Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia.
To determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH). This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern. During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.


Clinical characteristics and outcome of infective endocarditis among intravenous drug abusers in India.
Infective endocarditis (IE) is the most dreaded complication of intravenous drug abuse (IVDA). IVDA is present in significant proportions in India. Since there is scarcity of Indian data on IVDA associated IE, we report a study comparing IVDA to non IVDA associated IE. We compare differences in clinical profile, microbiology, echocardiography and clinical outcome from a tertiary care hospital. A total of 133 patients admitted from 1st January 2017 to 31st December 2019 who met the Modified Duke ''definitive'' criteria for IE were included. Detailed Information was collected regarding demography, clinical data and laboratory investigations. All patients underwent transthoracic echocardiography and trans-esophageal echocardiogram wherever necessary. Among a total of 133 patients, 54 patients (40.6%) were iv drug abusers. Patients in IVDA-group were younger, mostly males, more likely to have concomitant HCV and HIV infections compared to non IVDA-group. Chronic comorbidities such as DM and CKD were more common in non IVDA-group. Rate of positive blood culture was higher in IVDA-group compared to non IVDA-group (74.1%v/s 32.9%,p < 0.001) with different microbiological profile. Percentage of Methicillin resistant staphylococcus aureus (42.6%v/s17.7%,p = 0.003) and pseudomonas related IE (18.5%v/s2.5%,p = 0.003) was significantly higher among IVDA-group. IVDA-group most commonly had tricuspid valve involvement Whereas mitral and aortic valve were most commonly involved valve in non IVDA-group. Mortality was slightly higher among IVDA-group compared to non IVDA-group, though statistically non-significant. Left sided valve involvement and Congestive heart failure were independent predictors of mortality. IVDA-IE is a significant problem in India. Demographic, microbiological and echocardiographic profile is quite different in IVDA and non IVDA-group. There is urgent need to conduct larger studies.


The use of COPD maintenance therapy following spirometry in General Practice.
Several studies have shown that the use of pulmonary medication is widespread and often initiated without initial spirometry. Early detection of chronic obstructive pulmonary disease (COPD) by spirometry in General Practice is essential for an early and correct implementation of medical treatment. The aim of the present study was to evaluate the use of regular therapy following diagnostic spirometry for COPD in General Practice from February 2008 to February 2009. Spirometry data and results were linked through Statistics Denmark with information from the Register of Medicinal Product Statistics using the unique personal identification code. Data were analysed to evaluate the impact of screening on use of regular COPD therapy. Primary outcome was initiation of regular therapy following COPD diagnosis with spirometry. In a population of 3,376 individuals at risk, 1,458 underwent spirometric assessment with 631 being diagnosed with COPD; 110 of those received regular therapy before assessment with this figure increasing to 161 after spirometry. Of 827 participants not receiving a COPD diagnosis, 36 received regular therapy prior to assessment and 42 received regular therapy after spirometry despite no established COPD diagnosis. There is a significant chance of receiving regular therapy after being diagnosed with COPD. However, a large proportion of subjects diagnosed with COPD did not receive regular therapy following diagnosis. Efforts should be made to ensure correct diagnosis and correct medical treatment according to guidelines in individuals with COPD.


Patterns of opioid initiation at first visits for pain in United States primary care settings.
The primary objective of this study was to characterize variation in patterns of opioid prescribing within primary care settings at first visits for pain, and to describe variation by condition, geography, and patient characteristics. 2014 healthcare utilization data from Optum's Clinformatics™ DataMart were used to evaluate individuals 18 years or older with an initial presentation to primary care for 1 of 10 common pain conditions. The main outcomes assessed were (1) the proportion of first visits for pain associated with an opioid prescription fill and (2) the proportion of opioid prescriptions with >7 days' supply. We identified 205 560 individuals who met inclusion criteria; 9.1% of all visits were associated with an opioid fill, ranging from 4.1% (headache) to 28.2% (dental pain). Approximately half (46%) of all opioid prescriptions supplied more than 7 days, and 10% of prescriptions supplied ≥30 days. We observed a 4-fold variation in rates of opioid initiation by state, with highest rates of prescribing in Alabama (16.6%) and lowest rates in New York (3.7%). In 2014, nearly half of all patients filling opioid prescriptions received more than 7 days' of opioids in an initial prescription. Policies limiting initial supplies have the potential to substantially impact opioid prescribing in the primary care setting.


Trans-platinum(II) complexes with cyclohexylamine as expectator ligand induce necrosis in tumour cells by inhibiting DNA synthesis and RNA transcription.
Enhanced removal of cisplatin-DNA adducts has been reported as one of main causes of cell resistance to cisplatin. This particular resistance mechanism may be circumvented by platinum complexes that bind differently to DNA. One line of work is focussed on trans platinum complexes, some of which exhibit antitumour activity similar to or even higher than that of their cis counterparts. We synthesised new trans platinum complexes, trans-[PtCl2(cyclohexylamine)(dimethylamine)] and trans-[PtCl2(OH)2(cyclohexylamine)(dimethylamine)], previously evaluated as cytotoxic agents towards different cancer and normal cell lines. These trans platinum compounds were highly effective against a panel of tumoral cell lines either sensitive to or with acquired resistance to cisplatin. In the present work we examined the mechanisms induced by these compounds to cause tumour cells toxicity. We have found that these compounds induced a complete blockade at the S phase of the cell cycle inhibiting total mRNA transcription and precluding p53 activation. In contrast to other DNA-damaging agents, these compounds do not induce senescence-associated permanent arrest. Furthermore, only a small percentage of these cells enter into apoptosis, with most of the population dying by a necrosis-like mechanism.


Malakoplakia. Defect in digestion of phagocytized material due to impaired vacuolar acidification?
On the basis of light and electron microscopical findings in a case of malakoplakia of urinary bladder, (1) we concur with others that malakoplakia is a hyperplastic accumulation of histiocytes, and that the formation of Michaelis-Gutmann bodies is associated with incomplete digestion of phagocytized cell debris; (2) we hypothesize that digestion within phagolysosomes is impaired because of deficient acidification; and (3) we suggest that the defect in acidification in some cases may be related to treatment with drugs that affect the mechanism of phagocytic vacuolar acidification.


Structural analysis of a polysaccharide isolated from the aqueous extract of an edible mushroom, Pleurotus sajor-caju, cultivar Black Japan.
A water-soluble polysaccharide, isolated from the aqueous extract of an edible mushroom Pleurotus sajor-caju, cultivar Black Japan was found to consist of D-glucose and D-galactose in a molar ratio of 3:1. On the basis of total acid hydrolysis, methylation analysis, and NMR experiments (1H, 13C, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC) the structure of the polysaccharide was established as [Formula: see text].


Joint kinetics during Tai Chi gait and normal walking gait in young and elderly Tai Chi Chuan practitioners.
Tai Chi Chuan is becoming a popular exercise among elders. This study measured the inter-segmental forces and moments at the lower extremity joints during a Tai Chi gait as compared to those during normal walking gait, in both apparently healthy young and elderly Tai Chi Chuan practitioners. Three-dimensional inter-segmental joint reaction force and moment were computed using the Inverse Dynamic Approach based on the kinematics and ground reaction force measurements in a laboratory setting in six young (two females, mean age 28; SD 6 years) and six elderly (five females, mean age 72; SD 8 years) subjects who had previous training of Yang style Tai Chi Chuan. The results showed significant gait differences in both age groups, with significantly smaller peak compressive forces, larger peak shear forces in the ankle, knee and hip joints, and larger peak moments in the knee and hip joints during Tai Chi gait as compared to normal gait. Moreover, the peak shear force was oriented more in the medial-lateral direction at the ankle and knee joints, and the peak moment was in the frontal plane at the knee and hip joints. The results also showed significant age differences, with significantly smaller peak shear forces in all three joints in the elderly group than in the young group during Tai Chi gait. Tai Chi gait has an increased shear force and frontal plane torque at lower extremity joints than normal gait. The shear force at all three lower extremity joints during Tai Chi gait is lower in the elderly subjects than young subjects. This data suggest that, in Tai Chi Chuan training, elderly people with degenerative joint diseases in the lower extremity should use caution when practicing Tai Chi Chuan.


Theoretical and computational advances in biomolecular NMR spectroscopy.
Recent developments in experimental and computational aspects of NMR spectroscopy have had a significant impact on the accuracy and speed of macromolecular structure determination in solution, particularly with regard to systems of high complexity (such as protein complexes). These include experiments designed to provide long-range orientational and translational restraints, improvements in internal coordinate dynamics used for simulated annealing, and the development of database potentials of mean force to improve the description of the non-bonded contacts.


The effect of group art therapy on acculturative and academic stress of Chinese graduate students in South Korea.
Research has shown that international students, specifically Chinese graduate students in South Korea, are vulnerable to stress and depression because of various factors. These include environmental changes, economic constraints, interpersonal difficulties, discrimination, and cultural conflict. This study investigates the effectiveness of group art therapy in reducing acculturative stress and academic stress among Chinese graduate students in South Korea. Thirty participants were recruited and randomly assigned to the experimental (n = 15) and control groups (n = 15). The experimental group received eight 120-min sessions of group art therapy. Both groups were tested for acculturative stress (perceived discrimination, homesickness, perceived hate, fear, stress due to change/culture shock) and academic stress (schoolwork stress, future stress, social stress, living environment stress) before and after the art therapy intervention. Results were compared using the Mann-Whitney U test and the Wilcoxon signed-rank test. The results showed that there was a significantly greater reduction in acculturative and academic stress in the experimental than the control group. Group art therapy can provide psychological and emotional support to international students studying abroad.


