Consistent patterns of trophic niche specialization in host populations infected with a non-native copepod parasite.
Populations of generalist species often comprise of smaller sub-sets of relatively specialized individuals whose niches comprise small sub-sets of the overall population niche. Here, the role of parasite infections in trophic niche specialization was tested using five wild fish populations infected with the non-native parasite Ergasilus briani, a copepod parasite with a direct lifecycle that infects the gill tissues of fish hosts. Infected and uninfected fishes were sampled from the same habitats during sampling events. Prevalence in the host populations ranged between 16 and 67%, with parasite abundances of up to 66 parasites per fish. Although pathological impacts included hyperplasia and localized haemorrhaging of gill tissues, there were no significant differences in the length, weight and condition of infected and uninfected fishes. Stable isotope analyses (δ 13C, δ 15N) revealed that the trophic niche of infected fishes, measured as standard ellipse area (i.e. the isotopic niche), was consistently and significantly smaller compared with uninfected conspecifics. These niches of infected fishes always sat within that of uninfected fish, suggesting trophic specialization in hosts. These results suggested trophic specialization is a potentially important non-lethal consequence of parasite infection that results from impaired functional traits of the host.


Odynophagia/dysphagia in AIDS.
Odynophagia and dysphagia are common symptoms of treatable disorders of the esophagus in patients with AIDS. Esophageal candidiasis is the most frequent cause of these symptoms. In patients with AIDS or AIDS-related complex, thrush in combination with odynophagia or dysphagia almost certainly indicates the presence of esophageal candidiasis. Other causes of swallowing disorders in AIDS include opportunistic infection of the esophagus with herpes simplex virus, cytomegalovirus, or, rarely, cryptosporidiosis. Recently, ulcerative esophagitis in AIDS associated with unidentified viral-like particles has been described. Infrequently, Kaposi's sarcoma or lymphoma may involve the posterior pharynx or esophagus, respectively. Because Candida esophagitis is so frequently the cause of odynophagia and/or dysphagia in AIDS, it is suggested that in most cases, a therapeutic trial with an antifungal agent, like ketoconazole, may be appropriate before radiologic or endoscopic examination. Further investigation can be reserved for patients who do not respond to this trial or who have clinical evidence suggesting another esophageal disorder. Herpes simplex and cytomegalovirus esophagitis can be treated with antiviral agents, such as acyclovir and ganciclovir, respectively. Maintenance therapy with antifungal agents to prevent recurrent esophageal candidiasis may be beneficial, but the efficacy and cost effectiveness of this approach remain to be determined. Because of the increasing numbers of patients with AIDS, frequency of esophageal disorders, such as candidiasis, in these patients and the morbidity of these disorders, an expansion of clinical research efforts to determine effective treatment and prophylaxis for these disorders is warranted.


[Echographic evaluation of kidney transplant "en bloc"].
Kidney transplants from infant donors are associated in the literature with poor results as regards both functionality and the survival of the transplant. Hence the increasing frequency, for kidneys obtained from donors under 5 years of age, of a surgical technique defined as "en bloc", involving the transplant of both kidneys into a single receiver and using the donor aorta and vena cava for vascular anastomosis. This technique seems to provide results comparable with those obtained using adult organs. Ultrasound and Doppler investigations are routinely performed in patients undergoing such a transplant. This study presents ultrasound and Doppler images of "en bloc" transplants, with particular reference to one case of pseudoaneurysm of the donor aorta and one of stenosis of the renal artery, revealed by Echo-Color-Doppler. The importance of ultrasound in this kind of transplant is emphasized, as it enables post-operative monitoring of the physiological growth in volume of the two transplanted infant kidneys.


Infective endocarditis in adult patients with congenital heart disease.
Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE), but data about characterization and prognosis of IE in CHD patients is scarce. The ESC-EORP-EURO-ENDO study is a prospective international study in IE patients (n = 3111). In this pre-specified analysis, adult CHD patients (n = 365, 11.7%) are described and compared with patients without CHD (n = 2746) in terms of baseline characteristics and mortality. CHD patients (73% men, age 44.8 ± 16.6 years) were younger and had fewer comorbidities. Of the CHD patients, 14% had a dental procedure before hospitalization versus 7% in non-CHD patients (p < 0.001) and more often had positive blood cultures for Streptococcus viridans (16.4% vs 8.8%, p < 0.001). As in non-CHD patients, IE most often affected the left-sided valves. For CHD patients, in-hospital mortality was 9.0% vs 18.1% in non-CHD patients (p < 0.001), and also, during the entire follow-up of 700 days, survival was more favorable (log-rank p < 0.0001), even after adjustment for age, gender and major comorbidities (Hazard Ratio (HR) 0.68; 95%CI 0.50-0.92). Within the CHD population, multivariable Cox regression revealed the following effects (HR and [95% CI]) on mortality: fistula (HR 6.97 [3.36-14.47]), cerebral embolus (HR 4.64 [2.08-10.35]), renal insufficiency (HR 3.44 [1.48-8.02]), Staphylococcus aureus as causative agent (HR 2.06 [1.11-3.81]) and failure to undertake surgery when indicated (HR 5.93 [3.15-11.18]). CHD patients with IE have a better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE warrants further studies about the current use, need and efficacy of antibiotic prophylaxis in CHD patients.


Evaluation of the sensitivity of commercially available digoxin radioimmunoassay kits.
We have evaluated the technical minimum detection limits of 12 different commercially available kits and the practical minimum detection limits of 11 kits used for the determination of the serum digoxin level by radioimmunoassay. The poor technical ability of many of the kits to distinguish between digoxin levels of 0.1 ng/ml intervals between 0 and 0.5 ng/ml and, additionally, the detection of a digoxin level up to 0.3 ng/ml with some of the kits in glycoside-free sera impose a practical working minimum detection limit of 0.5 ng/ml for the majority of these kits. We, therefore, recommend caution with interpreting or evaluating serum digoxin levels below 0.5 ng/ml.


[Expression and relocation of B23 in the process of rat liver cell hyperplasia and liver regeneration].
To study the B23 expression and relocation in the process of liver regeneration at different time periods after partial hepatectomy (PH) on healthy rats, and to study the feasibility of using B23 as a proliferation marker. Eighteen rats underwent partial hepatectomy (PH). The regenerative liver tissues were obtained at day 1, 2, 3, 4,and 7 after PH. The expression of B23 in hepatocytes of the regenerative tissues was measured using monoclonal antibody against nucleophosmin/B23 by Western blot and immunohistochemistry. The expression of proliferate cell nuclear antigen (PCNA) in these cells were measured using monoclonal antibody against PCNA by both methods for comparison with that of B23. Expression of B23 in the steady state of liver cells before PH was hardly detected by both methods. The increased expression of B23 in the regenerative liver cells was quantitatively changed like a parabolic curve at day 1 to days 7 after PH, with the peak expression of B23 at day 3 after PH. This quantitative variation of B23 expression was similar to that of PCNA expression. The variation of location of B23 in the regenerative liver cells was observed from nucleolus (G1-S phase) to nucleoplasm (S-G2 phase) and to cytoplasm and mitotic chromosome (M phase). B23 expression is quantitatively increased and moves in location in the process of liver regeneration after PH. B23 may be regarded as a proliferation marker in liver regeneration and liver cell hyperplasia.


Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.
The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.


Native herbivores and environmental heterogeneity as mediators of an exotic grass invasion.
Given that many exotic plant species throughout the world are having large ecological and economic effects, it is vital to understand the forces that mediate their success in novel landscapes. Both native herbivores and recipient ecosystems can have substantial effects on the performance of exotic plant species, and may interact with each other or vary in their effects over time. Unfortunately, few studies have evaluated the importance of these kinds of context-dependent effects. Here, we use a 17-year-old exclosure experiment stratified across a coastal grassland in northern California to address the relative importance of a reintroduced mammalian herbivore, tule elk (Cervus canadensis nannodes), and environmental heterogeneity in mediating the growth, abundance, and recruitment of a problematic grass invader, Holcus lanatus. We found that elk reduced Holcus abundance, aboveground biomass, percent cover, frequency, and seedling recruitment, but that these effects often varied among habitat types, with effects being greater in open grasslands than shrub-dominated grasslands. The performance of Holcus populations also varied significantly among habitat types, with the invader usually having the greatest success in Baccharis-dominated grasslands. Our results suggest that environmental heterogeneity had much greater influence on Holcus success than elk, and that these effects were due largely to soil pH and moisture. The negative effects of elk on Holcus appeared after 4 years and did not intensify after an additional 13 years. Furthermore, despite their negative effects, these prominent herbivores did not prevent the spread of Holcus into previously uninvaded areas. Our research highlights the importance of assessing the individual and interactive effects of native herbivores and environmental heterogeneity on the success of invasive, exotic plant species. It emphasizes the reality that the negative effects of herbivores on exotic plant species will often vary across heterogeneous landscapes and may be insufficient to prevent the expansion of these invaders.


Estimation of voxel-wise dynamic cerebrovascular reactivity curves from resting-state fMRI data.
In this work, we investigate the linear dynamic interactions between fluctuations in arterial CO2 that occur during normal breathing, and the BOLD fMRI signal. We cast this problem within a systems-theoretic framework, where we employ functional expansions for the estimation of the impulse responses in large regions of interest, as well as in individual voxels. We also implement classification schemes in order to identify different brain regions with similar cerebrovascular reactivity characteristics. Our results reveal that it is feasible to obtain reliable estimates of cerebrovascular reactivity curves from resting-state data and that these curves exhibit considerable variability across different brain regions that may be related to the underlying anatomy.


