Cyclobranol: a substrate for C25-methyl sterol side chains and potent mechanism-based inactivator of plant sterol methyltransferase.
Cyclobranol 8A, an analog of the cycloartenol substrate 1A for the plant sterol C24-methyltransferase (SMT), was shown to be an acceptor of the soybean SMT1 as well as an inhibitor of enzyme action. The K(m) and k(cat) for 8A was 37 microM and 0.006 min(-1), respectively. The enzyme-generated product was identified by MS and (1)H NMR to be a C24, C25-doubly alkylated Delta(24(28))-olefin 10A. Inhibitor treatment was concentration and time-dependent affording an apparent K(i) of 25 microM, a maximum rate of inactivation of 0.15 min(-1) and a partition ratio (k(cat)/k(inact)) calculated to be 0.04.


Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice.
To identify the genes and signal pathways responsible for mechanical loading-induced bone formation, we evaluated differential gene expression on a global basis in the tibias of C57BL/6J (B6) mice after four days of four-point bending. We applied mechanical loads to the right tibias of the B6 mice at 9 N, 2 Hz for 36 cycles per day, with the left tibias used as unloaded controls. RNA from the tibias was harvested 24 h after last stimulation and subjected to microarray. Of the 20,280 transcripts hybridized to the array, 346 were differentially expressed in the loaded bones compared to the controls. The validity of the microarray data was established with the increased expression of bone-related genes such as pleiotrophin, osteoglycin, and legumain upon four-point bending and confirmation of increased expression of selected genes by real-time PCR. The list of differentially expressed genes includes genes involved in cell growth, differentiation, adhesion, proteolysis, as well as signaling molecules of receptors for growth factors, integrin, Ephrin B2, endothelin, and adhesion G protein coupled receptor. Pathway analyses suggested that 28 out of the 346 genes exhibited a direct biological association. Among the biological network, fibronectin and pleitrophin function as important signaling molecules in regulating periosteal bone formation and resorption in response to four-point bending. Furthermore, some expressed sequence tags (ESTs) with no prior known function have been identified as potential mediators of mechanotransduction signaling pathways. Further studies on these previously unknown genes will improve our understanding of the molecular pathways and mechanisms involved in bone's response to mechanical stress.


Biochemical interaction of six OP delayed neurotoxicants with several neurotargets.
Five organophosphorous insecticides: Leptophos, EPN, Cyanofenphos, trichloronate and salithion proved to cause irreversible ataxia not only to chicken but also to mice and sheep. TOCP was included as a reference. Cyanofenphos blocked the catecholamine B-receptor binding activity with 3H-norepinephrine at a level similar to that of the specific inhibitor propranolol in the mouse heart preparation. In the lamb heart preparation, the B-receptor was more sensitive to Leptophos, salithion and TOCP than to propranolol. The six compounds and their oxons were screened for their in-vitro inhibition to monamine oxidase (MAO), acetyl cholinesterase (AChE) and neurotoxic esterase (NTE) in the brain of either mouse, lamb or chicken. It is believed that their AChE inhibition stands for their acute toxicity, while NTE inhibition is responsible for their paralytic ataxia.


Efficacy and Safety of the Surgery-First Approach Compared to the Chemotherapy-First Approach for Treating Low-Risk Gestational Trophoblastic Neoplasia: A Systematic Review and Meta-Analysis.
For gestational trophoblastic neoplasia (GTN) affecting women of reproductive age, the chemotherapy-first approach is often preferred over the surgery-first approach. Low-risk GTN is treated with a chemotherapy-first approach, but the number of courses required can affect fertility. A surgery-first approach may decrease the number of chemotherapy courses, but its efficacy and safety compared to a chemotherapy-first approach are unclear. Thus, we investigated the efficacy and safety of the surgery-first approach compared to the chemotherapy-first approach in treating low-risk GTN. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases for relevant articles in July 2023. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. The primary outcomes were remission, the mean number of chemotherapy courses required to cure, and adverse events. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study protocol was registered in the Open Science Framework (https://osf.io/kysvn/). Studies for low-risk GTN included a qualitative synthesis (with 2,192 participants and ten studies, eight of which were about second uterine curettage and two about hysterectomy) and a meta-analysis (with 138 participants and two randomized controlled trials (RCTs) that compared first-line treatments of second uterine curettage and chemotherapy). Second uterine curettage may result in little to no difference in remission (risk ratio: 1.00, 95% confidence interval: 0.96-1.05; low certainty) and a slight reduction in adverse events (risk ratio: 0.87, 95% confidence interval: 0.47-1.60; low certainty). The evidence is very uncertain on the mean number of chemotherapy courses (mean difference: 2.84 lower, 95% confidence interval: 7.31 lower to 1.63 higher; very low certainty). Based on clinical outcomes, second uterine curettage can be comparable to the chemotherapy-first approach as a first-line treatment option for low-risk GTN; however, the overall certainty of the evidence was low or very low.