An investigation into current protocols and radiographer opinions on contrast extravasation in Irish CT departments.
Iodinated contrast extravasation is a serious complication associated with intravenous administration in radiology. Departmental protocols and the radiographer's approach on both prevention techniques and treatment will affect the prevalence of extravasation, and the eventual outcome for the patient when it does occur. To examine contrast extravasation protocols in place in Irish CT departments for alignment with European Society of Urogenital Radiology (ESUR) Guidelines (2014); to establish radiographer's opinions on contrast extravasation; and to examine radiographer adherence to protocols. Contrast extravasation protocols from a purposively selected sample of CT departments across Ireland (n = 6) were compared to ESUR guidelines, followed by an online survey of CT radiographers practicing in the participating centres. All participating CT departments (n = 5) had written protocols in place. High risk patients, such as elderly or unconscious, were identified in most protocols, however, children were mentioned in just one protocol and obese patients were not specified in any. The response rate of CT radiographers was 23% (n = 24). 58% (n = 14) of respondents indicated that contrast extravasation was more likely during CTA examinations. While high levels of confidence in managing extravasation were reported, suggested treatment approaches, and confidence in same, was more variable. Clinical workload in CT departments was also identified as a factor impacting on patient care and management. While contrast extravasation protocols were generally in line with ESUR Guidelines, high risk patients may not be getting sufficient attention. More radiographer awareness of patient monitoring needs, particularly in busy departments with a heavy workload may also reduce extravasation risk, and improve management of same.


Correlates of problem drinking among drug-using incarcerated women.
The association between drug use--regular use of crack cocaine or heroin--and problem drinking was examined in a sample of 159 sentenced women at Rikers Island correction facility in New York City. Using logistic regression, this study tested the association between drug use and alcohol use, controlling for psychosocial variables (sexual abuse history, negative and positive coping skills, and depression), familial drug use (number of family members currently abusing drugs, and those currently abusing alcohol), and demographic variables and criminal history. The association between current, regular crack use and problem drinking approached significance in the final model, which adjusted for criminal behavior, demographic, familial abuse, and psychosocial variables. The results of this study point toward childhood sexual abuse, negative coping skills, and familial alcohol abuse as variables related to problem drinking among incarcerated women.


Status of Cardiovascular Health in Chinese Children and Adolescents: A Cross-Sectional Study in China.
The American Heart Association defined "ideal cardiovascular health (CVH)" in pediatric populations to promote primordial prevention in cardiovascular diseases. Little is known about CVH and associated sociodemographic factors among Chinese children and adolescents. This study aimed to evaluate CVH and the associations with sociodemographic characteristics in Chinese children and adolescents. This cross-sectional study analyzed baseline data of 15,583 participants aged 7 to 17 years from a Chinese national intervention program against obesity (2013-2014). CVH status was estimated according to 4 health behaviors (nonsmoking, body mass index, physical activity, and diet) and 3 health factors (total cholesterol, blood pressure, and fasting plasma glucose), using revised American Heart Association criteria. Multinomial logistic regression was used to assess the association between sociodemographic characteristics and the number of ideal CVH metrics. The prevalence of ideal CVH status was 1.7% (males: 1.9%; females: 1.6%) in the study population. The prevalence of ideal CVH behaviors and ideal health factors was 3.1% (males 3.3%; females: 3.0%) and 53.6% (males: 52.4%; females: 54.9%), respectively. Ideal fasting plasma glucose was the most prevalent component (males: 94.4%; females: 97.4%), whereas ideal physical activity (males: 34.6%; females: 23.9%) and diet (males: 28.3%; females: 30.1%) were the least prevalent. Female sex, younger age, undeveloped economy, residence in the southern region, and no family history of cardiovascular diseases were associated with more ideal CVH metrics. Ideal CVH status in Chinese children and adolescents is alarmingly rare. Physical activity and diet are key to promotion of CVH. Effective interventions are needed to promote CVH and reduce health disparities in early life.


[Varicella: frequent questions on treatment and recommendations for management of contacts].
Dealing with varicella often causes doubts to general practitioners and pediatricians. In this article the author summaries guidelines based on solid evidence to treat varicella and prevent the disease in susceptible contacts in different clinical scenarios and presents his personal point of view in those controversial aspects commonly resolved by the authorized opinion of experts.


Possible role of calmodulin in stimulation of hexose transport by 12-O-tetradecanoylphorbol-13-acetate, a tumor promoter.
12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter stimulated the rate of 2-deoxy-D-glucose (2DG) transport. Three different kinds of calmodulin antagonists inhibited the TPA-stimulated 2DG transport, the mechanism of which was examined in kinetic analysis. These results indicate that the expression of the effect of TPA may depend on Ca2+-calmodulin system.


Immunotherapy-Mediated Luminal Gastrointestinal Toxicities.
The advent of immune checkpoint blockade and its application in the management of advanced malignancies has revolutionized cancer therapies, outcomes, and survival. As beneficial as these class of drugs have been proven to be, their use is not devoid of complications, viz., immune-related adverse events (irAEs). The gastrointestinal (GI) tract is the second most frequently affected organ system, and toxicities may vary in severity from mild disease to aggressive life-threatening clinical presentations. Timely diagnosis that incorporates clinical, biochemical, imaging, endoscopic, and histologic evaluation is imperative for efficacious management of this disease process to ensure good outcomes. Management varies depending on severity and can comprise supportive care in milder disease patterns as well as vigorous immunosuppression in aggressive cases.


The Chemokine System in Oncogenic Pathways Driven by Viruses: Perspectives for Cancer Immunotherapy.
Chemokines interact with glycosaminoglycans of the extracellular matrix and activate heptahelical cellular receptors that mainly consist of G Protein-Coupled Receptors and a few atypical receptors also with decoy activity. They are well-described targets of oncogenic pathways and key players in cancer development, invasiveness, and metastasis acting both at the level of cancer cells and cells of the tumor microenvironment. Hence, they can regulate cancer cell proliferation and survival and promote immune or endothelial cell migration into the tumor microenvironment. Additionally, oncogenic viruses display the potential of jeopardizing the chemokine system by encoding mimics of chemokines and receptors as well as several products such as oncogenic proteins or microRNAs that deregulate their human host transcriptome. Conversely, the chemokine system participates in the host responses that control the virus life cycle, knowing that most oncoviruses establish asymptomatic latent infections. Therefore, the deregulated expression and function of chemokines and receptors as a consequence of acquired or inherited mutations could bias oncovirus infection toward pro-oncogenic pathways. We here review these different processes and discuss the anticancer therapeutic potential of targeting chemokine availability or receptor activation, from signaling to decoy-associated functions, in combination with immunotherapies.


Frequency of private spiritual activity and cardiovascular risk in postmenopausal women: the Women's Health Initiative.
Spirituality has been associated with better cardiac autonomic balance, but its association with cardiovascular risk is not well studied. We examined whether more frequent private spiritual activity was associated with reduced cardiovascular risk in postmenopausal women enrolled in the Women's Health Initiative Observational Study. Frequency of private spiritual activity (prayer, Bible reading, and meditation) was self-reported at year 5 of follow-up. Cardiovascular outcomes were centrally adjudicated, and cardiovascular risk was estimated from proportional hazards models. Final models included 43,708 women (mean age, 68.9 ± 7.3 years; median follow-up, 7.0 years) free of cardiac disease through year 5 of follow-up. In age-adjusted models, private spiritual activity was associated with increased cardiovascular risk (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.02-1.31 for weekly vs. never; HR, 1.25; 95% CI, 1.11-1.40 for daily vs. never). In multivariate models adjusted for demographics, lifestyle, risk factors, and psychosocial factors, such association remained significant only in the group with daily activity (HR, 1.16; 95% CI, 1.03-1.30). Subgroup analyses indicate this association may be driven by the presence of severe chronic diseases. Among aging women, higher frequency of private spiritual activity was associated with increased cardiovascular risk, likely reflecting a mobilization of spiritual resources to cope with aging and illness.