Snail maintains metastatic potential, cancer stem-like properties, and chemoresistance in mesenchymal mouse breast cancer TUBO‑P2J cells.
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials. In addition, Snail silencing also reduced resistance to chemotherapy drugs and cancer stem-like properties, such as CD44 expression, aldehyde dehydrogenase (ALDH) activity, colony formation, and in vivo tumour formation and growth. However, radioresistance was not decreased by silencing Snail. Collectively, this study suggested that Snail is a main regulator of the maintenance of malignancy potentials and is a good target to prevent cancer metastasis and to increase chemotherapy susceptibility.


Phosphorylation decreases trypsin activation and apolipoprotein al binding to glycosylphosphatidylinositol-specific phospholipase D.
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is present in plasma as an apolipoprotein and as a cell-associated lipase. GPI-PLD mRNA levels are regulated, but it is unclear if posttranslational mechanisms also regulate GPI-PLD function. We examined the effect of protein kinase A phosphorylation on human serum GPI-PLD activity, trypsin activation, and apolipoprotein AI binding. Protein kinase A phosphorylation did not activate GPI-PLD activity in vitro, nor did phosphorylated GPI-PLD cleave a GPI-anchored protein from intact porcine erythrocytes. Trypsin cleaves the C-terminal beta propeller of purified human serum GPI-PLD to generate three immunodetectable fragments (75, 28, and 18 kDa) in association with a 12-fold increase in enzyme activity. After phosphorylation, the amounts of 28- and 18-kDa fragments were markedly decreased with trypsin treatment, and activity was only increased five-fold. Phosphorylation also inhibits binding of GPI-PLD to apolipoprotein AI. These data are the first demonstrating that phosphorylation may regulate GPI-PLD interaction with other proteins.


Membranous glomerulonephritis (MGN) in transplanted kidneys: morphologic investigation on 256 renal allografts.
Twenty-two cases of membraneous glomerulonephritis (MGN) were identified among 256 bioptically investigated transplanted patients. MGN was defined as de novo in 15 patients and recurrent in three. The type of MGN could not be ascertained with certainty in the other four. Several morphologic features unusual for the idiopathic form of MGN were found. Most cases disclosed focal segmental distribution of subepithelial deposits and showed the contemporaneous presence of different stages of the disease according to Ehrenreich and Churg classification. In addition mild-to-moderate mesangial cell proliferation was found in about one third of de novo MGN biopsies. Endocapillary hypercellularity was observed in 14 specimens and held to be due to an excess of mononuclear blood cells, related to a concomitant episode of rejection. Chronic transplant glomerulopathy was found in 47% of patients with de novo MGN and in 66% of those with recurrent MGN, being more frequently observed in specimens with diffuse distribution of deposits. Repeated biopsies showed progression of the stage and extension of deposits to a large number of capillary loops in four out of six patients. De novo MGN was documented 1 to 54 mo (mean value 20.2 mo) after transplantation, and the recurrence was observed after 12, 15, and 42 mo. All but two patients (who were anuric) complained of proteinuria, which was in the nephrotic range in 12. Apart from the significantly higher frequency in de novo MGN patients of DR4 antigen, whose significance must in any case be re-evaluated in a larger series, none of the factors so far suggested to be linked to the onset of de novo MGN has found further support in our study. On the contrary, relevance in favoring the appearance and the evolution of MGN has to be attributed to transplant glomerulopathy, which, moreover, seems to be more important than MGN itself in causing the unfavorable outcome of the graft.


Diagnostic value of expired gas analysis in heart failure with preserved ejection fraction.
Cardiopulmonary exercise testing (CPET) may potentially differentiate heart failure (HF) with preserved ejection fraction (HFpEF) from noncardiac causes of dyspnea (NCD). While contemporary guidelines for HF recommend using CPET for identifying causes of unexplained dyspnea, data supporting this practice are limited. This study aimed to determine the diagnostic value of expired gas analysis to distinguish HFpEF from NCD. Exercise stress echocardiography with simultaneous expired gas analysis was performed in patients with HFpEF (n = 116) and those with NCD (n = 112). Participants without dyspnea symptoms were also enrolled as controls (n = 26). Exercise capacity was impaired in patients with HFpEF than in controls and those with NCD, evidenced by lower oxygen consumption (VO2), but there was a substantial overlap between HFpEF and NCD. Receiver operating characteristic curve analyses showed modest diagnostic abilities of expired gas analysis data in differentiating individuals with HFpEF from the controls; however, none of these variables clearly differentiated between HFpEF and NCD (all areas under the curve < 0.61). Expired gas analysis provided objective assessments of exercise capacity; however, its diagnostic value in identifying HFpEF among patients with symptoms of exertional dyspnea was modest.


RNase H2-Dependent Polymerase Chain Reaction and Elimination of Confounders in Sample Collection, Storage, and Analysis Strengthen Evidence That microRNAs in Bovine Milk Are Bioavailable in Humans.
Evidence suggests that dietary microRNAs (miRs) are bioavailable and regulate gene expression across species boundaries. Concerns were raised that the detection of dietary miRs in plasma might have been due to sample contamination or lack of assay specificity. Objectives: The objectives of this study were to assess potential confounders of plasma miR analysis and to detect miRs from bovine milk in human plasma. Potential confounders of plasma miR analysis (circadian rhythm, sample collection and storage, calibration, and erythrocyte hemolysis) were assessed by quantitative reverse transcriptase polymerase chain reaction (PCR) by using blood from healthy adults (7 men, 6 women; aged 23-57 y). Bovine miRs were analyzed by RNase H2-dependent PCR (rhPCR) in plasma collected from a subcohort of 11 participants before and 6 h after consumption of 1.0 L of 1%-fat bovine milk. The use of heparin tubes for blood collection resulted in a complete loss of miRs. Circadian variations did not affect the concentrations of 8 select miRs. Erythrocyte hemolysis caused artifacts for some miRs if plasma absorbance at 414 nm was >0.300. The stability of plasma miRs depended greatly on the matrix in which the miRs were stored and whether the plasma was frozen before analysis. Purified miR-16, miR-200c, and cel-miR-39 were stable for ≤24 h at room temperature, whereas losses equaled ≤80% if plasma was frozen, thawed, and stored at room temperature for as little as 4 h. rhPCR distinguished between bovine and human miRs with small variations in the nucleotide sequence; plasma concentrations of Bos taurus (bta)-miR-21-5p and bta-miR-30a-5p were >100% higher 6 h after milk consumption than before milk consumption. Confounders in plasma miR analysis include the use of heparin tubes, erythrocyte hemolysis, and storage of thawed plasma at room temperature. rhPCR is a useful tool to detect dietary miRs.


Asymmetric keratoconus attributed to eye rubbing.
To report a series of cases with asymmetric keratoconus attributed to eye rubbing, discuss its pathogenesis, and review the literature. Case reports and literature review. A careful history obtained from 5 patients with asymmetric keratoconus revealed habitual eye rubbing of the more severely affected eye. Trauma, such as occurs with habitual eye rubbing, plays a role in the pathogenesis of keratoconus.


Impact of the coronavirus pandemic on maxillofacial trauma: A retrospective study in southern Spain.
The coronavirus pandemic has impacted health systems worldwide, with Spain being one of the most affected countries. However, little is known about the extent to which the effects of staying home, social distancing, and quarantine measures have influenced the epidemiology of patients with maxillofacial trauma. The aim of this study was to analyze the impact of the coronavirus pandemic on the incidence, demographic patterns, and characteristics of maxillofacial fractures in the largest hospital in southern Spain. Data from patients who underwent surgery for maxillofacial fractures during the first year of the pandemic between 16 March 2020 and 14 March 2021 (pandemic group) were retrospectively compared with a control group during the equivalent period of the previous year (pre-pandemic group). The incidence was compared by weeks and by lockdown periods of the population. Demographic information, aetioloy, fracture characteristics, treatment performed, and days of preoperative stay were evaluated. Descriptive and bivariate statistics were calculated (p<0.05). During the first year of the pandemic, there was a 35.2% reduction in maxillofacial fractures (n=59) compared to the pre-pandemic year (n=91, p=0.040). A significant drop was detected during the total home lockdown period of the population (p=0.028). In the pandemic group, there was a reduction in fractures due to interpersonal aggressions, an increase in panfacial fractures, a significant increase in other non-facial injuries associated with polytrauma (p=0.037), a higher number of open reduction procedures with internal fixation, and a significantly longer mean preoperative stay (p=0.016). The first pandemic year was associated with a decline in the frequency of maxillofacial trauma and a change in the pattern and characteristics of fractures. Inter-annual epidemiological knowledge of maxillofacial fractures may be useful for more efficient planning of resource allocation and surgical practice strategy during future coronavirus outbreaks and population lockdowns.


Radiation damage to histone H2A by the primary aqueous radicals.
Histone H2A has been examined for radiation-induced changes in structure and in amino acid composition. The effects of the individual radical intermediates--the hydroxyl radical, solvated electron, and superoxide radical--have been determined by irradiating in dilute aqueous solution under controlled environmental conditions. Amino acid analysis of irradiated histone H2A shows a selective attack on a few residues; only the aromatic residues, phenylalanine and tyrosine, and the heterocyclic residue, histidine, are significantly decreased. A significant increase in aspartic acid is also observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the hydroxyl radical is the effective radical for promoting changes in protein structure.


