Metastatic potential in T1 and T2 colorectal cancer.
Survival of patients with colorectal cancer confined to the muscularis propria (stage I) is excellent after curative resection. However, some patients are likely to develop lymph node and distant metastasis that can ultimately cause death. The purpose of this study was to identify the possible predictors of lymph node and distant metastasis in T1 and T2 colorectal cancers. In total 208 patients with T1 and T2 colorectal cancers who underwent surgical resection in Taipei Veterans General Hospital from July 1996 to December 2001 were enrolled. The clinicopathological variables including age, gender, tumor location (rectum/colon), preoperative carcinoembryonic antibody level, depth of tumor invasion, lymphovascular invasion, and unfavored histology corresponding to the metastasis assessed pathologically were analyzed. Categorical variables were analyzed using Chi-square with Yates' correction. The independent predictor of lymph node and distant metastasis was determined with multivariate binary logistic regression. Of the 208 T1 and T2 colorectal cancer patients, 36 (17.3%) had lymph node metastasis and 5 (2.4%) had distant metastasis at surgery. The risk of lymph node metastasis was 14.3% (8/56) in T1 and 18.4% (28/52) in T2 colorectal cancer. The tumors with evidence of lymphovascular invasion had a significantly higher incidence of lymph node metastasis than those without lymphovascular invasion (43.6% vs. 9.4%; p<0.001). The independent risk factor for lymph node metastasis was lymphovascular invasion only (95% confidence interval, 3.37-19.97; p<0.001), whereas that for distant metastasis was preoperative carcinoembryonic antibody level >5ng/mL only (95% confidence interval, 0.03-0.21; p<0.001). The negative predictive value of possible adverse risk factors including preoperative carcinoembryonic antibody level >5ng/mL, lymphovascular invasion, and unfavored differentiation for metastasis was 93.5%. Considering the negative predictive value of combined possible adverse risk factors, the risk of metastasis still was 6.5%. Therefore radical surgery was recommended for all T1 and T2 stage colorectal cancer patients except if the patient had a very high surgical risk.


Reliability of assessing postural control during seated balancing using a physical human-robot interaction.
This study evaluated the within- and between-visit reliability of a seated balance test for quantifying trunk motor control using input-output data. Thirty healthy subjects performed a seated balance test under three conditions: eyes open (EO), eyes closed (EC), and eyes closed with vibration to the lumbar muscles (VIB). Each subject performed three trials of each condition on three different visits. The seated balance test utilized a torque-controlled robotic seat, which together with a sitting subject resulted in a physical human-robot interaction (pHRI) (two degrees-of-freedom with upper and lower body rotations). Subjects balanced the pHRI by controlling trunk rotation in response to pseudorandom torque perturbations applied to the seat in the coronal plane. Performance error was expressed as the root mean square (RMSE) of deviations from the upright position in the time domain and as the mean bandpass signal energy (Emb) in the frequency domain. Intra-class correlation coefficients (ICC) quantified the between-visit reliability of both RMSE and Emb. The empirical transfer function estimates (ETFE) from the perturbation input to each of the two rotational outputs were calculated. Coefficients of multiple correlation (CMC) quantified the within- and between-visit reliability of the averaged ETFE. ICCs of RMSE and Emb for all conditions were ≥0.84. The mean within- and between-visit CMCs were all ≥0.96 for the lower body rotation and ≥0.89 for the upper body rotation. Therefore, our seated balance test consisting of pHRI to assess coronal plane trunk motor control is reliable.


Post-exercise alcohol ingestion exacerbates eccentric-exercise induced losses in performance.
The effect of acute alcohol intake on muscular performance in both the exercising and non-exercising legs in the days following strenuous eccentric exercise was investigated to ascertain whether an interaction between post-exercise alcohol use and muscle damage causes an increase in damage-related weakness. Ten healthy males performed 300 maximal eccentric contractions of the quadriceps muscles of one leg on an isokinetic dynamometer. They then consumed either a beverage containing 1 g of ethanol per kg bodyweight ethanol (as vodka and orange juice; ALC) or a non-alcoholic beverage (OJ). At least 2 weeks later they performed an equivalent bout of eccentric exercise on the contralateral leg after which they consumed the other beverage. Measurement of peak and average peak isokinetic (concentric and eccentric) and isometric torque produced by the quadriceps of both exercising and non-exercising legs was made before and 36 and 60 h post-exercise. Greatest decreases in exercising leg performance were observed at 36 h with losses of 28.7, 31.9 and 25.9% occurring for OJ average peak isometric, concentric, and eccentric torques, respectively. However, average peak torque loss was significantly greater in ALC with the same performance measures decreasing by 40.9, 42.8 and 44.8% (all p < 0.05). Performance of the non-exercising leg did not change significantly under either treatment. Therefore, consumption of moderate amounts of alcohol after damaging exercise magnifies the loss of force associated with strenuous eccentric exercise. This weakness appears to be due to an interaction between muscle damage and alcohol rather than the systemic effects of acute alcohol consumption.


Inhibitors of aminoglycoside resistance activated in cells.
The most common mechanism of resistance to aminoglycoside antibiotics entails bacterial expression of drug-metabolizing enzymes, such as the clinically widespread aminoglycoside N-6'-acetyltransferase (AAC(6')). Aminoglycoside-CoA bisubstrates are highly potent AAC(6') inhibitors; however, their inability to penetrate cells precludes in vivo studies. Some truncated bisubstrates are known to cross cell membranes, yet their activities against AAC(6') are in the micromolar range at best. We report here the synthesis and biological activity of aminoglycoside-pantetheine derivatives that, although devoid of AAC(6') inhibitory activity, can potentiate the antibacterial activity of kanamycin A against an aminoglycoside-resistant strain of Enterococcus faecium. Biological studies demonstrate that these molecules are potentially extended to their corresponding full-length bisubstrates by enzymes of the coenzyme A biosynthetic pathway. This work provides a proof-of-concept for the utility of prodrug compounds activated by enzymes of the coenzyme A biosynthetic pathway, to resensitize resistant strains of bacteria to aminoglycoside antibiotics.


[Superior horn of thyroid cartilage dysplasia in 1 case].
The external stimuli and other reasons may result in hyperplasia and abnormal angle of the upper corner of the thyroid cartilage. The upper corner of the thyroid cartilage has anatomical variations. To oppression stimulate carotid artery, cervical sympathetic dry section and so on, could causing pharyngeal foreign body sensation and sore throat. By surgical removal of the thyroid cartilage hyperplasia upper corner, postoperative symptoms would be resolved.


Osseous metaplasia in a kidney allograft.
Osseous metaplasia is defined by the presence of heterotopic normal bone tissue in a soft tissue. The bone matrix is associated with osteoblasts, osteoclasts, adipocytes and haematopoietic stem cells. Osseous metaplasia pathophysiology is not well known, but many factors have been incriminated including chronic inflammation and chronic ischaemia. We describe the second case of osseous metaplasia in a kidney allograft. Numerous factors might favour its development including factors linked to transplantation failure environment.


Polio in Afghanistan: The Current Situation amid COVID-19.
Polio is a deadly viral disease that has been paralyzing many children in Afghanistan. Despite fundamental efforts, primarily vaccination, to reduce the number of cases in Afghanistan, there are still many children who are deprived of the vaccine every year. Afghanistan is one of the two remaining countries endemic for polio, and the country has undergone various challenges that have hampered the eradication of this disease. The underlying challenges include inaccessibility of unsecured areas, illiteracy, refusal, and, most recently, COVID-19. The country is in the midst of a battle against COVID-19, and polio has almost entirely been neglected. Sadly, polio cases are increasing in the country, particularly in polio-free provinces. After an initial lockdown, many businesses have been allowed to resume, but the mass polio vaccination campaign has not restarted. New cases of polio will surge if endemic regions remain unvaccinated or inaccessible. To curb the further spread of polio, Afghanistan needs to resume nationwide house-to-house vaccination as restrictions due to COVID-19 are loosened.


A generalized sequential Bonferroni procedure using smoothed weights for genome-wide association studies incorporating information on Hardy-Weinberg disequilibrium among cases.
For genome-wide association studies (GWAS) with case-control designs, one of the most widely used association tests is the Cochran-Armitage (CA) trend test assuming an additive mode of inheritance. The CA trend test often has higher power than other association tests under additive and multiplicative disease models. However, it can have very low power under a recessive disease model in GWAS. Although tests (such as MAX3) robust to different genetic models have been developed, they often have relatively lower power than the CA trend test under additive and multiplicative models. The goal of this study is to propose an efficient method that not only has higher power than the CA trend test under dominant and recessive models but also maintains the power of the CA trend test under additive and multiplicative models. We employed the generalized sequential Bonferroni (GSB) procedure of Holm to incorporate information from a Hardy-Weinberg disequilibrium (HWD) test into the CA trend test based on estimating weights from the p values of the HWD test. We proposed to smooth the weights to reduce possible noise. Results from extensive simulation studies showed that the proposed GSB procedure can achieve the goal described above.


Urea standard Kt/V(urea) for assessing dialysis treatment adequacy.
Urea standard Kt/V(urea) (stdKt/V(urea)) has been proposed as a dose measure to assess the adequacy of dialysis treatments of arbitrary length and frequency. It is based on two fundamental assumptions: 1) that clinical outcomes for hemodialysis and peritoneal dialysis patients are equivalent and 2) that the equivalency of such clinical outcomes is achieved when the mean predialysis blood urea nitrogen or urea concentration is identical for both therapies. The relationships among urea stdKt/V(urea), equilibrated Kt/V(urea), and single-pool Kt/V(urea) are reviewed, and the assumptions required for the validity of urea stdKt/V(urea) as a universal dose measure to describe dialysis treatment adequacy are discussed. It is proposed that urea stdKt/V(urea) is a dose measure for both water-soluble and protein-bound toxin clearances; therefore, this parameter may be a practical dose measure for assessing the adequacy of dialysis during treatments of arbitrary length and frequency.


