Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms.
Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibited protein synthesis, cellular ATP level and functional mitochondrial activities in a dose-dependent manner. However, incubation of cells with NaF up to 12 mmol/L for 2 h depleted only 13% of cellular glutathione level. The IC50 of NaF on cellular ATP level was about 5.75 mmol/L. Preincubation of the cells with pyruvate and succinate did not protect cells from NaF-induced ATP depletion. At concentrations of 4 mmol/L, 8 mmol/L and 12 mmol/L, NaF inhibited 31%, 56% and 57% of mitochondrial functions, respectively, after 2 h incubation. No significant inhibition for NaF was found at concentrations lower than 2 mmol/L (40 ppm). These results indicate that NaF can be toxic to oral mucosal fibroblasts in vitro by its inhibition of protein synthesis, mitochondrial function and depletion of cellular ATP. Because of repeated and long-term usage of NaF, more detailed studies should be undertaken to understand its toxic effects in vitro and in vivo.


Interaction between magnetic fields and metallic ossicular prostheses.
A selection of commonly used metal ossicular prostheses were tested to see if they were attracted by the 5000-gauss magnetic field of a magnetic resonance imager. None of the prostheses tested was attracted by the magnetic field. Using a model system, it was found that some of the metal objects perturbed the magnetic field, thus affecting the image produced by the scanner. Therefore, while metal implants may be safe in a powerful magnetic field, they can alter the field, resulting in abnormal images.


Intraventricular sizeable colloid cyst with atypical radiological features: A case report and evidence-based review.
Colloid cysts are benign intracranial lesions, typically located in the anterior portion of the third ventricle near the interventricular foramina of Monro. The cysts usually consist of an epithelial lining filled with viscous gelatinous material of various components. Colloid cysts are generally asymptomatic, but once symptomatic, they can present in a variety of ways, including headaches, vomiting, visual and memory problems, and vertigo. Colloid cysts present classically on imaging as a well-delineated hyperattenuating lesion on unenhanced radiological modalities. Herein, we report a case of a patient who presented with hydrocephalus caused by a sizeable colloid cyst which demonstrated atypical imaging findings in the form of hypodensity on CT and hyperintensity on T2WI, making them difficult to identify and easy to miss. Although this atypical imaging appearance is uncommon with yet unknown true incidence, it is prudent to be aware of it because early management of colloid cysts has a favorable outcome, in contrast to untreated cysts that are associated with higher rates of morbidity and mortality. Additionally, we provide a comprehensive, evidence-based review of the medical entity of intracranial colloid cysts with highlights of current postulated pathological theories and management algorithms.


Effect of adrenalectomy and glucocorticoid therapy on lipid metabolism of lactating rats.
Although adrenal glucocorticoids were known to be important for adequate milk production, little is known about their effects on the metabolism of mammary glands during lactation. In this study, lactating Wistar rats on the 12th day of lactation were divided in the following groups: sham-operated (SO) and adrenalectomized (ADX) receiving no treatment; SO and ADX starved for 24 h and refed intragastrically with 2.5 ml of 50% glucose solution, 2 h before the experiment (SOR and ADXR) and ADX receiving substitute therapy with dexamethasone (ADX + DEX). Sacrifices were performed 2 days after surgery. Weight, lipid content and in vivo lipogenesis rate were evaluated in mammary gland (M.GLAND), liver, parametrial white adipose tissue (PARA) and interescapular brown adipose tissue (BAT). ATP citrate lyase activity was measured in M.GLAND, liver and PARA of SO, ADX and ADX + DEX. The rate of lipogenesis and 14CO2 production from 14C-glucose by isolated acini from M.GLAND and plasma glucose were also determined. In ADX rats, food intake, lipid content, in vivo lipogenesis rate and ATP citrate lyase activity in M.GLAND were significantly lower than those in SO rats. The M.GLAND lipogenesis rate of SOR group was similar to the value found in SO rats. In ADXR rats, the M.GLAND lipogenesis rate was not normalized. However, the therapy with DEX elevated lipid content, in vivo lipogenesis rate and ATP citrate lyase activity to levels similar to those in SO. These results suggest that the glucocorticoids are essential for the occurrence of normal lipid synthesis in M.GLAND during lactation.


Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season.
In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed. The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season. A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005). The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. ≥ 75 years of age.


The spatiotemporal variation, background, and baseline activities of radionuclides in the soil of Aragats Massif (Armenia).
The present study was performed to reveal the distribution patterns and spatiotemporal changes of radionuclides in the soil of the highest mountain of Armenia: Aragats Massif. In this regard, two surveys were implemented in 2016-2018 and 2021 with an altitudinal sampling strategy. The activities of radionuclides were determined by gamma spectrometry system with HPGe detector (CANBERRA). Correlation and linear regression analysis were applied to determine the dependence of radionuclides' distribution from altitude. Classical and robust statistical methods were used to assess the local background and baseline values. In two sampling profiles, the spatiotemporal variation of radionuclides was studied. A significant correlation was revealed between 137Cs and altitude pointing to global atmospheric migration as a primary source of 137Cs in Armenian environment. The predicted values of regression model revealed a 0.08-Bq/kg and 0.03-Bq/kg increase of 137Cs in each m on average, for the old and new survey, respectively. The assessment of background activities of NOR (naturally occurring radionuclides) enables setting the local background for 226Ra, 232Th, and 40 K in soils of Aragats Massif: 831.3 ± 20.2 Bq/kg and 540.6 ± 18.3 Bq/kg for 40 K, 85.5 ± 3.1 Bq/kg and 27.7 ± 2.6 Bq/kg for 226Ra, and 66.8 ± 3.2 and 46.4 ± 3.0 Bq/kg for 232Th, respectively, for the years of 2016-2018 and 2021. 137Cs baseline activity was estimated by altitude: 350 ± 3.7 Bq/kg and 108 ± 2.5 Bq/kg, respectively, for the years of 2016-2018 and 2021.


Mycotic aneurysm of the inferior mesenteric artery.
This is the first reported case of successful management of a mycotic aneurysm of the inferior mesenteric artery. The only helpful clinical manifestations were episodes of previous abdominal pain and a history of bacterial endocarditis. The surgical management involved simple excision without revascularization of the inferior mesenteric artery.


Mapping and validation of QTLs for cold tolerance at seedling stage in rice from an indica cultivar Habiganj Boro VI (Hbj.BVI).
Yellowing, stunting, and seedling death associated with cold stress is a common problem in many Asian countries for winter rice cultivation. Improvement of cultivars through marker-assisted selection of QTLs for cold tolerance at seedling stage from locally adapted germplasm/cultivar is the most effective and sustainable strategy to resolve this problem. A study was undertaken to map QTLs from 151 F2:3 progenies of a cross between a cold susceptible variety, BR1 and a locally adapted traditional indica cultivar, Hbj.BVI. A total of six significant QTLs were identified for two cold tolerance indices-cold-induced leaf discoloration and survival rate after a recovery period of seven days on chromosomes 6, 8, 11, and 12. Among these QTLs, qCTSL-8-1 and qCTSS-8-1 being co-localized into RM7027-RM339 on chromosome 8 and qCTSL-12-1 and qCTSS-12-1 into RM247-RM2529 on chromosome 12 showed 12.78 and 14.96% contribution, respectively, to the total phenotypic variation for cold tolerance. Validation of QTL effect in BC1F3 population derived a cross between a cold susceptible BRRI dhan28 and Hbj.BVI showed dominating effect of qCTSL-12-1 on cold tolerance at seedling stage and it became stronger when one or more other QTLs were co-segregated with it. These results suggest that the QTLs identified in this study are stable and effective on other genetic background also, which warrant the use of these QTLs for further study aiming to cultivar development for seedling stage cold tolerance.


Penile sarcomatoid urothelial carcinoma: A case report.
A 74-year-old man with a penile mass was diagnosed with sarcomatoid urothelial carcinoma. Further workup did not show any other lesions or metastases. He was treated with a total penectomy, bilateral inguinal lymph node dissection, and pelvic lymphadenectomy. Following surgery, he received six cycles of cisplatin and gemcitabine. Sarcomatoid carcinoma and carcinosarcoma of the urethra are rare; six prior cases have been reported in the literature, with this being the first urothelial with sarcomatoid component. Survival in patients with sarcomatoid carcinoma or carcinosarcoma of the urinary tract is poor, with the limited data supporting a multimodal approach to improve survival.


Treatment of central retinal vein occlusion-related macular edema with intravitreal bevacizumab (Avastin): preliminary results.
To assess the safety and efficacy of treatment of macular edema secondary to central retinal vein occlusion (CRVO) with intravitreal bevacizumab. The ongoing prospective study included 8 consecutive patients (8 eyes) with macular edema secondary to CRVO (6 non ischemic and 2 ischemic), treated with intravitreal injection of 1.25 mg (0.05 mL) of bevacizumab. Main outcome was best corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by optical coherence tomography monthly during one year. Retreatment criteria include decrease of BCVA, persistence of macular edema on angiograms and increase of CFT. Mean age of the eight patients was 68 years (range: 50-82 years). Mean duration of symptoms before injection was 98 days (range: 3-289). Mean follow-up was 3.25 months. At baseline, mean BCVA was 0.84 logMar and mean baseline CFT was 771 microm. Mean BCVA was 0.36 and mean CFT thickness was 275 microm (n = 8) at month 1, 0.41 and 411 microm at month 2 (n = 7), 0.3 and 344 microm at month 3 (n = 6), 0.3 and 397 microm at month 4 (n = 5), respectively. In 75 % of patients, a single injection was not sufficient, and retreatment needed. No serious adverse events were observed. Treatment of macular edema secondary to CRVO with intravitreal bevacizumab injection of 1.25 mg was well tolerated and associated with marked macular thickness reduction and BCVA improvement in all patients. A trend towards reduction of foveal thickness and improvement of visual acuity was observed in both acute and chronic CRVO.


