size drive, bird community composition in a low-input agro-ecosystem.
One of the most typical agro-ecosystems in the Llanos de Ojuelos, a semi-arid region of central Mexico, is that of fruit-production orchards of nopales (prickly pear cacti). This perennial habitat with complex vertical structure provides refuge and food for at least 112 species of birds throughout the year. Nopal orchards vary in their internal structure, size and shrub/tree composition, yet these factors have unknown effects on the animals that use them. To further understand the conservation potential of this agro-ecosystem, we evaluated the effects of patch-size and the presence of trees on bird community composition, as well as several habitat variables, through an information-theoretical modelling approach. Community composition was obtained through a year of census transects in 12 orchards. The presence of trees in the orchards was the major driver of bird communities followed by seasonality; bird communities are independent of patch size, except for small orchard patches that benefit black-chin sparrows, which are considered a sensitive species. At least 55 species of six trophic guilds (insectivores, granivores, carnivores, nectivores, omnivores, and frugivores) used the orchards. Orchards provide adequate habitat and food resources for several sensitive species of resident and migratory sparrows. The attributes that make orchards important for birds: trees, shrubs, herb seeds, and open patches can be managed to maintain native biodiversity in highly anthropized regions with an urgent need to find convergence between production and biological conservation.


Adapting a whole health model to home-based primary care: Bridging person-driven priorities with veteran and family-centered geriatric care.
Through the integration of Whole Health for Life into the Department of Veterans Affairs (VA) health care system, the VA aims to transform health care delivery from a disease management approach to one that embraces person-centered care. The home-based primary care (HBPC) program is a care model that, within the VA, provides holistic primary care services to homebound veterans with multiple chronic medical conditions, mental health issues, and functional declines. These veterans may have limited access to VA programs delivered in a traditional outpatient format. This article describes adaptations to the whole health model of care that could improve its accessibility and applicability to HBPC veterans, caregivers, and the interdisciplinary teams that serve this population. These modifications are informed by whole-person geriatric and gerontological and family-systems theories and address population-based differences in the focus and approach to care. The focus on care is expanded to (a) reflect the importance of attending to caregiver needs and well-being and (b) shift from a preventative model to one that prioritizes resilience and maintenance. The approach to care emphasizes alternative modes of delivery, adaptations to interventions, and integration of geriatric-specific medical considerations into the self-care domains and more directly centers the collaboration between family, the VA, and community partners. This adapted model also addresses the unique needs of health care teams providing in-home services to medically complex veterans and offers suggestions for enhancing self-care and preventing burnout. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Structural and immunologic characterization of bovine, horse, and rabbit serum albumins.
Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), horse (ESA) and rabbit (RSA) sera. The structural data are correlated with the results of immunological studies of SAs. We also analyze the conservation or divergence of structures and sequences of SAs in the context of their potential allergenicity and cross-reactivity. In addition, we identified a previously uncharacterized ligand binding site in the structure of RSA, and calcium binding sites in the structure of BSA, which is the first serum albumin structure to contain metal ions.


Determination of intrinsic mobility of a bilayer oxide thin-film transistor by pulsed I-V method.
Amorphous oxide semiconductor thin-film transistors (TFT) have been considered as outstanding switch devices owing to their high mobility. However, because of their amorphous channel material with a certain level of density of states, a fast transient charging effect in an oxide TFT occurs, leading to an underestimation of the mobility value. In this paper, the effects of the fast charging of high-performance bilayer oxide semiconductor TFTs on mobility are examined in order to determine an accurate mobility extraction method. In addition, an approach based on a pulse I D -V G measurement method is proposed to determine the intrinsic mobility value. Even with the short pulse I D -V G measurement, a certain level of fast transient charge trapping cannot be avoided as long as the charge-trap start time is shorter than the pulse rising time. Using a pulse-amplitude-dependent threshold voltage characterization method, we estimated a correction factor for the apparent mobility, thus allowing us to determine the intrinsic mobility.