BMP-4 polymorphisms in the susceptibility of cervical spondylotic myelopathy and its outcome after anterior cervical corpectomy and fusion.
To investigate the association between single nucleotide polymorphisms (SNPs) of bone morphogenic proteins-4 (BMP-4) gene and the susceptibility of cervical spondylotic myelopathy (CSM) and its outcome after surgical treatment. A total of 499 patients with CSM and 602 healthy volunteers were recruited. 425 CSM patients received anterior cervical corpectomy and fusion (ACF) and were follow-up until 12 months. The SNPs of BMP-4 were determined. For 6007C > T polymorphism, the cases had a significant lower prevalence of TT genotype than controls. With the CC genotype as reference, the TT genotype carriages significantly influence the CSM risk. The T allele carriage represented a higher risk for CSM as well. The TT of 6007C>T polymorphisms is also associated with higher chance to gain improvement from ACF surgery. The T allele carriage of 6007C>T had markedly higher chance to have a better post-operative outcome compared with C allele carriage. The genotype and allele distributions of -5826G>A polymorphism did not show positive association with risk and outcome of CSM in this study. BMP-4 genetic polymorphisms may be used as a molecular marker for the CSM susceptibility and its postoperative outcome in those underwent surgical treatment.


Morphological and phylogenetic studies of marine Myxobolus spp. from mullet in Ichkeul Lake, Tunisia.
Six species of the genus Myxobolus (Myxozoa) from the marine environment were collected from two species of mullet (Mugil cephalus and Liza ramada) in Ichkeul Lake, Tunisia. Four of these species were described previously (Myxobolus bizerti, Myxobolus ichkeulensis, Myxobolus spinacurvatura, and Myxobolus episquamalis) and two (Myxobolus exiguus and Myxobolus muelleri) are redescribed. The small subunit ribosomal (18S rDNA) sequences of these six myxozoans were obtained and compared to traditional criteria used in the identification and taxonomy of myxozoan species (such as spore morphology, host specificity, and tissue tropism). A distance analysis of 1,600-1,700 base pairs of the 18S rDNA of the six species indicates that they formed a monophyletic group separate from Myxobolus spp. found as parasites of freshwater fish. The sequence analyses also confirm that these morphologically different Myxobolus spp. that infect mullet represent different species. Lastly, M. exiguus and M. muelleri, which were found in the same host, exhibit clear differences in spore morphology but sequencing of two different regions of the 18S rDNA show they are closely related. These results demonstrate the utility of DNA sequence data in providing more detailed relationships among the Myxobolus species based upon existing morphological taxonomic approaches. We suggest that future descriptions of Myxobolus spp. provide both careful spore descriptions as part of the traditional criteria but also 18S rDNA sequence data that will aid in situations where morphological details may be absent or misleading.


Prediction of Salmonella serovars isolated from clinical and food matrices in Lebanon and genomic-based investigation focusing on Enteritidis serovar.
Salmonella enterica subsp. enterica serovars are considered major causes of food poisoning and we performed this study because Salmonella is a burden in Lebanon. The present study investigated the ability of genomic information to predict serovar using a collection of Salmonella isolates from infected humans (n = 24) and contaminated food (n = 63) in Lebanon. Further, the phylogenomic relationships of the serovar the predominated in Lebanon (i.e., S. Enteritidis; n = 25) were investigated in comparison with isolates from other countries (n = 130) based on coregenome single nucleotide polymorphisms (SNPs). Genetic elements, specifically Salmonella pathogenicity islands (SPIs), plasmid replicons, and antibiotic-resistance genes were screened in S. Enteritidis genomes (n = 155). Our results revealed that the Salmonella serovars identification by seroagglutination from the samples isolated in Lebanon (n = 87) was highly correlated with the genomic-based prediction of serovars (80.4-85.0% with SeqSero1 and 93.1-94.2% with SeqSero2). The Salmonella serovars isolated from human and food samples in Lebanon were mainly Enteritidis (28.7%) and Infantis (26%). To a rare extent, other serovars included Amager, Anatum, Bredeney, Chincol, Heidelberg, Hofit, Kentucky, Montevideo, Muenster, Newport, Schwarzengrund, Senftenberg and Typhimurium. In comparison with other countries, S. Enteritidis samples isolated in Lebanon (56 ± 27 intra-group pairwise SNP differences) presented a strong phylogenomic relativeness at the coregenome level with samples, as for example with samples isolated from Syria (65 ± 31 inter-group pairwise SNP differences). Most of the studied S. Enteritidis genomes encoded 10 SPIs involved in survival in immune cells (i.e. SPIs 1, 2, 3, 4, 5, 12, 13, 14, 16 and 17). The plasmid replicons IncFIB (S)_1 and IncFII (S)_1 encoding elements involved in virulence were identified in the majority of the S. Enteritidis genomes (94% and 96%, respectively), the majority exhibiting aminoglycosides (gene aac(6')-Iaa_1). The IncI_1_Alpha replicon responsible for ampicillin-resistance was only detected in 2 of 25 S. Enteritidis Lebanese strains. Genomic-based risk assessment of Salmonella serovars in Lebanon showed that food imported from Syria might be an origin of the S. Enteritidis human cases in Lebanon. The detection of several SPIs involved in the survival, plasmid replicons involved in virulence, and aminoglycoside-resistance genes, emphasizes that S. Enteritidis is of paramount importance for public health in Lebanon and other countries.


The role of the Zn(II) binding domain in the mechanism of E. coli DNA topoisomerase I.
Escherichia coli DNA topoisomerase I binds three Zn(II) with three tetracysteine motifs which, together with the 14 kDa C-terminal region, form a 30 kDa DNA binding domain (ZD domain). The 67 kDa N-terminal domain (Top67) has the active site tyrosine for DNA cleavage but cannot relax negatively supercoiled DNA. We analyzed the role of the ZD domain in the enzyme mechanism. Addition of purified ZD domain to Top67 partially restored the relaxation activity, demonstrating that covalent linkage between the two domains is not necessary for removal of negative supercoils from DNA. The two domains had similar affinities to ssDNA. However, only Top67 could bind dsDNA with high affinity. DNA cleavage assays showed that the Top67 had the same sequence and structure selectivity for DNA cleavage as the intact enzyme. DNA rejoining also did not require the presence of the ZD domain. We propose that during relaxation of negatively supercoiled DNA, Top67 by itself can position the active site tyrosine near the junction of double-stranded and single-stranded DNA for cleavage. However, the interaction of the ZD domain with the passing single-strand of DNA, coupled with enzyme conformational change, is needed for removal of negative supercoils.


Sustainability of population growth: a case study of urban settlements in Israel.
"One of the most sensitive criteria for gauging the degree of socio-economic prosperity of an urban settlement is the ability to sustain stable rates of population growth by attracting newcomers and retaining existing population. The present paper argues that after reaching a particular size (on the average, 20-30,000 residents), urban localities in Israel tend to experience substantial changes in components of their annual population growth. Starting with this inflection point, the growth of settlements gradually becomes less dependent on natural causes (birth and death rates) than on the ability to attract newcomers and retain current residents. On the basis of this conclusion, a strategy of ¿redirecting priorities' to developing the peripheral regions of the country is suggested."


The photo-orientation of azobenzene in viscous solutions, simulated by a stochastic model.
We report a computational study of the photo-orientation kinetics in a viscous solution of azobenzene in ethylene glycol, under irradiation with linearly polarized light. The development of anisotropy and its interplay with photoisomerization are simulated by a stochastic model. A distinctive feature of the model is that it takes into account the photo-orientation angular distributions, specific for each isomer, obtained by nonadiabatic dynamics simulations at the molecular level. We find that the anisotropy, as measured by optical absorption dichroism, does not necessarily increase monotonously with time. As expected, the photo-orientation turns out to be strongly coupled with photoisomerization, but the latter is not a mandatory ingredient of this phenomenon: we predict that any chromophore undergoing large amplitude geometry relaxation during its excited state dynamics can develop anisotropy under suitable conditions.


Hordeivirus replication, movement, and pathogenesis.
The last Hordeivirus review appearing in this series 20 years ago focused on the comparative biology, relationships, and genome organization of members of the genus ( 68 ). Prior to the 1989 review, useful findings about the origin, disease occurrence, host ranges, and general biological properties of Barley stripe mosaic virus (BSMV) were summarized in three comprehensive reviews ( 26, 67, 107 ). Several recent reviews emphasizing contemporary molecular genetic findings also may be of interest to various readers ( 15, 37, 42, 69, 70, 88, 113 ). In the current review, we briefly reiterate the biological properties of the four members of the Hordeivirus genus and describe advances in our understanding of organization and expression of the viral genomes. We also discuss the infection processes and pathogenesis of the most extensively characterized Hordeiviruses and frame these advances in the broader context of viruses in other families that have encoded triple gene block proteins. In addition, an overview of recent advances in the use of BSMV for virus-induced gene silencing is presented.