[Intestinal absorption of digoxin in systemic sclerosis (author's transl)].
Gastro-intestinal absorption of digoxin was evaluated in 18 patients with progressive systemic sclerosis. In 8 patients a single-dose crossover study was performed after oral and intravenous administration of 0.5 mg digoxin by comparing the aera under the eight-hour plasma concentration curve. The fraction of the dose absorbed was diminished in 4 patients to less than 55%. There was a significant positive correlation between the extent of digoxin absorption and xylose renal excretion. In addition, steady state digoxin plasma levels and 24-h urinary excretion of digoxin were determined during maintenance therapy in 12 patients. In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation. This finding corresponded well with digoxin plasma levels below the usual therapeutic range in most of the patients. The impaired absorption of digoxin failed to correlate with the extent of the skin manifestation or the time course of the disease while there was massive oesophageal dysfunction in most of these patients. The results suggest that an inadequate therapeutic response to cardiac glycosides in patients suffering from progressive systemic sclerosis is at least partially due to impaired digoxin absorption. Similar problems could occur in therapy of the disease itself due to insufficient enteral absorption of drugs used in treatment of systemic sclerosis.


Fatal thermal injury.
Two fatal cases of thermal injury are described, one of which was the result of heat stroke and the other was the result of the uncommon condition, neuroleptic malignant syndrome. The clinical profiles, management and post-mortem findings of these two separate conditions are compared to highlight their important differences.


Student and School Characteristics Associated With COVID-19-Related Learning Decline Among Middle and High School Students in K-12 Schools.
COVID-19-disrupted schools, including shifts to virtual learning which may have impacted academic progress. This study assessed characteristics associated with changes in academic grades (before and during the pandemic) for different learning modalities for US students ages 13-19. Students (N = 2152) completed a web survey on school-related experiences during the 2020-2021 school year. County social vulnerability and SARS-CoV-2 transmission data were merged with survey data. Multivariable logistic regression analysis for grade change was conducted with student and school characteristics for each learning modality, controlling for community characteristics. Greater proportions of remote/virtual (34.4%) and hybrid (30.1%) learning students reported grade decline compared to in-person students (19.9%). Among in-person students, odds of reporting same/improved grades were 65% lower among non-Hispanic black students and 66% lower among non-Hispanic students from other races, compared to non-Hispanic white students. Among hybrid students, odds of reporting same/improved grades for students reporting anxiety were 47% lower than students without anxiety, and odds of reporting same/improved grades among students reporting substance use were 40% lower than students not reporting substance use. Among remote/virtual students, odds of reporting same/improved grades among students with depression were 62% lower than odds of students not reporting depression symptoms. Remote/virtual students who received school-provided educational services also had 1.55 times the odds of reporting same/improved grades, compared to remote/virtual students not receiving these services. Academic grades were negatively impacted during COVID-19 and learning mode may have contributed. Understanding these impacts is critical to student health and academic achievement.


The development of student teachers' teacher self-efficacy before and during the COVID-19 pandemic.
This study used latent growth curve models to examine the impact of the COVID-19 pandemic on the development of teacher self-efficacy in student teachers. Results indicated that the teacher self-efficacy of student teachers taught during the first COVID-19 lockdown increased significantly less across a semester compared to student teachers taught prior to the pandemic, who gained practical experience in schools. There may be a cohort of student teachers at risk of entering the profession with lower self-efficacy than is typical. Universities and schools may wish to provide additional practical experiences to compensate for the missed opportunities during the COVID-19 pandemic.


Editorial: Racialized Trauma and Emotion Regulation in a Dysregulated World.
Racialized trauma can come directly from other people or can be experienced within a wider system. It can come as the result of a direct experience when racism is enacted on you, vicariously-such as when you see videos of other people facing racism-and/or transmitted intergenerationally. More and more, research in child and adolescent psychiatry has supported that race-related stress and racialized violence has systemic roots and psychological and physiological consequences. The term "emotion regulation" is generally used to describe a person's ability to effectively manage and respond to an emotional experience and to adapt to the demands of their environment. At the time of writing this editorial, youth of color have witnessed a pandemic in which their families and communities have been disproportionately impacted and devastated, the death of George Floyd and other racialized violence against unarmed people of color, murder of their elders in grocery stores and churches, their peers shot by assault weapons while attending school, all compounded by discrimination against sexual and gender minority people in some regions, climate change heating up our earth, and immigrant children separated from parents or dying at the border. What will be the response of the adults around them to protect them? What is the role of emotion regulation skills for youth experiencing race-related stress and trauma in a dysregulated world?


Suicide in England and Wales 1946-1985: an age-period-cohort analysis.
Four decades of suicide mortality data for England and Wales were analysed within an age-period-cohort framework. Marked differences in results were found by sex. The analysis of the male data showed that the risk of suicide increased with age until men were in their mid-fifties (after allowing for period and cohort effects), and that suicide risk declined for males born from 1876 to 1915, but had increased over 4-fold for certain later-born cohorts. Female suicide risk was found to decline with later nativity (after adjusting for age and period effects). The identification of period effects in terms of known changes in the carbon monoxide (CO) content of domestic gas successfully accounted for temporal variation in male suicide risk, but fitted less well to the data for females.


Ohio survey data assessing perceptions of abortion safety.
Despite overwhelming data supporting the safety of abortion care in the U.S., public perceptions of abortion safety vary widely. While evidence suggests that the public overestimates abortion risk, few studies have analyzed why people think abortion is safe or unsafe. Using data from the Ohio Survey of Women, a representative survey of women aged 18 to 44 years with a residential address in Ohio, we examined responses to 2 questions about abortion safety perceptions: the first asked respondents to rate abortion safety in Ohio, and the second asked respondents why they chose this rating of abortion safety. We analyzed these responses with inductive and deductive approaches. There were 2529 responses, of which 1368 (54%) provided a response to the open-ended question about abortion safety. From this subset, 529 gave open-ended responses indicating that they perceive abortion as safe, with 47% attributing this perception to the procedure being performed by a professional in a regulated environment. In contrast, 370 gave open-ended responses indicating that they perceive abortion as unsafe; the most common explanations referred to health risks (19%) and that safety depends on preexisting health conditions (19%). Many participants perceived abortion as safe because it is performed by professionals in a clinical environment or because of personal experiences with abortion. Those perceiving a lack of safety provided more varied responses, including that abortion was dangerous due to a detrimental effect on mental health or protesters at abortion clinics. We identified that women have a broad range of reasons for perceiving abortion as safe or unsafe. Providers should be aware of this diversity of abortion safety perceptions so that they can best engage with their patients.This updated characterization of pain experienced during an evidence-based medication abortion regimen may allow for better pain-related counseling, tailoring of opioid prescription practices, and improvement in patient satisfaction.


Egg morphology of nine species of Pollenia Robineau-Desvoidy, 1830 (Diptera: Calliphoridae).
Egg morphology of nine species of the cluster fly genus Pollenia Robineau-Desvoidy was studied with scanning electron microscopy. Funnel-shaped micropylar area, chorion covered with centrally depressed hexagons, well developed hatching pleats on the dorsal surface encompassing the median area were found in eggs of all species: P. amentaria (Scopoli), P. angustigena Wainwright, P. atramentaria (Meigen), P. labialis Robineau-Desvoidy, P. mayeri Jacentkovsky, P. pediculata Macquart, P. rudis (Fabricius), P. similis (Jacentkovsky), and P. vagabunda (Meigen). Untypical for Calliphoridae, a dual morphological structure of plastron-bearing area is described here for the first time. On the basis of our observations, all species studied share the presence of a plastron respiratory function on the entire surface between the hatching lines. Differences between species were found in the shape of the longitudinal hatching pleats and the proportion between 'island pattern' and 'hexagonal pattern' of their chorionic surface, and in the intensity of perforation of hexagons of the median area. Comparisons of Pollenia egg morphology with that of other representatives of Calliphoridae revealed its unique structure, allowing easy differentiation from other representatives of the family.


Finding synchrony in the desynchronized EEG: the history and interpretation of gamma rhythms.
Neocortical gamma (30-80 Hz) rhythms correlate with attention, movement and perception and are often disrupted in neurological and psychiatric disorders. Gamma primarily occurs during alert brain states characterized by the so-called "desynchronized" EEG. Is this because gamma rhythms are devoid of synchrony? In this review we take a historical approach to answering this question. Richard Caton and Adolf Beck were the first to report the rhythmic voltage fluctuations in the animal brain. They were limited by the poor amplification of their early galvanometers. Thus when they presented light or other stimuli, they observed a disappearance of the large resting oscillations. Several groups have since shown that visual stimuli lead to low amplitude gamma rhythms and that groups of neurons in the visual cortices fire together during individual gamma cycles. This synchronous firing can more strongly drive downstream neurons. We discuss how gamma-band synchrony can support ongoing communication between brain regions, and highlight an important fact: there is at least local neuronal synchrony during gamma rhythms. Thus, it is best to refer to the low amplitude, high frequency EEG as an "activated", not "desynchronized", EEG.