Transcutaneous electrical nerve stimulation in the management of acute postoperative pain.
Twenty patients undergoing decompressive lumbar laminectomy were randomly allocated, in a double-blind manner, to receive active or inactive transcutaneous electrical nerve stimulation (TENS) as part of the management of their postoperative pain. All patients received the same non-narcotic general anaesthetic. The efficacy of the TENS was assessed by using a patient-controlled analgesia system (PRODAC) which delivered morphine i.v. This system recorded the number of demands for analgesia and the total dose administered in the first 24 h. In addition, plasma morphine concentrations were measured hourly for the first 6 h and again at 24 h. There was no statistical difference between the two groups in the number of patient demands for analgesia, morphine dose or plasma morphine concentration. TENS offered no advantage over a placebo in the management of acute postoperative pain in these patients.


[Changes of pathogenic bacteria in pediatric patients of septicemia and drug resistance there of in Zhejiang Children's Hospital 1991 approximately 2000].
To investigate the changes of pathogenic bacteria detected from the blood culture of pediatric patients with septicemia in the past 10 years, and to observe the drug resistance thereof in the past two years. The blood samples of 4 425 pediatric patients aged 0 approximately 14 with the diagnosis of septicemia 1991 approximately 2000 in Zhejiang Children's Hospital were cultured in broth (1991 approximately 1996) or VITA AER blood culture apparatus (1997 approximately 2000). Analytic Product Inc. (API ) system and KB paper strip method and VITEK automicroscan were used to identify the species and conduct drug resistance test. The results were interpreted according to the guideline of National Committee for Clinical Laboratory Standards. In the past 10 years, Gram-positive bacteria remained the more frequent pathogens than Gram-negative bacteria in pediatric patients with septicemia. The proportion of coagulase-negative staphylococcus (CNS) had been increasing and reached 69% in 2000. The proportions of Staphylococcus aureus and Escherichia coli decreased from 35.4% and 18.2% in 1991 to 5.3% and 1.5% in 2000. In the past two years, the drug resistance rate of staphylococci against penicillin and erythromycin were more than 90% and 70% respectively. The oxacillin resistance rate of CNS was 60.3%, significantly higher than that of Staphylococcus aureus (10.3%). No strain of Staphylococcus and Enterococcus resistant to vancomycin was found. Escherichia coli and Psudomonas aeruginosa and other species of Enterobacteriae were sensitive to imipenem/cilastin sodium, whereas the resistance rate of them to ampicillin and first generation cephalosporins was more than 50%. (1) Gram-positive bacteria are the predominant pathogens of pediatric patients with septicemia, with the species of Staphylococcus ranking first among which CNS is the main pathogen for infants and Staphylococcus aureus is the main pathogen for school children. (2) Escherichia coli is the most frequently found pathogenic Gram-negative bacterium in infants with septicemia whereas Salmonella in school children. (3) Drug resistance of isolated pathogenic bacteria in department of pediatrics is a serious problem. Monitoring the change of pathogen and the trends of antimicrobial resistance is very important in guiding therapy.


Psoriatic arthritis: genetics and pathogenesis.
Psoriatic arthritis is a complex disease affecting primarily peripheral and axial joints and entheses together with the skin. The pathogenesis is characterized by a genetic background and by inflammatory mechanisms which may be triggered by environmental factors. Several susceptibility genes have been investigated; they include HLA genes, genes within the HLA region and genes outside the HLA region. T cells, including the recently described subset Th17, are thought to play an important role in the acute and chronic phases of the disease. Some of these findings allowed novel therapeutic interventions or opened new promising approaches in treatment. The most relevant data of the literature are summarized and discussed.


Not fibrin(ogen), but fibrinogen or fibrin.
In this issue of Blood, Prasad et al describe a mouse model with a mutation in the Aα chain of fibrinogen such that no fibrin polymer is formed in vivo, allowing for the first time the differentiation of the role of fibrinogen vs fibrin oligomer or polymer in antimicrobial host defense and in hemostasis/thrombosis.


Six-decade change in water chemistry of large freshwater Lake Taihu, China.
Taihu lake has become a hot spot internationally due to its algae bloom. However, its natural water chemistry (major ions) received little attention though it is equally important for drinking water and aquatic ecology. Using historical data (1950s-2012) we explored the drastic change of Taihu water chemistry over the past six decades and the driving factors. Results show that major ions increased around 2-7-fold and TDS increased nearly 3-fold during the last 60 years. The dominant cation has shifted from Ca(2+) to Na(+), and the current Cl(-) is dominant over HCO3(-), the predominant anion before the 2000s. Analyses show that population increase and human activities were the major driving factors responsible for the drastic change. Whereas the mechanism of increase was different for ions, i.e., Na(+) and Cl(-) increase was directly related to the population increase and sewage discharge in the basin; SO4(2-) was related to atmospheric deposition derived from increasing coal consumption and SO2 emissions; hardness (Ca and Mg) increase was closely linked to the acidic precipitation. No increase trend of HCO3(-) was attributable to frequent outbreaks of algae bloom which consumed HCO3(-). Estimation indicated that sewage discharge in the basin contributed 23% to the lake in terms of Cl(-), exceeding the contribution from rock weathering. Current water chemistry of Taihu lake has become "anthropogenic dominance" from its original rock dominance.


Preparation of Porous Scaffold Based on Poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) and FucoPol.
This work focused on the development of porous scaffolds based on biocomposites comprising two biodegradable and biocompatible biopolymers: a terpolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx), and the bacterial polysaccharide FucoPol. The PHBHVHHx terpolymer was composed of 3-hydroxybutyrate (55 wt%), 3-hydroxyvalerate (21 wt%), and 3-hydroxyhexanoate (24 wt%). This hydrophobic polyester has low crystallinity and can form elastic and flexible films. Fucopol is a fucose-containing water-soluble polysaccharide that forms viscous solutions with shear thinning behavior and has demonstrated emulsion-forming and stabilizing capacity and wound healing ability. Emulsion-templating was used to fabricate PHA-based porous structures in which FucoPol acted as a bioemulsifier. Compared with the scaffolds obtained from emulsions with only water, the use of FucoPol aqueous solutions resulted in structures with improved mechanical properties, namely higher tensile strength (4.4 MPa) and a higher Young's Modulus (85 MPa), together with an elongation at break of 52%. These features, together with the scaffolds' high porosity and pore interconnectivity, suggest their potential to sustain cell adhesion and proliferation, which is further supported by FucoPol's demonstrated wound healing ability. Therefore, the developed PHBHVHHx:FucoPol scaffolds arise as innovative porous bioactive structures with great potential for use in tissue engineering applications.


Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors.
The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.


Weissella cryptocerci sp. nov., isolated from gut of the insect Cryptocercus kyebangensis.
A taxonomic study of a Gram-stain-positive, rod-shaped, non-motile, non-spore-forming, catalase-negative bacterium, isolated from the gut of an insect, Cryptocercus kyebangensis collected from the mountainous area of Seoraksan, Yangyang-gun, Republic of Korea, was conducted. Its 16S rRNA gene sequence showed high similarity values to Weissella ghanensis LMG 24286T (95.9 %), Weissella beninensis 2L24P13T (95.9 %), Weissella fabalis M75T (95.7 %) and Weissella fabaria 257T (95.7 %). The phylogenetic tree indicated that the novel organism formed a cluster with W. ghanensis LMG 24286T, W. beninensis 2L24P13T, W. fabalis M75T and W. fabaria 257T. The G+C content was 41.1 mol% on the basis of the whole-genome sequence. Polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified aminophospholipids, one unidentified phospholipid and four unidentified lipids. The major cellular fatty acids were C18 : 1 ω9c, C16 : 0, C14 : 0, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and summed feature 8 (C16 : 1 ω7c and/or C16 : 1 ω6c). The cell-wall peptidoglycan was of A4α type with the interpeptide bridge of Gly-d-Glu. Based on these results, strain 26KH-42T could be classified as a novel species of the genus Weissella, for which the name Weissellacryptocerci sp. nov. is proposed. The type strain is 26KH-42T (=KACC 18423T=NBRC 113066T).


Abdominal Applications of Pediatric Body MR Angiography: Tailored Optimization for Successful Outcome.
OBJECTIVE. The purpose of this article is to summarize current common techniques and indications for pediatric abdominopelvic MR angiography and strategies for optimizing them to achieve successful outcomes. We also discuss newer MR angiography techniques, including whole-body imaging and blood pool contrast agents, as well as various approaches to reducing the need for anesthesia in pediatric MRI. CONCLUSION. Pediatric body vascular imaging presents a unique set of challenges that require a tailored approach. Emerging pediatric abdominopelvic MR angiography techniques hold promise for continued improvement in pediatric body MR angiography.


SDHC methylation in gastrointestinal stromal tumors (GIST): a case report.
Gastrointestinal stromal tumors (GIST) recently have been recognized as a genetically and biologically heterogeneous disease. In addition to KIT or PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH) subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit genes, some are SDHx wild type. Epigenetic regulation by DNA methylation of CpG islands recently has been found to be an alternative mechanism underlying the lack of SDH complex in GIST. We report a particular case of dSDH GIST, previously analyzed with microarrays and next-generation sequencing, for which no molecular pathogenetic events have been identified. Gene expression analysis showed remarkable down-modulation of SDHC mRNA with respect to all other GIST samples, both SDHA-mutant and KIT/PDGFRA-mutant GIST. By a bisulfite methylation assay targeted to 2 SDHC CpG islands, we detected hypermethylation of the SDHC promoter. Herein we report an additional case of dSDH GIST without SDHx mutation but harboring hypermethylation in the SDHC promoter, thus confirming the complexity of the molecular background of this subtype of GIST.