Feasibility of point of care testing for prevention and management of breast cancer therapy associated comorbidities in 6 African countries: short communication.
Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer (BC) survivors using aromatase inhibitors (AIs). This study was conducted to assess the impact of point of care technology (PCOT) as part of pathology supported genetic testing (PSGT) to prevent BC therapy-associated comorbidities in African settings. The study revealed that high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) are predictors of cardiovascular (CVD) related adverse events in obese postmenopausal patients subjected to AIs. There were statistically significant variations in total body fat (TBF), weight, hs-CRP, body mass index (BMI), homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. The above inflammatory markers can be incorporated in pathology supported genetic testing (PSGT) using HyBeacon® probe technology at POC for prediction and management of AI-associated adverse events among postmenopausal breast cancer survivors and associated comorbidities. The barriers for implementation of POCT application among six African countries for diagnosis of breast cancer were documented as insufficient of BC diagnosis and management capacity at different levels of health system.


Localization of two myosin-subfragment-1 binding contacts in the 96-132 region of actin subdomain-1.
Many direct observations and indirect experimental approaches have pin-pointed two segments (sequences 1-28 and 360-372) in actin subdomain-1 which bind to myosin subfragment-1. In a previous investigation [Labbé, J. P., Méjean, C., Benyamin, Y. & Roustan, C. (1990) Biochem. J. 271, 407-413], we have observed competition between myosin subfragment-1 and anti-actin antibodies specific to epitopes including Thr103. A multisite interface model has also been proposed to take into account myosin-head binding to the N-terminal and C-terminal regions and to more central 40-113 sequence of actin. In the present study, two limited actin segments encompassing residues 96-103 and 112-125 were identified as myosin-head-binding sites. Myosin subfragment-1 competed for monomeric actin with the antibodies directed against sequences 96-105 and 114-120 and its binding to the tryptic 96-113 and synthetic 112-125 actin peptides was prevented by magnesium pyrophosphate but not by calcium pyrophosphate. In the presence of ATP-Mg2+, myosin subfragment-1 was dissociated by filamin from its complex with monomeric actin or with peptide 105-120. Contact points of filamin on actin were previously located in the 105-120 and 360-372 actin sequences [Méjean, C., Lebart, M. C., Boyer, M., Roustan, C. & Benyamin, Y. (1992) Eur. J. Biochem. 209, 555-562]. The in vitro inhibitory effect of filamin on actin-activated Mg2+-ATPase would thus be explained by this competition. Furthermore, the (27-kDa-50-kDa-20-kDa) trypsin-split myosin subfragment-1 which could no longer be activated by actin, did not bind at all to the two sites located in the 96-125 region, but it still interacted with the 360-372 segment. Our results regarding the position of the myosin head on actin monomers in rigor conditions provide evidence on the presence of two topologically independent contact points in the myosin-head/actin interface. One group exposed residues in the 1-7, 21-29, 77-95 and 96-103 actin segment, another, on the opposite side of subdomain-1, included residues from 112-125 and 360-372 sequences.


[Psoriatic arthritis: considerations on recent studies: serum beta 2 microglobulin and circulating T-gamma lymphocytes].
The results of two recent studies of our group have been reported. They regard two immunological parameters of psoriatic arthritis: the proportions of T gamma lymphocytes in peripheral blood and the beta 2 microglobulin in the serum. The data obtained in psoriatic arthritis patients have been compared to those found in normal controls and in rheumatoid arthritis patients. T gamma mean values in psoriatic arthritis were significantly lower than those present in healthy subjects and in rheumatoid patients. These last patients showed beta 2 microglobulin mean values significantly higher than those observed in normal controls and in psoriatic arthritis patients. Conversely, the mean of beta 2 microglobulin levels in psoriatic arthritis has been found to be similar to that observed in normal controls, but a superimposition in the range of individual values of these two groups with the concentrations determined in rheumatoid subjects has been found. These results seem to be of interest in relation to the immunopathogenetic mechanism of psoriatic arthritis, but are of little help in the clinical differentiation of the two rheumatological affections considered.


Dental anxiety among Australians.
This study aimed to estimate the prevalence of dental anxiety and examine its associations among a representative sample of Australians aged 18 and over. A random sub-sample of participants in a national dental telephone interview survey completed a follow-up postal questionnaire (response rate 85.2 per cent) which included Corah's Dental Anxiety Scale (DAS). The prevalence of dental anxiety (defined by a DAS score of 13 or more) in the sample was 14.9 per cent, with overall severity represented by the mean score of 9.04 (sd, 3.45). The prevalence and severity of dental anxiety were greater among women than men, and in the 35-44 age group. High-anxiety individuals reported more deferring of dental care, and more frequently reported an episodic dental visiting pattern. Although there were no differences in dental anxiety by self-reported dental status, individuals who reported impact from their oral conditions had higher dental anxiety. These associations with social impacts and deferment of care indicate that dental anxiety may be an important dental public health problem in Australia.


Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization.
We used immunohistochemistry to detect tumor necrosis factor (TNF) and in situ hybridization to detect TNF messenger RNA (mRNA) in the intimal mesenchymal-appearing cells and in the medial smooth muscle cells of human atherosclerotic arteries. Medial smooth muscle cells showed localization of immunoreactive TNF on the cell surface and did not express TNF mRNA. Conversely, in intimal mesenchymal-appearing cells, TNF was localized in the cytoplasm and TNF mRNA was expressed by in situ hybridization. Thus 89% of intimal cells were immunohistochemically positive for TNF, 96% of them were positive by in situ hybridization, and 76% were positive for the smooth muscle cell marker, HHF35. Our results suggest that intimal mesenchymal-appearing cells are mostly, but not exclusively, derived from smooth muscle cells. These cells express TNF, whereas the medial smooth muscle cells in the atherosclerotic human arteries do not. The expression of TNF by these mesenchymal-appearing cells may have implications regarding the evolution of the atherosclerotic plaque.


Towards Remote Lightning Manipulation by Meters-long Plasma Channels Generated by Ultra-Short-Pulse High-Intensity Lasers.
Remote manipulation (triggering and guiding) of lightning in atmospheric conditions of thunderstorms has been the subject of intense scientific research for decades. High power, ultrashort-pulse lasers are considered attractive in generating plasma channels in air that could serve as conductors/diverters for lightning. However, two fundamental obstacles, namely the limited length and lifetime of such plasma channels prevented their realization to this date. In this paper, we report decisive experimental results of our multi-element broken wire concept that extends the generated plasma channels to the required tens of meters range. We obtain 13-meter-long plasma wire, limited only by our current experimental setup, with plasma conditions that could be sufficient for the leader initiation. This advance, coupled with our demonstrated method of laser heating for long time sustenance of the plasma channel, is a major, significant step towards controlling lightning.


[Uncommon mycobacterial infections in domestic and zoo animals: four cases with special emphasis on pathology].
Infections caused by classical tubercle bacilli are rare during the last years. Nevertheless, diseases caused by other mycobacteria have to be considered clinically and in diagnostic pathology especially in cases of immunosuppression and due to their potential zoonosis risk. An infection by mycobacteria was diagnosed in four animals (Mayotte Maki, Blue-headed Parrot, Patagonian sealion, Beagle) necropsied between 1995 and 2002 in the Institute of Veterinary-Pathology of the University of Leipzig. The Maki, the blue-headed parrot and the dog showed a disseminated character of the disease caused by Mycobacterium genavense (monkey and bird) resp. Mycobacterium avium (dog), while an open chronical tuberculosis of the lungs due to a pathogenic member of Mycobacterium tuberculosis complex was observed in the seal. All these bacteria are potential causes of zoonoses. So, if granulomatous or disseminated histiocytic alterations are detected in diagnostic pathology, mycobacterial infections should always be included in differential diagnoses and require careful aetiological investigations by histopathological and bacteriological methods.


Unusual characteristics of amino-terminal and hydrophobic domains in nuclear-encoded thylakoid signal peptides.
Thylakoid transfer signals carry information specifying translocation by either a Sec- or delta pH-dependent protein translocator in the chloroplast thylakoid membrane, yet all resemble classical signal peptides in overall structural terms. Comparison of known transfer signals reveals two differences: (a) signals for the delta pH-driven system invariably contain a critical twin-arginine (Arg-Arg) motif prior to the hydrophobic (H) domain, whereas known Sec-dependent signals contain lysine, and (b) the H-domains of Sec-dependent signals are generally longer. Previous work has shown that a twin-Arg motif before the H-domain is critical for targeting by the delta pH-dependent pathway; in this report we show that the charge characteristics of this region are not important for sorting by the Sec pathway. Twin-Lys, twin-Arg or single Arg are all acceptable to the Sec system, although single Lys/Arg is preferred. The single Lys in pre-plastocyanin can even be replaced by an uncharged residue without apparent effect. We have also generated a pre-plastocyanin mutant containing an H-domain which, in terms of hydropathy profile, is identical to that of a delta pH-dependent protein. This mutant is also transported efficiently by the Sec system, demonstrating that hydrophobicity per se is not a key sorting determinant. However, the characteristics of the H-domain may be important in avoiding a different form of mis-targeting: to the endoplasmic reticulum. Thylakoid signal peptides have undergone substantial structural changes during the evolution of the chloroplast from endosymbiotic cyanobacterium: plastid-encoded and cyanobacterial signals contain H-domains that are highly hydrophobic and enriched in Leu and aromatic residues, whereas nuclear-encoded counterparts are Ala-rich and far less hydrophobic. We speculate that this trend may reflect a need to avoid mistargeting through recognition by cytosolic signal recognition particle, which preferentially interacts with more hydrophobic signal peptides.


HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction.
To explore effects of hepatocyte growth factor (HGF) combined with insulin-like growth factor 1 (IGF-1) on transplanted bone marrow mesenchymal stem cells (BMSCs), for treatment of acute myocardial ischaemia. After ligation of the left anterior descending artery, rabbits were divided into a Control group, a Factors group (HGF+IGF-1), a BMSC group and a Factors+BMSCs group. Allogenous BMSCs (1 × 10(7)) and/or control-released microspheres of 2 μg HGF+2 μg IGF-1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSCs, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro, BMSCs were exposed to HGF, IGF-1 and both (50 ng/ml) and subsequently proliferation, migration, myocardial differentiation and apoptosis induced by hypoxia, were analysed. Four weeks post-operatively, the above indices were significantly improved in Factors+BMSCs group compared to the others (P < 0.01), although Factors and BMSCs group also showed better results than Control group (P < 0.05). In vitro, HGF promoted BMSC migration and differentiation into cardiomyocytes, but inhibited proliferation (P < 0.05), while IGF-1 increased proliferation and migration, and inhibited apoptosis induced by hypoxia (P < 0.05), but did not induce myocardial differentiation. Combination of HGF and IGF-1 significantly promoted BMSCs capacity for migration, differentiation and lack of apoptosis (P < 0.05). Combination of HGF and IGF-1 activated BMSCs complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSCs to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury.


New hexactinellid sponges from deep Mediterranean canyons.
During the exploration of the NW Mediterranean deep-sea canyons (MedSeaCan and CorSeaCan cruises), several hexactinellid sponges were observed and collected by ROV and manned submersible. Two of them appeared to be new species of Farrea and Tretodictyum. The genus Farrea had so far been reported with doubt from the Mediterranean and was listed as "taxa inquirenda" for two undescribed species. We here provide a proper description for the specimens encountered and sampled. The genus Tretodictyum had been recorded several times in the Mediterranean and in the near Atlantic as T. tubulosum Schulze, 1866, again with doubt, since the type locality is the Japan Sea. We here confirm that the Mediterranean specimens are a distinct new species which we describe. We also provide18S rDNA sequences of the two new species and include them in a phylogenetic tree of related hexactinellids.


[The impact factor and editorial decisions].
Although it is questioned, the impact factor continues to be the indicator of quality of medical publications and a hierarchical instrument of information. The authors review the influence of the search for the highest impact factor in editorial decisions for both the journal format and in the procedure of accepting manuscripts. In addition, the role of the denominator modifications and the language of the publication as well as how the acceptance of an article may be influenced not only by the quality parameters but also in the interest of the publication are reviewed. The strategic policy of a journal influences the editorial decisions and the gamble made to achieve a growing impact factor condition these decisions.


The Canadian National EMS Research Agenda: a mixed methods consensus study.
Research is essential for the development of evidence-based emergency medical services (EMS) systems of care. When resources are scarce and gaps in evidence are large, a national agenda may inform the growth of EMS research in Canada. This mixed methods consensus study explores current barriers and existing strengths within Canadian EMS research, provides recommendations, and suggests EMS topics for future study. Purposeful sampling was employed to invite EMS research stakeholders from various roles across the country. Study phases consisted of 1) baseline interviews of a subsample, 2) roundtable discussion, and 3) an online Delphi survey, in which participants scored each statement for importance. Consensus was defined a priori and met if 80% scored a statement as "important" or "very important." Fifty-three stakeholders participated, representing researchers (37.7%), EMS administrators (24.6%), clinicians/providers (20.7%), and educators (17.0%). Participation rates were as follows: interviews, 13 of 13 (100%); roundtable, 47 of 53 (89%); survey round 1, 50 of 53 (94%); survey round 2, 47 of 53 (89%); and survey round 3, 40 of 53 (75%). A total of 141 statements were identified as important: 20 barriers, 54 strengths/opportunities, 31 recommendations, and 36 suggested topics for future research. Like statements were synthesized, resulting in barriers (n = 10), strengths/opportunities (n = 24), and recommendations (n = 19), which were categorized as time, opportunities, and funding; education and mentorship; culture of research and collaboration; structure, process, and outcome of research; EMS and paramedic practice; and the future of the EMS Research Agenda. Consensus-based key messages from this agenda should be considered when designing, funding, and publishing EMS research and will advance EMS research locally, regionally, and nationally.