Early integration of palliative cancer care: patients' and caregivers' challenges, treatment preferences, and knowledge of illness and treatment throughout the cancer trajectory.
Early integration of palliative care (EIPC) into oncology is beneficial for cancer patients and their caregivers. Best practice models of EIPC throughout the course of cancer treatment aim to support patients and caregivers in meeting their individual needs. So far, we know little about whether EIPC offers should be phase-specific or patient-centered. This study investigated patients' and caregivers' needs considering individual challenges, treatment preferences, and knowledge over the cancer trajectory. Semi-structured qualitative interviews and pre-interview questionnaires were conducted with 11 cancer patients and 9 caregivers. A modified grounded theory approach was used to analyze the interview data applying thematic analysis and reflective principles by using MAXQDA. Our data showed no clearly distinct pattern of illness-phase-specific needs of patients and caregivers. Support needs were dependent on the significance and interpretation of events by patients and caregivers. Mastering challenges was highly individual and influenced by personal and contextual factors. Our results showed that subjective theories of illness significantly influenced experience, information requirements, treatment preferences, and the feeling of patients and caregivers "to be in good hands." The physician-patient relationship was of central relevance and has a major gatekeeper function for EIPC. Access to the medical care system, resources, and information appeared to be based on chance. For optimal EIPC, it is necessary to improve structural conditions such as more structured information about resources and procedures. Subjective theories of illness need to be continuously considered by practitioners in order to recognize the individual need for support.


An Enantioselective Approach to 4-O-Protected-2-cyclopentene-l,4-diol Derivatives via a Rhodium-Catalyzed Redox-Isomerization Reaction.
Kinetic resolution of a series of cyclopentene-1,4-diol derivatives has been successfully achieved with enantiomeric excess up to 99.4% and a kf/ks ratio of 55 by a rhodium-catalyzed redox-isomerization reaction in a noncoordinating solvent.


Pressurized liquid extraction-gas chromatography-mass spectrometry for confirming the photo-induced generation of dioxin-like derivatives and other cosmetic preservative photoproducts on artificial skin.
The stability and photochemical transformations of cosmetic preservatives in topical applications exposed to UV-light is a serious but poorly understood problem. In this study, a high throughput extraction and selective method based on pressurized liquid extraction (PLE) coupled to gas chromatography-mass spectrometry (GC-MS) was validated and applied to investigate the photochemical transformation of the antioxidant butylated hydroxytoluene (BHT), as well as the antimicrobials triclosan (TCS) and phenyl benzoate (PhBz) in an artificial skin model. Two sets of photodegradation experiments were performed: (i) UV-Irradiation (8W, 254nm) of artificial skin directly spiked with the target preservatives, and (ii) UV-irradiation of artificial skin after the application of a cosmetic cream fortified with the target compounds. After irradiation, PLE was used to isolate the target preservatives and their transformation products. The follow-up of the photodegradation kinetics of the parent preservatives, the identification of the arising by-products, and the monitorization of their kinetic profiles was performed by GC-MS. The photochemical transformation of triclosan into 2,8-dichloro-dibenzo-p-dioxin (2,8-DCDD) and other dioxin-like photoproducts has been confirmed in this work. Furthermore, seven BHT photoproducts, and three benzophenones as PhBz by-products, have been also identified. These findings reveal the first evidences of cosmetic ingredients phototransformation into unwanted photoproducts on an artificial skin model.


The architecture of starch blocklets follows phyllotaxic rules.
The starch granule is Nature's way to store energy in green plants over long periods. Irrespective of their origins, starches display distinct structural features that are the fingerprints of levels of organization over six orders of magnitude. We hypothesized that Nature retains hierarchical material structures at all levels and that some general rules control the morphogenesis of these structures. We considered the occurrence of a «phyllotaxis» like features that would develop at scales ranging from nano to micrometres, and developed a novel geometric model capable of building complex structures from simple components. We applied it, according to the Fibonacci Golden Angle, to form several Golden Spirals, and derived theoretical models to simulate scattering patterns. A GSE, constructed with elements made up of parallel stranded double-helices, displayed shapes, sizes and high compactness reminiscent of the most intriguing structural element: the 'blocklet'. From the convergence between the experimental findings and the theoretical construction, we suggest that the «phyllotactic» model represents an amylopectin macromolecule, with a high molecular weight. Our results offer a new vision to some previous models of starch. They complete a consistent description of the levels of organization over four orders of magnitude of the starch granule.


Molecular characterisation of a versatile peroxidase from a Bjerkandera strain.
The cloning and sequencing of the rbpa gene coding for a versatile peroxidase from a novel Bjerkandera strain is hereby reported. The 1777 bp isolated fragment contained a 1698 bp peroxidase-encoding gene, interrupted by 11 introns. The 367 amino acid-deduced sequence includes a 27 amino acid-signal peptide. The molecular model, built via homology modelling with crystal structures of four fungal peroxidases, highlighted the amino acid residues putatively involved in manganese binding and aromatic substrate oxidation. The potential heme pocket residues (R44, F47, H48, E79, N85, H177, F194 and D239) include both distal and proximal histidines (H48 and H177). RBP possesses potential calcium-binding residues (D49, G67, D69, S71, S178, D195, T197, I200 and D202) and eight cysteine residues (C3, C15, C16, C35, C121, C250, C286, C316). In addition, RBP includes residues involved in substrate oxidation: three acidic residues (E37, E41 and D183)--putatively involved in manganese binding and H83 and W172--potentially involved in oxidation of aromatic substrates. Characterisation of nucleotide and amino acid sequences include RBP in versatile peroxidase group sharing catalytic properties of both LiP and MnP. In addition, the RBP enzyme appears to be closely related with the ligninolytic peroxidases from the Trametes versicolor strain.


Early Avastin management in acute retinal vein occlusion.
To evaluate the safety, functional and anatomical effects of intravitreal Avastin (bevacizumab) in treatment of recent retinal venous occlusion. Prospective interventional series non-comparative study. Department of Ophthalmology, Faculty of Medicine, El-Minia University, Egypt. The study included 30 eyes of 30 patients with recent retinal venous occlusion of less than 3 months duration 12 eyes (40%) of patients with central retinal vein occlusion (CRVO) and 18 eyes (60%) with branch retinal vein occlusion (BRVO) were injected with intravitreal bevacizumab 1.25 mg (0.05 ml) of commercially available bevacizumab [Avastin; Genentech, Inc., San Francisco, CA] at a concentration of 25 mg/ml as a primary treatment. The mean number of injections was 2.7 (range, 1-6 injections) 6-8 weeks intervals and follow-up for 12 months (range, 9-13 months). Patients underwent visual acuity testing (VA) as functional assessment. Anatomically, optical coherence tomography (OCT) is used for measurement of central retinal thickness (CRT) to detect macular edema (ME), fundus photography and fluorescein angiography (FA) to detect venous tortuosity, optic disc edema and surface wrinkling rather than ME. All finding at baseline and each follow-up visit were reported. The mean age of all patients was 65.3 years ± 8.5 (range, 55-82 years), 20 males and 10 females patients. The mean baseline VA was 20/240 (log MAR 1.08 ± 0.52) and improved to 20/60 (log MAR 0.48 ± 0.32) with statistically significance difference change (P < 0.001). The mean baseline CRT was 455 μm ± 126 (range, 386-510), decreased to 356 μm ± 118 (range, 296-416) after 1 month with statistically significance difference change (P < 0.02) and to 402 μm ± 170 (range, 338-468) after 6 months (P < 0.067) and to 250 μm ± 48 (range, 200-298) at last follow-up with statistically significance difference change from the baseline (P < 0.001). There were great proportional decrease in venous tortuosity, optic disc edema and surface wrinkling after 1 month of injection. Neither systemic nor intraocular adverse events were reported. Intravitreal Avastin (IVA) is safe well tolerated, effectively improve VA, fundus picture and stabilize anterior segment neo-vascular activity in patients with recent retinal venous occlusion.


Short Form 36 and Hospital Anxiety and Depression Scale. A comparison based on patients with testicular cancer.
The aim of this study was to compare the scorings of anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HADS-A [Anxiety] and HADS-D [Depression]) with the scorings on the eight subscales of Short Form 36 (SF-36) and the Physical (PCS) and Mental Component Summary (MCS) assessed by the same patients. In a cross-sectional study 736 long-term survivors after treatment for testicular cancer (TC) completed HADS and SF-36. Pearson's correlation coefficients were calculated on item and scale level to assess the associations between the HADS and the SF-36 scales and, in particular, between HADS and PCS and MCS, respectively. Independent predictors for PCS and MCS were identified by linear regression analysis. HADS-A and HADS-D were significantly associated with the SF-36 summary scales. HADS-A explained 5% of the variance of PCS and 49% of the variance of MCS. The comparable figures for HADS-D were 10% and 45%, respectively. In the multivariate analysis the HADS-D scoring independently predicted the level of PCS together with the patients' educational level, long-lasting working disability and age (variance: 30%). Both HADS-D and HADS-A remained independent parameters for MCS (variance: 58%) together with the patient's civil status. HADS-D item D4 ("slowed down") was similarly associated with both PCS and MCS. In univariate analyses HADS-D and HADS-A were statistically associated with PCS and MCS. The highest r values were observed for the associations between HADS and MCS, in particular between HADS-A and MCS. In the multivariate analyses HADS-D, but not HADS-A, contributed to PCS, whereas both HADS-A and HADS-D were associated with MCS. This pattern of different predictions of the summary scales of SF-36 supports a clinical practice that anxiety and depression should be assessed separately. Additional use of a self-rating instrument for depression and anxiety, such as HADS, is recommended when SF-36 is used for quality of life (QL) assessment.


Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population.
Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes.