DNA polyintercalating drugs. Proton magnetic resonance studies of a new acridine dimer. Conformations and interactions with mono- and dinucleotides.
The conformation in aqueous solution of one acridine dimer which is able to bisintercalate in DNA (1, 14-bis(5-methoxy-6-chloro-9-acridinyl)-1,5,10,14-tetraazatetradecane tetrahydrochloride) (AcDi) and its interactions with mono- and dinucleotides have been investigated by fast Fourier transform proton magnetic resonance spectroscopy. Variations in chemical shifts of the most distingusihable protons of the acridine dimer with temperature bring evidence of a folded in equilibrium unfolded fast conformational equilibrium in the temperature range of 4-85 degrees C. Equilibrium parameters were estimated. The folded conformation has been deduced from iso-shielding curves of the acridine ring. In the complex between AcDi and 3'- or 5"AMP, and adenine ring is intercalated between the two acridine rings to give a sandwich-like complex. Studies of the interaction with adenylyl(3' leads to 5') adenosine (ApA) show two different complexes in equilibrium with the 3' or 5' moiety of ApA intercalated in the acridine dimer. These conclusions are derived from comparative studies with 2-methoxy-6-chloro-9-(3-dimethylaminopropylamino)acridine dihydrochloride which is the corresponding acridine monomer-(AcMo). In that case the self-association constant was determined. A model of the AcMo-5'-AMP complex was deduced from the analysis of the chemical shifts of the adenine protons. In this model, the N10+-D bond of the acridine points toward the negatively charged phosphate of the nucleotide.


Sesamoid osteonecrosis treated with radial extracorporeal shock wave therapy.
Sesamoid osteonecrosis is a disabling condition resulting in severe forefoot pain, for which there are limited treatment options. We present a 52-year-old man with 1-year history of pain, aggravated by walking and playing tennis. On examination, pain was localised to plantar aspect of the first metatarsophalangeal joint. Imaging revealed evolving end-stage avascular necrosis of lateral sesamoid with early secondary degenerative changes. Previous exhaustive conservative treatment had been unsuccessful in alleviating his pain. As an alternative to surgery, radial extracorporeal shock wave therapy (rESWT) was proposed. Treatment protocol was 2000 pulses at frequency of 5 Hz, and pressure was varied from 1.2 to 1.8 bar according to patient tolerance. A total of eight sessions were delivered. At completion of treatment, the patient reported minimal discomfort to no pain and was able to return to playing tennis with no recurrence. We propose rESWT to be an effective novel conservative treatment for sesamoid osteonecrosis.


Structure and properties of an amorphous metal-organic framework.
ZIF-4, a metal-organic framework (MOF) with a zeolitic structure, undergoes a crystal-amorphous transition on heating to 300 degrees C. The amorphous form, which we term a-ZIF, is recoverable to ambient conditions or may be converted to a dense crystalline phase of the same composition by heating to 400 degrees C. Neutron and x-ray total scattering data collected during the amorphization process are used as a basis for reverse Monte Carlo refinement of an atomistic model of the structure of a-ZIF. The structure is best understood in terms of a continuous random network analogous to that of a-SiO2. Optical microscopy, electron diffraction and nanoindentation measurements reveal a-ZIF to be an isotropic glasslike phase capable of plastic flow on its formation. Our results suggest an avenue for designing broad new families of amorphous and glasslike materials that exploit the chemical and structural diversity of MOFs.


Moesin regulates the trafficking of nascent clathrin-coated vesicles.
Clathrin-coated vesicles are responsible for the trafficking of several internalized biological cargos. We have observed that the endogenous F-actin-linker moesin co-distributes with constitutive components of clathrin-coated structures. Total internal reflection fluorescence microscopy studies have shown that short interference RNA of moesin enhances the lateral movement of clathrin-coated structures and provokes their abnormal clustering. The aggregation of clathrin-coated structures has also been observed in cells overexpressing N-moesin, a dominant-negative construct unable to bind to F-actin. Only overexpressed moesin constructs with an intact phosphatidylinositol 4,5-bisphosphate-binding domain co-distribute with clathrin-coated structures. Hence, this N-terminal domain is mostly responsible for moesin/clathrin-coated structure association. Biochemical endosome fractioning together with total internal reflection fluorescence microscopy comparative studies, between intact cells and plasma-membrane sheets, indicate that moesin knockdown provokes the accumulation of endocytic rab5-clathrin-coated vesicles carrying the transferrin receptor. The altered trafficking of these endocytic rab5-clathrin-coated vesicles accounts for a transferrin receptor recycling defect that reduces cell-surface expression of the transferrin receptor and increases the amount of sequestered transferrin ligand. Therefore, we propose that moesin is a clathrin-coated vesicle linker that drives cargo trafficking and acts on nascent rab5-clathrin-coated vesicles by simultaneously binding to clathrin-coated vesicle-associated phosphatidylinositol 4,5-bisphosphate and actin cytoskeleton. Hence, functional alterations of moesin may be involved in pathological disorders associated with clathrin-mediated internalization or receptor recycling.


Effects of 5-hydroxy-4'-nitro-7-propionyloxy-genistein on inhibiting proliferation and invasion via activating reactive oxygen species in human ovarian cancer A2780/DDP cells.
5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG), a novel synthetic isoflavone derivative, was demonstrated to possess antitumor activity in gastric cancer and breast cancer in vitro, but its antitumor effect and mechanism in ovarian cancer has not been characterized. The aim of the present study was to investigate the effects of HNPG on inhibiting the proliferation and invasion in human ovarian cancer A2780 cell lines of cisplatin resistance (A2780/DDP) and elucidate its underlying molecular mechanism. The results indicated that HNPG presented with marked antitumor activity against A2780/DDP cells in vitro, significantly inhibited the rates of proliferation, clone formation, invasion and metastasis, and markedly induced apoptosis in dose- and time-dependent manner. Simultaneously, levels of reactive oxygen species (ROS) were increased and mitochondrial membrane potential was decreased. In addition, Bcl-2 expression was downregulated, Bax expression was upregulated, and the ratio of Bcl-2/Bax was decreased. Concurrently, levels of Cyt-C were markedly enhanced and the caspase cascade was triggered. Taken together, the results suggested that HNPG exerted anticancer effects through promoting ROS accumulation in cells, triggering mitochondrial apoptotic pathways and ultimately resulting in cells apoptosis. Therefore, HNPG serves as a potential candidate in the chemoprevention and/or treatment of cisplatin-resistant human ovarian cancer.


Differentially expressed genes in the head of the 2nd instar pre-molting larvae of the nm2 mutant of the silkworm, Bombyx mori.
Molting is an important physiological process in the larval stage of Bombyx mori and is controlled by various hormones and peptides. The silkworm mutant that exhibits the phenotype of non-molting in the 2nd instar (nm2) is incapable of molting in the 2nd instar and dies after seven or more days. The ecdysone titer in the nm2 mutant is lower than that in the wildtype, and the mutant can be rescued by feeding with 20E and cholesterol. The results of positional cloning indicated that structural alteration of BmCPG10 is responsible for the phenotype of the nm2 mutant. To explore the possible relationship between BmCPG10 and the ecdysone titer as well as the genes affected by BmCPG10, digital gene expression (DGE) profile analysis was conducted in the nm2 mutant, with the wildtype strain C603 serving as the control. The results revealed 1727 differentially expressed genes, among which 651 genes were upregulated and 1076 were downregulated in nm2. BLASTGO analysis showed that these differentially expressed genes were involved in various biological processes, cellular components and molecular functions. KEGG analysis indicated an enrichment of these differentially expressed genes in 240 pathways, including metabolic pathways, pancreatic secretion, protein digestion and absorption, fat digestion and absorption and glycerolipid metabolism. To verify the accuracy of the DGE results, quantitative reverse transcription PCR (qRT-PCR) was performed, focusing on key genes in several related pathways, and the results were highly consistent with the DGE results. Our findings indicated significant differences in cuticular protein genes, ecdysone biosynthesis genes and ecdysone-related nuclear receptors genes, but no significant difference in juvenile hormone and chitin biosynthesis genes was detected. Our research findings lay the foundation for further research on the formation mechanism of the nm2 mutant.


[The hip in musculoskeletal disorders--nonsurgical management].
Basic principles of nonsurgical management of hip diseases encountered in most frequent rheumatic conditions are described. Non-pharamacologic therapy like correction of predisposing factors, weight reduction in the obese patients and correction of valgus and varus knee deformities are emphasised. Individually prescribed rehabilitation and education assissts the patient in reaching his or her maximal potential. Nonsteroidal antiinflammatory drugs (NSAR) are the drugs of first choice in pharmacological management. They are widely used; in low dosages NSAR are effective analgesics; in higher dosages, they have anti-inflammatory activity.