Suicidal ideation and suicide plans or attempts in adults with Asperger's syndrome attending a specialist diagnostic clinic: a clinical cohort study.
Asperger's syndrome in adulthood is frequently associated with depression, but few studies have explored the lifetime experience of self-reported suicidal ideation and suicide plans or attempts in this clinical group. We aimed to assess this prevalence in a clinical cohort of patients in the UK. In a clinical cohort study, we undertook a retrospective analysis of clinical survey data from adults newly diagnosed with Asperger's syndrome at a specialist diagnostic clinic between Jan 23, 2004, and July 8, 2013, in England. Patients completed a self-report questionnaire before clinical assessment, recording lifetime experience of depression, suicidal ideation, and suicide plans or attempts, along with self-reported measures of autistic traits and empathy. We compared the rate of suicidal ideation in the sample with published rates of suicidal ideation in the general population and other clinical groups. We also assessed associations between depression, autistic traits, empathy, and likelihood of suicidal ideation and suicide plans or attempts. 374 adults (256 men and 118 women) were diagnosed with Asperger's syndrome in the study period. 243 (66%) of 367 respondents self-reported suicidal ideation, 127 (35%) of 365 respondents self-reported plans or attempts at suicide, and 116 (31%) of 368 respondents self-reported depression. Adults with Asperger's syndrome were significantly more likely to report lifetime experience of suicidal ideation than were individuals from a general UK population sample (odds ratio 9·6 [95% CI 7·6-11·9], p<0·0001), people with one, two, or more medical illnesses (p<0·0001), or people with psychotic illness (p=0·019). Compared with people diagnosed with Asperger's syndrome without depression, people with Asperger's syndrome and depression were more likely to report suicidal ideation (p<0·0001) and suicide plans or attempts (p<0·0001). Our findings lend support to anecdotal reports of increased rates of suicidal ideation in adults with Asperger's syndrome, and depression as an important potential risk factor for suicidality in adults with this condition. Because adults with Asperger's syndrome often have many risk factors for secondary depression (eg, social isolation or exclusion, and unemployment), our findings emphasise the need for appropriate service planning and support to reduce risk in this clinical group. The Three Guineas Trust, the Baily Thomas Foundation, the Medical Research Council, NIHR-CLAHRC-EoE, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), and the Autism Research Trust.


Social support for self-management behaviors among people with epilepsy: a content analysis of the WebEase program.
Social support is an important component in managing epilepsy; however little is known about support provided to people with epilepsy. This study examined whom people with epilepsy identify as supportive, and how those individuals support people with epilepsy's self-management efforts. Data come from the WebEase project, an effective online epilepsy self-management program. People with epilepsy who participated in the pilot (n=35) and efficacy trials (n=118) were included. A content analysis was conducted on responses to open-ended questions related to support. The majority of participants provided information about their supporters. The number of support providers ranged from 0 to 6, with about 12% indicating no support. Parents and significant others were most commonly listed as supporters. Support providers mainly offer emotional and instrumental support, reminders and aid for taking medication, and support for self-management strategies. These results could be useful for interventions aimed at bolstering support in order to improve self-management.


Z-138 cell line was derived from a patient with blastoid variant mantle cell lymphoma.
The Z-138 cell line, reported in the journal in 1998, was derived from a patient who developed a leukemia initially classified as chronic lymphocytic leukemia in 1987. Splenectomy for massive involvement was required in 1998 and the neoplasm subsequently transformed to an aggressive, mature B-cell leukemia 2 years later. At time of transformation, the neoplasm had a complex karyotype, including the t(11;14)(q13;q32). In light of the extensive updates in lymphoma classification that have occurred since that time, we reviewed the slides of the patient's neoplasm. The initial peripheral blood and bone marrow aspirate smears and the spleen were involved by numerous small lymphocytes with mature chromatin. The last bone marrow specimen was involved by slightly larger, irregular lymphocytes with immature chromatin and a high mitotic rate. Immunohistochemical analysis performed on the spleen and last bone marrow for this report showed that the neoplastic cells over-expressed cyclin D1. According to the criteria of the current World Health Organization lymphoma classification, this neoplasm is best classified as mantle cell lymphoma, with blastoid transformation present in the terminal phase of disease.


Machine learning identifies multi-parametric functional PET/MR imaging cluster to predict radiation resistance in preclinical head and neck cancer models.
Tumor hypoxia and other microenvironmental factors are key determinants of treatment resistance. Hypoxia positron emission tomography (PET) and functional magnetic resonance imaging (MRI) are established prognostic imaging modalities to identify radiation resistance in head-and-neck cancer (HNC). The aim of this preclinical study was to develop a multi-parametric imaging parameter specifically for focal radiotherapy (RT) dose escalation using HNC xenografts of different radiation sensitivities. A total of eight human HNC xenograft models were implanted into 68 immunodeficient mice. Combined PET/MRI using dynamic [18F]-fluoromisonidazole (FMISO) hypoxia PET, diffusion-weighted (DW), and dynamic contrast-enhanced MRI was carried out before and after fractionated RT (10 × 2 Gy). Imaging data were analyzed on voxel-basis using principal component (PC) analysis for dynamic data and apparent diffusion coefficients (ADCs) for DW-MRI. A data- and hypothesis-driven machine learning model was trained to identify clusters of high-risk subvolumes (HRSs) from multi-dimensional (1-5D) pre-clinical imaging data before and after RT. The stratification potential of each 1D to 5D model with respect to radiation sensitivity was evaluated using Cohen's d-score and compared to classical features such as mean/peak/maximum standardized uptake values (SUVmean/peak/max) and tumor-to-muscle-ratios (TMRpeak/max) as well as minimum/valley/maximum/mean ADC. Complete 5D imaging data were available for 42 animals. The final preclinical model for HRS identification at baseline yielding the highest stratification potential was defined in 3D imaging space based on ADC and two FMISO PCs ([Formula: see text]). In 1D imaging space, only clusters of ADC revealed significant stratification potential ([Formula: see text]). Among all classical features, only ADCvalley showed significant correlation to radiation resistance ([Formula: see text]). After 2 weeks of RT, FMISO_c1 showed significant correlation to radiation resistance ([Formula: see text]). A quantitative imaging metric was described in a preclinical study indicating that radiation-resistant subvolumes in HNC may be detected by clusters of ADC and FMISO using combined PET/MRI which are potential targets for future functional image-guided RT dose-painting approaches and require clinical validation.


A sandwich-type electrochemical immunosensor based on the biotin- streptavidin-biotin structure for detection of human immunoglobulin G.
A sandwich-type immunosensor is designed and fabricated to detect the human immunoglobulin G (HIgG) using polyaniline and tin dioxide functionalized graphene (GS-SnO2-PAN) as the platform and biotin-functionalized amination magnetic nanoparticles composite (B-Fe3O4@APTES) as the label. GS-SnO2-PAN is used as the sensing agent to capture the primary anti-HIgG (Ab1) and SnO2 reduces the stack of GS. The B-Fe3O4@APTES with a large surface area and excellent biocompatibility captures second antibody (Ab2) efficiently based on the highly selective recognition of streptavidin to biotinylated antibody. The B-Fe3O4@APTES has better electro-catalytic activity in the reduction of hydrogen peroxide (H2O2) and the "biotin-streptavidin-biotin" (B-SA-B) strategy leads to signal amplification. Under optimal conditions, the immunosensor has a wide sensitivity range from 1 pg/L to 10 ng/L and low detection limit of 0.33 pg/L (S/N = 3) for HIgG. The immunosensor has high sensitivity, fast assay rate, as well as good reproducibility, specificity, and stability especially in the quantitative detection of biomolecules in serum samples.


Tumor interstitial fluid and gastric cancer metastasis: an experimental study to verify the hypothesis of "tumor-phlegm microenvironment".
To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue. An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".


[Optimization of water extraction condition of LiYan granule by Doehlert design].
To study optimal water extraction condition of LiYan granule. HPLC methods were developed for the determination of irisfloremin in LiYan granule. The contents of irisfloremin and extraction rate were selected as assessment indices. Three factors were studied by Doehlert design, including water-adding amount, decoction time and times of decoction. The optimal extracting condition was water consumed as 8 times of curd herb, and 3 times for 2 hours each time. The water extraction process is feasible, and the experiment result can provide basic and instruction data for the ascertainment of water extraction process of LiYan granule.


The optical mouse as an inexpensive region-of-interest position recorder in optical microscopy.
In optical microscopy, the microscopic features of interest typically have to be derived from regions that are spatially distributed over the sample. While the features to be analyzed may be minute, the regions from where they must be obtained from may be located quite far apart from one another. If the features are not distinct enough to allow easy visual discrimination, it would be tedious and time-consuming to attempt to recall and revisit these regions of interest. One method to overcome this difficulty would be to note and record the graduated markings on the microscope, or to use built-in position encoders. The former is tedious while the latter is generally expensive. Here, a region-of-interest position-recording implement based on the use of an optical mouse is presented. It is inexpensive and easily adaptable to the manual stage of any optical microscope.


Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice.
Non-alcoholic fatty liver disease is an obesity-related chronic liver disorder ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. Tto investigate the role of Toll-like receptor (TLR) 4 in mediating the transition from steatosis to inflammation. ApoE(-/-)/TLR4(mut) mice and ApoE(-/-)/TLR4 wild-type mice (ApoE(-/-)/TLR4-WT) were generated by cross-breeding an ApoE-deficient (ApoE(-/-)) strain with TLR4-mutant (TLR4(mut)) mice, which were fed with high-fat, high-cholesterol (HFHC) diet to induce obesity. ApoE(-/-)/TLR4-WT mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH, which is associated with obesity and the metabolic syndrome. By contrast, ApoE(-/-)/TLR4(mut) mice lacking functional TLR4 were resistant to HFHC diet-induced liver inflammation and injury and were less susceptible to the diet-induced production of reactive oxygen species (ROS) and proinflammatory cytokines. In ApoE(-/-)/TLR4-WT mice, X-box binding protein-1 (XBP-1), a transcription factor involved in the unfolded protein responses, was activated in the liver by an HFHC diet, whereas XBP-1 activation was abrogated in ApoE(-/-)/TLR4(mut) mice. In primary rat Kupffer cells, endotoxin induced XBP-1 activation through ROS production, whereas siRNA-mediated knockdown of XBP-1 expression resulted in a marked attenuation in endotoxin-evoked NF-κB activation and cytokine production. Furthermore, adenovirus-mediated expression of dominant negative XBP-1 led to a significant attenuation in HFHC diet-induced liver inflammation and injury in mice. These findings support the key role of TLR4 in Kupffer cells in mediating the progression of simple steatosis to NASH, by inducing ROS-dependent activation of XBP-1.