USING MACHINE LEARNING TO MITIGATE THE EFFECTS OF REVERBERATION AND NOISE IN COCHLEAR IMPLANTS.
In listening environments with room reverberation and background noise, cochlear implant (CI) users experience substantial difficulties in understanding speech. Because everyday environments have different combinations of reverberation and noise, there is a need to develop algorithms that can mitigate both effects to improve speech intelligibility. Desmond et al. (2014) developed a machine learning approach to mitigate the adverse effects of late reverberant reflections of speech signals by using a classifier to detect and remove affected segments in CI pulse trains. This study aimed to investigate the robustness of the reverberation mitigation algorithm in environments with both reverberation and noise. Sentence recognition tests were conducted in normal hearing listeners using vocoded speech with unmitigated and mitigated reverberant-only or noisy reverberant speech signals, across different reverberation times and noise types. Improvements in speech intelligibility were observed in mitigated reverberant-only conditions. However, mixed results were obtained in the mitigated noisy reverberant conditions as a reduction in speech intelligibility was observed for noise types whose spectra were similar to that of anechoic speech. Based on these results, the focus of future work is to develop a context-dependent approach that activates different mitigation strategies for different acoustic environments.


Luminescence of tartrate bridged dinuclear 2,2'-bipyridine platinum(ii) complexes: emission color controlled by intra- and inter-molecular interactions in the solid state.
Novel dinuclear PtII complexes with a chiral (l-) and an achiral (meso-) tartrate [{PtII(bpy)}2(μ-x-tart)] (bpy: 2,2'-bipyridine; tartH22-: tartrate; x = l (1), meso (2)) and with a racemic (dl-) tartrate [{PtII(bpy)}2(μ-d-tart)][{PtII(bpy)}2(μ-l-tart)] (3) were synthesized, and the influence of their stereochemistry on their molecular and crystal structures affecting their luminescence was discussed. Effects of the dinuclearity on the structures and luminescence were revealed by comparison with those of a novel racemic mononuclear complex [PtII(bpy)(d-tartH2)][PtII(bpy)(l-tartH2)] (4). The X-ray crystallography showed the crystallization of 1 in two polymorphs, namely monoclinic 3[1·6H2O] (1α) and triclinic 2[1·6H2O] (1β), and those of other complexes in monoclinic hydrate crystals 2·12.5H2O, 3·4H2O, and 4·H2O. The chiral complexes in 1α, 1β, and 3·4H2O showed clamshell-like structures with Pt-Pt and π-π interactions, while the achiral complex in 2·12.5H2O displayed a twisted form without intramolecular interactions. The complexes in 1α were assembled in a right-handed helical arrangement through significant Pt-Pt interactions, and those in 1β and 3·4H2O were stacked in one-dimensional columns through significant and slight π-π interactions, respectively. The complex in 2·12.5H2O constructed an intermolecular dimer through Pt-Pt interactions with its adjacent complex. The crystal structure of 4·H2O displayed a three-dimensional network architecture through π-π interactions and hydrogen bonding. These crystals exhibited luminescence depending on their molecular and crystal structures (λmax nm = 535 (4·H2O), 569 (3·4H2O), 621 (2·12.5H2O), 649 (1β), and 656 (1α)). The formations of intermolecular dimers and clamshell-like structures through Pt-Pt interactions in 2·12.5H2O and in 3·4H2O, respectively, lead to red-shifts in emissions compared to 4·H2O, and further low-energy emissions of 1α and 1β were derived from the intermolecular Pt-Pt and π-π interactions, respectively.


Knockdown of von Hippel-Lindau protein decreases lung cancer cell proliferation and colonization.
Although von Hippel-Lindau protein (pVHL) is known as a tumor suppressor in kidney and other organs, it remains unclear whether pVHL plays a role in lung cancer development. We investigated the role of pVHL in lung cancer cell proliferation, migration, and colonization using stable A549 cells with knockdown of pVHL. We found that knockdown of pVHL promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. Knockdown of pVHL decreased tumor colonization in a tail-vein injection model and decreased cell proliferation, whereas overexpression of constitutive active HIF increased tumor colonization, suggesting a HIF-independent function of pVHL in lung. Knockdown of pVHL decreased phosphorylation of FAK and expression of integrin, suggesting that pVHL regulates lung cancer development via integrin/FAK signaling pathway.