Impact of Epidural Versus General Anesthesia on Major Lumbar Surgery in Elderly Patients.
This was a retrospective comparative study. The main objective of this study was to investigate the effects of epidural anesthesia (EA) versus general anesthesia (GA) in elderly patients undergoing lower lumbar spine fusion surgeries. Lumbar spine surgery can be performed under GA or regional anesthesia. GA is more commonly used in lumbar spine surgery, which renders the patient motionless throughout the procedure and provides a secure airway. Although EA is associated with superior hemodynamic status, reduced duration of operation, less health care cost, and lower rate of surgical complications when compared with GA. Controversy still exists with regard to the optimum choice of anesthesia for major lumbar spine surgery, especially in elderly patients. From September 2016 to August 2017, consecutive patients aged 70 years or older who underwent lower lumbar fusion surgery with EA or GA were enrolled in the study. Recorded data for all patients included: age, sex, medical conditions; surgical time, operation procedure, blood loss; intraoperative hypertension and tachycardia; occurrence of nausea, vomiting, delirium, or cardiopulmonary complications. Postoperative pain and satisfaction were also assessed. A total of 89 patients were included. Of these, 42 patients underwent GA and 47 patients underwent EA. The number of patients experiencing hypertension and tachycardia during anesthesia was significantly increased in the GA group when compared with EA. Patients with EA had significantly less delirium, nausea, and vomiting. The average Visual Analog Scale scores were significantly higher in the GA group at 0-8 hours after surgery. Patients underwent EA were more satisfied than patients with GA. There was an association between those who received EA and superior perioperative outcomes. However, some concerns including airway security, operation duration, and obesity, must be carefully evaluated. In addition, it should be noted that this study was retrospective and selection bias may probably exist which may interfere with the results.


Chinese NiTi wire--a new orthodontic alloy.
Chinese NiTi wire was studied by means of a bending test to determine wire stiffness, springback, and maximum bending moments. Chinese NiTi wire has an unusual deactivation curve (unlike steel and nitinol wires) in which relatively constant forces are produced over a long range of action. The characteristic flexural stiffness of NiTi wire is determined by the amount of activation. At large activations NiTi wires has a stiffness of only 7% that of a comparable stainless steel wire, and at small activations 28% of steel wire. For the same activation at large deflections, the forces produced are 36% that of a comparable nitinol wire. Chinese NiTi wire demonstrates phenomenal springback. It can be deflected 1.6 times as far as nitinol wire or 4.4 times as far as stainless steel wire without appreciable permanent deformation. NiTi wire is highly useful in clinical situations that require a low-stiffness wire with an extremely large springback.


Pediatric allergic rhinitis and asthma: can the march be halted?
The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.


Non-ionic detergents facilitate non-specific binding of M13 bacteriophage to polystyrene surfaces.
Phage-displayed random peptide libraries are widely used for identifying peptide interactions with proteins and other substrates. Selection of peptide ligands involves iterative rounds of affinity enrichment. The binding properties of the selected phage clones are routinely tested using immunoassay after propagation to high titre in a bacterial host and precipitation using polyethylene glycol (PEG) and high salt concentration. These immunoassays can suffer from low sensitivity and high background signals. Polysorbate 20 (Tween(®) 20) is a non-ionic detergent commonly used in immunoassay washing buffers to reduce non-specific binding, and is also used as a blocking reagent. We have observed that Tween 20 enhances non-specific M13 library phage binding in a peptide-independent manner. Other non-ionic detergents were also found to promote significant, dose-dependent non-specific phage binding in ELISA. This effect was not observed for assays using phage concentrated by ultracentrifugation, suggesting that interactions occur between detergents and the PEG-precipitated phage, irrespective of the displayed peptide motif. This artefact may impact on successful affinity selection of peptides from phage-display libraries. We propose alternative methods for screening phage libraries for identifying binding interactions with target ligands.


Moving forward the Italian nursing education into the post-pandemic era: findings from a national qualitative research study.
During the CoronaVIrus-19 (COVID-19) pandemic, nursing education has been dramatically transformed and shaped according to the restrictions imposed by national rules. Restoring educational activities as delivered in the pre-pandemic era without making a critical evaluation of the transformations implemented, may sacrifice the extraordinary learning opportunity that this event has offered. The aim of this study was to identify a set of recommendations that can guide the Italian nursing education to move forward in the post-pandemic era. A qualitative descriptive design was undertaken in 2022-2023 and reported here according to the COnsolidated criteria for REporting Qualitative research guidelines. A network was established of nine Italian universities offering a bachelor's degree in nursing for a total of 6135 students. A purposeful sample of 37 Faculty Members, 28 Clinical Nurse Educators and 65 Students/new graduates were involved. A data collection was conducted with a form including open-ended questions concerning which transformations in nursing education had been implemented during the pandemic, which of these should be maintained and valued, and what recommendations should address the transition of nursing education in the post-pandemic era. Nine main recommendations embodying 18 specific recommendations have emerged, all transversally influenced by the role of the digital transformation, as a complementary and strengthening strategy for face-to-face teaching. The findings also suggest the need to rethink clinical rotations and their supervision models, to refocus the clinical learning aims, to pay attention towards the student community and its social needs, and to define a pandemic educational plan to be ready for unexpected, but possible, future events. A multidimensional set of recommendations emerged, shaping a strategic map of action, where the main message is the need to rethink the whole nursing education, where digitalization is embodied. Preparing and moving nursing education forward by following the emerged recommendations may promote common standards of education and create the basis on for how to deal with future pandemic/catastrophic events by making ready and prepared the educational systems.


Accumulation, nature, and possible functions of the malachite green affinity material in ejaculated human spermatozoa.
An electron microscopic study was conducted on human sperm over an incubation period of 5 to 6 hours in Tyrode's solution at room temperature. Examination of aliquots of the cells, fixed at timed intervals, with glutaraldehyde, malachite green, and postosmication revealed that malachite green affinity material (MGA-M) was barely discernible at first but did accumulate considerably upon standing. Biochemical analysis of MGA-M, which is extractable by glutaraldehyde, revealed that MGA-M is a mixture of extractable phospholipids and of their lyso-derivatives. Some of these substances have fusogenic properties; i.e., they are able to fuse together the membranes of two different cells. The appearance and accumulation of these fusogens occurred during the incubation period of 5 to 6 hours, which was previously shown to be required to capacitate human sperm in vitro. It is probable, therefore, that human sperm, during their initial period of incubation either in vivo or in vitro, not only become capacitated and undergo the acrosome reaction but also develop the fusogenic substance(s) which are necessary for the imminent fusion of their plasma membrane to the vitelline membrane of the mature oocyte.


Escherichia coli mutants defective in the gamma subunit of proton-translocating ATPase: intracistronic mapping of the defective site and the biochemical properties of the mutants.
Various hybrid plasmids carrying a portion of the gene for the gamma subunit of the H+-ATPase of Escherichia coli complemented five mutants defective in the enzyme in a genetic test, indicating that the mutants are defective in the gamma subunit. Since the nucleotide sequence of genomic DNA carried on the plasmids is known, the defective site(s) of the mutants could be located within the gene for the gamma subunit as follows: KF10 and NR70, KF1, and KF12 and KF13 have a mutation causing a defect(s) in amino acid residues 1 to 82, 83 to 167, and 168 to 287, respectively, of the gamma subunit. The biochemical properties of all these mutants except NR70 were analyzed in terms of proton permeability of the membranes and assembly of F1. Results suggested that KF1 and KF10 have defective F1 without at least the alpha and beta subunits on their membranes, whereas KF12 and KF13 have F1's of rather similar structure to that of the wild type. Attempts were made to purify F1 oF KF12 as a single complex. Although the F1 complex dissociated during purification, active alpha and beta subunits of KF12 were partially purified. On the basis of these biochemical and genetic results, it is suggested that structural alterations in the primary sequence of the gamma subunit corresponding to residues 1 to 167 cause more extensive defects in the assembly of F1 than alteration in the sequence of residues 168 to 287.


"The Gold Standard" and Related Considerations for a Maturing Science of Substance Abuse Treatment. Therapeutic Communities; A Case in Point.
The randomized control trial (RCT) is commonly celebrated as the "Gold Standard" of research designs. However, such evidentiary distinctions contain serious implications for the scientific acceptance, funding, and public perception of various treatments for substance abuse. This issue and related considerations are briefly discussed from the perspective of therapeutic community treatment and research.


Snake venom rhodocytin induces plasma extravasation via toxin-mediated interactions between platelets and mast cells.
Venomous snakebites can induce local tissue damage, including necrosis of soft tissues, haemorrhage, blistering and local swelling associated with plasma extravasation, which can lead to lethal complications such as hypovolemic shock. However, the details of the underlying mechanisms remain unknown. In this study, we showed that intradermal treatment of mice with venom rhodocytin from the Malayan viper Calloselasma rhodostoma induced plasma extravasation, dependent on C-type lectin-like receptor 2 (CLEC-2) on platelets. Rhodocytin-induced plasma extravasation also relied on mast cells and histamine. In vitro co-culture of rhodocytin-activated platelets with mast cells induced histamine release from mast cells in an ATP/P2X7-dependent manner. Consistent with this, blockade or deficiency of P2X7 in mast cells suppressed rhodocytin-induced plasma extravasation in the skin. Together, these findings indicate that rhodocytin induces plasma extravasation by triggering platelet activation via CLEC-2, followed by activation of mast cells and histamine release via the ATP/P2X7 pathway. These results reveal a previously unrecognized mechanism by which snake venom increases vascular permeability via complex venom toxin-mediated interactions between platelets and mast cells.