Extracellular proteases of Acanthamoeba castellanii (encephalitis isolate belonging to T1 genotype) contribute to increased permeability in an in vitro model of the human blood-brain barrier.
Granulomatous amoebic encephalitis (GAE) is a serious human infection with fatal consequences, however, the pathogenic mechanisms associated with this disease remain unclear. Several lines of evidence suggest that haematogenous spread is a prerequisite for Acanthamoeba encephalitis but it is not clear how circulating amoebae cross the blood-brain barrier to gain entry into the central nervous system. Objectives of this study were to determine the effects of Acanthamoeba on the permeability of an in vitro blood-brain barrier model and factors contributing to these changes. Using human brain microvascular endothelial cells, an in vitro blood-brain barrier model was constructed in 24-well Transwell plates. Acanthamoeba (GAE isolate belonging to T1 genotype) or its conditioned media were used to determine permeability changes. Zymography assays were performed to characterise Acanthamoeba proteases. In addition, the ability of Acanthamoeba to bind brain microvascular endothelial cells was determined using adhesion assays. We observed that Acanthamoeba produced an increase of more than 45% in the blood-brain barrier permeability. Acanthamoeba-conditioned media exhibited similar effects indicating Acanthamoeba-mediated blood-brain barrier permeability is contact-independent. Prior treatment of conditioned media with phenylmethyl sulfonyl fluoride (PMSF, serine protease inhibitor), abolished permeability changes indicating the role of serine proteases. Of interest, methyl alpha-d-mannopyranoside inhibited Acanthamoeba binding to human brain microvascular endothelial cells but had no effect on Acanthamoeba-mediated blood-brain barrier permeability. Zymography assays revealed that Acanthamoeba produced two major proteases, one of which was inhibited by PMSF (serine protease inhibitor) and the second with 1,10-phenanthroline (metalloprotease inhibitor). We have for the first time shown that Acanthamoeba produces human brain microvascular endothelial cells permeability, which can be blocked by PMSF. A metalloprotease of approx. molecular weight of 150 kDa is produced by A. castellanii (GAE isolate belonging to T1 genotype) and its role in the disease is suggested.


Calcium signals monitored from leopard frog optic tectum after the optic nerve has been selectively loaded with calcium sensitive dye.
We loaded adult leopard frog optic nerves with the calcium-sensitive dye Calcium Green-1 3000 mw dextran conjugate. The dye was transported to the optic tectum in approximately 6 days and selectively labeled optic nerve terminals as seen with confocal microscopy. Viewed with an intensified CCD system, electrical stimulation of the optic nerve in vitro increases Calcium Green-1 fluorescence significantly. With increasing number of pulses in pulse trains there was increased presynaptic facilitation as measured by increased fluorescence. Addition of nicotine to the bathing solution increased baseline fluorescence. These results suggest that Calcium Green-1 dextran conjugate can be actively transported in adult nerve fibers over a significant distance and is retained in presynaptic terminals in a form that allows monitoring of presynaptic calcium levels.


A Systematic Review of the Effect of Rotavirus Vaccination on Diarrhea Outcomes Among Children Younger Than 5 Years.
Rotavirus is the leading cause of vaccine-preventable diarrhea among children under 5 globally. Rotavirus vaccination has been shown to prevent severe rotavirus infections with varying efficacy and effectiveness by region. We sought to generate updated region-specific estimates of rotavirus vaccine efficacy and effectiveness. We systematically reviewed published vaccine efficacy and effectiveness studies to assess the region-specific effect of rotavirus vaccination on select diarrheal morbidity and mortality outcomes in children under 5 years of age. We employed meta-analytic methods to generate pooled effect sizes by Millennium Development Goal region. Rotavirus vaccination was both efficacious and effective in preventing rotavirus diarrhea, severe rotavirus diarrhea and rotavirus hospitalizations among children under 5 across all regions represented by the 48 included studies. Efficacy against severe rotavirus diarrhea ranged from 90.6% [95% confidence interval (CI): 82.3-95.0] in the developed region to 88.4% (95% CI: 67.1-95.9) in Eastern/Southeastern Asia, 79.6% (95% CI: 71.3-85.5) in Latin America and the Caribbean, 50.0% (95% CI: 34.4-61.9) in Southern Asia and 46.1% (95% CI: 29.1-59.1) in sub-Saharan Africa. Region-specific effectiveness followed a similar pattern. There was also evidence of vaccine efficacy against severe diarrhea and diarrheal hospitalizations. Our findings confirm the protective efficacy and effectiveness of rotavirus vaccination against rotavirus diarrheal outcomes among children under 5 globally.


Structural Aspects of Plant Ferredoxin : NADP(+) Oxidoreductases.
Ferredoxin reductase (FNR) is ubiquitous among photosynthetic organisms as the enzyme directly responsible for the generation of NADPH. Structural studies over the last 15 years have generated over 30 crystal structures of wild-type and mutant FNRs that have yielded a great deal of insight into its structure-function relations. These insights are summarized and combined to propose a structurally informed cycle for FNR catalysis in vivo.


The influence of Chinese scholars on global research.
The rise of China as a scientific research superpower has been frequently discussed in media and literature. However, past analyses are usually based on the geographical database and they ignore how the millions of emigrated Chinese students, who are now being considered the major research workforce in many countries, affect their academic outputs. Here we quantitatively analyze the contribution of Chinese scholars in physical science around the globe by their publications in a country's papers from 2010 to 2021 as well as their citations. Contrary to common perception, we find that increasing the number of Chinese scholars does not correlate with the net publication growth or decline in their host countries before the Chinese population exceeds a critical value. On the other hand, increasing Chinese authors in a paper improves its citations. The phenomena, though anomalous, are observed in many subfields of physics across the globe. Our analysis suggests that although Chinese scholars do not change the perceived publication capabilities of many countries but may have reshaped their research culture as well as workforce distributions. The results would be valuable for R&D, higher education, and immigration policymakers.


JC virus infection in colorectal neoplasia that develops after liver transplantation.
Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia. JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively. JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P < 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 +/- 3.2% versus 42.7 +/- 2.8%, P < 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 +/- 0.08% versus 0.39 +/- 0.06%, P = 0.05). The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs.


Determination of halothane distribution in the rat head using 19F NMR technique.
The distribution of halothane in the rat head was examined with 19F NMR rotating-frame zuegmatography and 2DFT 19F NMR imaging. The rotating frame experiments were conducted at varying times following anesthesia to assess the time dependence of the halothane distribution. The results of these experiments demonstrate that halothane and halothane metabolite are unequally partitioned through the rat tissues examined. 19F spin-echo imaging experiments were conducted immediately following anesthesia. The results of these experiments are compared with those of the spectroscopic technique.


Simultaneous, Quantitative Characterization of Protein ADP-Ribosylation and Protein Phosphorylation in Macrophages.
The posttranslational modifications (PTMs) ADP-ribosylation and phosphorylation are important regulators of cellular pathways, and while mass spectrometry (MS)-based methods for the study of protein phosphorylation are well developed, protein ADP-ribosylation methodologies are still in a rapidly developing stage. The method described in this chapter uses immobilized metal affinity chromatography (IMAC), a phosphoenrichment matrix, to enrich ADP-ribosylated peptides which have been cleaved down to their phosphoribose attachment sites by a phosphodiesterase, thus isolating the ADP-ribosylated and phosphorylated proteomes simultaneously. To achieve the robust, relative quantification of PTM-level changes we have incorporated dimethyl labeling, a straightforward and economical choice which can be used on lysate from any cell type, including primary tissue. The entire pipeline has been optimized to work in ADP-ribosylation-compatible buffers and with protease-laden lysate from macrophage cells.


Characterization of the metabolic differences between male and female C57BL/6 mice.
The present study aims to compare the responses between male and female C57BL/6 mice to multiple metabolic challenges to understand the importance of sex in the control of energy homeostasis. Male and female C57BL/6 mice were subjected to nutritional and hormonal challenges, such as food restriction and refeeding, diet-induced obesity, feeding response to ghrelin and leptin, ghrelin-induced growth hormone secretion, and central responsiveness to ghrelin and leptin. The hypothalamic expression of transcripts that control energy homeostasis was also evaluated. Male mice lost more weight and lean body mass in response to food restriction, compared to females. During refeeding, males accumulated more body fat and exhibited lower energy expenditure and glycemia, as compared to females. Additionally, female mice exhibited a higher protection against diet-induced obesity and related metabolic imbalances in comparison to males. Low dose ghrelin injection elicited higher food intake and growth hormone secretion in male mice, whereas the acute anorexigenic effect of leptin was more robust in females. However, the sex differences in the feeding responses to ghrelin and leptin were not explained by variations in the central responsiveness to these hormones nor by differences in the fiber density from arcuate nucleus neurons. Female, but not male, mice exhibited compensatory increases in hypothalamic Pomc mRNA levels in response to diet-induced obesity. Our findings revealed several sexually differentiated responses to metabolic challenges in C57BL/6 mice, highlighting the importance of taking into account sex differences in metabolic studies.