[Synthesis and antiulcer activity of 3,4-dihydro-hainanensine analogs].
In order to search for new compounds with new mode of action, high antiulcer activity and lower toxicity, 26(13 pairs of diastereoisomer A and B) 3,4-dihydro-hananensine analogs were synthesized. All compounds were tested in M1 receptor combined assay and gastric ulcer induced by cold-immersion stress in rats. Most compounds showed antiulcer activity, among them IX3A, IX7A, IX8A, IX12A, IX12B and IX13A exhibited more potent antiulcer activity than the control compound cimetidine. Meanwhile, the relationship between their structures and activity was discussed.


Training nurses to facilitate and implement CURA in palliative care institutions: development and evaluation of a blended learning program.
Healthcare professionals in palliative care are found to be confronted with moral challenges on a frequent basis. CURA is a low-threshold instrument for dialogical ethical reflection that was developed to deal with these challenges. A previous study identified the need of healthcare professionals to be trained to introduce CURA in their organization, initiate and facilitate reflections with CURA, and contribute to the implementation of CURA. The aim of this study was to develop and evaluate a training for professionals to become 'CURA-ambassadors'. The training was developed in a participatory way in two cycles. We trained 72 healthcare professionals. The training was evaluated by means of a questionnaire and six semi-structured interviews. The study resulted in a blended learning training combining training sessions with an e-module and with practicing with organizing and facilitating CURA in daily healthcare practice. The main objectives of the training are to enable CURA-ambassadors to introduce CURA within their organization, initiate and facilitate ethical reflections using CURA, and contribute to the implementation of CURA. Participants were generally positive about the training program and the trainers. Technical difficulties related to the e-module were mentioned as main point of improvement. The training program can generate ownership, responsibility, and competency among CURA-ambassadors, which are essential foundations for implementing complex interventions in healthcare practice. The training program received positive evaluations shortly after completing the program. This study adds to our understanding of what is needed for healthcare professionals to use CURA, in order to support them in dealing with moral challenges and to foster their moral resilience. Further research is needed to assess whether participants experience the training as sufficient and effective when using and implementing CURA structurally in their organizations over a longer period of time.


What needs to change.
Earlier this year we heard how Southern Health NHS Foundation Trust had failed to investigate the deaths of more than 1,000 patients with mental health problems. It was a reminder to me of the importance of my work as a clinical adviser to the Parliamentary and Health Service Ombudsman, the body that makes final decisions on unresolved complaints about the NHS in England.


Designing malaria vaccines to circumvent antigen variability.
Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.


Long-Term Outcomes of the PRESERFLO MicroShunt Implant in a Heterogeneous Glaucoma Cohort.
The Preserflo MicroShunt represents a novel glaucoma treatment device, necessitating long-term follow-up data to accurately assess its efficacy. The aim of this study is to report real-world data of a heterogenous glaucoma cohort who received Preserflo implantation at a specialized glaucoma clinic. A total of 160 eyes of 160 patients who underwent Preserflo MicroShunt implantation were retrospectively enrolled in this study. Patient characteristics, as well as success and failure rates, were assessed. The numbers of adverse events and revision procedures were recorded, along with any reduction in supplementary medication. The progression of intraocular pressure (IOP) was assessed over the course of 12 months, and fluctuations were analyzed. The overall success rate was 61.9% (complete success: 51.3%, qualified success: 10.6%). Revision surgery was performed in 25% of cases. Excessive hypotony occurred postoperatively in 54.4% of patients and regressed after 7 days in 88.8% of all cases. Median IOP decreased from 22 (interquartile range (IQR): 17-27) mmHg preoperatively to 14 (IQR 12-16) mmHg at 12 months postoperatively (p < 0.01). The median number of antiglaucomatous agents decreased from three to zero at latest follow-up. The Preserflo MicroShunt achieved a noticeable reduction in IOP over the course of 12 months in glaucoma patients, irrespective of disease severity or disease subtype. The frequency of postoperative adverse events and number for revision surgeries over the course of the follow-up period were low.