Induction of CYP1A1 gene expression in H4-II-E rat hepatoma cells by benzo[e]pyrene.
In the rat, expression of the CYP1A1 gene is closely associated with arylhydrocarbon hydroxylase (AHH) enzyme activity. AHH is an inducile enzyme activity known to play an important role in the bioactivation of polycyclic aromatic hydrocarbons (PAHs) to mutagenic and carcinogenic metabolites. PAH-induced expression of the CYP1A1 gene appears to be regulated by several trans-acting factors, including the Ah receptor and the 4S PAH-binding protein. In this study, we used the PAH isomers benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) to further evaluate the role of the 4S PAH-binding protein in induction of the CYP1A1 gene in H4-II-E rat hepatoma cells. Although BaP is believed to bind to both the Ah receptor and the 4S protein, BeP has been reported to bind exclusively to the 4S protein. The results of the study presented here indicate that BaP and BeP induce the expression of the CYP1A1 gene, as measured by ethoxyresorufin O-deethylase (EROD) activity, in a concentration-dependent manner. However, BaP is about 25 times as potent as BeP in inducing EROD activity in these cells. Slot-blot analysis of total RNA isolated from these cells indicated that BeP, BaP, and 3-methylcholanthrene increased the level of CYP1A1 mRNA expression. Sucrose-gradient analysis of BeP binding activity indicated that BeP bound with high affinity to the 4S PAH-binding protein, but not to the Ah receptor. These results suggest that the 4S protein may play a role in the PAH-induced expression of the CYP1A1 gene in rat H4-II-E cells.


Enzyme-responsive polymeric micelles of cabazitaxel for prostate cancer targeted therapy.
Cabazitaxel, a novel tubulin inhibitor with poor affinity for P-glycoprotein, is a second-generation taxane holding great promise for the treatment of metastatic castration-resistant prostate cancer. However, its poor solubility and lack of target-ability limit its therapeutic applications. Herein, we develop a biodegradable, enzyme-responsive, and targeted polymeric micelle for cabazitaxel. The micelle is formed from two amphiphilic block copolymers. The first block copolymer consists of PEG, an enzyme-responsive peptide, and cholesterol; whereas the second block copolymer consists of a targeting ligand, PEG and cholesterol. The enzyme-responsive peptide is cleavable in the presence of matrixmetaloproteinase-2 (MMP-2), which is overexpressed in the tumor microenvironment of prostate cancer. The micelle showed a very low critical micelle concentration (CMC), high drug loading, and high entrapment efficiency. Release of cabazitaxel from the micelle is dependent on the cleavage of the enzyme-responsive peptide. Moreover, the micelle showed dramatically higher cellular uptake in prostate cancer cells compared to free cabazitaxel. Importantly, the ligand-coupled polymeric micelle demonstrated better inhibition of tumor growth in mice bearing prostate cancer xenografts compared to unmodified micelle and free cabazitaxel. Taken together, these findings suggest that the enzyme-responsive cabazitaxel micelle is a potent and promising drug delivery system for advanced prostate cancer therapy. STATEMENT OF SIGNIFICANCE: Herein, we develop a biodegradable, enzyme-responsive, and actively targeted polymer micelle for cabazitaxel, which is a novel tubulin inhibitor with poor affinity for P-glycoprotein. Despite cabazitaxel's great promise for metastatic castration-resistant prostate cancer, its poor solubility, lack of target-ability, and high systemic toxicity limit its therapeutic applications, and therefore a targeted delivery system is highly needed for cabazitaxel. Our results demonstrate the importance of active targeting in targeted prostate cancer therapy. Encapsulating cabazitaxel in the micelle increases its activity and is expected to reduce its systemic toxicity, which is a major hurdle in its clinical applications. Moreover, the polymeric micelle may servers as a promising nanoscale platform for the targeted delivery of other chemotherapeutic agents to prostate cancer.


Headspace for parents: qualitative report investigating the use of a mindfulness-based app for managing parents' stress during COVID-19.
Stress can compromise parental well-being and may contribute to harsh and critical parenting styles, which are in turn associated with children's conduct problems. Coronavirus disease 2019 (COVID-19)-related restrictions are likely to have exacerbated parental stress as, for many, UK-based family life was altered considerably. Mindfulness has been demonstrated to improve stress management and emotion regulation when delivered to parents in person, however, more accessible online interventions are under-researched. To provide preliminary data on family well-being and parent-child relationships as well as the acceptability and usability of the Headspace app - a self-delivered mindfulness-based intervention - for parents in low-risk families during the early days of the COVID-19 pandemic. We provided 12 parents with access to Headspace, and collected qualitative data (semi-structured interviews and 5 minute speech samples) immediately following the initial COVID-19 lockdown in the UK. The resulting transcripts were thematically analysed. Most parents reported Headspace to be acceptable and useful - improvements in parents' own sleep were particularly noted - and there was high adherence to the intervention. However, difficulties related to family well-being and parent-child relationships following the lockdown were also reported. As a result of the confounding impact of COVID-19 restrictions, and varied access to app content, we were unable to determine any outcomes to be a result of practising mindfulness specifically. However, COVID-19 has had a profound impact on many UK-based families, including those previously at low risk, and our results demonstrate that Headspace may have beneficial effects for parents. There is a need to more rigorously test this tool with a broader range of families.


Quality of Life in Long-Term Renal Transplant Patients: A Controversial Subject.
Kidney transplant (KT) is the best technique for renal replacement treatment in terms of survival, costs, and quality of life. Several factors have been related to health-related quality of life (HRQOL) at different times after KT. The objectives of the study were to quantify the HRQOL in a prevalent cohort of KT patients and to describe the variables that influenced HRQOL. In this cross-sectional study of a cohort of 64 KT patients, we measured HRQOL using the 36-item Short Form Health Survey. Variables measured included the following: physical functioning, role physical (RP), bodily pain (BP), general perception of health, vitality, social functioning (SF), role emotional (RE), and mental health. Demographic and analytical variables were collected. We describe the variables that influenced HRQOL. A large dispersion was observed in the RP, BP, SF, and RE categories. There were no differences in values between men and women who underwent KT. Diabetes, previous dialysis, deceased donor, age, kidney function, anemia, and malnutrition were associated with worse scores. This study suggests that HRQOL in KT patients is very heterogeneous and highly polarized. The factors that influence HRQOL are multiple and need to be addressed globally. Further studies are needed to understand the factors that influence HRQOL in the long term.


Association of extremely skewed X-chromosome inactivation with Taiwanese women presenting with recurrent pregnancy loss.
X-chromosome inactivation (XCI) is a phenomenon that occurs in female mammals. Typically, maternally and paternally-derived X chromosomes are inactivated at approximately the same frequency. If preferential inactivation occurs, the person is considered to have skewed XCI. Skewed XCI has been reported to occur more frequently in women who experience recurrent pregnancy loss (RPL). In this study, we sought to investigate if there is an association between skewed XCI and unexplained RPL in Taiwanese women. A total of 194 women who had experienced unexplained RPL were recruited into the study. Human androgen receptor or DXS6673E and DX15-134 loci were used in the XCI assay. The results of our study suggested that a cut-off point less than 90% may not be justified for skewed XCI. Only extremely skewed (more than 95%) XCI is associated with RPL. Extremely skewed XCI occurs in a subset of Taiwanese women with RPL.


Evaluating replicability of laboratory experiments in economics.
The replicability of some scientific findings has recently been called into question. To contribute data about replicability in economics, we replicated 18 studies published in the American Economic Review and the Quarterly Journal of Economics between 2011 and 2014. All of these replications followed predefined analysis plans that were made publicly available beforehand, and they all have a statistical power of at least 90% to detect the original effect size at the 5% significance level. We found a significant effect in the same direction as in the original study for 11 replications (61%); on average, the replicated effect size is 66% of the original. The replicability rate varies between 67% and 78% for four additional replicability indicators, including a prediction market measure of peer beliefs.


Linking molecular interactions to consequent effects of persistent organic pollutants (POPs) upon populations.
There is great concern about the potential adverse effects of persistent organic pollutants (POPs) on wildlife. Threats come from toxic chemicals with long half lives in the environment that were released worldwide on a large scale in the past, at a time when little was known of their potential effects on the environment. Although the Stockholm Convention (2001) initially targeted 12 POP chemicals--organochlorinated compounds--for the reduction/elimination of releases, the problem can be extended to persistent toxic substances more generally. Therefore, identifying early biomarkers for possible toxic effects to populations in the long term is a challenge for ecotoxicologists. Regional decline in fish, bird and/or invertebrate populations resulting from exposure to POPs, such as DDT (dichlorodiphenyltrichloroethane), PCBs (polychlorinated biphenyls), PCDD (polychlorinated dibenzo-p-dioxins), and TBT (tributyltin) could be related to some biochemical, endocrine and physiological effects in individuals. Examples of known mechanisms of POP ecotoxicity will be illustrated in the first part. The next parts will be devoted to (i) data gaps and limitations to extrapolation from lower to higher levels of biological organization, (ii) confusing factors in field studies and the combined effects of persistent toxic pollutants and (iii) recommendations for the design and interpretation of experimental studies.


Sitosterol in juvenile type II hyperlipoproteinemia.
The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia.


Amphicarpum purshii and the "pessimistic strategy" in amphicarpic annuals with subterranean fruit.
Amphicarpum purshii Kunth is an annual amphicarpic grass of recently disturbed sandy areas in the Coastal Plain of eastern North America, producing small aerial and larger subterranean seeds. At study sites on the eastern edge of the Pine Barrens of New Jersey, the temporal aspects of reproductive allocation were investigated through biweekly whole-plant field harvests of 25 plants each throughout the 1980 growing season, and the survivorship of plants arising from aerial and subterranean seeds was monitored in a total of 10 high and 10 low density quadrats at two sites differeing in soil moisture. Plants arising from subterranean propagules began to allocate early (July 16) considerable energy to subterranean reproduction (ca 40% of whole-plant dry weight by the last half of August); allocation to aerial culms and flowers did not begin until mid-August and never exceeded 3% on a population basis. Plants arising from aerial propagules ("aerial plants") produced only subterranean flowers, and these flowers first appeared 2 wk later than they did on "subterranean plants." Survivorship was greater for the subterranean seedlings at both the dry and wet sites and at low and high densities, and aerial plants showed significantly less total growth and seed production than subterranean plants. The "pessimistic strategy" (early allocation of energy to large subterranean propagules) in the annual Amphicarpum has its selective basis in the relative vigor, survival, and timing and amount of reproduction of the two types of seedlings, and appears comparable to the allocation strategies of at least eight other amphicarpic annuals in at least five other families of plants.


Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines.
Malaria vaccine development is hampered by the lack of small animal models that recapitulate human immune responses to Plasmodium falciparum. We review the burgeoning literature on humanized mice for P. falciparum infection, including challenges in engraftment of human immune cells, hepatocytes, and erythrocytes. Recent advances in immune-compromised mouse models and stem cell technology have already enabled proof of concept that the entire parasite life cycle can be sustained in a murine model and that adaptive human immune responses to several parasite stages can be measured. Nonetheless, optimization is needed to achieve a reproducible and relevant murine model for malaria vaccine development. This review is focused on the complexities of T cell development in a mouse humanized with both a lymphoid system and hepatocytes. An understanding of this will facilitate the use of humanized mice in the development of liver-stage vaccines.


Human papillomavirus E6/E7 mRNA expression in women younger than 30 years of age.
The prevalence of human papillomavirus (HPV) is high in women younger than 30 years of age, most infections being transient. It is not clear, however, to what extent the E6/E7 transcripts are being expressed. This may be of prognostic importance. In this study, we have determined the prevalence of HPV DNA and mRNA in 283 women younger than 30 years of age. E6/E7 transcripts from HPV types 16, 18, 31, 33 and 45 were detected using PreTect HPV-Proofer, while the presence of HPV DNA was detected using Gp5+/6+ consensus PCR and type-specific PCR. A total of 92 women (32.5%) were positive by consensus PCR, 59 (20.8%) were positive by type-specific PCR, while 41 (14.5%) were positive by PreTect HPV-Proofer. E6/E7 mRNA expression was detected in 38 (64.4%) of the 59 HPV type-specific DNA positive women. For HPV 16, E6/E7 mRNA expression was observed in 8 (32%) of the 25 DNA positive women. No high-grade lesions were observed in the concomitant cytology. Among young women having a normal Pap smear, a high HPV prevalence was found. Hence, use of consensus PCR will most probably give a low prognostic value for identifying subsequent severe dysplasia. The five HPV types 16, 18, 31, 33 and 45 accounted for the majority of infections with two out of three having a detectable E6/E7 mRNA expression. Yet, repeated type-specific testing for HPV mRNA may identify young women with a persistent transforming infection being at increased risk for severe dysplasia.


Shoulder pain in the competitive tennis player.
Shoulder pain in the elite tennis player is of the overuse variety and is usually attributable to impingement symptoms. Nonoperative approaches favor the quickest return to competitive tennis, and when surgery is necessary, arthroscopic procedures are preferred.


Constructed wetlands may lower inorganic nutrient inputs but enhance DOC loadings into a drinking water reservoir in North Wales.
The objective of this study was to monitor a newly constructed wetland (CW) in north Wales, UK, to assess whether it contributes to an improvement in water quality (nutrient removal) of a nearby drinking water reservoir. Inflow and outflow of the Free Water Surface (FWS) CW were monitored on a weekly basis and over a period of 6 months. Physicochemical parameters including pH, conductivity and dissolved oxygen (DO) were measured, as well as nutrients and dissolved organic and inorganic carbon (DOC, DIC) concentration. The CW was seen to contribute to water quality improvement; results show that nutrient removal took place within weeks after construction. It was found that 72 % of initial nitrate (N03 (-)), 53 % of initial phosphate (PO4 (3-)) and 35 % of initial biological oxygen demand (BOD) were removed, calculated as a total over the whole sampling period. From our study, it can be concluded that while inorganic nutrients do decline in CWs, the DOC outputs increases. This may suggest that CWs represent a source for DOC. To assess the carbon in- and output a C budget was calculated.


Obstructive sleep apnea syndrome: hooked appearance of the soft palate in awake patients--cephalometric and CT findings.
To determine whether a hooked appearance of the soft palate can be seen in awake patients with snoring with or without obstructive sleep apnea syndrome (OSAS) on cephalometric radiographs and computed tomographic (CT) scans. One hundred thirty-one patients with snoring underwent cephalometric radiography, with which the posterior airway space, soft palate length and width, and distance between the hyoid bone and mandibular plane were measured, and/or pharyngeal CT, with which the luminal areas of the airway at the naso-, oro-, and hypopharyngeal levels were measured. Of the 131 patients, 96 had OSAS, and 35 had snoring. Nine of 96 patients with OSAS had soft palate hooking on awake pharyngeal CT or cephalometric images. No patient with snoring alone had hooking. Patients with hooking had a larger posterior airway space than did patients with OSAS without hooking (P = .05), and an enlarged (> or = 15-mm) posterior airway space was more frequent in patients with hooking (eight of nine patients) than in those without hooking (34 of 87) (P < .01). Oropharyngeal and hypopharyngeal areas were significantly larger in patients with hooking than in patients without hooking or in patients with snoring (P < or = .04). Cephalometric radiography and CT can demonstrate hooking of the soft palate in awake patients. This finding indicates a high risk for OSAS.


[Inequalities in mortality in Seville [Spain]].
To describe social inequalities in mortality in Seville from 1994 to 1998 according to socioeconomic status. Life expectancy, crude and age-adjusted rates of total mortality as well as mortality by causes and potential years of life lost were estimated using the number of deaths and the population of Seville, aggregated by Basic Health Areas (BHA). BHA were divided in three levels according to the unemployment rate among men. The relative risks of total mortality and mortality by causes were estimated for men and women in each of these levels, using Poisson regression. The unemployment rate of each of the BHA was related to total mortality and to some of its causes. Differences in life expectancy of up to 7.9 years for men and 4.6 years for women were found among BHA. Concerning potential years of life lost, the areas with the highest mortality showed 4.1 times greater mortality in men and 2.6 times greater mortality in women than those with the lowest mortality. Total mortality increased with unemployment rate: the BHA with the highest unemployment rate showed a 15% increase in mortality in men and a 6% increase in that in women than those with the lowest unemployment rate. Among causes of mortality, AIDS showed the greatest inequalities in both men and women. From 1994 to 1998, Seville presented inequalities in total mortality and premature mortality, as well as in mortality by causes per BHA. Inequalities were present in men and women, although they were greater in men. There was a clear association between socioeconomic variables and mortality.


Pain as a symptom in depressive disorders and its relationship to platelet monoamine oxidase activity.
144 depressed in-patients were rated by means of the Comprehensive Psychopathological Rating Scale (CPRS) and platelet monoamine oxidase (MAO) was determined. 49 per cent of the patients were found to have pain as a symptom, and 21 per cent were found to have more severe pain. The patients with more severe pain were found to have lower platelet MAO activity than the patients without pain or with slight pain. As platelet MAO activity may reflect the turn-over in the serotinergic systems in CNS it is hypothesized that patients with depressive disorders with pain as a symptom may have more pronounced disturbances in the serotinergic systems than patients without pain as a symptom.


Tracheobronchial mucoepidermoid carcinoma in childhood and adolescence: case report and review of the literature.
In children and adolescents, primary neoplasms of the tracheobronchial tree and lungs are rare, with most tumors involving the respiratory system being metastatic, small, blue cell tumors of childhood. Of the primary pulmonary neoplasms, most are malignant with mucoepidermoid carcinoma representing about 10% of these malignant tumors. We present an 8-year-old Hispanic male with hemoptysis and several episodes of pneumonia which initially was thought to be infectious upon biopsy during bronchoscopy, but proved to be mucoepidermoid carcinoma of the tracheobronchial tree by microscopic examination during an open lung biopsy. This rare tumor is more common in adults than in children, and infrequently presents with hemoptysis. Mucoepidermoid tumors of the tracheobronchial tree carry a more favorable prognosis in children than adults. In the adult population, the overall mortality is slightly less than 30%. In contrast, of the 31 reported cases of tracheobronchial mucoepidermoid carcinoma in pediatrics, all children are free of tumor involvement with a mean follow-up period of 5.8 years (range, 0.7-21 years). Based upon the available clinical outcome and survival data, it would appear that tracheobronchial mucoepidermoid carcinoma may be successfully managed by surgical intervention alone in children and adolescents.


Yacon syrup reduces postprandial glycemic response to breakfast: A randomized, crossover, double-blind clinical trial.
Yacon is a root rich in fructooligosaccharides (FOS), which act as prebiotics. Numerous studies have shown promising results in the technological aspects of producing yacon syrup. However, uncertainties exist concerning whether yacon syrup can modulate postprandial glucose and lipid profiles. In order to assess the effect of yacon syrup on postprandial glucose, insulin and triglyceride (TG) responses, a randomized, crossover, double-blind clinical intervention with 40 women (20 normal weight and 20 grade I obese) was performed. Participants underwent two-arms of intervention with at least a one-week wash-out period between visits. On each intervention day, after 12 h of fasting, an aliquot of blood was collected. For intervention A, volunteers consumed breakfast +40 g of placebo, whereas for intervention B, participants consumed breakfast +40 g of yacon syrup (14 g of FOS). Blood samples were drawn at 15, 30, 45, 60, 90, and 120 min. Glucose and insulin concentrations were lowered after yacon syrup intake as compared to placebo at following times: 30 min for glucose and 15, 30 and 45 min for insulin. In conclusion, yacon syrup has a postprandial decreasing effect glucose and insulin concentrations in adult women. This effect was not evident for triglyceride concentration. Clinical trial registry: RBR-33wf46. Available in: http://www.ensaiosclinicos.gov.br/rg/RBR-33wf46/.