How general is ensemble perception?
People can summarize features of groups of objects (e.g., the mean size of apples). Claims of dissociations or common mechanisms supporting such ensemble perception (EP) judgments have generally been made on the basis of correlations between pairs of tasks. These correlations can be inflated because they use the same stimuli, summary statistics and/or task format. Performance on EP tasks also correlates with that on object recognition (OR) tasks. Here, we seek evidence for a general EP ability that is also distinct from OR ability. Two-hundred participants completed three tasks that did not overlap in stimuli, summary statistic or task format. Participants performed a diversity comparison for arrays of nonsense blobs, a mean identity judgment with ensembles of Transformer toys, and the novel object memory task with novel objects (NOMT-Greeble). We hypothesized that EP contributes to the first two of these tasks, while OR contributes only to the last two. Performance on the two tasks suggested to tap an EP ability were correlated after controlling for the third task. Confirmatory factor analysis was used to test our predictions without the confound of measurement error. Correlations between factors assumed to share influence from EP or from OR were higher than that between the factors that we expect did not share these influences. The results provide the first clear evidence for a domain-general EP ability distinct from OR. We argue that understanding such a general ability will require a change in designs and analytical approaches in the study if individual differences in EP.


Advancing Dermatological Care: A Comprehensive Narrative Review of Tele-Dermatology and mHealth for Bridging Gaps and Expanding Opportunities beyond the COVID-19 Pandemic.
Mobile health (mHealth) has recently had significant advances in tele-dermatology (TD) thanks to the developments following the COVID-19 pandemic. This topic is very important, as telemedicine and mHealth, when applied to dermatology, could improve both the quality of healthcare for citizens and the workflow in the health domain. The proposed study was centered on the last three years. We conducted an overview on the opportunities, the perspectives, and the problems involved in TD integration with mHealth. The methodology of the narrative review was based on: (I) a search of PubMed and Scopus and (II) an eligibility assessment, using properly proposed parameters. The outcome of the study showed that during the COVID-19 pandemic, TD integration with mHealth advanced rapidly. This integration enabled the monitoring of dermatological problems and facilitated remote specialist visits, reducing face-to-face interactions. AI and mobile apps have empowered citizens to take an active role in their healthcare. This differs from other imaging sectors where information exchange is limited to professionals. The opportunities for TD in mHealth include improving service quality, streamlining healthcare processes, reducing costs, and providing more accessible care. It can be applied to various conditions, such as (but not limited to) acne, vitiligo, psoriasis, and skin cancers. Integration with AI and augmented reality (AR), as well as the use of wearable sensors, are anticipated as future developments. However, integrating TD with mHealth also brings about problems and challenges related to regulations, ethics, cybersecurity, data privacy, and device management. Scholars and policymakers need to address these issues while involving citizens in the process.


Blood volume of children with leukemia.
Blood volume was measured using 125iodinated human serum albumin in 27 children with acute lymphoblastic leukemia, and in 7 children with various types of leukemia. Total blood volume was normal in patients without marked enlargement of spleen and liver, and increased progressively as spleen and liver size increased. The hypervolemia was entirely due to expansion of plasma volume. In the children with marked hepatosplenomegaly, only hematocrit (but not red cell mass) was below the normal range in most cases. Both hematocrit and red cell mass were subnormal in the majority of patients without considerably enlarged spleen and liver. Therefore, anemia in children with marked hepatosplenomegaly may be partly caused by hemodilution of red blood cells in expanded plasma volume.


Optimum condition of anisotropic plasma etching for improving bending properties of ionic polymer-metal composites.
We presented an anisotropic plasma etching technique by reactive ion etcher (RIE) as a new pretreatment method of fabrication of ionic polymer-metal composite (IPMC). We already found that the new technique provided large displacement to the fabricated IPMC in the presence of low applied voltage. However, we did not examine the optimum condition for the anisotropic plasma etching. In this research, we tried to figure out optimum treatment condition of film in etcher. Nafion (by DuPont) films were etched using various etching time and shadow masks with various slit and space sizes. The etched samples were plated with Pt at top and bottom side by Oguro's reduction method. The surface morphology of fabricated IPMCs was characterized by SEM. And, we've measured surface resistance, bending displacement, and driving force in order to check the IPMC properties out. Here, we found that optimum condition for pre-treatment of Nafion was 1 min for etching time under shadow mask with 200 microm slit and 100 microm space.


Single lanthanide-doped oxide nanoparticles as donors in fluorescence resonance energy transfer experiments.
We used lanthanide-ion doped oxide nanoparticles, Y(0.6)Eu(0.4)VO(4), as donors in fluorescent resonance energy transfer (FRET) experiments. The choice of these nanoparticles allows us to combine the advantages of the lanthanide-ion emission, in particular the long lifetime and the large Stokes shift between absorption and emission, with the detectability of the nanoparticles at the single-particle level. Using cyanine 5 (Cy5) organic molecules as acceptors, we demonstrated FRET down to the single-nanoparticle level. We showed that, due to the long donor lifetime, unambiguous and precise FRET measurements can be performed in solution even in the presence of large free acceptor concentrations. Highly efficient energy transfer was obtained for a large number of acceptor molecules per donor nanoparticle. We determined FRET efficiencies as a function of Cy5 concentration which are in good agreement with a multiple acceptor-multiple donor calculation. On the basis of the donor emission recovery due to acceptor photobleaching, we demonstrated energy transfer from single-nanoparticle donors in fluorescence microscopy experiments.


Diffusion and dimer formation of CO molecules induced by femtosecond laser pulses.
We investigate two fundamental steps of a nonadiabatic surface process, the photo-induced movement and approach of CO molecules on the Cu(111) surface, at a hitherto unachieved single-molecule level through scanning tunneling microscope imaging. For the close approach of two CO molecules, we not only determine the nonadiabatic diffusion barrier (87 meV), but also discover a femto-second-laser-induced transient attraction (30 meV) of the usually repelling CO molecules.


Tooth bleaching and pit and fissure stain.
To investigate if tooth whitening had any effect on the shade of occlusal pit and fissure stains and whether reservoirs in bleaching trays affected bleaching of occlusal pit and fissure stains. 96 extracted molars were randomly divided into three paired groups for whitening using a 10% carbamide peroxide solution (Opalescence) or a 22% carbamide peroxide solution (Nite White Excel 3), or tap water for a control. One of each pair utilized reservoirs in their custom bleaching trays. Three dentists evaluated the shade of a specified occlusal area of pit and fissure stain twice before bleaching and twice after bleaching. Pit and fissure stain showed significant lightening of shade for either of the bleaching systems (P < 0.0005) but not the control (P = 0.816). There was no significant difference in pit and fissure stain shade lightening following treatment between those groups utilizing reservoirs in the custom trays and those without reservoirs (P = 0.658).


Cytotoxic mechanisms by M239V presenilin 2, a little-analyzed Alzheimer's disease-causative mutant.
Although neurotoxic functions are well characterized in familial Alzheimer's disease (FAD)-linked N141I mutant of presenilin (PS)2, little has been known about M239V-PS2, another established FAD-causative mutant. We found that expression of M239V-PS2 caused neuronal cytotoxicity. M239V-PS2 exerted three forms of cytotoxicity: one was sensitive to both an antioxidant glutathione-ethyl-ester (GEE) and a caspase inhibitor Ac-DEVD-CHO (DEVD); the second was sensitive to GEE but resistant to DEVD; and the third was resistant to both. The GEE/DEVD-sensitive cytotoxicity by M239V-PS2 was likely through NADPH oxidase and the GEE-sensitive/DEVD-resistant cytotoxicity through xanthine oxidase (XO). Both mechanisms by M239V-PS2 were suppressed by pertussis toxin (PTX) and were mediated by Galpha(o), but not by Galpha(i). Although Abeta1-43 itself induced no cytotoxicity, Abeta1-43 potentiated all three components of M239V-PS2 cytotoxicity. As these cytotoxic mechanisms by M239V-PS2 are fully shared with N141I-PS2, they are most likely implicated in the pathomechanism of FAD by PS2 mutations. Notably, cytotoxicity by M239V-PS2 could be inhibited by the combination of two clinically usable inhibitors of superoxide-generating enzymes, apocynin and oxypurinol.


Urinary Bladder Matrix Grafting: A Simple and Effective Alternative to Flap Coverage for Wounds in High-Risk Orthopaedic Trauma Patients.
Complex traumatic and/or infected wounds and their sequelae are a significant burden for high-volume trauma centers. Local or free flap coverage options are well described; however, they may be high risk in poor hosts with multiple comorbidities and active infections. In addition, flap coverage can result in delays in wound coverage depending on specialist availability. Porcine urinary bladder matrix grafting has been shown to be a simple definitive wound coverage option that can be performed without delay in multiple patient populations for wounds that would otherwise require flap coverage. The purpose of this article was to describe a technique for urinary bladder matrix grafting and report on a series of orthopaedic trauma patients treated with this technique.


Calcium-dependent nerve growth factor-stimulated hydrolysis of phosphoinositides in PC12 cells.
The effect of nerve growth factor (NGF) on the hydrolysis of phosphoinositides in PC12 cells was examined. Addition of NGF to PC12 cells prelabeled with [3H]-inositol resulted in an increase in the formation of labeled inositol trisphosphate ([3H]IP3), inositol bisphosphate ([3H]IP2), and inositol monophosphate ([3H]IP), an observation indicating that NGF stimulated hydrolysis of the polyphosphoinositides. The increase in these inositol phosphates was detected as early as 15 s after addition of NGF. In the presence of LiCl, the accumulation of [3H]IP was linear for at least 20 min. The NGF-stimulated accumulation of [3H]IP was dose-dependent with a Kact of 0.17 nM and was dependent on the presence of extracellular calcium. In a calcium-free buffer containing EGTA, the NGF-dependent increase in accumulation of [3H]IP was not seen, and the basal level of [3H]IP accumulation was lower than that observed in the presence of extracellular calcium. Lanthanum inhibited both the basal and NGF-stimulated accumulation of [3H]IP, whereas the calcium ionophore A23187, in the absence of NGF, stimulated an accumulation of [3H]IP. The maximal accumulation of [3H]IP in the presence of A23187 was the same as that observed in the presence of NGF. Incubation of the cells with both A23187 and NGF resulted in an accumulation of [3H]IP that was not significantly different from the effect of either agent alone. These results suggest that NGF rapidly stimulates the hydrolysis of phosphoinositides in PC12 cells and that this NGF-stimulated hydrolysis of phosphoinositides occurs by a calcium-dependent mechanism.