The Association between Cognitive Reserve and Depressive Mood in Older Inpatients: Gender and Age Differences.
Cognitive Reserve (CR) plays a protective role in neurological and acute/chronic diseases. Its effect on mood, however, is still unclear, although it may be relevant in a hospital setting. We aimed to explore the relationship between CR and depressive mood in older inpatients, evaluating possible gender- and age-related differences. This study involved 86 inpatients aged ≥65 years with an MMSE ≥15. Participants underwent a multidimensional evaluation that included the assessment of CR with the Cognitive Reserve Index questionnaire, divided into three sections (Education, Working Activity, and Leisure Time). Depressive mood was assessed with the 15-item Geriatric Depression Scale (GDS). The relationship between CR and GDS was evaluated by multivariable linear regressions. Significant inverse associations between CR and GDS scores emerged in the total sample (β = -0.03 [SD = 0.02], p = .047), especially in men (β = -0.05 [SD = 0.02], p = .005) and in individuals aged <85 years (β = -0.07 [SD = 0.03], p = .01). Among the single CRI sections, CRI-Leisure Time was significantly associated with GDS in the total sample, in men, and participants <85 years. CR seems to be inversely associated with depressive mood in older inpatients. This relationship is particularly marked for CR related to Leisure Time, which may be modifiable even in older age through social support and interaction.


A Review on Plant Bioactive Compounds and Their Modes of Action Against Coronavirus Infection.
The rapid outbreak of coronavirus disease 2019 (COVID-19) has demonstrated the need for development of new vaccine candidates and therapeutic drugs to fight against the underlying virus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Currently, no antiviral treatment is available to treat COVID-19 as treatment is mostly directed to only relieving the symptoms. Retrospectively, herbal medicinal plants have been used for thousands of years as a medicinal alternative including for the treatment of various viral illnesses. However, a comprehensive description using various medicinal plants in treating coronavirus infection has not to date been described adequately, especially their modes of action. Most other reports and reviews have also only focused on selected ethnobotanical herbs such as Traditional Chinese Medicine, yet more plants can be considered to enrich the source of the anti-viral compounds. In this review, we have screened and identified potential herbal medicinal plants as anti-coronavirus medication across major literature databases without being limited to any regions or ethnobotanic criteria. As such we have successfully gathered experimentally validated in vivo, in vitro, or in silico findings of more than 30 plants in which these plant extracts or their related compounds, such as those of Artemisia annua L., Houttuynia cordata Thunb., and Sambucus formosana Nakai, are described through their respective modes of action against specific mechanisms or pathways during the viral infection. This includes inhibition of viral attachment and penetration, inhibition of viral RNA and protein synthesis, inhibition of viral key proteins such as 3-chymotrypsin-like cysteine protease (3CLpro) and papain-like protease 2 (PLpro), as well as other mechanisms including inhibition of the viral release and enhanced host immunity. We hope this compilation will help researchers and clinicians to identify the source of appropriate anti-viral drugs from plants in combating COVID-19 and, ultimately, save millions of affected human lives.


Sarcoma in a Patient with Laryngeal Papillomatosis: A Case Report.
Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. Sarcoma of the larynx is rare. Here, we present a case of sarcoma in a patient repeatedly treated for RRP. We report a case of a 73- year old Caucasian male diagnosed with adult-onset recurrent respiratory papillomatosis (AORRP) at the age of 63y. o. During the previous 10 years, he underwent multiple surgeries. In the last therapeutic intervention, he was treated with laser excision of the papilloma and topical mitomycin application. Two months after treatment, papilloma recurred and sarcoma was diagnosed. RRP is a benign lesion. Affected patients usually require multiple interventions. It rarely degenerates to malignancy. Sarcoma in the larynx in the presence of RRP is a rare case. Extended surgical removal remains the treatment of choice. Adjuvant therapies consist of chemotherapy and radiation and are reserved for unresectable or recurrent cases.


Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system.
Liposome-encapsulated drugs often exhibit reduced toxicity and have also been shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs in liposomes has often resulted in an improved overall therapeutic efficacy. The results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for therapy of intracellular M. avium infection show enhanced cellular delivery of liposome-encapsulated antibiotics and suggest that efficiency of intracellular targeting is sufficient to mediate enhanced antimycobacterial effects. The antitubercular drugs encapsulated in lung specific stealth liposomes have enhanced efficacies against tuberculosis infection in mice. These results from stealth liposome study indicate that antitubercular drugs encapsulated in liposome may provide therapeutic advantages over the existing chemotherapeutic regimen for tuberculosis. Liposomes with encapsulated amikacin are able to protect collagen almost completely from adherence of bacterial cells of all strains examined and prevent from invading of bacteria.


The Comparative Estimation of Primary Students' Programming Outcomes Based on Traditional and Distance Out-of-School Extracurricular Informatics Education in Electronics Courses during the Challenging COVID-19 Period.
The authors decided to investigate the impact of the lockdown period and the resulting limitations in informatics education, especially programming, in out-of-school electronics courses using traditional and distance learning modes in primary school COVID-19 pandemic settings. Two extracurricular courses were held successively; the first electronics course was performed in a traditional out-of-school learning mode using Arduino kits, while the other was held using the TinkerCad circuits virtual environment in distance learning mode. A structured questionnaire was administered to students to map their knowledge of programming. The questionnaire consists of three emotional dimensions: enjoyment, satisfaction and motivation. The fourth dimension was dedicated to the students' programming outcomes. Three emotional dimensions were addressed to primary school students, while the fourth dimension was addressed to the tutors' observations toward the students' programming outcomes. The obtained results revealed that learning modes have no significant impact on students perceiving the programming issues. However, three emotional dimensions revealed a significant difference in the students' enjoyment, satisfaction and motivation in favor of the traditional learning mode. Our findings are of particular interest in light of possible crisis-prompted distance education in the future but can also serve to inform government institutions and policymakers seeking to develop effective concepts for successful distance learning.


Cellular Interactions in the Tumor Microenvironment: The Role of Secretome.
Over the past years, it has become evident that cancer initiation and progression depends on several components of the tumor microenvironment, including inflammatory and immune cells, fibroblasts, endothelial cells, adipocytes, and extracellular matrix. These components of the tumor microenvironment and the neoplastic cells interact with each other providing pro and antitumor signals. The tumor-stroma communication occurs directly between cells or via a variety of molecules secreted, such as growth factors, cytokines, chemokines and microRNAs. This secretome, which derives not only from tumor cells but also from cancer-associated stromal cells, is an important source of key regulators of the tumorigenic process. Their screening and characterization could provide useful biomarkers to improve cancer diagnosis, prognosis, and monitoring of treatment responses.


A new approach to the rapid determination of protein side chain conformations.
Two efficient algorithms have been developed which allow amino acid side chain conformations to be optimized rapidly for a given peptide backbone conformation. Both these approaches are based on the assumption that each side chain can be represented by a small number of rotameric states. These states have been obtained by a dynamic cluster analysis of a large data base of known crystallographic structures. Successful applications of these algorithms to the prediction of known protein conformations are presented.


Surgical decision making.
Decision making is an integral part of surgical practice and is a skill that is as important as the ability to operate. Sound decision making is the result of acquiring 'surgical wisdom', which is achieved through learning, experience and reflection. This paper reviews the processes of surgical decision making with respect to choosing the correct procedure and deciding when to operate, and how operative decisions are made, together with the factors that influence our surgical decisions.


Sclerosing epithelioid fibrosarcoma: rare and serious.
Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare form of soft tissue sarcoma. It is characterized by a slow evolution, with local recurrences and late metastases that are mainly pulmonary and pleural in about 50% of cases. The treatment is based on the surgery which must be as wide as possible. The efficacy of adjuvant therapy in the control of SEF is not yet demonstrated. Chemotherapy is used in recurrences, some have also proposed radiotherapy. Long-term follow-up of patients with SEF is therefore essential.


Micro soft tissues visualization based on x-ray phase-contrast imaging.
The current imaging methods have a limited ability to visualize microstructures of biological soft tissues. Small lesions cannot be detected at the early stage of the disease. Phase contrast imaging (PCI) is a novel non-invasive imaging technique that can provide high contrast images of soft tissues by the use of X-ray phase shift. It is a new choice in terms of non-invasively revealing soft tissue details. In this study, the lung and hepatic fibrosis models of mice and rats were used to investigate the ability of PCI in microstructures observation of soft tissues. Our results demonstrated that different liver fibrosis stages could be distinguished non-invasively by PCI. The three-dimensional morphology of a segment of blood vessel was constructed. Noteworthy, the blood clot inside the vessel was visualized in three dimensions which provided a precise description of vessel stenosis. Furthermore, the whole lung airways including the alveoli were obtained. We had specifically highlighted its use in the visualization and assessment of the alveoli. To our knowledge, this was the first time for non-invasive alveoli imaging using PCI. This finding may offer a new perspective on the diagnosis of respiratory disease. All the results confirmed that PCI will be a valuable tool in biological soft tissues imaging.


EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer.
To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). The working panel performed a literature review of the new data (2013-2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Relapse after local therapy is defined by a rising prostate-specific antigen (PSA) level >0.2ng/ml following radical prostatectomy (RP) and >2ng/ml above the nadir after radiation therapy (RT). 11C-choline positron emission tomography/computed tomography is of limited importance if PSA is <1.0ng/ml; bone scans and computed tomography can be omitted unless PSA is >10ng/ml. Multiparametric magnetic resonance imaging and biopsy are important to assess biochemical failure following RT. Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5ng/ml and salvage RP, high-intensity focused ultrasound, cryosurgical ablation or salvage brachytherapy of the prostate in radiation failures. Androgen deprivation therapy (ADT) remains the basis for treatment of men with metastatic prostate cancer (PCa). However, docetaxel combined with ADT should be considered the standard of care for men with metastases at first presentation, provided they are fit enough to receive the drug. Follow-up of ADT should include analysis of PSA, testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Level 1 evidence for the treatment of metastatic CRPC (mCRPC) includes, abiraterone acetate plus prednisone (AA/P), enzalutamide, radium 223 (Ra 223), docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel, AA/P, enzalutamide, and radium are approved for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications. The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are the first endorsed by the European Society for Therapeutic Radiology and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/). In men with a rise in their PSA levels after prior local treatment for prostate cancer only, it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients. For patients diagnosed with metastatic castrate-resistant prostate cancer, several new drugs have become available which may provide a clear survival benefit but the optimal choice will have to be made on an individual basis.