Heart rates of participants in wheelchair sports.
The relative stress of participation in wheelchair basketball, volleyball, tennis, and racquetball were determined by monitoring the heart rates of wheelchair athletes. Heart rates were recorded for 5 seconds every 30 seconds during monitoring sessions of 10 min or longer under game or practice conditions. Subjects were volunteer paraplegic athletes with lesions below T5 or with equivalent disability according to an international sport classification system. Average heart rates were 89 beats/min for tennis 'practice', 96 for racquetball 'practice' 107 for volleyball 'practice', 114 for volleyball 'game', 127 for tennis 'game', 129 for basketball 'practice', 135 for racquetball 'game', and 149 for basketball 'game' conditions. The percentage of time when heart rates were above 140 beats/min, followed the same pattern as the average heart rates and ranged from 0 to 62%.


Metabolic engineering of Clostridium ljungdahlii for the production of hexanol and butanol from CO2 and H2.
The replacement of fossil fuels and petrochemicals with sustainable alternatives is necessary to mitigate the effects of climate change and also to counteract diminishing fossil resources. Acetogenic microorganisms such as Clostridium spp. are promising sources of fuels and basic chemical precursors because they efficiently utilize CO and CO2 as carbon source. However the conversion into high titers of butanol and hexanol is challenging. Using a metabolic engineering approach we transferred a 17.9-kb gene cluster via conjugation, containing 13 genes from C. kluyveri and C. acetobutylicum for butanol and hexanol biosynthesis, into C. ljungdahlii. Plasmid-based expression resulted in 1075 mg L-1 butanol and 133 mg L-1 hexanol from fructose in complex medium, and 174 mg L-1 butanol and 15 mg L-1 hexanol from gaseous substrate (20% CO2 and 80% H2) in minimal medium. Product formation was increased by the genomic integration of the heterologous gene cluster. We confirmed the expression of all 13 enzymes by targeted proteomics and identified potential rate-limiting steps. Then, we removed the first-round selection marker using CRISPR/Cas9 and integrated an additional 7.8 kb gene cluster comprising 6 genes from C. carboxidivorans. This led to a significant increase in the hexanol titer (251 mg L-1) at the expense of butanol (158 mg L-1), when grown on CO2 and H2 in serum bottles. Fermentation of this strain at 2-L scale produced 109 mg L-1 butanol and 393 mg L-1 hexanol. We thus confirmed the function of the butanol/hexanol biosynthesis genes and achieved hexanol biosynthesis in the syngas-fermenting species C. ljungdahlii for the first time, reaching the levels produced naturally by C. carboxidivorans. The genomic integration strain produced hexanol without selection and is therefore suitable for continuous fermentation processes.


Sonochemical fabrication of inorganic nanoparticles for applications in catalysis.
Catalysis covers almost all the chemical reactions or processes aiming for many applications. Sonochemistry has emerged in designing and developing the synthesis of nano-structured materials, and the latest progress mainly focuses on the synthetic strategies, product properties as well as catalytic applications. This current review simply presents the sonochemical effects under ultrasound irradiation, roughly describes the ultrasound-synthesized inorganic nano-materials, and highlights the sonochemistry applications in the inorganics-based catalysis processes including reduction, oxidation, degradation, polymerization, etc. Or all in all, the review hopes to provide an integrated understanding of sonochemistry, emphasize the great significance of ultrasound-assisted synthesis in structured materials as a unique strategy, and broaden the updated applications of ultrasound irradiation in the catalysis fields.


The triad of pneumonitis, pleuritis, and pericarditis in juvenile rheumatoid arthritis.
There are few reports of pleuroparenchymal and pericardial involvement secondary to juvenile rheumatoid arthritis (JRA) in the literature. This article presents two such cases and gathers scattered information about this combination previously reported by few others. We wish to emphasize that the combination of pericardial and pleuropulmonary involvement in a youngster may be the only presenting clinical manifestations of rheumatoid arthritis, whereas in others, it may be associated with arthritic symptoms at the same time.


LncRNA HABON promoted liver cancer cells survival under hypoxia by inhibiting mPTP opening.
Hypoxia is an important feature of the tumor microenvironment (TME). While targeting hypoxic TME is emerging as a potential strategy for treating solid tumors including liver cancer. Recent studies have shown that hypoxia can regulate tumor adaptation to hypoxic TME through long non-coding RNA (lncRNA). In the previous study, we identify a novel hypoxia-activated lncRNA and termed it as HABON. Here, we demonstrated that knockdown of HABON caused necroptosis of tumor tissue and inhibited the subcutaneous tumor growth of SMMC-7721 cells in nude mice. Moreover, knockdown of HABON increased RIPK1 and MLKL expression as well as their phosphorylation level in SMMC-7721 and Huh7 liver cancer cells. Meanwhile, Necrostatin-1 and GSK872 could restore cell death of liver cancer cells caused by knockdown of HABON under hypoxia. The above results suggested that HABON could inhibit hypoxia-induced necroptosis of liver cancer cells. Mechanically, knockdown of HABON in liver cancer cells aggravated mitochondrial dysfunction caused by hypoxia. Furthermore, the RNA pull-down combined with mass spectrometry analysis identified HABON can interact with mitochondria-related protein VDAC1 and the RNA immunoprecipitation (RIP) analysis proved the interaction. In addition, we proved that VDAC1 mediated the mitochondrial permeability transition pore (mPTP) opening, mitochondrial dysfunction, as well as necroptosis caused by knockdown of HABON. Overall, our work demonstrates HABON can reduce hypoxia-induced necroptosis of liver cancer cells and suggests that inhibition of HABON in the hypoxic TME is a potential therapeutic strategy for treating liver cancer.


Infrared fluorescence videomicroscopy with indocyanine green (Cardiogreen).
After intravenous injection indocyanine green binds almost completely to the plasma proteins and may be detected in the skin capillaries by an infrared sensitive fluorescence videomicroscopy system. The technique opens a way to measure full capillary diameter and dimension of the plasma layer in an almost atraumatic way.


The effect of parental expressed emotion on glycaemic control in children with Type 1 diabetes. Parental expressed emotion and glycaemic control in children.
To measure expressed emotion (EE) in parents of young children with diabetes and to examine the relation between EE and glycaemic control in children with Type 1 diabetes in a longitudinal study over 24 months. We hypothesised that good glycaemic control, as measured by low glycated haemoglobin levels, would be predicted by high parental emotional over-involvement, low frequency of critical comments and absence of hostility. We predicted that these effects would be stronger in maternal than paternal scores. Forty-seven children attending a Paediatric Diabetes Clinic and their parents were studied over 24 months. Glycated haemoglobin was measured on three occasions, at the start of the study period, 12 and 24 months later. At 12 months, parental EE was measured using an adapted version of the Camberwell Family Interview, and child emotional and behavioural problems were measured using the parent version of the Child Behavior Checklist. Multiple regression models were used to test the hypotheses. Forty-three maternal and 33 paternal interviews of adequate quality for analysis were obtained. Paternal hostility was found to be associated with elevated glycated haemoglobin measured 12 months before interview and 12 months after interview, accounting for 22% and 29% of the variation in glycated haemoglobin respectively. We did not find that parental emotional over-involvement or criticism predicted glycaemic control. Presence of hostility was important, but in contrast to our hypothesis, this was paternal rather than maternal hostility. We suggest that (i) relatively absent, rejecting fathers play little role in diabetes management and children perceive this negatively, or (ii) mothers who are unsupported by fathers cannot in turn support their children in diabetes care.


A genetic marker of human IgE heavy chains, Em(1).
A monoclonal anti-IgE antibody was obtained that reacted with some IgE myeloma proteins and with all but a few normal sera. Family studies proved that a genetic marker of IgE had been detected. This allotype, called Em(1), segregates in association with certain Gm-Am haplotypes. The available quantitative evidence warrants the conclusion that human IgE has genetic variants, but no subclasses. Samples from various populations of five continents, representative for the respective prevalent Gm-Am haplotypes, were tested for Em(1). Em(1) was absent mainly in haplotypes carrying A2m(2) and G2m(n). These closely linked genes are located in a chromosomal region that comprises the gamma 2-gamma 4-epsilon-alpha 2 CH genes. A hypothesis for the generation of Em(1) is given.


Eyelid Margin and Meibomian Gland Characteristics and Symptoms in Lens Wearers.
To describe the lid margin characteristics of contact lens wearers and relate them to comfort during lens wear. Three study sites enrolled habitual contact lens wearers. Subjects completed the Comfort domain of the Contact Lens User Experience (CLUE) questionnaire, and each eye was graded for the presence of mucocutaneous junction (MCJ) displacement, lid margin irregularity, and lid margin vascularity. Examiners counted the number of meibomian gland (MG) orifices in the central centimeter of the lower eyelid and the number of those that showed pouting/plugging and vascular invasion. MG expressibility was graded according to the Shimazaki schema. Subjects were grouped based on presence/absence of each characteristic, total number of orifices (≥5 vs. <5), and expressibility (grade 0 vs. >0). Descriptive statistics are reported. A linear model was used to assess the fixed effect of each characteristic on combined CLUE score and each CLUE statement, if the effect on combined CLUE score showed p < 0.10. The study included 203 subjects (67.5% female) with mean age (±SD) of 30.3 ± 9.6 years. The most commonly observed characteristics were orifice pouting/plugging, compromised MG expressibility, and lid margin vascularity (35.0, 30.3, and 20.4%, respectively). MCJ displacement and MG expressibility had an effect on the combined CLUE score such that individual CLUE statements were analyzed (p = 0.01 and p = 0.06, respectively). MCJ displacement had an effect on comfort upon insertion (p = 0.01), comfort after 5 minutes (p = 0.03), end-of-day comfort (p = 0.01), and ability to maintain ocular moisture (p = 0.030). MG expressibility had a significant effect on general comfort (p = 0.01), comfort throughout the day (p = 0.02), and the ability to maintain ocular moisture (p = 0.02). MCJ displacement and MG expressibility have an effect on contact lens comfort.