Kawasaki disease among Egyptian children: A case series.
Kawasaki disease is an acute vasculitis of early childhood. Its incidence varies among different ethnic groups with higher rates among Asians. In this case series, we presented four cases of Kawasaki disease with incomplete or atypical presentations in Egyptian children. Two cases presented with meningitis, which is not a criteria for the diagnosis of Kawasaki disease. The other two cases presented with pharyngitis and fever, which did not respond to antibiotics. The clinical criteria for diagnosis of Kawasaki disease were either incomplete or appeared sequentially. Coronary artery aneurysms were detected in one case, while the others had normal coronary by echocardiography. All cases were followed in our clinic, according to international guidelines. Early diagnosis and management of Kawasaki disease are important to ensure a good outcome and a high index of suspicion in febrile children is required irrespective of the clinical presentation.


Tumor necrosis factor-alpha regulates in vivo nitric oxide synthesis and induces liver injury during endotoxemia.
Tumor necrosis factor-alpha is a principal mediator of the pathophysiological effects of endotoxemia and endotoxin shock. Tumor necrosis factor-alpha also contributes to the stimulation of nitric oxide synthesis by the induction of the enzyme nitric oxide synthase in a variety of tissues. Although the importance of tumor necrosis factor-alpha in the induction of nitric oxide synthase activity in vitro is well known, its role in in vivo nitric oxide synthesis has not been convincingly established. We were interested in determining whether tumor necrosis factor-alpha plays a significant role in the in vivo induction of nitric oxide synthesis. In Corynebacterium parvum-primed mice, lipopolysaccharide injection resulted in elevated serum tumor necrosis factor-alpha levels early and increased hepatic enzyme release (641 +/- 80 IU AST/L; 22.7 +/- 1.9 IU ornithine carbamoyltransferase per liter) and plasma nitrite and nitrate (804 +/- 84 mumol/L) 5 hr after lipopolysaccharide injection. Polyclonal rabbit anti-mouse anti-tumor necrosis factor-alpha reduced in vivo tumor necrosis factor-alpha levels (1 hr, 7,332 +/- 1,492 U tumor necrosis factor-alpha per milliliter) and reduced nitric oxide synthesis as measured by plasma nitrite and nitrate (352 +/- 69 mumol/L). Polyclonal rabbit anti-mouse anti-tumor necrosis factor-alpha also reduced lipopolysaccharide-induced hepatic enzyme release (428 +/- 33 IU AST/L; 16.0 +/- 2.5 IU ornithine carbamoyltransferase per liter). NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthesis, also decreased plasma nitrite and nitrate (104 +/- 9 mumol/L) but increased the lipopolysaccharide-induced hepatic injury (797 +/- 66 IU AST/L; 33.1 +/- 2.1 IU ornithine carbamoyltransferase per liter).(ABSTRACT TRUNCATED AT 250 WORDS)


Pre-stained slides for the demonstration of rosette-forming cells.
Twenty-one specimens of cerebrospinal fluid (CSF) were examined for T lymphocytes (sheep erythrocyte rosette-forming cells, E-RFC). Conventional wet slide preparations and prestained slides were compared. The mean difference between parallel preparations was 2.5%. Prestained slides are convenient for the examination of RFC. Preparations are easily made without any disfigurement of the cells or disruption of rosettes.


[Isolation and characterization of gentamicin resistance plasmids of coliform bacteria from the waste water of a water treatment plant].
Gentamicin resistance coliforms detected continuously in raw and purified waste water samples of a sewage treatment plant made up less than 0.1% of all coliforms. 43.9%; 31.4%; 13.3% and 11.3% of gentamicin-resistant coliforms were identified as Enterobacter, E. coli, Klebsiella and Citrobacter, respectively. R plasmids encoding a gentamicin resistance phenotype were isolated and characterized. They range between 55 and 60 MD in size and belong to 3 incompatibility groups (IncOF, IncM, IncK). Using restriction endonucleolytic digestion of plasmids, they could be further characterized and subtyped. In contrast to moderate molecular alterations observed among the IncM plasmids, the IncOF plasmids reveal a high stability of restriction pattern. This IncOF plasmid was predominantly found in E. coli wild strains and detected continuously.