Epigenetic stability increases extensively during Drosophila follicle stem cell differentiation.
Stem and embryonic cells facilitate programming toward multiple daughter cell fates, whereas differentiated cells resist reprogramming and oncogenic transformation. How alterations in the chromatin-based machinery of epigenetic inheritance contribute to these differences remains poorly known. We observed random, heritable changes in GAL4/UAS transgene programming during Drosophila ovarian follicle stem cell differentiation and used them to measure the stage-specific epigenetic stability of gene programming. The frequency of GAL4/UAS reprogramming declines more than 100-fold over the nine divisions comprising this stem cell lineage. Stabilization acts in cis, suggesting that it is chromatin-based, and correlates with increased S phase length. Our results suggest that stem/early progenitor cells cannot accurately transmit nongenetic information to their progeny; full epigenetic competence is acquired only gradually during early differentiation. Modulating epigenetic inheritance may be a critical process controlling transitions between the pleuripotent and differentiated states.


High-throughput protein structural analysis using site-directed fluorescence labeling and the bimane derivative (2-pyridyl)dithiobimane.
We present a site-directed fluorescence labeling (SDFL) study of 25 different T4 lysozyme protein samples labeled with the thiol-cleavable fluorophore, (2-pyridyl)dithiobimane (PDT-Bimane). Our results demonstrate PDT-Bimane can be used in cysteine-scanning studies to detect protein secondary structure, and to map proximity between sites in proteins by monitoring tryptophan quenching of bimane fluorescence. In addition, the reducible nature of PDT-Bimane can be exploited to resolve problems often faced in SDFL studies: ensuring specific labeling of cysteine residues, determining the extent of free label contamination, and accurately determining labeling efficiency even at low concentrations. The ability to cleave PDT-Bimane off the protein enables rapid determination of these parameters, and positions it as an ideal fluorophore for automated, high-throughput structural studies of protein folding, the detection of protein-protein interactions, and the monitoring of real-time conformational changes.


Computational method to evaluate ankle postural stiffness with ground reaction forces.
We examined an existing method for evaluating postural sway based on force-plate technology. Through an improved mathematical model of postural dynamics, we propose a new method, which better evaluated postural sway and, in addition, computed ankle moment and ankle postural stiffness directly from the measured ground reaction forces. An example is detailed that demonstrates the utility of this approach. The proposed method does not involve filtering or numerical integration and considers the platform inclination. Results from normal subjects show a linear relation between the ankle moment and the sway angle during quiet standing.


Impact of work demand constraints on psychological distress through workplace bullying and personality traits: A moderated-mediation model.
This study addressed the human aspects of sustainable development in organizations by applying work demand resource theory and the main focus of the study is to investigate the negative aspects of workplace bullying on human's mental health. This study investigated how the work demand constraints play a role in increasing psychological distress among employees through the mediation of workplace bullying. This study also considers personality traits that play a role in preventing psychological distress resulting from workplace bullying. The authors collected data by means of a self-administered questionnaire. The questionnaire was distributed among 1000 employees selected using a systematic sampling technique, patronized among three service sectors: the health sector, education sector, and forest department in the city of Lahore in Pakistan. The data was analyzed by employing Partial Least Square Structural Equation Modeling (PLS-SEM) using Smart PLS 3.3.3. Results of this study reveal that work demand constraints (WDC) play a significant role in workplace bullying and impact increasing psychological distress. Personality traits play a moderating role between work demand constraints and workplace bullying behavior on the one hand and psychological distress on the other hand; however, openness to experiences was found to have a moderating relationship between work demand constraints and workplace bullying. Meanwhile, agreeableness and openness to experiences were found to have a moderating relationship between work demand constraints (WDC) and psychological distress. This study also has practical implications for employers, such as providing psychological counseling, personality development training at the workplace etc. The relationship of work demand constraints with psychological distress and workplace bullying through direct and indirect moderating effects of personality traits in Pakistan's service sector are unique contributions of this study.


Opioid-Related Public Health Communication Campaigns: An Environmental Scan.
The opioid overdose epidemic continues to devastate lives across the United States and has worsened during the COVID-19 pandemic. In this paper, we review 166 online-accessible opioid-related campaigns to understand the current state of the science and practice of campaigns to address the opioid crisis. The findings suggest that health promotion practitioners can have a greater impact on reducing overdose deaths if they move beyond awareness-raising messaging about opioid misuse and place a greater emphasis on driving demand for evidence-based treatments such as medications for opioid use disorder and on reducing stigma related to treatment and recovery.


Experimental Study on the Effects of Vegetation on the Dissipation of Supersaturated Total Dissolved Gas in Flowing Water.
High dam discharge can lead to total dissolved gas (TDG) supersaturation in the downstream river, and fish in the TDG-supersaturated flow can suffer from bubble disease and even die. Consequently, it is of great value to study the transport and dissipation characteristics of supersaturated dissolved gas for the protection of river fish. Floodplains may form downstream of high dams due to flood discharge, and the plants on these floodplains can affect both the hydraulic characteristics and TDG transport of the flowing water. In this study, the velocity distribution and the retention response time under different flow conditions and vegetation arrangements were studied in a series of experiments. The retention time was significantly extended by the presence of vegetation, and an empirical formula for calculating the retention time was proposed. In addition, the responses of the dissipation process of supersaturated TDG to hydraulic factors, retention time, and vegetation area coefficient were analyzed. The dissipation of supersaturated TDG significantly increased with increases in the vegetation area coefficient in the water. To quantitatively describe the TDG dissipation process in TDG-supersaturated flow under the effect of vegetation, the TDG dissipation coefficient was fitted and analyzed. The basic form of the formula for the dissipation coefficient involving various influence factors was determined by dimensional analysis. An equation for calculating the TDG dissipation coefficient of flowing water with vegetation was proposed by multivariate nonlinear fitting and was proven to have great prediction accuracy. The calculated method developed in this paper can be used to predict TDG dissipation in flowing water with vegetation and is of great significance for enriching TDG prediction systems.


Involvement of autophagy via mammalian target of rapamycin (mTOR) inhibition in tributyltin-induced neuronal cell death.
Tributyltin chloride (TBT) is a neurotoxic environmental pollutant that inhibits mitochondrial adenosine triphosphate (ATP) synthase. Autophagy is one of the major protein degradation systems induced by a decrease of intracellular ATP following activation of AMP-activated protein kinase (AMPK). Because we previously found that TBT induces activation of AMPK, here we examined whether TBT induces autophagic neuronal death. Exposure of cortical neurons to 500 nM TBT reduced the phosphorylation of mammalian target of rapamycin (mTOR), a regulator of autophagy. An autophagy inhibitor, 3-methyladenine (3-MA), markedly decreased TBT-induced neuronal death. TBT also induced the formation of LC3-II, an autophagy marker. These results suggest that TBT-induced neuronal death is at least partly autophagic.


Personal Protective Equipment: Current Best Practices for Orthopedic Teams.
The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome (SARS-CoV-2) virus is challenging healthcare providers across the world. Current best practices for personal protective equipment (PPE) during this time are rapidly evolving and fluid due to the novel and acute nature of the pandemic and the dearth of high-level evidence. Routine infection control practices augmented by airborne precautions are paramount when treating the COVID-19-positive patient. Best practices for PPE use in patients who have unknown COVID-19 status are a highly charged and emotional issue. The variables to be considered include protection of patients and healthcare providers, accuracy and availability of testing, and responsible use of PPE resources. This article also explores the concerns of surgeons regarding possible transmission to their own family members as a result of caring for COVID-19 patients.


G-Computation and Agent-Based Modeling for Social Epidemiology: Can Population Interventions Prevent Posttraumatic Stress Disorder?
Agent-based modeling and g-computation can both be used to estimate impacts of intervening on complex systems. We explored each modeling approach within an applied example: interventions to reduce posttraumatic stress disorder (PTSD). We used data from a cohort of 2,282 adults representative of the adult population of the New York City metropolitan area from 2002-2006, of whom 16.3% developed PTSD over their lifetimes. We built 4 models: g-computation, an agent-based model (ABM) with no between-agent interactions, an ABM with violent-interaction dynamics, and an ABM with neighborhood dynamics. Three interventions were tested: 1) reducing violent victimization by 37.2% (real-world reduction); 2) reducing violent victimization by100%; and 3) supplementing the income of 20% of lower-income participants. The g-computation model estimated population-level PTSD risk reductions of 0.12% (95% confidence interval (CI): -0.16, 0.29), 0.28% (95% CI: -0.30, 0.70), and 1.55% (95% CI: 0.40, 2.12), respectively. The ABM with no interactions replicated the findings from g-computation. Introduction of interaction dynamics modestly decreased estimated intervention effects (income-supplement risk reduction dropped to 1.47%), whereas introduction of neighborhood dynamics modestly increased effectiveness (income-supplement risk reduction increased to 1.58%). Compared with g-computation, agent-based modeling permitted deeper exploration of complex systems dynamics at the cost of further assumptions.