[The effect of chlorine diffusion potential on electrophoretic mobility and erythrocyte sedimentation in diluted suspensions].
Electrophoretic activity of human erythrocytes in isotonic medium with reduced NaCl content does not depend on the outer electric field strength when pH decreases from 7.3 to 5.5. At pH approximately equal to 5.3 the measured values of electrophoretic mobility drop with decrease of the outer electric field strength starting at 600-700 V/m. Simultaneously signs of the solitary settlement of erythrocytes diluted suspensions are disturbed. Estimated values of the chlorine diffusion potential in these conditions exceed the value 70-80 mV, at which the erythrocyte membrane permeability changes. It is suggested that the observed dependency of electrophoretic mobility on the field strength is caused by ion flows through the erythrocyte membrane leading to diffusion non-equilibrium in the electrolyte layer close to the membrane.


Contact finite element stress analysis of porous ingrowth acetabular cup implantation, ingrowth, and loosening.
Two-dimensional linear and contact finite element analyses were conducted of total hip arthroplasty using metal-backed, porous ingrowth acetabular components. The stress transmission characteristics from the component to the surrounding bone were given special attention. Resultant loads of 20 and 40 degrees medial of vertical were studied, and the influence of adding a metal flange to the rim of the cup was evaluated. The results indicated that when a conventional metal-backed component (without a flange) is initially implanted and subjected to normal loading, these components may experience distraction between the component and the surrounding bone at inferior sites. Compressive stresses in the superior dome cancellous bone, however, will be substantial. If complete porous ingrowth is achieved, the superior dome compressive stresses will be reduced and substantial shear stresses created. In addition, high local bone stresses were found at the component rim. If bone ingrowth is achieved only in specific locations, stress transmission will be dictated by those locations and may differ markedly from the case of complete bone ingrowth. In the event that no porous ingrowth is achieved and a fibrous layer forms around the component, the interface stresses will be similar to those calculated for the natural hip. The addition of a flange to the rim of the cup will reduce the magnitude of the radial stresses transmitted to the cancellous bone superiorly and medially by directly transferring some of the load to the lateral wall of the pelvis. The flange will also help to relieve the high local stresses that are found at the component rim.


Semliki Forest virus vectors for overexpression of 101 G protein-coupled receptors in mammalian host cells.
Semliki Forest virus vectors were applied for the evaluation of 101 G protein-coupled receptors in three mammalian cell lines. Western blotting demonstrated that 95 of the 101 tested GPCRs showed positive signals. A large number of the GPCRs were expressed at high levels suggesting receptor yields in the range of 1 mg/L or higher, suitable for structural biology applications. Specific binding assays on a selected number of GPCRs were carried out to compare the correlation between total and functional protein expression. Ligands and additives supplemented to the cell culture medium were evaluated for expression enhancement. Selected GPCRs were also expressed from mutant SFV vectors providing enhanced protein expression and reduced host cell toxicity in attempts to further improve receptor yields.


Multisensory integration: how visual experience shapes spatial perception.
The localisation of auditory and tactile events is strongly affected by visual information, reflecting the dominant role of vision in spatial perception. New research suggests that early visual experience is critical for the establishment of such multisensory links.


Increase of ABCG2/BCRP+ side population stem cells in myocardium after ventricular unloading.
A significant decrease in mean cardiomyocyte DNA content and increased numbers of diploid cardiomyocytes after unloading has been demonstrated, suggesting a numerical increase of cardiomyocytes. Despite a thorough search in that study, no mitoses explaining a potential net increase of cardiomyocytes has been observed. The heart harbors several stem cell populations, including c-kit (CD117)(+) stem cells and side population cells (SPC), which may proliferate after unloading and thus contribute to the generation of diploid cardiomyocytes. In this study we sought to determine, whether there is an increase of ABCG2(+) SPC and CD117(+) stem cells after unloading. In paired myocardial samples (prior to and after LVAD), the number of cells with immunoexpression of ABCG2, c-kit/CD117 and MEF-2 was assessed by immunohistochemistry. Their number was morphometrically determined and these data were correlated with the mean cardiomyocyte DNA content. A significant increase of SPC and cells with coexpression of c-kit and MEF-2 after unloading was observed from 0.00013% in CHF to 0.0011%, and 0.013% to 0.035%, respectively after unloading (p = 0.001). A significant positive correlation between both SPC and cells with coexpression of c-kit and MEF-2 expression was observed (p = 0.007 and 0.01). No correlation was found between the number of SPC and the mean cardiomyocyte DNA content. SPC are increased significantly in the myocardium after ventricular unloading, suggesting a role for stem cell proliferation during "reverse cardiac remodeling." These cells might proliferate and commit to different cell lineages, such as cardiomyocytes or endothelium, and thus ameliorate cardiac function.


Fucoidan from sea cucumber Holothuria polii: Structural elucidation and stimulation of hematopoietic activity.
The structural elucidation of polysaccharides is essential for understanding their structure-bioactivity relationship and related drug development. In this study, fucoidan (Fuchp) was extracted and purified from sea cucumber Holothuria polii. Its sulfate content was 39.5 ± 1.4%, and the "weight-average" molecular mass was 103.1 ± 2.8 kDa. The primary structure of Fuchp was clarified using a combination of acid degradation, tandem mass spectrometry, and nuclear magnetic resonance spectroscopy analysis. As a result, Fuchp was found to be composed of a tetrafucose repeating unit [→3-α-l-Fucp-1 → 3-α-l-Fucp2(OSO3-)-1 → 3-α-l-Fucp2(OSO3-)-1 → 3-α-l-Fucp2,4(OSO3-)-1→]. The stimulating hematopoiesis was further evaluated in a mouse model induced by cyclophosphamide. Based on these findings, intraperitoneally administered Fuchp may accelerate the recovery of white blood cells and neutrophils, in which its activity exceeded that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Meanwhile, in the background of cyclophosphamide-induced immunosuppression, treatment with Fuchp reduces platelet aggregation caused by CTX, so it might have the effect of reducing the risk of thrombosis. Therefore, Fuchp can be exploited as potentially promising stimulator of hematopoiesis in the future.


Human tissue distribution of platinum after cis-diamminedichloroplatinum.
Using X-ray fluorescence spectrometry, platinum concentrations were determined in autopsy tissue samples from 12 patients who had received cis-diamminedichloroplatinum (DDP) 20-120 mg/m2 up to 6 months antemortem. Tissue platinum concentrations were highest in liver (0.5-3.7 micrograms/g wet weight), prostate (1.6-3.6 micrograms/g), and kidney (0.4-2.9 micrograms/g), somewhat lower in bladder, muscle, testicle, pancreas, and spleen, and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum, Platinum concentrations in tumors were generally somewhat lower than the concentration in the organ in which the tumor was located, with the exception of intracerebral tumors. Different metastatic sites in the same patient had substantially different platinum concentrations and hepatic metastases had the highest concentrations. Intra-arterial administration of drug may augment tissue concentrations of platinum. In a patient undergoing therapeutic abortion 4 days after treatment, the platinum concentration was 0.5 micrograms/g in the placenta and 0.3 micrograms/g in the fetus. The data suggest that for in vitro sensitivity testing, DDP concentrations of less than or equal to 7 micrograms/ml should be used.


Progress report on phase I/II clinical trial of Ad-OC-TK plus VAL therapy for metastatic or locally recurrent prostate cancer: Initial experience at Kobe University.
There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.


HTERT mRNA partially regulates telomerase activity in gastric adenocarcinoma and adjacent normal gastric mucosa.
The extent to which human telomerase reverse transcriptase (hTERT) mRNA and its splice variants control telomerase activity in human cancers is controversial. Telomerase and hTERT mRNA were assessed quantitatively in paired samples of gastric adenocarcinoma and adjacent normal tissue. Splice variants within the hTERT reverse transcriptase domain (alpha, beta, alphabeta) were detected by RT-PCR. In gastric adenocarcinoma, compared to normal tissue, median telomerase activity increased significantly (from 0 total product generated [tpg; 95% confidence interval CI, 0-2.3] to 16.1 tpg [95% CI, 3.7-97]; P = 0.008) and median hTERT mRNA levels also increased (from 2.21 [95% CI, 1.40-4.62] to 7.08 [95% CI, 3.26-10.8]; P = 0.0054). hTERT mRNA and telomerase activity correlated in normal gastric mucosa (r = 0.819, P = 0.0002). Alpha, beta, and alphabeta deletions were similar in both groups. We conclude that hTERT mRNA partially regulates telomerase activity in normal gastric mucosa and gastric adenocarcinoma. In contrast, hTERT mRNA splicing is not involved in the regulation of enzyme activity.


The therapeutic use of humor for psychiatric disturbances of adolescents and adults.
The use of humor in psychiatric care and treatment is examined within a life-span-development context, comparing its utility in late adolescence with that in early adulthood. The literature of the past two decades, based on careful experimental research as well as on more subjective clinical experience, tend to support the following conclusions: A well-developed sense of humor provides a beneficial ingredient to the patient's coping or adjustive ability. The salutary physiological effects of laughter are the same for adolescents and adults. In terms of psychosocial factors, individual rather than developmental stage differences in the patient's personality, psychopathology and humor preference will alter the effectiveness of humor application. According to a cognitive-behavioral analysis, the mechanism by which positive emotions (including laughter) operate to reduce or eliminate the undesirable negative emotions resides in the interplay of the physiological and psychological processes involved in the stress reaction and its management. Finally, to be optimally effective the psychiatrist should undertake formal training in the use of humor techniques comparable to the traditional training in the usual assessment and therapeutic procedures.