[Relation between estrogen and progesterone receptors and response to hormone therapy].
In mammary cancers, and more especially at the stage of generalization, the detection of estrogen receptors plays a prominent role in the choice of treatment. Recent studies indicate that nearly half of cancers containing receptors are responsive to various hormone treatments while only a minority of cancers not containing receptors are responsive to the same treatments. The present review emphasizes the benefits of a quantitative dosage of these receptors compared to their simple detection. It also evaluates the predictive value of progesterone receptors as an additional test for hormonodependence. Finally, it analyses the part played by receptors dosage in the current therapeutic strategy as well as in the development of new clinical protocols.


Na/K-ATPase Signaling and Cardiac Pre/Postconditioning with Cardiotonic Steroids.
The first reports of cardiac Na/K-ATPase signaling, published 20 years ago, have opened several major fields of investigations into the cardioprotective action of low/subinotropic concentrations of cardiotonic steroids (CTS). This review focuses on the protective cardiac Na/K-ATPase-mediated signaling triggered by low concentrations of ouabain and other CTS, in the context of the enduring debate over the use of CTS in the ischemic heart. Indeed, as basic and clinical research continues to support effectiveness and feasibility of conditioning interventions against ischemia/reperfusion injury in acute myocardial infarction (AMI), the mechanistic information available to date suggests that unique features of CTS-based conditioning could be highly suitable, alone /or as a combinatory approach.


Ultrastructural localization of epidermal growth factor receptor in human parotid gland.
The epidermal growth factor receptor (EGFR) is widely distributed in several organs in which, following interaction with its ligand, it can affect development and differentiation. The aim of this study was to define the distribution of EGFR in human parotid gland by means of a post-embedding immunogold staining method. Normal human parotid glands obtained at surgery were routinely prepared for electron microscopy. Semithin and ultrathin sections were treated for immunocytochemistry using a mouse monoclonal antibody specific for EGFR and a goat anti-mouse gold conjugated secondary antiserum. At the light microscope level, EGFR reactivity was revealed by a specific dark staining in both acinar and ductal cells. At the electron microscope level, EGFR was strongly stained in the cytoplasmic compartments and occasionally labeled on cell surfaces. In acinar cells, it appeared to be associated with small vesicles of uncertain nature that were scattered among the secretory granules. EGFR-positive vesicles were also observed in the ductal cells, with the most intense labeling being localized in striated ducts. Since cytoplasmic vesicles were previously found to be EGF-positive, these results may be due to the presence of the EGF-EGFR complex that is internalized after binding of EGF to the surface EGFR.


[Effects of irrigating fluid absorption in percutaneous nephrolithotripsy].
To determine the hemodynamic status, fluid-electrolyte changes and complications associated with irrigation time in percutaneous nephrolithotripsy. A total of 68 renal calculi patients (31 males and 37 females) were recruited. The lateral recumbent percutaneous nephrolithotripsy was operated with Ho laser under ultrasonic guidance. 0.9% NaCI was used as perfusion fluid. The following items were recorded: mean arterial blood pressure (MAP), heart rate, central venous pressure (CVP), hemoglobin, sodium, potassium and chloride; perfusion time during operation; peri-operative and post-operative complications. (1) Peri-operative and post-operative conditions: the average operative time was 83.1 +/- 22.21 minutes. Two cases stopped because of bleeding after puncture and the tube of stoma was placed for stone clearance of the second time. There was more bleeding in 11 patients, but the operations were continued with blood transfusion and close monitoring. Two operations ceased because of a premunition of congestive heart failure. Nine patients needed post-operative blood transfusion and 18 had a post-operative fever. One patient bled in and around the tube and had a peri-renal infection a week later. (2) Changes of observation parameters: there was no significant difference in CVP, heart rate, hemoglobin, sodium, potassium and chloride (P > 0.05). The post-perfusion value of MAP increased (P < 0.05) especially in the cases of more bleeding and long time of irrigation. Peri-operative and post-operative injection of furosemide could reduce the CVP value. The average irrigation time in the fever group was longer than the non-fever group (P < 0.05) and the CVP value of the fever group was higher than the non-fever group (P < 0.05). Low pressure and short time of perfusion are safe in clinical practice. Congestive heart failure after the perfusion and the occurrence of post-operative infections are difficult to avoid when there are a long time of irrigation and more bleeding during operation.