Screening for dementia in the outpatient setting: the time and change test.
To develop and validate the Time and Change (T&C) test, a simple, standardized method for detecting dementia in a diverse older outpatient population with varying levels of education. A prospective cohort validation study. Two outpatient clinics at an urban teaching hospital. The concurrent validation sample consisted of 100 consecutive outpatients 70 years of age or older who were 58% non-white and had a 16% dementia prevalence rate and educational levels ranging from 0 to 17+ years. Reliability was tested in a sample of 42 consecutive outpatients 75 years of age or older with a 36% dementia prevalence rate. T&C ratings were validated against a reference standard based on the Blessed Dementia Rating Scale and the Mini-Mental State Examination. Reliability, contribution to physician recognition of dementia, and ease of use were assessed. In the outpatient setting, the T&C had a sensitivity of 63%, specificity of 96%, a negative predictive value of 93%, a positive predictive value of 77%, and test-retest and inter-observer reliability agreement rates of 95% and 100%, respectively. When T&C results were added to the physician's documentation of dementia, the number of missed cases decreased from 44% to 19%, and the number of overcalled cases decreased by 100%. When timed cut points were added, the T&C test had a sensitivity of 94 to 100%, specificity of 37 to 46%, negative predictive value of 98 to 100%, positive predictive value of 23 to 25%, and test-retest and inter-observer agreement rates of 82% and 70 to 75%, respectively. The T&C test is a simple, accurate, reliable, performance-based tool that can improve physician ability to recognize dementia in diverse outpatient populations.


Implantation of leadless pacing systems in patients early after tricuspid valve surgery: A feasible option.
After tricuspid valve (TV) surgery due to tricuspid regurgitation (TR), patients needing a permanent pacemaker often receive an epicardial lead implantation. This may result in delayed recovery from open-chest surgery and increased postoperative risk. Leadless pacemaker (LPM) implantation may represent a valuable option. A total of 14 consecutive patients underwent LPM implantation (Micra Transcatheter Pacing System, Medtronic, Minneapolis, MN) early after TV surgery. The pacing indication in those patients was atrial fibrillation with a slow atrio-ventricular (AV) conduction or atrial fibrillation and a concomitant AV block III. Three patients already had a pacemaker prior to surgery, which was explanted during TV repair. Three patients received a valve replacement with a bioprosthesis, while the remaining eight patients received a TV repair. All procedural data and device measurements during and after LPM implantation were recorded. Transthoracic echocardiography was performed prior and post LPM implantation, showing no changes in TV or bioprosthesis performance. The device measurements were within an adequate range: threshold: 0.83 ± 0.34 V @ 0.24 ± 0 ms, impedance: 480 ± 58.88 ohm, and R-wave: 10.10 ± 3.60 mV. LPM implantation was successful in all patients with a mean procedural time of 32 ± 11.8 minutes, fluoroscopy time of 3.71 ± 3.15 minutes, and dose-area product of 536.67 ± 811.26 cGy/m2 . Implantation of an LPM early after TV surgery is a feasible option. LPM implantation does not affect TV or bioprosthesis performance in transthoracic echocardiography.


Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack.
Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. Patients admitted to the stroke unit or TIA clinic of the Erasmus Medical Center with ischemic stroke or TIA and impaired glucose tolerance (2-hour postload glucose level of 7.8-11.0 mmol/L) were consecutively enrolled between July 2009 and June 2012. The oral glucose tolerance test was repeated after 3 months and patients were classified as having transient impaired glucose tolerance or persistent impaired glucose tolerance. We developed a prediction model by means of a multivariable logistic regression model. We calculated the area under the receiver operating characteristic curve (AUC) to quantify the performance of the model and the internal validity by bootstrapping. Of the 101 patients included, 53 (52%) had persistent impaired glucose tolerance or progression to diabetes. These patients were older and more often had hypertension and used statins. A prediction model including age, current smoking, statin use, triglyceride, hypertension, previous ischemic cardiovascular disease, body mass index, and fasting plasma glucose accurately predicted persistent impaired glucose tolerance (bootstrapped AUC, .777), with statin use, triglyceride, and fasting plasma glucose as the most important predictors. Half of the patients with impaired glucose tolerance after a TIA or ischemic stroke have persistent impaired glucose tolerance. We provide a prediction model to identify patients at risk of persistent impaired glucose tolerance, with statin use, triglyceride, and fasting plasma glucose as the most important predictors, which after external validation might be used to optimize secondary prevention.


Postoperative CT changes.
An analysis is made of 36 cases of severe postoperative changes, some of which are undoubtedly of iatrogenic origin. CT has considerably improved the possibilities of postoperative control. By this means it is easy to check the result of the operation. Moreover the neuroradiologist can verify the quality (indication and technique) of the work of his surgical colleagues in the same way that the neurosurgeon can verify the neuroradiologist's work in the operating theater. This will result in a better knowledge of each other and, even more important, in better care of the patient.


A simple technique for a new working heterotopic heart transplantation model in rats.
A new working model of heterotopic heart transplantation in rats was established using a simplified technique. Sprague-Dawley rats were used as donors and recipients. The donor left common carotid artery and left pulmonary artery were anastomosed to the recipient left renal artery and vein by a "sleeve and cuff" method, respectively. The donor left ventricle was blood volume loaded by anastomosing the left atrium to the recipient's abdominal aorta in end-to-side fashion. The characteristics of the donor heart were evaluated by palpating the abdominal wall of the rats. We examined the surgical success rate, changes in heart weight, and histology at 1 month after transplantation. The model was attempted in 32 rats with the success rate of 93.7% (30/32); the 2 failed cases died due to postoperative bleeding. There was no significant difference in mean weight changes between the donor and native hearts at 1 month after transplantation (1.13 ± 0.13 g vs 1.09 ± 0.12 g, P = .244). The donor heart myocardium showed regularly shaped, unidirectional, healthy muscle similar to the native heart. The technique was easily learned, allowing less recipient surgical stress. The hemodynamic performance appeared to be similar to the normal cardiac physiological situation, and thus may be more suitable for pre-clinical studies.


A review on the physicochemical and biological applications of biosurfactants in biotechnology and pharmaceuticals.
Biosurfactants are the chemical compounds that are obtained from various micro-organisms and possess the ability to decrease the interfacial tension between two similar or different phases. The importance of biosurfactants in cosmetics, pharmaceuticals, biotechnology, agriculture, food and oil industries has made them an interesting choice in various physico-chemical and biological applications. With the aim of representing different properties of biosurfactants, this review article is focused on emphasizing their applications in various industries summarizing their importance in each field. Along with this, the production of recently developed chemically and biologically important biosurfactants has been outlined. The advantages of biosurfactants over the chemical surfactants have also been discussed with emphasis on the latest findings and research performed worldwide. Moreover, the chemical and physical properties of different biosurfactants have been presented and different characterization techniques have been discussed. Overall, the review article covers the latest developments in biosurfactants along with their physico-chemical properties and applications in different fields, especially in pharmaceuticals and biotechnology.


Meniscectomy in children: results in 59 knees.
Forty-nine children undergoing meniscectomy have been reviewed. Fifty-nine knees were examined with a mean follow-up period of 7.5 years. There was an equal number of operations in both sexes, with a high proportion of operations on the lateral meniscus. A good result was noted in 68 per cent of boys and 29 per cent of girls. Only 27 per cent of patients had normal radiographs; 19 per cent had early osteoarthrosis. The preoperative diagnosis was correct in only 65 per cent of cases. It is concluded that meniscectomy is not a benign procedure in children, and that preoperative assessment should include arthroscopy and possibly arthrography.


Annotated references in epidemiology.
The burden that heart failure imposes on the health care systems of the developed world is substantial and increasing. This article reviews the world literature on the epidemiology of heart failure and discusses the key methodological issues for research in this field.


Liver tumour blood flow and responses to arterial embolization measured by dynamic hepatic scintigraphy.
Liver and tumour blood flow has been studied in 30 patients with multiple liver metastases and in 14 patients with solitary liver tumours by means of dynamic hepatic scintigraphy. Observations were compared with those of a group of 33 control subjects. Haemodynamic changes were also measured in 10 patients who underwent hepatic arterial embolization (HAE). The mesenteric fraction (MF) to tumour regions in 32 subjects showed a wide range compared with control subjects. In 9 patients the MF to the tumour region was within the normal range suggesting that some tumours may possess a portal venous supply. The MF to the uninvolved liver regions was below the normal range in 25% of patients, indicating that HAE could be hazardous in this group. Following HAE the MF rose in all 4 tumour regions and fell in 4 non-embolized uninvolved liver regions. No increase in colloid clearance rate (k) was seen though a significant decrease occurred in 4 patients. These changes may well represent increased portal venous flow into tumours.