Suicide rates during and after the first COVID-19 lockdown in Germany in 2020.
The impact of the COVID-19 pandemic and of measures implemented to curb the spread of the virus on suicidal behavior has been investigated in different regions of the world, but does not yet allow to draw conclusions for Germany. Especially lockdowns might have effects on suicide rates via impact on mental disorders, changes in the choice of suicide method, a decrease in help seeking behavior, or a deterioration in the quality of medical care for people with mental disorders. The following research questions were addressed: i) did suicide rates in Germany in 2020 change during lockdown and non-lockdown periods when compared to a ten-year baseline? ii) was there a change in the proportion of suicide methods during the lockdown compared to baseline? An interrupted time-series analysis based on a linear regression was used. For the comparisons of predicted and observed suicide rates, excess suicide mortality rates (ESMR) were chosen among others. Changes in the choice of method were analyzed by comparing the rates of different methods to those at baseline. Although the mean suicide rate in 2020 was not significantly different from baseline, the weekly analysis of suicide rates revealed a significant difference (χ2 = 64.16; df = 39; p = 0.007), with some weeks showing higher and others lower rates than previous years. The effects for separate weeks were attenuated to non-significance after correction for multiple testing. Suicide mortality during the first lockdown in 2020 was significantly lower than expected (ESMR = 0.933; 95% CI: 0.890; 0.985) whereas, in the post-lockdown period, the registered suicide mortality was not significantly different from the expected one (ESMR = 1.024; 95% CI: 0.997; 1.051). During lockdown, there was a significant increase of the percentage of the suicide method categories jumping and 'other methods' and a decrease of poisoning and lying in front of a moving object. Being able to determine whether the choice of more or less lethal methods during lockdown versus non-lockdown periods partly explains this finding would require a representative assessment of attempted suicides.


Fabrication of Highly Luminescent Quasi Two-Dimensional CsPbBr3 Perovskite Films in High Humidity Air for Light-Emitting Diodes.
Perovskite light-emitting diodes (LEDs) have attracted extensive attention in recent years due to their outstanding performance and promise in lighting and display applications. However, the fabrication of perovskite LEDs usually requires a low-humidity atmosphere, which is unfavorable for industrial production. Herein, we report an effective strategy to fabricate highly luminescent quasi two-dimensional CsPbBr3 perovskite films in an ambient atmosphere with a humidity up to 60%. We reveal that the hole transport layer (HTL) plays a significant role in the morphology and optical properties of the perovskite films. Using hydrophobic self-assembled monolayer materials as HTLs can remarkably improve the quality of the perovskite films processed in high humidity air. The resultant perovskite LEDs show reduced leakage current and significantly enhanced performance. Furthermore, surface treatment is conducted to prevent water invasion and promote radiative recombination in perovskite films and LEDs. Eventually, the perovskite LEDs exhibit bright green emission with an external quantum efficiency of 4.87%. The present work provides a feasible pathway to overcome the humidity limitation for obtaining bright perovskite films and LEDs, which would contribute to further reducing the fabrication cost of perovskite LEDs and promoting their applications.


Ureteropelvic junction obstruction: does CT angiography allow better selection of therapeutic modalities and better patient outcome?
To determine whether preoperative helical CT angiography (CTA) with three-dimensional (3D) reconstructed images improves outcome in patients with ureteropelvic junction obstruction (UPJO) by identifying crossing vessels that may lead to surgical failure. Twenty-five patients with UPJO underwent imaging with CTA to identify crossing vessels. Patients with crossing vessels or severe hydronephrosis underwent laparoscopic dismembered pyeloplasty. In the absence of crossing vessels, and with >25% renal function on MAG-3 scan, the patient underwent an endopyelotomy. Procedures were assessed as successful by resolution of patient symptoms as well as relief of obstruction on renal scintography. Twenty-seven procedures (14 laparoscopic dismembered pyeloplasties [9 in the setting of a crossing vessel], 11 ureteroscopic endopyelotomies, and two antegrade endopyelotomy procedures) were performed. Follow-up ranged from 2.4 to 40 months (mean 21.6 months). Twenty-three of the primary procedures (92.0%) were successful. Primary laparoscopic pyeloplasty was successful in 100% of patients, while primary endopyelotomy had a success rate of 83.3%. Both secondary procedures were successful rendering the patients unobstructed and pain free. No complications occurred. The sensitivity and specificity of CTA in determining crossing vessels was 78% and 40%, respectively. Helical CT angiography with 3D reconstructed images provides valuable preoperative information in patients with UPJO scheduled for surgical intervention. This study may be used in selecting patients for proper operative intervention according to the anatomy of crossing vessels to attain high treatment success rates.