Applying participatory approaches in the evaluation of surveillance systems: A pilot study on African swine fever surveillance in Corsica.
The implementation of regular and relevant evaluations of surveillance systems is critical in improving their effectiveness and their relevance whilst limiting their cost. The complex nature of these systems and the variable contexts in which they are implemented call for the development of flexible evaluation tools. Within this scope, participatory tools have been developed and implemented for the African swine fever (ASF) surveillance system in Corsica (France). The objectives of this pilot study were, firstly, to assess the applicability of participatory approaches within a developed environment involving various stakeholders and, secondly, to define and test methods developed to assess evaluation attributes. Two evaluation attributes were targeted: the acceptability of the surveillance system and its the non-monetary benefits. Individual semi-structured interviews and focus groups were implemented with representatives from every level of the system. Diagramming and scoring tools were used to assess the different elements that compose the definition of acceptability. A contingent valuation method, associated with proportional piling, was used to assess the non-monetary benefits, i.e., the value of sanitary information. Sixteen stakeholders were involved in the process, through 3 focus groups and 8 individual semi-structured interviews. Stakeholders were selected according to their role in the system and to their availability. Results highlighted a moderate acceptability of the system for farmers and hunters and a high acceptability for other representatives (e.g., private veterinarians, local laboratories). Out of the 5 farmers involved in assessing the non-monetary benefits, 3 were interested in sanitary information on ASF. The data collected via participatory approaches enable relevant recommendations to be made, based on the Corsican context, to improve the current surveillance system.


Psychometric evaluation of the Self-Awareness in Daily Life-3 Scale (SADL-3) for the assessment of self-awareness after acquired brain injury.
The Self-Awareness in Daily Life-3 Scale (SADL-3) was designed to assess self-awareness in the chronic phase after acquired brain injury (ABI). The main objective was to evaluate its feasibility and usability for clinical practice, reliability and validity. Participants were 89 patients with ABI. SADL-3 core distributions, floor and ceiling effects and percentage of missing items were used. Ratings made by two staff members and ratings at two time points were compared. SADL-3 ratings were compared with Awareness Questionnaire (AQ) ratings, Patient Competency Rating Scale (PCRS) ratings, and ratings made on the Clinician's Rating Scale for evaluating Impaired Self-Awareness and Denial of Disability (CRS-ISA-DD). Staff members completed a questionnaire concerning the usability of the SADL-3. No floor or ceiling effects were present. Results show sufficient inter-rater reliability (ICC > .40), acceptable test-retest reliability (ρs > .75) and sufficient convergent validity (ρs > .30). The median administration time was 15 minutes (SD = 21.2). Most staff members rated the SADL-3 as fairly easy to very easy to complete. The SADL-3 is a brief scale with sufficient psychometric properties. Teams can use it in clinical practice to identify patients' self-awareness in the chronic phase after ABI.


v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage.
An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of γH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v-Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells.


Genome-Wide Identification, Expression and Stress Analysis of the GRAS Gene Family in Phoebe bournei.
GRAS genes are important transcriptional regulators in plants that govern plant growth and development through enhancing plant hormones, biosynthesis, and signaling pathways. Drought and other abiotic factors may influence the defenses and growth of Phoebe bournei, which is a superb timber source for the construction industry and building exquisite furniture. Although genome-wide identification of the GRAS gene family has been completed in many species, that of most woody plants, particularly P. bournei, has not yet begun. We performed a genome-wide investigation of 56 PbGRAS genes, which are unequally distributed across 12 chromosomes. They are divided into nine subclades. Furthermore, these 56 PbGRAS genes have a substantial number of components related to abiotic stress responses or phytohormone transmission. Analysis using qRT-PCR showed that the expression of four PbGRAS genes, namely PbGRAS7, PbGRAS10, PbGRAS14 and PbGRAS16, was differentially increased in response to drought, salt and temperature stresses, respectively. We hypothesize that they may help P. bournei to successfully resist harsh environmental disturbances. In this work, we conducted a comprehensive survey of the GRAS gene family in P. bournei plants, and the results provide an extensive and preliminary resource for further clarification of the molecular mechanisms of the GRAS gene family in P. bournei in response to abiotic stresses and forestry improvement.


[Prevalence of H. pylori infection in the Polish child population].
Helicobacter pylori is one of the most frequent pathogens of human. It plays a decisive role in the diseases of upper alimentary tract. Most infected subjects live in the developing countries. The aim of the study was to estimate the prevalence of H. pylori infection in children depending on age, sex and place of living. For the purpose of epidemiological studies the District Center of Informatics and Regional Data Bank have randomly drawn 1500 children; 500 from each: City District of Wroclaw, Oleśnica district, and rural district of Oleśnica--the regions varying in the wealth of inhabitants, monthly wages and unemployment rate. The children were selected in five ranges of age: under 1 year of age, 2-5 years old, 6-10 years old, 11-15 years old, and 16-18 years old. The proportion of both sexes in each subpopulation was taken into consideration. Altogether 478 from the selected children (31.89%) participated in the study. The average rate of H. pylori infection amounted to 34.5%. It was the lowest in Wroclaw--18.3%. In Oleśnica town district it was 42.2% and in Oleśnica rural district--38.8%. Higher rate of H. pylori infections was observed in youngsters aged 15 to 19 years living in rural area. No indication of the effects of H. pylori infections on the occurrence of symptoms from digestive system was observed. The studies have demonstrated an influence of social and economic conditions on the frequency of H. pylori infection in children.


Individual and additive effects of mothers' and fathers' chronic pain on health outcomes in young adults with a childhood history of functional abdominal pain.
To evaluate effects of mothers' and fathers' chronic pain on health outcomes in adult sons and daughters with a childhood history of functional abdominal pain (FAP). Adults (n = 319; Mean age = 22.09 years) with a childhood history of FAP reported parental history of chronic pain and their own current health (chronic pain, somatic symptoms, disability, use of medication and health care, illness-related job loss). Positive histories of maternal and paternal chronic pain were each associated with poorer health in sons and daughters, regardless of child or parent gender. Having 2 parents with chronic pain was associated with significantly poorer health than having 1 or neither parent with chronic pain. Chronic pain in both mothers and fathers is associated with poor health and elevated health service use in young adults with a childhood history of FAP. Having both parents with chronic pain increases risk for adverse outcomes.


Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.
We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.


Swimming training down-regulates plasma leptin levels, but not adipose tissue ob mRNA expression.
The aim of the present study was to assess the effects of endurance training on leptin levels and adipose tissue gene expression and their association with insulin, body composition and energy intake. Male Wistar rats were randomly divided into two groups: trained (N = 18) and sedentary controls (N = 20). The trained group underwent swimming training for 9 weeks. Leptin and insulin levels, adiposity and leptin gene expression in epididymal and inguinal adipose tissue were determined after training. There were no differences in energy intake between groups. Trained rats had a decreased final body weight (-10%), relative and total body fat (-36 and -55%, respectively) and insulin levels (-55%) compared with controls (P < 0.05). Although trained animals showed 56% lower leptin levels (2.58 +/- 1.05 vs 5.89 +/- 2.89 ng/mL in control; P < 0.05), no difference in leptin gene expression in either fat depot was demonstrable between groups. Stepwise multiple regression analysis showed that lower leptin levels in trained rats were due primarily to their lower body fat mass. After adjustment for total body fat, leptin levels were still 20% (P < 0.05) lower in exercised rats. In conclusion, nine weeks of swimming training did not affect leptin gene expression, but did lead to a decrease in leptin levels that was independent of changes in body fat.


[Treatment of hyperprolactinemic amenorrhea by pulsatile administration of gonadotropin-releasing hormone].
Two patients with hyperprolactinemic secondary amenorrhoea were treated with gonadotropin releasing hormone (GnRH). Both desired children and had an incompatibility to treatment with Dopamin agonists (Zyklomat). Both patients ovulated and had regular follicular maturation in spite of rising prolactin levels. The pregnancies occurred in the first treatment cycles. The pulsatile intravenous administration of GnRH is apparently a viable alternative plan of management in patients with a moderate hyperprolactinemia and incompatibility to Dopamine agonists to the treatment with gonadotropins which was in use up to now.


Patterns in syntactic dependency networks.
Many languages are spoken on Earth. Despite their diversity, many robust language universals are known to exist. All languages share syntax, i.e., the ability of combining words for forming sentences. The origin of such traits is an issue of open debate. By using recent developments from the statistical physics of complex networks, we show that different syntactic dependency networks (from Czech, German, and Romanian) share many nontrivial statistical patterns such as the small world phenomenon, scaling in the distribution of degrees, and disassortative mixing. Such previously unreported features of syntax organization are not a trivial consequence of the structure of sentences, but an emergent trait at the global scale.


Integrating Mechanistic and Toxicokinetic Information in Predictive Models of Cholestasis.
Drug development involves the thorough assessment of the candidate's safety and efficacy. In silico toxicology (IST) methods can contribute to the assessment, complementing in vitro and in vivo experimental methods, since they have many advantages in terms of cost and time. Also, they are less demanding concerning the requirements of product and experimental animals. One of these methods, Quantitative Structure-Activity Relationships (QSAR), has been proven successful in predicting simple toxicity end points but has more difficulties in predicting end points involving more complex phenomena. We hypothesize that QSAR models can produce better predictions of these end points by combining multiple QSAR models describing simpler biological phenomena and incorporating pharmacokinetic (PK) information, using quantitative in vitro to in vivo extrapolation (QIVIVE) models. In this study, we applied our methodology to the prediction of cholestasis and compared it with direct QSAR models. Our results show a clear increase in sensitivity. The predictive quality of the models was further assessed to mimic realistic conditions where the query compounds show low similarity with the training series. Again, our methodology shows clear advantages over direct QSAR models in these situations. We conclude that the proposed methodology could improve existing methodologies and could be suitable for being applied to other toxicity end points.