[Topographic correlation of angiographic and CT findings in cerebrovascular disease (author's transl)].
Problems of correlating ischemic lesions of the brain with the cerebral vessel involved originate in the axial scanning direction. It is almost impossible to line out precisely the borders of the cerebral lobes--far less are we able to describe exactly the areas supplied by the cortical branches of the anterior or middle cerebral artery. Using a method based on detailed perception of the base of the skull and physiological calculations, it is possible to reconstruct the individual baseline of the scan and to project the outlines of the slices upon the lateral view of the angiogram. Thereby a reliable topographical association between CT findings and angiogram is given.


Cellular fibronectin and tenascin in an orbital nylon prosthesis removed because of infection caused by Staphylococcus aureus.
An orbital nylon prosthesis was removed because of an infection caused by Staphylococcus aureus that was resistant to antimicrobials. It was processed for histopathology and immunohistochemistry. Within 3 weeks the implant had an extensive ingrowth of fibrovascular tissue containing chronic inflammatory cells, foreign body giant cells, and myofibroblasts. By using the indirect immunofluorescent method, this tissue was found to react with monoclonal antibodies (Mabs) against extradomain A of cellular fibronectin (EDA-cFN) and tenascin (TN). The presence of EDA-cFN and TN within the implant are indicative of an active healing process, since both of these proteins, scarce in adult tissues, have been shown to be reexpressed during tissue regeneration. The findings suggest that fibronectin plays a definite role in bacterial adherence and foreign body infections.


Multiple sclerosis. Generic glatiramer acetate--a step toward cheaper MS drugs?
A randomized, double-blind, phase III trial of generic glatiramer acetate has shown equivalent efficacy and safety compared with the approved formulation, Copaxone. The impact of approval of generic glatiramer acetate, however, will mainly depend on the pricing of the drug.


[Detection of pregnancy-specific beta 1-glycoprotein (SP1), of proteins of the "pregnancy zone" (PZ), of pregnancy-associated plasma protein A (PAPP-A) with 24-hour radial immunodiffusion. Detection of pregnancy-specific beta 1-glycoprotein (SP1) with turbidimetry. Current significance of the proteins].
The estimations of pregnancy specific beta 1-glycoprotein (SP1), pregnancy associated alpha 2-glycoprotein (PZ) and pregnancy associated plasma protein A (PAPP-A) in serum samples are useful for supervision of pregnancy and diagnosis of gestational diseases. In clinical practice simple inexpensive and short time methods are preferred. Two simple short time methods were described. The 24 hour radial immuno-diffusion (RID) was compared with the usual 48 hour RID in 30 serum samples of normal pregnant women. The SP1-values ascertained with the 24 hour RID and the 48 hour RID correlated with a high coefficient (r = 0.99). In ranges of high SP1-concentrations the correlation was decreased. The correlation coefficients for PZ and PAPP-A amounted to 0.89 and 0.925. The estimation of proteins with turbidimetry is a real short time method. This method was performed in 19 serum samples of pregnant women and the results were compared with the 24 hour RID. The correlation coefficient amounted to 0.81. Between the results of 24 hour RID for SP1 and PAPP-A there was no correlation.


ELAVL1 promotes LPS-induced endothelial cells injury through modulation of cytokine storm.
Sepsis is a life-threatening systemic organ dysfunction caused by the host's unregulated response to a widespread bacterial infection. Endothelial injury is a major pathophysiologic symptom of sepsis and is considered a critical factor in promoting the progression of disease severity. ELAV like RNA binding protein 1(ELAVL1) is a ubiquitously expressed RNA-binding protein that may play an important role during sepsis. Nonetheless, the molecular mechanisms of ELAVL1 on endothelial cell damage in sepsis have not been well defined. Here, we aimed to confirm the role of ELAVL1 in sepsis-induced endothelial cell damage using lipopolysaccharide (LPS)-induced zebrafish and endothelial cells (ECs) models. We found that zebrafish larvae treated with LPS exhibited systemic endothelial cell damage, mostly manifested as pericardial edema, curved tail, and impaired angiogenesis. LPS treatments also significantly induced the expression levels of inflammatory cytokines (interleukin-6 (IL-6), IL-8, and tumor necrosis factor (TNF)-α) in vivo. In vitro, we observed the increase of ELAVL1 cytoplasmic translocation with LPS treatment. Mechanistically, targeted disruption of the ELAVL1 gene decreased the expression of TNF-α, IL-6, and IL-8 during induction of sepsis and alleviated LPS-induced blood vessel injury in zebrafish. Taken together, our study indicates that ELAVL1 knockdown may alleviate sepsis-induced endothelial cells injury by suppressing cytokine storm. Our research suggests that inhibition of ELAVL1 could reduce the level of inflammatory cytokine production induced by LPS and protect against endothelial cell injury. ELAVL1 might be a potential therapeutic target to block endothelial cells injury associated with sepsis.


Serum concentration and properties of alpha-fetoprotein and serum level of albumin in sucking piglets.
Porcine alpha-fetoprotein (AFP) was purified from the sera of four-day-old piglets using an immunoadsorbent column. The molecular weight of the AFP was 80,000 when determined by gel filtration on Sephadex G-200 and 75,000 when determined by sodium dodecylsulphate polyacrylamide gel electrophoresis. The isoelectric point of the AFP was pH 4.85 at 0 degree C. The maximum concentration of serum AFP was reached on the fourth day after birth (mean value 1.1 mg ml-1), and it then decreased to 10 micrograms ml-1 when the piglets were 35 days old. The concentration of serum albumin increased rapidly between birth and seven days old, reaching 16 to 17 mg ml-1 at seven days old. Between birth and seven days old, the serum concentrations of AFP and albumin were approximately inversely proportional.


Usefulness of (18)F-FDG PET/CT to Detect Metastatic Mucinous Adenocarcinoma Within an Inguinal Hernia.
Metastatic mucinous adenocarcinoma in an inguinal hernia is a rare disease and the image findings of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) are little known. Here, we introduce a 57-year-old man with metastatic mucinous adenocarcinoma in an inguinal hernia. On initial (18)F-FDG PET/CT, hypermetabolism was observed in mucinous adenocarcinoma of the cecum, and adenocarcinomas of the transverse and ascending colon, respectively. Follow-up (18)F-FDG PET/CT revealed newly developed multiple hypermetabolism in peritoneal seeding masses and nodules in the pelvic cavity and scrotum. Peritoneal carcinomatosis in the right pelvic side wall was extended to the incarcerated peritoneum and mesentery in the right inguinoscrotal hernia.(18)F-FDG PET/CT was useful to reveal unexpected peritoneal seeding within the inguinal hernia. Also, this case demonstrated that metastatic mucinous adenocarcinomas had variably intense FDG uptake.


Topical vitamin D₃ analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.
Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1β and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1β and TNF-α, thereby ameliorating psoriatic plaques.


Transcranial alternating current stimulation over multiple brain areas with non-zero phase delays other than 180 degrees modulates visuospatial working memory performance.
While zero-phase lag synchronization between multiple brain regions has been widely observed, relatively recent reports indicate that systematic phase delays between cortical regions reflect the direction of communications between cortical regions. For example, it has been suggested that a non-zero phase delay of electroencephalography (EEG) signals at the gamma frequency band between the bilateral parietal areas may reflect the direction of communication between these areas. We hypothesized that the direction of communication between distant brain areas might be modulated by multi-site transcranial alternating current stimulation (tACS) with specific phase delays other than 0° and 180°. In this study, a new noninvasive brain stimulation (NIBS) method called multi-site multi-phase tACS (msmp-tACS) was proposed. The efficacy of the proposed method was tested in a case study using a visuospatial working memory (VWM) paradigm in which the optimal stimulation conditions including amplitudes and phases of multiple scalp electrodes were determined using finite element analysis adopting phasor representation. msmp-tACS was applied over the bilateral intraparietal sulci (IPS) and showed that 80 Hz tACS with the phase for the right IPS leading that for the left IPS by 90° (= 3.125 ms) partialized VWM performance toward the right visual hemifield. The three stimulation conditions were synchronized, RL, and LR, which refers to stimulation condition with no phase lag, stimulation phase of right IPS (rIPS) leading left IPS (lIPS) by 90° and the stimulation of lIPS leading rIPS by 90°, respectively. The lateralization of VWM significantly shifted towards right visual hemifield under the RL condition compared to the synchronized and LR conditions. The shift in VWM was the result of the stimulation affecting both left and right visual hemifield trials to certain degrees, rather than significantly increasing or decreasing VWM capacity of a specific visual hemifield. Altered brain dynamics caused by msmp-tACS partialized VWM performance, likely due to modulation of effective connectivity between the rIPS and lIPS. Our results suggest that msmp-tACS is a promising NBS method that can effectively modulate cortical networks that cannot be readily modulated with conventional multi-site stimulation methods.


Trends in death attributed to heart failure over the past two decades in Europe.
Little is known regarding temporal trends in mortality attributed to heart failure (HF) from a population perspective. The aim of this study was to assess the mortality related to HF as an underlying cause during the last 20 years in seven European countries. The number of deaths with HF as the underlying cause was collected in seven European states: Germany, Greece, England and Wales, Spain, France, Finland, and Sweden from 1987 to 2008. Disease coding for HF was based on the International Classification of Diseases (ICD 9th and 10th versions). We computed age-standardized death rates (SDRs) per 100 000 inhabitants. Mean age at death from HF was also calculated for the same period. In the seven studied countries, the HF SDR decreased continuously from 54.2 (1987) to 32.6 (2008). Despite differences in the early 1990s, SDRs related to HF seemed to converge, in these seven European countries, to ∼30 deaths per 100 000 population in the near future, for both men and women. During the study period, the mean age at death increased from 80.0 to 82.7 years. Half of the deaths from HF occurred in hospital, without change over time. There has been a 40% reduction of the SDR due to HF in seven European countries during two decades and a concomitant increase in the mean age at death from HF. We hypothesize that these results may be related to a better management of chronic and acute HF patients over the past 20 years.