Primary lung sarcoma treated with stereotactic ablative radiotherapy: a case report.
Primary lung sarcoma (PLS) is an extremely rare, very aggressive malignancy. Surgical removal is considered the treatment of choice, and patients who have been given conventional radiotherapy have had inferior outcomes. This study is the first describing a case of PLS treated with stereotactic ablative radiotherapy (SABR), which precisely targets a small tumor with a markedly higher biologically effective dose than conventional radiotherapy. The patient was an 82-year-old man who was diagnosed with primary lung leiomyosarcoma based on radiology, pathology, and immunohistochemical examinations. The PLS was located in the right lower lobe and measured 2.5 cm. No regional nodal or distant organ metastasis was observed. He was inoperable medically. The SABR was performed using volumetric modulated arc therapy and a dose of 56 Gy in four fractions. Follow-up computed tomography 2 months after SABR revealed a complete tumor response. The toxicity was limited to mild respiratory symptoms. The patient is alive and has had no evidence of disease for 2 years. This study suggests that SABR can be a safe and effective treatment option for PLS.


A Dimeric Bis(melamine)-Substituted Bispidine for Efficient Transmembrane H+ /Cl- Cotransport.
A 3,7-diazabicyclo[3.3.1]nonane linking to two melamines is a unique transmembrane H+ /Cl- carrier. In the solid state, the V-shaped compound forms a HCl-bound zig-zag network through cooperative protonation and hydrogen bond interactions. In the lipid membrane, the receptor forms a dimeric self-assembly involving multiple H+ and Cl- leading to the efficient transport of the acid. The pH-dependent Cl- efflux observed for the compound was rationalized based on a gradual protonation model that confers an active transmembrane carrier at physiological pH.


[DRGs at high risk of inappropriateness in Italy: evaluation of regional thresholds.].
This study evaluates interregional variability in threshold levels fixed by the various regions, for DRGs at high risk of inappropriateness, and analyses regional and national objectives achieved with respect to the reduction of hospital admissions (years 2001-2004). A reduction of inappropriate admissions has been observed.


PHINDaccess Hackathons for COVID-19 and Host-Pathogen Interaction: Lessons Learned and Recommendations for Low- and Middle-Income Countries.
Hackathons are collaborative events that bring together diverse groups to solve predefined challenges. The COVID-19 pandemic caused by SARS-CoV-2 has emphasized the need for portable and reproducible genomics analysis pipelines to study the genetic susceptibility of the human host and investigate human-SARS-CoV-2 protein interactions. To build and strengthen institutional capacities in OMICS data analysis applied to host-pathogen interaction (HPI), the PHINDaccess project organized two hackathons in 2020 and 2021. These hackathons are aimed at developing bioinformatics pipelines related to the SARS-CoV-2 viral genome, its phylodynamic transmission, and the identification of human genome host variants, with a focus on addressing global health challenges, particularly in low- and middle-income countries (LMIC). This paper outlines the preparation, proceedings, and lessons learned from these hackathons, including the challenges faced by participants and our recommendations based on our experience for organizing hackathons in LMIC and beyond.


Synthesis and properties of MoCl4 complexes with thio- and seleno-ethers and their use for chemical vapour deposition of MoSe2 and MoS2 films.
Treatment of trans-[MoCl4(MeCN)2] with L (L = Me2S, Me2Se, THT, ½MeSCH2CH2SMe) in CH2Cl2 solution, or reaction of MoCl5 with excess L' (L' = nBu2S, nBu2Se, ½MeSCH2CH2SMe, ½iPrSCH2CH2SiPr, ½MeSCH2CH2CH2SMe, ½MeSeCH2CH2CH2SeMe) in MeCN, produces the Mo(iv) complexes, [MoCl4(L)2] and [MoCl4(L')2], respectively, in good yield. The new complexes have been characterised by IR and UV-vis spectroscopy, elemental analysis and magnetic measurements, whilst crystal structure analyses of trans-[MoCl4(Me2S)2], cis-[MoCl4{RS(CH2)2SR}] (R = Me, iPr) and cis-[MoCl4{MeS(CH2)3SMe}] confirmed their identities and distorted octahedral geometries. The potential of [MoCl4(nBu2E)2] (E = S, Se) as the first examples of molybdenum halide derived single source CVD precursors for the growth of MoE2 thin films was first probed by TGA, which showed multi-step decomposition processes, with the masses of the final residues consistent with MoSe2 (E = Se) and MoCl4 (E = S), respectively. Low pressure CVD experiments conducted at 750 °C (E = S) and 525 °C (E = Se) gave silvery and golden yellow films, respectively. Grazing incidence and in plane XRD data confirmed these to be 2H-MoE2, whilst the texture of the MoSe2 was investigated using pole figure measurements. SEM and EDX data, optical and Raman data on the films are also reported.