Curiosa paediatrica X: precocious sternebral fusion.
The few reported cases of precocious sternebral fusion occurring in early childhood appear always to have been associated with other congenital physical abnormalities. The instance presented here was clinically without such association and its precocious appearance cannot be attributed to an aberrant embryological polyvalent induction.


Giardia intestinalis: volume recovery in response to cell swelling.
The trophozoite from of the protozoan parasite Giardia intestinalis is subjected to a changing osmotic environment in the small intestine of the host, and consequently effective osmoregulation and control of cell volume are essential to its survival. As a first step toward investigating the mechanism by which hypoosmotically-activated transport is controlled in this organism, we used a light scattering technique to monitor continuously changes in cell volume after osmotic challenge. There was a hyperbolic relationship between A550 and giardial protein concentration, resulting in linear double reciprocal plots and allowing the calculation of relative Giardia cell volumes from A550 values. The initial rate of cell swelling was directly proportional to the hypoosmotic gradient when the hypoosmotic difference was greater than 50 mOsm kg-1. However, a hypoosmotic challenge of < 30 mOsm kg-1 had little effect on cell swelling, suggesting that giardial cell rigidity can resist small changes in medium osmolarity. The use of light scattering as a measure of giardial cell volume changes was validated using a rapidly penetrating solute, ethylene glycol, to induce isoosmotic cell swelling. We have previously shown that trophozoites swelled initially when subjected to a hypoosmotic challenge and that a subsequent regulatory volume decrease was accompanied by rapid alanine efflux and activation of the uptake of an alanine analog, 2-aminoisobutyrate. The ethylene glycol-induced isoosmotic cell swelling was also followed by a regulatory volume decrease, accompanied by a similar rapid release of intracellular alanine and activation of 2-aminoisobutyric acid uptake. This suggests that an increase in cell volume is the primary stimulus for the rapid alanine efflux after hypoosmotic challenge.


[Bioactive materials. A critical review].
The bioactive materials should be divided into osteoinductive and osteostimulative materials according to their effect in bone regeneration. Already this statement requires a definition of the words used, in order to assure a real discussion. By means of the recommendations for definitions this paper is a basis for those discussions. In order to classify the bioactive materials into types of materials the potential effect onto the bone regeneration process should be considered. On the other hand the synthetic or biological origin, and the physical or biochemical structure are of great significance. Beside the classification made by the above called criteria the types of materials with their advantages and disadvantages are described. In the following discussion some problems are described like the mechanical and chemical instability, the coating of metallic substrata, the sterilization and the possibilities for the analytic characterization of hydroxylapatite.


Epigenetics in Congenital Heart Disease.
Embryonic heart development is an intricate process that mainly involves morphogens, transcription factors, and cardiac genes. The precise spatiotemporal expression of these genes during different developmental stages underlies normal heart development. Thus, mutation or aberrant expression of these genes may lead to congenital heart disease (CHD). However, evidence demonstrates that the mutation of genes accounts for only a small portion of CHD cases, whereas the aberrant expression regulated by epigenetic modification plays a predominant role in the pathogenesis of CHD. In this review, we provide essential knowledge on the aberrant epigenetic modification involved in the pathogenesis of CHD. Then, we discuss recent advances in the identification of novel epigenetic biomarkers. Last, we highlight the epigenetic roles in some adverse intrauterine environment-related CHD, which may help the prevention, diagnosis, and treatment of these kinds of CHD.


Bonding and structure of disilenes and related unsaturated group-14 element compounds.
Structure and properties of silicon-silicon doubly bonded compounds (disilenes) are shown to be remarkably different from those of alkenes. X-Ray structural analysis of a series of acyclic tetrakis(trialkylsilyl)disilenes has shown that the geometry of these disilenes is quite flexible, and planar, twist or trans-bent depending on the bulkiness and shape of the trialkylsilyl substituents. Thermal and photochemical interconversion between a cyclotetrasilene and the corresponding bicyclo[1.1.0]tetrasilane occurs via either 1,2-silyl migration or a concerted electrocyclic reaction depending on the ring substituents without intermediacy of the corresponding tetrasila-1,3-diene. Theoretical and spectroscopic studies of a stable spiropentasiladiene have revealed a unique feature of the spiroconjugation in this system. Starting with a stable dialkylsilylene, a number of elaborated disilenes including trisilaallene and its germanium congeners are synthesized. Unlike carbon allenes, the trisilaallene has remarkably bent and fluxional geometry, suggesting the importance of the π-σ* orbital mixing. 14-Electron three-coordinate disilene-palladium complexes are found to have much stronger π-complex character than related 16-electron tetracoordinate complexes.


The prevalence and importance of frailty in heart failure with reduced ejection fraction - an analysis of PARADIGM-HF and ATMOSPHERE.
Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of 'health deficits' across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF). Using a cumulative deficits approach, we constructed a 42-item frailty index (FI) and applied it to identify frail patients enrolled in two HFrEF trials (PARADIGM-HF and ATMOSPHERE). In keeping with previous studies, patients with FI ≤0.210 were classified as non-frail and those with higher scores were divided into two categories using score increments of 0.100. Clinical outcomes were examined, adjusting for prognostic variables. Among 13 625 participants, mean (± standard deviation) FI was 0.250 (0.10) and 8383 patients (63%) were frail (FI >0.210). The frailest patients were older and had more symptoms and signs of heart failure. Women were frailer than men. All outcomes were worse in the frailest, with high rates of all-cause death or all-cause hospitalization: 40.7 (39.1-42.4) vs. 22.1 (21.2-23.0) per 100 person-years in the non-frail; adjusted hazard ratio 1.63 (1.53-1.75) (P < 0.001). The rate of all-cause hospitalizations, taking account of recurrences, was 61.5 (59.8-63.1) vs. 31.2 (30.3-32.2) per 100 person-years (incidence rate ratio 1.76; 1.62-1.90; P < 0.001). Frailty is highly prevalent in HFrEF and associated with greater deterioration in quality of life and higher risk of hospitalization and death. Strategies to prevent and treat frailty are needed in HFrEF.


Fibrosing cholestatic hepatitis in HIV/HCV co-infected transplant patients-usefulness of early markers after liver transplantation.
We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.


Monomer and Excimer Emission in Electrogenerated Chemiluminescence of Pyrene and 2,7-Di-tert-butylpyrene Associated with Electron Transfer Distance.
Electrogenerated chemiluminescence (ECL) is a light emission phenomenon caused by electrochemically generated radical anions (R•-) and cations (R•+), in which the ion annihilation results in the formation of a pair of excited (R*) and ground state (R) of a luminescent molecule. Here, the ECL properties of pyrene (Py) and 2,7-di-tert-butylpyrene (di-t-BuPy) are reported. It was found that at a commonly employed concentration (1 mM), the ECL spectra were time-dependent because of increasing the oligomer emission and increasing the concentration of R near R*, leading to an enhancement of the excimer emission. At a low concentration range (20-30 μM), the shape of the ECL spectra containing the monomer and excimer emission was determined by isolated pairs of R* and R, which were generated through ion annihilation of R•- and R•+. It was found that in the ECL of Py and di-t-BuPy originated from the isolated pairs of R•- and R•+, 58 and 48% of the excited states were the excimer states, respectively. Diffusion equation analysis indicates that the lower excimer formation in the case of di-t-BuPy is because of a farther initial separation distance between R* and R, i.e., a longer electron transfer distance between the radical ions. The Marcus model for the electron transfer kinetics suggests that the farther electron transfer distance is mainly caused by the larger molecular size, which resulted in a smaller reorganization energy of the solvent acetonitrile molecule. Taking advantage of the photophysical and electrochemical properties of Py and di-t-Bu Py, the monomer and excimer emission in ECL is discussed.


[Anatomy of the retina].
The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the diencephalon, the neuroretina is a layered tissue composed of six types of neuronal cells (two types of photoreceptors: cones and rods, horizontal, bipolar, amacrine and ganglion cells) and three types of glial cells (Müller glial cells, astrocytes and microglial cells). The neuroretina lays on the retinal pigmentary epithelium, that together form the retina. The existence of the internal and external blood-retinal barriers and intra-retinal junctions reflects the fineness of regulation of the retinal exchanges with the circulation and within the retina itself. The central zone of the human retina, which is highly specialized for visual acuity, has anatomical specificities. Recent imaging methods make it possible now to enrich our knowledge of the anatomical and functional characteristics of the retina, which are still imperfectly described.


An educator's perspective on the emerging Cuba and multiculturalism.
Plagued by many years of frequent leadership changes, and influences from power brokers whose policies and politics were oftentimes detrimental to Cuba's emerging as an industrialized and diverse economy nation, Cuba is now attempting to move beyond the survival mode. After the symbiotic relationship between the Soviet Union was dismantled in the 90s, Cuba is now undergoing metamorphoses of growth and change, socially, politically and culturally, while still remaining a mixture of worlds both rural and urban. This narrative article describes the multicultural experiences that an American university professor recently experienced while visiting Cuba.