Mimicking Native Heart Tissue Physiology and Pathology in Silk Fibroin Constructs through a Perfusion-Based Dynamic Mechanical Stimulation Microdevice.
In vitro cardiomyocyte (CM) maturation is an imperative step to replicate native heart tissue-like structures as cardiac tissue grafts or as drug screening platforms. CMs are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behavior, organization, and maturation. In this regard, a silk-based cardiac tissue (CT) coupled with a dynamic perfusion-based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro is tried to be delivered. Silk fibroin (SF) is used to fabricate lamellar scaffolds to provide native tissue-like anisotropic architecture and is found to be nonimmunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds display excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when places in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, are applied to the cardiomyocyte culture seeded on lamellar silk scaffolds in the DMM. A strain-dependent difference in cardiomyocyte maturation, gene expression, sarcomere elongation, and extracellular matrix formation is observed. These silk-based CTs matured in the DMM can open up several avenues toward the development of host-specific grafts and in vitro models for drug screening.


Endogenous selective inhibitors of 11beta-hydroxysteroid dehydrogenase isoforms 1 and 2 of adrenal origin.
In earlier studies [Latif, S.A., Sheff, M.F., Ribeiro, C.E., Morris, D.J., 1997. Selective inhibition of sheep kidney 11beta-hydroxysteroid-dehydrogenase isoform 2 activity by 5alpha-reduced (but not 5beta) derivatives of adrenocorticosteroids. Steroids 62, 230-237], only derivatives of steroid hormones possessing the 5alpha-Ring A-reduced configuration selectively inhibited 11beta-HSD2-dehydrogenase, whereas their 5beta-derivatives were inactive. This present study focuses on an expanded group of endogenous 11-oxygenated, 5alpha and 5beta-Ring A-reduced metabolites of adrenocorticosteroids, and progestogen and androgen steroid hormones. These substances were tested for their inhibitory properties against 11beta-HSD2, 11beta-HSD1-dehydrogenase and 11beta-HSD1 reductase. The present studies showed that the following compounds stand out as potent inhibitors. These are 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone, 11beta-OH-progesterone, 11beta-OH-allopregnanolone, 11beta-OH-testosterone, and 11beta-OH-androstanediol, inhibitors of 11beta-HSD1-dehydrogenase; 3alpha,5alpha-TH-11-dehydro-corticosterone, 11-keto-progesterone, 11-keto-allopregnanolone, and 11-keto-3beta,5alpha-TH-testosterone, inhibitors of 11beta-HSD1 reductase; 3alpha,5alpha-TH-aldosterone, 5alpha-DH-corticosterone, 3alpha,5alpha-TH-corticosterone,11-dehydro-corticosterone, 3alpha,5alpha-TH-11-dehydro-corticosterone, 11beta-OH-progesterone, 11-keto-progesterone, 11beta-OH-allopregnanolone, 11-keto-allopregnanolone, 11beta-OH-testosterone, and 11-keto-testosterone, inhibitors of 11beta-HSD2. All of these substances have the potential to be derived from adrenally synthesized corticosteroids. Substances with similar structures to those described may help in the design of exogenous agents for the management of a variety of disease states involving 11beta-HSD isoenzymes.


Main parameters and the dynamics of volatile compounds during the fermentation of Chinese Mao-tofu from Huangshan region.
The physico-chemical parameters and kinetics of the volatile compounds during the fermentation of Chinese Mao-tofu was investigated. The levels of water soluble proteins, amino nitrogen and acidity increased gradually throughout the fermentation process, while that of reducing sugars peaked after 2 days before gradually declining. The protease activity increased significantly and reached the maximum levels at day 3, then it slightly decreased. The hardness and firmness decreased during the first 3 days, but both increased subsequently. The viscosity and adhesiveness was inversely related to the hardness and firmness. Forty-four volatile compounds were identified and quantified. Correlation analysis revealed significant correlation of the content of water soluble proteins and amino nitrogen with most volatile compounds. Acidity levels were positively correlated with that of ethyl caproate and hexyl alcohol, and negatively with 2-methyl butyric acid, palmitic acid, ethyl laurate, 1-octen-3-ol and 1-nonanol. Reducing sugar content was also positively correlated with ethyl caproate.


Myelofibrosis arising in treated histiocytosis X.
Myelofibrosis, or fibrous replacement of hematopoietic bone marrow, is rarely encountered in pediatric patients. An unusual, reversible case arising in the setting of treated histiocytosis X is reported, a previously undescribed association. The clinical, pathologic, radiographic, and scintigraphic characteristics of myelofibrosis are reviewed.


Effects of verapamil on the cellular accumulations and toxicity of several antitumor drugs in 9-hydroxy-ellipticine-resistant cells.
9-OH-Ellipticine (9-OH-E)-resistant cells are not only resistant to the DNA topoisomerase II inhibitors, but also to some other antitumor agents, such as actinomycin D (AD), adriamycin (ADM), daunorubicin and vincristine. It was previously shown that a decreased uptake accounts for the cross-resistance of these cells to AD and ADM which then suggested that the 9-OH-E-resistant cells might display some of the properties usually associated with the multidrug resistance phenotype. In this work, we have examined the effects of verapamil, a drug which is known to overcome the multidrug resistance, on the toxicity and the cellular accumulation of four cytotoxic agents: 9-OH-E, 2N-methyl-9-hydroxy-ellipticinium (NMHE), AD and ADM, either on 9-OH-E resistant cells or on a multidrug resistant subline derived from the same sensitive parental cells. Verapamil inhibited the cellular accumulation of the ellipticine derivatives in the sensitive DC-3F cells, and the toxicity of these drugs on these cells was correspondingly decreased. On either one of the resistant cell lines, verapamil had no effect on the toxicity and the cellular accumulation of 9-OH-E. In contrast, in the presence of verapamil, the cellular accumulation of NMHE by the 9-OH-E and the multidrug resistant cells was about 50% and 300% increased, respectively. The increased NMHE cellular concentration in the multidrug resistant cells was associated with an 8-fold increased toxicity. The major structural characteristics which might account for this difference between the sensitivities of both ellipticine derivatives to the effects of verapamil on the multidrug resistant cells is the presence of a positive charge on the nitrogen in position 2 of the 6H-pyridocarbazole molecule. Finally, verapamil circumvented partially the cross-resistance of DC-3F/9-OH-E cells to AD and ADM by increasing the accumulation of these drugs inside the cells.


Factors influencing self-management behavior during the "Blanking Period" in patients with atrial fibrillation: A cross-sectional study based on the information-motivation-behavioral skills model.
Atrial fibrillation (AF) is becoming increasingly common. Effective self-management during the "Blanking Period" is critical. The Information-Motivation-Behavioral skills (IMB) model can be used to study health behaviors in chronic disease patients, but it has not been studied in AF patients. The goal of this study was to explore the influencing factors and interaction pathways of self-management behavior in AF patients during the "Blanking Period" using the IMB model. From June to December 2021, a cross-sectional design was conducted. Patients with AF during the "Blanking Period" (N=220) were recruited. They filled out several quantitative questionnaires, including the Jessa Atrial Fibrillation Knowledge Questionnaire, the Confidence in Atrial Fibrillation Management Scale, the Perceived Social Support Scale, the All Aspects of Health Literacy Scale, and the Self-care Scale for Chronic Atrial Fibrillation Patients. Data were analyzed using correlation analysis, multiple regression analysis, and path analysis. Total score of self-management behavior was (33.83 ± 10.66). AF knowledge (β = 0.252, P < 0.001), self-management confidence (β = 0.219, P < 0.001), social support (β = 0.291, P < 0.001), and health literacy (β = 0.262, P < 0.001) were all positively correlated with patients' self-management behavior, accounting for 66.50 percent of the total variance. During the "Blanking Period", the IMB model can be used to predict the factors that influence self-management behavior in AF patients. By using IMB model, interventions targeting patient-specific influencing factors could improve self-management behavior and quality of life in AF patients.


Skin to origin of mesenteric artery study (STOMA): prospective study of distances between stoma location and proximal superior mesenteric artery.
Traditional siting of stomas, in the lower abdomen, has been guided by surgical dogma lacking evidence. In the lower abdomen, the combination of a thick and pendulous abdominal apron, can create a challenging and suboptimal site for a stoma. The anatomical determinant limiting delivery of a stoma to the abdominal skin is the distance of the SMA from the lower border of the pancreas. The aim of this cross-sectional study was to compare the distance between the traditional stoma site, and upper abdominal stoma sites, to both the superior mesenteric artery (SMA) origin and SMA at the inferior border of the pancreas on abdominal computed tomography (CT). A cross-sectional study at a single academic university hospital of adult patients who underwent abdominal CT in Australia. Two hundred and thirteen patients were included. Stoma sites in the upper abdomen were 57-76 mm shorter to the origin of the SMA and inferior border of the pancreas than those positioned at the traditional stoma site (P < 0.001). The mean panniculus thickness in the upper abdomen was 10 mm thinner than in the lower abdomen and increased with increasing BMI (P < 0.001). The ratio between the distance from the xiphisternum to umbilicus, and the umbilicus to pubic symphysis, was 1.10; this ratio increased with increasing BMI. The distance of the SMA to the skin is always shorter in the upper abdomen compared to the traditional stoma site. Consideration should be given to placing stomas in the upper abdomen, particularly in overweight or obese patients.