Antipsychotic treatment of schizotypy and schizotypal personality disorder: a systematic review.
Schizotypal personality disorder (SPD) is characterised by thought disorders, experiences of illusions, obsessive ruminations, bizarre or eccentric behaviour, cognitive problems and deficits in social functioning - symptoms that SPD shares with schizophrenia. Efforts have been undertaken to investigate the relationship between these conditions regarding genetics, pathophysiology, and phenomenology. However, treatment of SPD with antipsychotics has received less scientific attention. Embase and PubMed databases were searched using all known generic names of antipsychotics as search terms in combination with the following diagnostic terms: latent schizophrenia, schizotypal disorder, latent type schizophrenia, or SPD. Studies were categorised according to evidence level on the basis of their methodology from A, being the best, to E, being the worst. Five hundred and nine studies were retrieved and scrutinised. Sixteen studies, from the period 1972 to 2012, on antipsychotic treatment of SPD were extracted. Four studies were categorised as evidence level A, two as level B, six as level C and three as level D, with one study level E. Only four randomised, double-blind, placebo-controlled trials, on subjects with well-defined diagnoses, exists. Only amisulpride, risperidone and thiothixene have been studied according to evidence level A. This result warrants further high quality studies of the effects of antipsychotic treatment of SPD.


Role of early thoracoscopy for management of penetrating wounds of the chest.
Most nonlife-threatening penetrating wounds of the chest (PWC) are treated with a chest tube alone. This may be inadequate because missed injuries, retained hemothorax, or foreign material may be difficult to address later. Early thoracoscopy should improve outcome. We conducted a retrospective review of 88 stable patients with PWC initially treated with a chest tube and had retained a hemothorax beyond 48 hours. Twenty-seven underwent an early video-assisted thoracoscopy (VATS). Fifty-five were observed, chest tubes were manipulated, or an additional one placed. The outcome was compared with the National Trauma Data Bank and controlled for Injury Severity Score. Early VATS reduced length of stay (4.3 vs 9.4 days), days in the intensive care unit (1.3 vs 3.2), and open thoracotomy (0 vs 7). A chest tube undertreats a nonlife-threatening PWC correctable by timely VATs.


Association study between the dopamine receptor D(4) gene and obsessive-compulsive disorder.
Pharmacological and neuroanatomical evidence suggest the involvement of the dopaminergic system in obsessive-compulsive disorder (OCD). Analysis of the 48-bp dopamine receptor D(4) (DRD4) gene polymorphism in a sample of 210 OCD patients and 202 healthy control subjects showed a significant association (chi(2)=27.5, df=6, p=0.0003). This difference was attributable to a lower frequency of allele 4R in OCD patients compared with the control group (chi(2)=9.33, p=0.0027). However, we did not replicate previous findings of an association between the 7R allele and OCD patients with tics. Finally, we analyzed a sub-sample of 86 OCD families. E-TDT analysis in 70 informative parents did not confirm the association observed in our case-control analysis. In conclusion, the current study cannot exclude an association between DRD4 gene and OCD in the largest sample analyzed. However, further studies will be required to confirm if the DRD4 gene is involved in the pathogenesis of this disorder.


A Stability-Indicating RP-HPLC Assay Method for 5-Fluorouracil.
The present study describes the development of a validated RP-HPLC method for the determination of 5-fluorouracil in presence of its degradation products or other pharmaceutical excipients. Stress studies were performed on 5-fluorouracil and it was found that it degrades sufficiently in alkaline conditions, while negligible degradation was observed in acidic, neutral, oxidative and photolytic conditions. The peaks of the degradation products were not observed in the chromatogram due to the nonchromophoric nature of the degradation moiety formed. The separations were carried out on a C-18 reversed phase column (Phenomenex; Prodigy ODS3V, 250x4.6 mm, 5 mu) using 50mM KH(2)PO(4) (pH, 5.0) as mobile phase at a flow rate of 1.2 ml/min and temperature of 30 degrees . The wavelength of detection was 254 nm. A retention time of nearly 6 minutes was obtained. Analytical validation parameters such as specificity and selectivity, linearity, accuracy and precision were evaluated. The calibration curve for 5-fluorouracil was linear (r(2)=0.999+/-0.0005) from range of 10 mug/ml to 100 mug/ml. Relative standard deviation values for all the key parameters, was less than 2.0 %. The recovery of the drug after standard addition to the degraded sample was found to be 104.69%. Thus, the developed RP-HPLC method was found to be suitable for the determination of 5-fluorouracil in bulk as well as stability samples of the pharmaceutical dosage forms containing various excipients.


Being a supportive presence in online courses: attending to students' online presence with each other.
As a teacher involved in distance education, being a supportive presence includes attending to and facilitating students' knowing and connecting with other. This creates places for learning that are safe, fair, and respectful, which reflects the concerns of the interpretive pedagogies (Diekelmann & Diekelmann, in press). Reflecting a larger issue is the importance of contemporary nurses' knowing and connecting with other team members, and with patients, online in ways that engender community and achieve desired outcomes. With this in mind, attending to the Concernful Practices that enable students to know and connect in ways other than face-to-face encounters becomes even more relevant in preparing for today's practice environments.