Alterations in apoptosis of cord and adult peripheral blood mononuclear cells induced by in vitro infection with respiratory syncytial virus.
Respiratory syncytial virus (RSV), a major cause of morbidity in children, results in severe lower respiratory tract infections. With an in vitro infection system of isolated cord or adult peripheral blood mononuclear cells, addition of virus to cell cultures resulted in significant reductions in cell deaths, as measured by 2 independent assays: quantitation of cells with subdiploid levels of DNA and cells with DNA strand breaks. Decreased cell death was observed in lymphocytes and monocytes of cord and adult samples, with more dramatic effects evident in cells from cord blood. This may be linked to the increased virulence observed in infants with RSV infection. These data suggest that RSV may be equipped with some mechanism to prevent apoptosis, which is a major component of the host defense system used to eliminate virally infected cells.


Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects.
Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient's growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design criteria for shunt diameter changes. Then, two stages of prototyping were performed to design, build and test responsive hydrogel systems that facilitate tuning of the shunt diameter by adjusting the hydrogel's degree of crosslinking. We examined two mechanisms to drive crosslinking: infusion of chemical crosslinking agents and near-UV photoinitiation. The growth model showed that 15-18% increases in shunt diameter were required to accommodate growing patients' increasing blood flow; similarly, the computational models demonstrated that blood flow magnitudes were in agreement with previous reports. These target levels of diameter increases were achieved experimentally with model hydrogel systems. We also verified that the photocrosslinkable hydrogel, composed of methacrylated dextran, was contact-nonhemolytic. These results demonstrate proof-of-concept feasibility and reflect the first steps in the development of this novel blood shunt. A tunable shunt design offers a new methodology to rebalance blood flow in this vulnerable patient population during growth and development.


Nursing students' experience of practice placements.
Clinical practice placements are an essential component of pre-registration nursing programmes. Integration into a new team in an unfamiliar setting, which has its own values, practices, culture and language, can be stressful for nursing students. This article presents and discusses students' reflections on preparing for, entering and leaving practice placements. Ten students who participated in fortnightly group reflective sessions, discussed and analysed their learning experiences while on practice placements in an acute hospital. The challenges the students encountered were deconstructed using a group narrative approach. The students experienced ethical dilemmas around patient dignity, consent and advocacy as well as factors external to the practice setting, such as navigating systems and processes to access information before starting practice placements, managing household duties and academic workloads while working long shifts, and managing fatigue and loneliness. The students devised recommendations for other students to enable them to navigate their practice placements effectively and enhance their learning experience. Raising awareness among academic and practice placement staff of the challenges students encounter before and during their practice placement is essential to assist students to succeed and maximise their learning potential.


Study of the porcine dermal collagen repair patch in morpho-functional recovery of the rotator cuff after minimum follow-up of 2.5 years.
Tendon augmentation grafts have the potential to facilitate the repair of massive or otherwise unrepairable rotator cuff tears. In our clinic, between 2009 and 2013, 25 patients underwent surgery to treat massive symptomatic rotator cuff tears with porcine dermal collagen patch. This study is a clinical and instrumental assessment of 9 patients with the longest follow-up. These patients were evaluated with Constant score, the American Shoulder and Elbow Surgeons Evaluation Form, ultrasound imaging, magnetic resonance imaging, and electromyography. The clinical evaluations have shown good outcomes. The magnetic resonance imaging results were comparable with those of the ultrasound scan. In all cases, we found covering of humeral head, centering of the humeral head, maintenance of the tropism of the supraspinatus, no appearance of fatty degeneration, no worse in cases with fatty degeneration. With the electromyographic examination a complete functional recovery was observed with the possibility of performing maximal contraction against resistance in all cases. We believe that porcine dermal collagen is effective as an augmentation graft in the treatment of chronic extensive rotator cuff tears, providing excellent pain relief with an improvement in active ranges of motion and strength.


The sports science of curling: a practical review.
Curling is a sport played on ice in which two teams each deliver 8 granite stones towards a target, or 'house'. It is the only sport in which the trajectory of the projectile can be influenced after it has been released by the athlete. This is achieved by sweeping the ice in front of the stone to change the stone-ice friction and thereby enable to stone to travel further, curl more or stay straight. Hard sweeping is physically demanding. Different techniques of sweeping can also have different effects on the stone. This paper will review the current research behind sweeping a curling stone, outline the physiological demands of sweeping, the associated performance effects and suggest potential strategies of sweeping that can be used by both coaches and curling teams. Key pointsSweeping a curling stone can be highly physically demanding.Effective sweeping requires a combination of downward force and brush head speed, determined by the stone velocity.Sweeping on the left or right of a stone can help the stone to remain straight or curl more depending on the rotation of the stone.This can lead to the development of sweeping and playing tactics and contribute to team selection.


Fatal clostridium septicum myonecrosis in a captive canada lynx (Lynx canadensis).
A 1-yr-old female Canada lynx (Lynx canadensis) presented for sudden onset of rapidly progressive bilateral pelvic limb paralysis. The lynx was chemically immobilized to perform a physical examination but expired shortly thereafter. On postmortem radiographs, there were myriad small irregular, round-to-spherical gas densities within the skeletal muscle of the right thigh and epaxial musculature. At gross necropsy, the muscles of the right thigh, right lateral abdominal wall, and epaxial region were emphysematous and necrohemorrhagic, with subcutaneous and muscular crepitant swelling. Multiple skin puncture wounds, consistent with bites, were present over the affected tissues. Clostridium septicum was isolated in pure anaerobic culture from the musculature of the right hind limb. Histopathologic examination confirmed the diagnosis of acute, severe necrohemorrhagic and gangrenous myositis and cellulitis. Gram stains demonstrated large gram-positive bacilli with subterminal spores. This is the first known documented case of C. septicum myonecrosis in a nondomestic felid.


A rat brain Na+ channel alpha subunit with novel gating properties.
We have constructed a full-length rat brain Na+ channel alpha subunit cDNA that differs from the previously reported alpha subunit of Noda et al. at 6 amino acid positions. Transcription of the cDNA in vitro and injection into Xenopus oocytes resulted in the synthesis of functional Na+ channels. Although the single-channel conductance of the channels resulting from cloned cDNA was the same as that of channels resulting from injection of rat brain RNA, we observed two significant differences in the gating properties of the channels. The Na+ currents from cloned cDNA displayed much slower macroscopic inactivation compared with those from rat brain mRNA. In addition, the current-voltage relationship for currents from cloned cDNA was shifted 20-25 mV in the depolarizing direction compared with currents from rat brain RNA. Coinjection of low MW rat brain RNA restored normal inactivation of the channels indicating the presence of a component, either a structural subunit of the channel complex or a modifying enzyme, necessary for normal gating of the channel.


Ultrasonographic appearance of Dandy Walker-like Syndrome in a Boston Terrier.
Congenital cerebellar disorders can be caused by in utero or neonatal infections, genetic aberrations causing malformations, and neurodegenerative processes. Most congenital cerebellar disorders are diagnosed definitively with histopathology. However, antemortem diagnosis of cerebellar malformations can be made by imaging the brain. This paper describes the antemortem appearance of a congenital cerebellar malformation in a Boston Terrier puppy on ultrasound images. This appearance was compared with the postmortem findings that were comparable to Dandy Walker Syndrome in humans. A previous report of this syndrome in Boston Terriers suggests the problem may be inherited in this breed.


Factors Related to Locomotive Syndrome in School-Aged Children in Okazaki: A Cross-Sectional Study.
The relationship of locomotive syndrome with other physical characteristics and lifestyle habits in children has not been fully elucidated. The aim of this study was to assess the prevalence of children's locomotive syndrome, and to determine its relationship with the above-mentioned factors. This was a cross-sectional study of 285 elementary school children who volunteered to participate in a medical checkup for physical function. Data was collected via medical examination, clinical measurements, and questionnaires. A multivariable logistic regression model was used to determine the relationship (odds ratios; ORs) of participants' characteristics, physical functions, and other outcomes determined by questionnaire on locomotive syndrome. The following factors were related to locomotive syndrome: older age (OR = 1.421, 95% confidence interval [CI] [1.039, 1.945]), male sex (OR = 4.011, 95% CI [2.189, 7.347]), and more time spent watching television per day (OR = 1.281, 95% CI [1.001, 1.640]). These results may assist in the encouragement of children to perform appropriate physical activities and avoid unhealthy lifestyle habits, reducing the occurrence of locomotive syndrome.