CSA and CSB play a role in the response to DNA breaks.
CS proteins have been involved in the repair of a wide variety of DNA lesions. Here, we analyse the role of CS proteins in DNA break repair by studying histone H2AX phosphorylation in different cell cycle phases and DNA break repair by comet assay in CS-A and CS-B primary and transformed cells. Following methyl methane sulphate treatment a significant accumulation of unrepaired single strand breaks was detected in CS cells as compared to normal cells, leading to accumulation of double strand breaks in S and G2 phases. A delay in DSBs repair and accumulation in S and G2 phases were also observed following IR exposure. These data confirm the role of CSB in the suppression of NHEJ in S and G2 phase cells and extend this function to CSA. However, the repair kinetics of double strand breaks showed unique features for CS-A and CS-B cells suggesting that these proteins may act at different times along DNA break repair. The involvement of CS proteins in the repair of DNA breaks may play an important role in the clinical features of CS patients.


'Bringing respite in the burden of illness' - dog handlers' experience of visiting older persons with dementia together with a therapy dog.
To illuminate meanings of the lived experiences of dog handlers' when visiting older persons with dementia with their therapy dog. Studies indicate that care of persons with dementia should focus on a person-centred approach with the person's interests in the centre. Animal-assisted therapy using a therapy dog in the care of persons with dementia has been shown to increase well-being and decrease problematic behaviours associated with the illness. A qualitative lifeworld approach was adopted for this study. Data were collected from open-ended interviews with nine dog handlers, and the analysis conducted using the phenomenological hermeneutical method. The structural analysis resulted in one theme, 'Respite from the burden of illness for persons with dementia'. Visiting a person with dementia can be seen as an act of caring, providing temporary respite from their illness, and creating a special relationship between handler and patient. A therapy dog visit can represent a moment of communion between the handler and the person with dementia. Dog handlers use their skills and knowledge to promote a situation that reduces symptoms of illness and encourages healthier behaviour. The results of this study may be of interest to researchers, clinical practitioners, caregivers and dog handlers who care for persons with dementia using therapy dog teams on prescription as an alternative method to minimise behavioural and psychological symptoms of dementia.


BSAC Vanguard Series: Artificial intelligence and antibiotic stewardship.
Antimicrobial stewardship is a key facet in preventing antimicrobial resistance but can be difficult to put into practice. Frontline providers are faced with the unknowns of pending culture data plus the urgency of appropriate antibiotic choice to prevent sepsis-related mortality; this often leads to broad-spectrum antibiotic prescribing. Currently available resources lack a customized approach to individual patients. Artificial intelligence (AI) focused on antimicrobial stewardship may create a unique opportunity to provide individualized, real-time recommendations to providers on appropriate, but narrower spectrum, antibiotic options. We envision that, with further advances in AI, personalized clinical decision support tools to optimize antibiotic prescribing could be available within the next decade.


Microscopic polyangiitis causing diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis.
Diffuse alveolar hemorrhage complicating small vessel vasculitis is a life-threatening emergency and should be considered in the differential diagnosis of patients who develop rapidly progressive dyspnea with alveolar opacities on chest imaging. In these patients, the coexistence of pulmonary and renal involvement suggests a multisystem disease. We present a case of a man who presented to our hospital with diffuse alveolar hemorrhage, severe anemia, and rapidly progressive glomerulonephritis.