Epstein-Barr Virus-related mucocutaneous ulcer lymphoma associated with Crohn's disease, treated with monoclonal antibody anti-CD30.
Epstein-Barr virus-related mucocutaneous ulcer lymphoma is a rare entity promoted by immunosuppression. It is less described in inflammatory bowel diseases, and mostly these are refractory diseases. CD30 acts to Epstein-Barr virus (EBV) local proliferation and thus could be an interesting target. Brentuximab vedotin could become a new helpful tool.


Perineal ultrasound evaluation of the urethrovesical junction angle and urethral mobility in nulliparous women and women following vaginal delivery.
The objective of this study was to demonstrate the differences in the urethrovesical junction angle and urethral mobility by means of perineal ultrasounds in women following vaginal delivery with respect to nulliparous women. We have enrolled 34 women, 12 nulliparous (Group A) and 22 women in the post-partum period (Group B). The ultrasounds were employed to measure the urethrovesical junction angle ("urethro-pelvic" angle) and the urethral mobility. Data obtained show that the urethro-pelvic angle is narrower in Group A (97.3 degrees) with respect to Group B (112.5 degrees). Urethral mobility while coughing was significantly higher in Group B (30.4 degrees) with respect to Group A (-2 degrees). This study demonstrates the difference in the urethral support at rest and during cough in nulliparous versus recently delivered parous women.


Poly[[aqua-{μ4-2-[(carb-oxy-meth-yl)sulfan-yl]nicotinato-κ(4) O:O':O'':O'''}copper(II)] trihydrate].
In the polymeric title complex, {[Cu(C8H5NO4S)(H2O)]·3H2O} n , the Cu(II) cation is coordinated by one water mol-ecule and four carboxyl-ate O atoms from four 2-[(carb-oxy-meth-yl)sulfan-yl]nicotinate anions in a distorted square-pyramidal geometry. The 2-[(carb-oxy-meth-yl)sulfan-yl]nicotinate anion bridges four Cu(II) cations, forming a two-dimensional polymeric complex parallel to the bc plane. In the crystal, O-H⋯O, O-H⋯N and O-H⋯S hydrogen bonds link the complex mol-ecules and lattice water mol-ecules into a three-dimensional supra-molecular architecture.


Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.
It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC.


Dynamics and dynamic modelling of H2S production in sewer systems.
Accurate and reliable predictions of sulfide production in a sewer system greatly benefit formulation of appropriate strategies for optimal sewer management. Sewer systems, rising main systems in particular, are highly dynamic in terms of both flow and wastewater composition. In order to get an insight in sulfide production as a response to the dynamic changes in sewer conditions, several measurement campaigns were conducted in two rising mains in Gold Coast, Australia. The levels of various sulfur species and volatile fatty acids (VFAs) were monitored through hourly sampling for periods ranging from 8 to 29 h. The results of these field studies showed large temporal as well as spatial variations in sulfide generation. A dynamic sewer model taking into account the hydraulics and the biochemical transformation processes was formulated and calibrated and validated using the data collected during the four measurement campaigns at the two sites. The model was demonstrated to reasonably well describe the temporal and spatial variations in sulfide, sulfate and VFA concentrations. Application of the model was illustrated with a case study aimed to optimize oxygen injection to one of the two mains studied, which is being used as a means to control sulfide production on this site. The model predicted that, moving the current oxygen injection point to a location close to the end of the sewer line could achieve the same degree of sulfide control with only 50% of the current oxygen use. This study highlighted that the location at which oxygen is injected plays a major role in sulfide control and a dynamic model could be used to make a proper choice of the location.


Calcitonin gene-related peptide in cardiovascular tissues of the rat.
The distribution of calcitonin gene-related peptide immunoreactivity in the cardiovascular system of the rat was investigated by radioimmunoassay and immunocytochemistry. The nature of the immunoreactivity was studied by gel permeation and high performance liquid chromatography. Immunocytochemistry demonstrated the existence of calcitonin gene-related peptide-containing nerve fibres throughout the cardiovascular system. These were present in all regions of the heart, particularly in association with the coronary arteries, within the papillary muscles and within the sinoatrial and atrioventricular nodes. Calcitonin gene-related peptide-containing fibres were found mainly in the adventitia of the arteries and veins. Calcitonin gene-related peptide concentrations were high in major arteries and veins but comparatively low in the heart, aortic arch and thoracic aorta. Chromatography showed that approximately 70% of the total immunoreactivity was identical to synthetic calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations in the blood vessels of rats treated neonatally with capsaicin were not found to be significantly different from those in control animals although capsaicin caused significant reductions of calcitonin gene-related peptide levels in certain other tissues. The results of this study suggest that calcitonin gene-related peptide-containing fibres are likely to be of importance in the innervation of vascular tissues and raise the possibility that these fibres are different in character from calcitonin gene-related peptide-containing fibres found in other tissues.


Team Coordination Style Is an Adaptive, Emergent Property of Interactions Between Critical Care Air Transport Team Personnel.
Critical Care Air Transport (CCAT) teams care for critically ill or injured patients during long-duration flights. Despite the differences between the CCAT domain and a more traditional clinical setting, CCAT clinicians are not explicitly trained how to coordinate care in the aircraft environment. We characterized the team coordination patterns adopted by CCAT teams and explored any links between team coordination style and performance. This retrospective study used transcripts from 91 CCAT teams as they completed simulated patient care scenarios during an advanced training course. Qualitative and quantitative measures were used to characterize team behavior. Vocalized content varied by team role, with physicians acting as leaders. The type of content verbalized by each team role depended on the team coordination style. The team coordination style and the content of vocalized messages were not affected by prior team member deployment or the characteristics of particular scenarios, and the team coordination style did not predict measures related to patient status. Individual team member coordination behaviors vary depending on the coordination style used by the team as a whole. Coordination style appears to arise from the interactions among individual team members rather than in response to situational factors external to the team.


mRNA detection in living cells: A next generation cancer stem cell identification technique.
Cancer stem cells (CSC) are a distinct subpopulation within a tumor shown to drive tumor progression, metastasis, and recurrence. A review of the literature reveals poor consensus, with the use of a wide variety of surface markers and functional assays to identify and isolate cancer stem cells. Utilizing a novel technology that enables live-cell mRNA quantitation, we have demonstrated the ability to identify and sort viable CSC based on markers associated with stemness in pluripotent cells. Fresh tumor samples from a variety of cancer types were examined by flow cytometry for Nanog expression. Levels of CSC detected ranged from 6% to 19%. This method of CSC detection was cross-validated with other commonly used surface markers with good correlation. Matrigel invasion assays confirmed that CSC isolated using this method are both highly motile and invasive. This approach simplifies the process of identifying viable CSC from fresh tumor tissue, providing a level of accuracy not previously available. This method may also provide a valuable tool for screening and validating new CSC biomarkers.


Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.
Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus < 65 years 1.3 (95% confidence interval (CI): 1.14-1.58); OR ⩾ 75 versus < 65 years 1.6 (1.25-1.94)), emergency resection (OR 1.8 (1.41-2.32)), anastomotic leakage (OR 8.1 (6.14-10.62)), referral to another hospital for adjuvant chemotherapy (OR 1.9 (1.36-2.57)) and prolonged postoperative hospital admission (OR 4.7 (3.30-6.68)). Starting 5-8 weeks post-surgery showed no decrease in OS compared to initiation within 4 weeks (Hazard ratio (HR) 5-6 weeks 0.9 (0.79-1.11); HR 7-8 weeks 1.1 (0.91-1.30)). However, commencing beyond 8 weeks was associated with decreased OS compared to initiation within 8 weeks (HR 9-10 weeks 1.4 (1.21-1.68); HR 11-12 weeks 1.3 (1.06-1.59); HR 13-16 weeks 1.7 (1.23-2.23)). Our data support initiating adjuvant chemotherapy in stage III colon cancer patients within 8 weeks post-surgery.


Fibronectin matrix: antibody-induced reorganization in human fibroblast cultures.
Fibronectin, a major pericellular glycoprotein of adherent cells, was predominantly present in fibrillar structures in human fibroblast cultures as shown by indirect immunofluorescence. In conventional "patching experiments" where one day old cells were exposed to anti-fibronectin IgG in the cold, washed, and reincubated at 37 degrees no redistribution was seen. However, continuous exposure of the cultures to IgG at 37 degrees resulted in redistribution. The fibrillar structures were lost and fibronectin aggregates (patches) were found. Fab-fragments had no such effect. These results support the findings that fibronectin is predominantly a matrix protein and show that matrix components may be redistributed in cell culture conditions.