The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis.
Analysis of myeloid-related protein 8 and 14 complex (MRP8/14) serum concentrations is a potential new tool to support the diagnosis of systemic-onset juvenile idiopathic arthritis (SJIA) in the presence of fever of unknown origin. To test the ability of MRP8/14 serum concentrations to monitor disease activity in patients with SJIA and stratify patients at risk of relapse. Serum concentrations of MRP8/14 in 52 patients with SJIA were determined by a sandwich ELISA. The monitoring of therapeutic regimens targeting interleukin 1 and tumour necrosis factor α, and methotrexate treatment was analysed and diagnostic power to predict flares was tested. MRP8/14 levels were clearly raised in active disease and decreased significantly in response to successful treatments. Serum concentrations of MRP8/14 increased significantly (p<0.001) (mean±95% CI 12.030±3.090 ng/ml) during disease flares compared with patients with inactive disease (864±86 ng/ml). During clinical remission MRP8/14 serum levels of >740 ng/ml predicted disease flares accurately (sensitivity 92%, specificity 88%). MRP8/14 levels correlated well with clinical disease activity, as assessed by physician's global assessment of disease activity (r=0.62), Childhood Health Assessment Questionnaire (r=0.56), active joint count (r=0.46) and with C-reactive protein (r=0.71) and erythrocyte sedimentation rate (r=0.72) (for all p<0.001). MRP8/14 serum concentrations correlate closely with response to drug treatment and disease activity and therefore might be an additional measurement for monitoring anti-inflammatory treatment of individual patients with SJIA. MRP8/14 serum concentrations are the first predictive biomarker indicating subclinical disease activity and stratifying patients at risk of relapse during times of clinically inactive disease.


Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke.
Inflammatory mechanisms contribute substantially to secondary tissue injury after brain ischemia. Regulatory T cells (Tregs) are key endogenous modulators of postischemic neuroinflammation. We investigated the potential of histone deacetylase inhibition (HDACi) to enhance Treg potency for experimental stroke in mice. HDACi using trichostatin A increased the number of Tregs and boosted their immunosuppressive capacity and interleukin (IL)-10 expression. In vivo treatment reduced infarct volumes and behavioral deficits after cortical brain ischemia, attenuated cerebral proinflammatory cytokine expression, and increased numbers of brain-invading Tregs. A similar effect was obtained using tubastatin, a specific inhibitor of HDAC6 and a key HDAC in Foxp3 regulation. The neuroprotective effect of HDACi depended on the presence of Foxp3(+) Tregs, and in vivo and in vitro studies showed that the anti-inflammatory cytokine IL-10 was their main mediator. In summary, modulation of Treg function by HDACi is a novel and potent target to intervene at the center of neuroinflammation. Furthermore, this novel concept of modulating endogenous immune mechanisms might be translated to a broad spectrum of diseases, including primary neuroinflammatory and neurodegenerative disorders.


Photosynthetic intermediates, the warburg effect, and glycolate synthesis in isolated spinach chloroplasts.
Increasing levels of CO(2) have been shown to stimulate the rate of photosynthesis, eliminate the oxygen inhibition of photosynthesis (Warburg effect), and decrease glycolate formation in isolated spinach chloroplasts. Ribose 5-phosphate and fructose 1,6-diphosphate at concentrations of 5 to 10 mum also stimulate the rate of plastid photosynthesis and eliminate the Warburg effect. In contrast to the effect of high CO(2) levels, these sugar phosphates have little effect on glycolate formation. Evidence is presented to show that the level of intermediates of the photosynthetic carbon reduction cycle may influence the Warburg effect in vivo. It is postulated that the formation of glycolate is not the causal factor of the Warburg effect.


Anesthesia and postoperative shivering: its etiology, treatment and prevention.
Postoperative shivering following anesthesia varies between 5 and 65%. The etiology of postoperative shivering is unclear. Pharmacologic agents are still the most popular mode of treatment for postanesthetic shivering, such as meperidine, clonidine and physostigmine. Nonpharmacologic approaches such as maintaining ambient temperature and warming air blankets and intravenous infusions remain as effective preventive measures for postoperative shivering. This review will address its etiology, treatment and prevention.


Nitric oxide-releasing compounds inhibit the production of interleukin-2, -4 and -10 in activated human lymphocytes.
In the present study, we investigated the effects of nitric oxide donors, GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3(3,4-dichlorophenyl)-chloride), GEA 3175 (1,2,3,4-oxatriazolium,3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl) sulfonyl]amino]-, hydroxide inner salt) and S-nitroso-N-acetylpenicillamine (SNAP), on the production of Th1 [interleukin (IL)-2] and Th2 (IL-4 and IL-10) type cytokines in activated human lymphocytes. Lymphocytes were stimulated with concanavalin A or a combination of thapsigargin and phorbol myristate acetate in the absence or in the presence of nitric oxide donors. Concanavalin A induced expression of IL-2 mRNA and production of IL-2, and the combination of thapsigargin and phorbol myristate acetate induced expression of IL-4 and IL-10 mRNAs and production of IL-4 and IL-10. These effects were inhibited by the nitric oxide donors in a dose-dependent manner, GEA 3162 and GEA 3175 being more potent than SNAP on a molar basis. The results show that nitric oxide donors have immunomodulatory properties in both Th1- and Th2-derived responses.


Septated urinomas in the neonate.
Perirenal urinomas may develop when obstruction to urinary flow creates sufficient back pressure to produce extravasation of urine. Such fluid collections have been described as mainly sonolucent. However, in the last 2 years, we have imaged five neonates with multiple, marked septations of the urinoma, four with posterior urethral valves and one with a ureteropelvic junction obstruction. Diagnostic confusion may arise when the kidney is not identified, when the septated nature of the urinoma is not recognized, and when urinary tract obstruction is not seen.


Effect of sodium bicarbonate in an experimental model of radiocontrast nephropathy.
The aim of this study is to investigate the efficacy and mechanism of action of intravenous (IV) bicarbonate in preventing radiocontrast nephropathy (RCN). Twenty-eight Wistar rats were randomized into four groups including control (group 1), radiocontrast (group 2), bicarbonate (group 3), and radiocontrast plus bicarbonate (group 4). Once blood chemistry and arterial blood gases were examined and 24 h urine samples were collected, all rats were administered furosemide (2 mg/kg subcutaneous) and deprived of water for 24 h. Iothalamate sodium (6 mL/kg) was administered to group 2 and group 4. IV bicarbonate (8.4%) was administered to group 3 and group 4 (3 h before the administration of iothalamate). On the fourth day, 24 h urine was collected, and at the end of the day rats were sacrificed and blood chemistry and arterial blood gases were reexamined. Myeloperoxidase (MPO), nitric oxide (NO), total glutathione, and malondialdehyde were quantified on the renal tissue. H&E slides were examined. Basal creatinine and creatinine clearance were similar between groups. There was no significant difference between creatinine and creatinine clearance by the end of the experiment. Glutathione level in group 2 was lower than in group 4. Histopathologically, there was no injury in the control group (group 1) whereas there was an intermediate-severe injury (71.4%) in the radiocontrast group (group 2). The percentage of intermediate-severe injury was significantly lower (71.4% vs. 28.6%, p = 0.02) in the radiocontrast plus bicarbonate group (group 4). Sodium bicarbonate attenuates the development of radiocontrast-induced tubular necrosis.


Re an Adoption Application (Surrogacy), 11 March 1987.
The Court was asked to make an adoption order in favor of a couple who had paid another woman to bear a child for them using the husband's sperm. The Court made the order, noting that the Surrogacy Arrangements Act 1985, which bans commercial surrogacy agencies, negotiations, and advertisements had not been enacted at the time of this arrangement. It also held that the arrangement did not violate the Adoption Act 1958, which prohibits payments or rewards for or in consideration of adoption, because the payment to the surrogate was not made in contemplation of adoption. Moreover, it concluded that even if the payment had been made in contemplation of adoption, the Adoption Act gave the Court the power to authorize the payment retrospectively.


Peripheral benzodiazepine receptor (PBR) new insight in cell proliferation and cell differentiation review.
The peripheral benzodiazepine receptor (PBR), is an 18 kDa protein of the mammalian mitochondrial membrane and is a highly conserved protein among the mammalian. PBR is involved in numerous biological functions, including steroid biosynthesis, mitochondrial oxidative phosporylation and cell proliferation. The presence of PBR at the nuclear subcellular level has been demonstrated in aggressive breast cancer cell line and human glioma cells, where it seems to be involved in cell proliferation. In our previous studies we investigated the presence of nuclear PBR in different hepatic tumour cell lines with regard to binding to [3H] PK 11,195 and protein analysis. The results obtained by saturation binding experiments and Scatchard analysis of nuclear PBR density in parallel with the results on the growth curves of the cell lines tested, indicate that the nuclear PBR density correlates inversely with cell doubling time. Moreover, the cell line with high nuclear PBR proliferates in response to PBR ligands, whereas that with low nuclear PBR does not. All these findings support the idea that PBR could play a pivotal role in cell proliferation and this receptor protein could be potentially important either in early diagnosis or chemopreventive strategies against degenerative disease.


Physical Activity and Exergames Among Older Adults: A Scoping Review.
Recently, exergames have been widely applied as exercise platforms among older adults. However, studies on the influence of exergames on older adults' physical activity remain scarce. The review article highlights the potential benefit of exergames as a physical activity tool for older adults. The literature search followed the PRISMA guidelines on databases PubMed (Public/Publisher MEDLINE), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, and Scopus. The literature included studies that evaluated the influence of exergames on older adults' physical activity. Articles were excluded if the mixed intervention was used, emphasizing specific limbs, improving specific tasks, or not mentioning intervention. The review article identified 25 studies that reported on 855 older adults 55 years of age and older. In addition, the common exergaming technology platforms examined were Microsoft Kinect™, Nintendo® Wii™, cybercycling, and interactive video dance games. Meanwhile, 11 studies used a pretest/post-test design and randomized controlled trial design in 14 studies. The review found that exergames significantly impacted the older adults' physical activity level as participants experienced improved balance and cognitive function, and enjoyed playing exergame, thus prolonging their game engagement. Although research on exergames is still new, current evidence showed a significant potential benefit of exergames as a physical activity tool for older adults. To overcome the limitation on various parameters that showed different effects and outcomes of exergames, the study recommends implementing randomized controlled trials with long-term observation using a mixed-method approach. Moreover, a multidisciplinary method involving exercise and neuromotor control experts could determine potential mechanisms of action that benefited from the exercises.


Systematic identification of Ctr9 regulome in ERα-positive breast cancer.
We had previously identified Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), as a key factor regulating a massive ERα target gene expression and ERα-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at a few ERα-target loci. However, it remains to be determined whether Ctr9 controls ERα-target gene expression by regulating the global chromatin occupancy of ERα and RNAPII in the presence of estrogen. In this study, we determined the genome-wide ERα and RNAPII occupancy in response to estrogen reatment and/or Ctr9 knockdown by performing chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). We found that loss of Ctr9 dramatically decreases the global occupancy of ERα and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ERα-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ERα and Ctr9 target genes, and further delineated the independent function of Ctr9 from other subunits in PAFc when regulating transcription. Our data demonstrated that Ctr9, independent of other PAFc subunits, controls ERα-target gene expression by regulating global chromatin occupancies of ERα and RNAPII.


Regulation of k influx in barley : effects of low temperature.
Influx and accumulation of K(+) in barley (Hordeum vulgare L. cv Fergus) roots were measured at two temperatures (10 degrees C and 20 degrees C) in plants which had been grown with roots and shoots at 20 degrees C (HT plants), with roots and shoots at 10 degrees C (LT plants), and with roots at 10 degrees C and shoots at 20 degrees C (DT plants). Under conditions where K(+) was in limited supply during the prior growth period, K(+) influx and accumulation were consistently higher in roots of DT and LT plants than in those of HT plants. Thus, it would appear that this low temperature response is not limited specifically to conditions in which temperature differentials are maintained between roots and shoots. Nevertheless, it was generally the case that increases of influx were larger in DT and LT plants so that the temperature differentials may intensify the low temperature response. When K(+) influx was examined over a wide range of root [K(+)], it was seen that the characteristic reduction of influx associated with increased internal [K(+)] was substantially greater in HT than DT or LT plants. Transfer of plants grown under HT conditions to DT or LT regimes led to both short-term and long-term adjustments of influx. The former became apparent within 6 hours of exposure to the new conditions and decayed within minutes of transfer back to 20 degrees C. The long-term adjustments were only apparent after prolonged exposure (days) to the lower root temperature and these did not decay as rapidly. Regardless of shoot temperature, the transfer of roots from 20 degrees C to 10 degrees C caused a gradual increase of root [K(+)] so that 4 days later LT and DT roots contained, respectively, 53.3 and 49.83 micromoles per gram compared to 17.82 micromoles per gram for roots maintained at 20 degrees C.


[Immunohistological demonstration of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells].
The localization of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells was examined by immunohistochemistry. All of the 15 mucinous tumors had argyrophil cells which resemble the enterochromaffin cells seen in the gastrointestinal tract, and peptide hormones such as gastrin and somatostatin were found in 3 of 5 benign, in 3 of 5 borderline, and in all of 5 malignant tumors. Serotonin was found in 4 benign, 3 borderline and 2 malignant tumors. Of 19 endometrioid adenocarcinomas, type I argyrophil cells which resemble enterochromaffin cells were found in 4 tumors, type II argyrophil cells which contain argyrophil granules mainly in the apical portion or throughout the whole cytoplasm were found in 14, and mixed type cells were found in one. Somatostatin-positive cells were found only in type I cells of a tumor with mixed type argyrophil cells. Serotonin-positive cells were found in 3 tumors containing type I cells. The results obtained were discussed in the comparison with those of cervical and endometrial adenocarcinomas of the uterus. In conclusion, the present study suggests that type I or similar argyrophil cells in ovarian tumors may have endocrine activity.


Highly efficient broadband silicon nitride polarization beam splitter incorporating serially cascaded asymmetric directional couplers.
The implementation of a polarization beam splitter (PBS) on a silicon nitride platform remains challenging owing to its relatively low index. We therefore propose a silicon nitride PBS that exploits serially cascaded asymmetric directional couplers (ADCs), leading to a high polarization extinction ratio (PER) over a broad bandwidth. The ADC spatially routes incident light through polarization-selective mode coupling under a small footprint of 112 µm. The proposed PBS does not require an active phase control. It is thus effectively realized via a single-step lithography process. The measured transverse-electric and transverse-magnetic PERs were determined to be above 23 dB and 10 dB over an 80-nm bandwidth, respectively, spanning λ=1520-1600nm. The proposed device is thus anticipated to play a key role in providing polarization diversity in photonic-integrated circuits.


Effects of Saccharomyces cerevisiae supplementation on apparent total tract digestibility of nutrients and fermentation profile in healthy horses.
Supplementation with Saccharomyces cerevisiae (SC) in horses may have some potential to modify microbial populations and thereby improve fibre digestibility. The aim of this study was to investigate the effects of SC on apparent total tract digestibility (ATTD) of nutrients, with a special focus on fibre digestion in healthy horses. The fermentation profile of microbial populations was another focus of interest. Twelve geldings were randomly assigned to three groups. The basal diet consisted of cracked corn (2 g starch/kg body weight [BW]) and hay (1.2 kg/100 kg BW). During adaptation (3 weeks) and the total faecal collection period (5 days), cracked corn was fed once daily either as control (0 g SC) or supplemented with 1 or 3 g SC (1 g SC = 2 × 10(10) colony-forming units [cfu]). There was a 4-week wash-out period between the different SC regimes. Faeces were sampled by rectal collection for the analysis of pH, nitrogen, lactic acid, short-chain fatty acids (SCFA) and SC. In faeces, mean SC cfu was significantly lower than the quantity supplemented: 0 g SC, no detection; 1 g SC, 1.1 × 10(6) cfu; 3 g SC, 3.6 × 10(6) cfu. Apparent total tract digestibility of crude fibre varied approximately 40% without any treatment-related effects. Short-chain fatty acids, lactic acids and pH in faeces were not significantly affected by SC supplementation. Saccharomyces cerevisiae supplementation was not associated with any changes in the fermentation profiles, and fibre digestion accordingly remained unchanged in intact and healthy horses. Taking into account that fibre digestion remained unchanged and recovery rate of SC in faeces was mariginal, colonization and proliferation of SC in the healthy equine intestinal tract seems to be unlikely.


Alterable correlates of extrinsic and intrinsic job satisfaction at a state residential facility.
A cross-section of employees at a state residential facility for mentally retarded persons was administered a composite questionnaire to assess factors associated with job satisfaction. Using a multivariate statistical approach, we examined two measures of job satisfaction (extrinsic and intrinsic) in relation to employee perceptions of organizational climate and selected job characteristics. Unique multiple regression analyses indicated that constraining conformity, decision frequency, and clarity of supervisor instructions were related to both measures of job satisfaction; organizational clarity, reward, and satisfaction with materials were related only to extrinsic satisfaction; and organizational standards and degree of resident contact were related only to intrinsic job satisfaction. Differences in variable contributions "ignoring" and controlling for other variables were emphasized. Variables were ranked according to their importance in predicting job satisfaction. Investigators are encouraged to consider the distinction between extrinsic and intrinsic job satisfaction in future research.


The association between biological subtype and locoregional recurrence in newly diagnosed breast cancer.
We investigated the association between the risk of locoregional recurrence (LRR) and biological subtypes defined by hormonal receptors (HR) and HER-2 status in women with invasive breast cancer (BC). A total of 618 newly diagnosed BC patients were identified from a cancer registry within a single institution with standardized methods of tumor assessment for estrogen receptor (ER), progesterone receptor (PR), and HER-2. Patients were stratified based on surgical treatment, breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well as biological subtypes: HR+/HER-2- (ER-positive or PR-positive, HER-2-negative), HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR-/HER-2+ (ER-negative and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2-negative). The association between clinicopathological factors, biological subtype and LRR was evaluated with univariate and multivariate Cox analysis. With a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate analysis, TN, tumor size ≥2 cm and lymph node (LN) positivity were associated with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively). In BCT group, HR-/HER-2+ and LN positivity were associated with increased risk of LRR (HR 11.13; 95% CI 2.78-44.53; P = 0.0007 and HR 5.40; 95% CI 1.67-17.43; P = 0.0048, respectively). In MRM group, TN subtype and LN positivity were associated with increased risk of LRR (HR 4.72; 95% CI 1.53-14.52; P = 0.0069 and HR 3.23; 95% CI 1.44-7.29; P = 0.0047, respectively). Compared to HR+/HER-2-, HR-/HER-2+ treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER, PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of LRR based on surgical treatment. Our findings suggest a different follow-up and locoregional treatment for patients with HR-/HER-2+ and TN subtypes.


DNA damage bypass pathways and their effect on mutagenesis in yeast.
What is the origin of mutations? In contrast to the naïve notion that mutations are unfortunate accidents, genetic research in microorganisms has demonstrated that most mutations are created by genetically encoded error-prone repair mechanisms. However, error-free repair pathways also exist, and it is still unclear how cells decide when to use one repair method or the other. Here, we summarize what is known about the DNA damage tolerance mechanisms (also known as post-replication repair) for perhaps the best-studied organism, the yeast Saccharomyces cerevisiae. We describe the latest research, which has established the existence of at least two error-free and two error-prone inter-related mechanisms of damage tolerance that compete for the handling of spontaneous DNA damage. We explore what is known about the induction of mutations by DNA damage. We point to potential paradoxes and to open questions that still remain unanswered.


The role of miR-485-5p/NUDT1 axis in gastric cancer.
Cancers can survive the oxidative conditions by upregulating nucleoside diphosphate linked moiety X-type motif 1 (NUDT1). However, the mechanisms underlying gastric carcinogenesis and the dys-regulation of NUDT1 in gastric cancer (GC) remain unknown. Our study aimed to explore the role of NUDT1 and its regulatory pathway by miR-485-5p in GC. Gastric cancer tissues and paired noncancerous tissue samples were collected, and the expression level of NUDT1 and miR-485-5p were detected. Two cohorts from The Cancer Genome Atlas (TCGA) database and another cohort from the Tianjin Medical University Cancer Institute and Hospital were further analyzed. Luciferase assays were performed, and the effects of the miR-485-5p/NUDT1 axis on GC cells and normal gastric cells were determined by subsequent experiments. We found that the expression of miR-485-5p was clearly repressed in GC tissues, while NUDT1 expression level was dramatically increased. The overexpression of NUDT1 correlated closely with an increase in invasive depth and a decrease in survival in GC patients. MiR-485-5p could directly bind to the 3'UTR of NUDT1 mRNA and induce its degradation, thus down-regulate its expression. The miR-485-5p/NUDT1 axis could lead to the changes of 8-oxo-dG in GC cells. And the increased expression of NUDT1 resulting from the downregulation of miR-485-5p could accelerate cell proliferation and metastasis in GC. However, the growth and migration of normal gastric cells did not depend on the protection of NUDT1, while the overexpression of NUDT1 could promote malignant transition in normal gastric cells. MiR-485-5p acts as a tumor suppressor by targeting NUDT1 in GC. The miR-485-5p/NUDT1 axis is involved in the processes of cell growth and cell motility and plays a key role in the tumorigenesis of GC.


Consistency of a Nonword Repetition Task to Discriminate Children with and without Developmental Language Disorder in Catalan-Spanish and European Portuguese Speaking Children.
Nonword repetition has been proposed as a diagnostic marker of developmental language disorder (DLD); however, the inconsistency in the ability of nonword repetition tasks (NRT) to identify children with DLD raises significant questions regarding its feasibility as a clinical tool. Research suggests that some of the inconsistency across NRT may be due to differences in the nature of the nonword stimuli. In this study, we compared children's performance on NRT between two cohorts: the children in the Catalan-Spanish cohort (CS) were bilingual, and the children in the European Portuguese cohort (EP) were monolingual. NRT performance was assessed in both Spanish and Catalan for the bilingual children from Catalonia-Spain and in Portuguese for the monolingual children from Portugal. Results show that although the absolute performance differed across the two cohorts, with NRT performance being lower for the CS, in both Catalan and Spanish, as compared to the EP cohort in both, the cut-points for the likelihood ratios (LH) were similar across the three languages and mirror those previously reported in previous studies. However, the absolute LH ratio values for this study were higher than those reported in prior research due in part to differences in wordlikeness and frequency of the stimuli in the current study. Taken together, the findings from this study show that an NRT consisting of 3-, 4-, and 5-syllable nonwords, which varies in wordlikeness ratings, when presented in a random order accurately identifies and correctly differentiates children with DLD from TD controls the child is bilingual or monolingual.


[Eighty years of Japanese immigration in Brazil].
"Japanese emigration to Brazil started in 1908 with some eight hundred subsidized contract workers for coffee plantations. Hard conditions made many of them flee, and the paulista government suppressed subsidies for these projects; however, the Japanese emigration to Brazil kept on under Japanese subsidies from 1925 until 1934 when Brazil imposed immigration quotas unfavorable to Japanese immigration. International circumstances in the late 1930s and local prohibition on the use of the Japanese language in Brazil caused many immigrants to return to Japan between 1939-1941. Emigration to Brazil restarted as diplomatic relations between Japan and Brazil were reestablished in 1952 but decreased in the late 1960s. Subsequent economic evolution in both countries caused Japanese emigrants in Brazil and their [descendants] to initiate dekasegui [labor] migration from Brazil to Japan as from the late 1980s." (SUMMARY IN ENG)


[External ophthalmomyiasis: case reports].
We report two cases with external ophthalmomyiasis due to infestation with the larvae of Oestrus ovis. During an ophthalmologic examination, motile larvae were seen on the conjunctiva, which were removed and sent to the Department of Parasitology for identification. Microscopic examination of the specimens revealed that both patients were infested with the first stage larvae of O. ovis. The patients were treated with topical antibiotics and steroids and recovered without any complications. O. ovis larvae are the most common cause of ophthalmomyiasis worldwide. They are usually seen in underdeveloped, agricultural areas with high numbers of livestock, especially during Spring and Summer. These kind of infestations should be kept in mind in cases of conjunctivitis in the warm months of the year.


Randomized controlled trial on adjunctive cognitive remediation therapy for chronically hospitalized patients with schizophrenia.
Cognitive remediation therapy (CRT) is one of the promising new non-drug approaches to reducing cognitive deficits of patients with schizophrenia that has not yet been fully evaluated in China. Assess the efficacy of CRT in improving the cognitive functioning, social functioning and insight of patients with chronic schizophrenia. 126 clinically stable inpatients with chronic schizophrenia were randomly allocated to an intervention group (with CRT) and a treatment as usual group (TAU) (which used standard occupational and recreational therapy methods). The treatment frequency and duration were the same for the two groups: five times per week for three months. The Wisconsin Card Sorting Test (WCST) was used to evaluate before versus after changes in cognitive function, the Scale of Social Skills of chronic schizophrenia Inpatients (SSSI) was used to assess social functioning, and the Insight and Treatment Attitude Questionnaire (ITAQ) was use to assess insight. Four patients dropped out during the study leaving 60 in the CRT group and 62 in the TAU group in the final analysis. Both groups showed significant improvement in WCST measures over the three-month trial but the improvement in the CRT group was significantly greater than that for the TAU group on all of the WCST measures assessed. The total SSSI score improved significantly in both groups over the three months, but the improvement in the two groups was not significantly different. The total ITAQ score also showed significant improvement in both groups over the three months and the degree of improvement was significantly greater in the CRT group than in the TAU group. As an adjunctive treatment to antipsychotic medication, a three month course of CRT is more effective at improving the cognitive functioning and insight of hospitalized patients with chronic schizophrenia than routine occupational and recreational therapy.


A diagnostic challenge: investigating suspected tracheobronchial and pharyngoesophageal tears. Are there gold standards?
Pneumomediastinum and surgical emphysema of the neck as a result of blunt chest trauma occurs rarely. We report a case of pneumomediastinum and extensive surgical emphysema of the face and neck due to blunt chest trauma (assault), without evidence of laryngotracheal or pharyngoesophageal tear from the clinical assessment and the radiological examinations. Diagnosis, management, evaluation of investigations and potential mechanisms are discussed. In the presence of suspicious tracheal rupture bronchoscopy is mandatory but not the gold standard to confirm the location of the tear, as seen in our case. In the absence of respiratory compromise, conservative management is appropriate.


Differential transcriptome analysis of zebrafish (Danio rerio) larvae challenged by Vibrio parahaemolyticus.
Zebrafish embryo and larva represent a useful in vivo model for identification of host innate immune responses to bacterial infection. Vibrio parahaemolyticus is a typical zoonotic pathogen worldwide that causes acute gastroenteritis in humans and vibriosis in fishes. However, the mechanism of the innate immune response in the zebrafish larvae infected by V. parahaemolyticus has not been clear. We analysed the transcriptomic profile of 3 days post-fertilization (dpf) zebrafish larvae immersed in V. parahaemolyticus 13 (Vp13) strain suspension for 2 hr. A total of 602 differentially expressed genes (DEGs) were identified in the infection group, of which 175 (29.07%) genes were upregulated and 427 (70.93%) genes were downregulated. These altered genes encoded complement and coagulation cascades, chemokine, TNF signalling pathway, NF-κB signalling pathway and JAK-STAT signalling pathway. Some significant DEGs, such as mmp13, cxcr4a, ccl20, hsp70, gngt, serpina1l, il8, cofilin and il11, were subjected to quantitative gene expression analysis, and the results were consistent with those of the transcriptome profile. These results clearly demonstrated that exposure to V. parahaemolyticus for 2 hr could activate innate immune response in 3dpf larvae by altered expression of downstream signalling pathway genes of pattern recognition receptors (PRRs). Our results also provide a useful reference for future analysis of signal transduction pathways and pathogenesis mechanisms underlying the systemic innate immune response to the external bacteria of V. parahaemolyticus.


Medicaid expansion creates new dilemmas for state programs.
At the same time advocates for the poor are rejoicing over Medicaid program expansions passed as part of the FY 1991 federal budget, state Medicaid directors are wondering how to accommodate all the potential new recipients. Ironically, because of budget pressures at the state level, the new federal mandates could force some current program recipients off the rolls in order to allow new ones on. "Expanding obstetrical and prenatal care is something we want to do because it's sound social policy--but the mandates have been compressed into time frames that are too short for state budgets," says one state Medicaid director.


Accurate and Reliable Gait Cycle Detection in Parkinson's Disease.
There is a growing interest in the use of Inertial Measurement Unit (IMU)-based systems that employ gyroscopes for gait analysis. We describe an improved IMU-based gait analysis processing method that uses gyroscope angular rate reversal to identify the start of each gait cycle during walking. In validation tests with six subjects with Parkinson disease (PD), including those with severe shuffling gait patterns, and seven controls, the probability of True-Positive event detection and False-Positive event detection was 100% and 0%, respectively. Stride time validation tests using high-speed cameras yielded a standard deviation of 6.6 ms for controls and 11.8 ms for those with PD. These data demonstrate that the use of our angular rate reversal algorithm leads to improvements over previous gyroscope-based gait analysis systems. Highly accurate and reliable stride time measurements enabled us to detect subtle changes in stride time variability following a Parkinson's exercise class. We found unacceptable measurement accuracy for stride length when using the Aminian et al gyro-based biomechanical algorithm, with errors as high as 30% in PD subjects. An alternative method, using synchronized infrared timing gates to measure velocity, combined with accurate mean stride time from our angular rate reversal algorithm, more accurately calculates mean stride length.


Discovery of hemocompatible bacterial biofilm-resistant copolymers.
Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative (Pseudomonas aeruginosa) and one Gram positive (Staphylococcus aureus) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone.


Influence of umbelliferone on glycoprotein components in diabetic rats.
ABSTRACT Umbelliferone (7-hydroxycoumarin), a derivative of coumarin, is benzopyrone in nature, and it is present in the fruits of golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). The present study was designed with the objective of evaluating the effect of umbelliferone (UMB) on glycemic control and glycoprotein components in the plasma and tissues (liver, kidney, heart, and brain) of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180 to 200 g, were induced diabetes by administration of STZ (40 mg/kg b.w.) intraperitoneally. The normal and diabetic rats were treated with UMB dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days. In our study, diabetic rats had decreased plasma insulin and elevated blood glucose, sialic acid, total hoxoses, fucose, and hexosamines in the plasma and tissues. Treatment with UMB brought the levels of glucose, sialic acid, total hoxoses, fucose, and hexosamines to near-normal level. Thus, our results show that treatment with UMB has improved glycemic control and thereby reduced the formation of glycoprotein components. This leads to the normalization of circulatory and tissue sialic acid, fucose, hexoses, and hexosamines in STZ-diabetic rats, which reflects a protective effect of UMB from the risk of diabetic complications.


High-power quantum-dot tapered tunable external-cavity lasers based on chirped and unchirped structures.
A high-power tunable external cavity laser configuration with a tapered quantum-dot semiconductor optical amplifier at its core is presented, enabling a record output power for a broadly tunable semiconductor laser source in the 1.2 - 1.3 µm spectral region. Two distinct optical amplifiers are investigated, using either chirped or unchirped quantum-dot structures, and their merits are compared, considering the combination of tunability and high output power generation. At 1230 nm, the chirped quantum-dot laser achieved a maximum power of 0.62 W and demonstrated nearly 100-nm tunability. The unchirped laser enabled a tunability range of 32 nm and at 1254 nm generated a maximum power of 0.97 W, representing a 22-fold increase in output power compared with similar narrow-ridge external-cavity lasers at the same current density.


Phorbol ester inhibits the phosphorylation of the retinoblastoma protein without suppressing cyclin D-associated kinase in vascular smooth muscle cells.
To elucidate the role of protein kinase C in vascular smooth muscle cell proliferation, we examined the effects of phorbol 12-myristate 13-acetate (PMA) on G1 events in human arterial cells. About 15 h after G0 cells were stimulated with fetal bovine serum and basic fibroblast growth factor, [3H]thymidine incorporation started. PMA (10 nM) inhibited the incorporation over 90% when added earlier than 3 h after stimulation, but had no effect when added 12 h or later. PMA inhibited the phosphorylation of the retinoblastoma protein (pRb), which normally began at about 9 h. PMA did not inhibit the gene expression of Cdk2, Cdk3, Cdk4, Cdk5, and cyclins G, C, and D, all of which began at 0-3 h. However, PMA reduced the expression of cyclins E and A, which usually began at 3-9 h and about 15 h, respectively. PMA inhibited the histone H1 kinase activity of Cdk2, which increased from about 9 h, whereas PMA did not inhibit the pRb kinase activities of cyclin D-associated kinase(s) and Cdk4, detectable from 0-3 h. These results suggested that the PMA-induced inhibition of pRb phosphorylation is not mediated by suppressing cyclin D-associated kinase(s) including Cdk4, but involves the suppression of Cdk2 activity that results from the reduced expression of cyclins E and A.


Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.
The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior.


Catastrophic Mechanical Complications of Extracorporeal Membrane Oxygenation.
Technical advances in extracorporeal membrane oxygenation (ECMO) have increased the number of cases that maintain longer duration. Long-term use of ECMO results in ECMO-related complications. Anticipation of the life-threatening mechanical complications and their management are critical for safe ECMO. In this study, we analyzed the incidence, nature, and risk factors of life-threatening mechanical complications during ECMO support. Furthermore, we presented our bedside algorithms to manage catastrophic ECMO complications. Data from 549 patients who underwent ECMO between December 2008 and December 2018 were retrospectively analyzed. The incidence of all life-threatening mechanical complications was 4.0%. Accidental decannulation (1.3%) was most common, followed by abrupt falling circuit flows (1.1%), pump failure (1.1%), circuit rupture (0.4%), and air in circuit (0.2%). Most (90.9%) of life-threatening events required circuit and cannula change, while 9.1% required vein collapse relief procedure. There was no death related to the event; however, six (27.3%) died during ECMO due to the underlying disease for which ECMO was required, and three (13.6%) died after weaning from ECMO. Multivariate regression analysis showed that awake ECMO and long-term ECMO support were significantly associated with life-threatening mechanical complications (p < 0.01). Our algorithm safely managed catastrophic ECMO problems without event-related deaths.


Parent-Child Discrepancies in Perceived Parent-Child Communication and Depressive Symptoms in Early Adolescents in China.
Although recent studies demonstrated that parent-child discrepancies in the perceived family processes were associated with children's developmental outcomes, few studies have addressed this issue in different types of families in mainland China. The present study investigated that how discrepancies in parents' and adolescents' perceptions of parent-adolescent communication were associated with early adolescent depressive symptoms in a nationally representative sample (N = 15,377) with 7010 father-adolescent dyads (adolescents: Mage = 14.24 years, SD = 1.25 years; 5960 adolescents from two-parent families, 443 adolescents from single-father families) and 8367 mother-adolescent dyads (adolescents: Mage = 14.02 years, SD = 1.18 years; 6670 adolescents from two-parent families, 1362 adolescents from single-mother families) in China. Adolescent respondents completed a measure of depressive symptoms and all informants reported on the perceived levels of parent-adolescent communication. Results indicated that adolescents reported parent-child communication more negatively than did their parents. Father-adolescent discrepancies were also greater in intact families than non-intact families. Polynomial regression analyses indicated that while there was a significant interactive effect of father-reported and adolescent-reported father-adolescent communication in Chinese two-parent families, no significant interaction was found for mother-adolescent dyad. Besides, adolescent-reported mother-child communication interacted with mother-reported communication in Chinese single-mother families only. The findings clarify parent-adolescent discrepancies in parent-child communication in different types of families in China and they have theoretical and practical implications on the role of discrepancies in parents and adolescent children on perceived parent-adolescent communication in early adolescent depressive symptoms.


Investigation of catalysts M/CeO2 (M = Pt, Rh, or Pd) for purification of CO2 derived from oxycombustion in the absence or presence of water.
Oxyfuel combustion is a promising technology to produce a CO2-rich flue gas ready suitable for sequestration or valorization. But its storage as well as its further valorization requires to increase the CO2 purification as a small amount of CO and NOx are produced during combustion. Based on the technology developed for three-way converters, similar systems, i.e., M/CeO2 where M is Pt, Pd, or Rh, were studied for NO-CO abatement in a gas stream similar to those obtained when an oxyfuel combustion is performed. The results evidenced that the role of the metal nature influences the performances obtained on NO-CO abatement, platinum supported on ceria being the most efficient catalyst. We also measured the impact of the presence of water in the reaction stream on the catalytic activity of these materials. It appears that the presence of water has a beneficial effect on the different reactions due to a water gas shift reaction that increases the reduction of the NO and favors the formation of N2. The study pointed out that platinum supported on ceria remained the best catalyst, under these wet operating conditions close to industrial ones, for purification of oxyfuel combustion exhausts.


[Immigration in a country of immigration: the Canadian experience].
"Until well after the Second World War, Canadian immigration policy favoured immigration in general, but it was characterised by ethnic and racial preferences and waves of discrimination. Only after 1962 was a less discriminatory point system...implemented which selected immigrants according to their standard of education and the demands of the Canadian labour market. This policy still indirectly favoured 'old' immigration groups. Since 1978 a new immigration law has been the basis of an annual immigration plan taking into account social, humanitarian, and economic criteria. One of its consequences has been the shift towards a greater proportion of Asian immigrants. This change has led to various tensions in the Canadian public." (SUMMARY IN ENG AND FRE)


Cost containment and diffusion of MRI: oil and water?. Japanese experience.
The total number of MR units available in Japan relative to the population is the highest in the world. The total number of MR units installed in 1996 was 2,663, equivalent to 24 per million population. The average charge per procedure in Japan is only one fifth of that in the United States (USA), approximately US$200 and US$950, respectively, suggesting that economic considerations in Japan may not take the highest priority. Despite the low costs, the utilisation (the number of patients examined each year or per week) of MR units in Japan is only about half that in the USA. As such, an increase in the number of MR units per se does not result in excessive health care costs.