MicroRNA-125b-5p mediates post-transcriptional regulation of hepatitis B virus replication via the LIN28B/let-7 axis.
MicroRNAs (miRNAs) are able to modulate hepatitis B virus (HBV) replication and play an important role in the pathogenesis of HBV infection. Recently, we have identified that serum miR-125b-5p levels correlated with HBV DNA levels and liver necroinflammation. In the present study, we addressed how miR-125b-5p regulated HBV replication at the different steps, inclduing viral transcription, assembly, and virion production and investigated the underlying mechanisms. We found that miR-125b-5p overexpression increased HBV replication without altering HBV transcription. This is the first demonstration of post-transcriptional miRNA regulation of HBV replication. In contrast, transfection of miR-125b-5p inhibitor resulted in downregulation of HBV replication in hepatoma cells. Further, miR-125b-5p inhibited the phosphorylation of retinoblastoma protein and blocked cell cycle progression at the G1/S phase in hepatoma cell lines. Our results indicate that certain miRNAs are able to arrest the cell cycle at G1 phase and may increase HBV replication. RNA sequencing revealed several liver-specific metabolic pathways regulated by miR-125b-5p, which was also found to suppress LIN28B and induce let-7 family members. Additional data demonstrated that miR-125b-5p targeted the LIN28B/let-7 axis to stimulate HBV replication at a post-transcriptional step.


Characterization of a new toxin from the entomopathogenic fungus Metarhizium anisopliae: the ribotoxin anisoplin.
Metarhizium anisopliae is an entomopathogenic fungus relevant in biotechnology with applications like malaria vector control. Studies of its virulence factors are therefore of great interest. Fungal ribotoxins are toxic ribonucleases with extraordinary efficiency against ribosomes and suggested as potential insecticides. Here we describe this ribotoxin characteristic activity in M. anisopliae cultures. Anisoplin has been obtained as a recombinant protein and further characterized. It is structurally similar to hirsutellin A, the ribotoxin from the entomopathogen Hirsutella thompsonii. Moreover, anisoplin shows the ribonucleolytic activity typical of ribotoxins and cytotoxicity against insect cells. How Metarhizium uses this toxin and possible applications are of interest.


The N-silylation of sulfoximines.
The copper-catalyzed N-silylation of sulfoximines was achieved in the presence of di-tert-butyl peroxide. Notably, alkyl, phenyl and alkoxyl silanes were all suitable reaction partners. Mechanistic studies revealed that N-silyl acetamide serves as the intermediate.


Impact of the histological phenotype of extrahepatic bile duct carcinoma.
The classification of histological phenotypes was originally conceived for pancreatic intraductal papillary mucinous neoplasms. Recently, it has been introduced for extrahepatic cholangiocarcinoma. The aim of the present study was to clarify the associations between histological phenotype and clinicopathological features of extrahepatic cholangiocarcinoma, using 99 cases of surgically-resected extrahepatic cholangiocarcinoma. All cases were divided into one of two histological phenotypes: Biliary-type (BT; 56 cases, 56.6%) or metaplastic-type (MT; 43 cases, 43.4%). The clinicopathological features were compared between these two phenotypes. BT tumors exhibited significantly poorer differentiation, more frequent lymph node metastasis (BT vs. MT, 42.9 vs. 30.2%; P=0.042), more severe venous invasion (v2-3: BT vs. MT, 64.3 vs. 23.3%; P<0.001), and more severe perineural invasion (ne2-3: BT vs. MT, 78.6 vs. 48.8%, P=0.002). Furthermore, the overall (P=0.015) and disease-free (P=0.003) survival times were significantly decreased in patients with BT vs. MT tumors. In conclusion, extrahepatic cholangiocarcinoma with a BT phenotype has greater malignant potential, and may be an important predictive factor for poor prognosis.


Simultaneous heterotrophic nitrification and aerobic denitrification at high concentrations of NaCl and ammonia nitrogen by Halomonas bacteria.
To improve the efficiency of simultaneous heterotrophic nitrification and aerobic denitrification (SND) at high concentrations of NaCl and ammonia nitrogen (NH4+-N), we investigated the SND characteristics of Halomonas bacteria with the ability to synthesize the compatible solute ectoine. Halomonas sp. strain B01, which was isolated, screened and identified in this study, could simultaneously remove nitrogen (N) by SND and synthesize ectoine under high NaCl conditions. Gene cloning and sequencing analysis indicated that this bacterial genome contains ammonia monooxygenase (amoA) and nitrate reductase (narH) genes. Optimal conditions for N removal in a solution containing 600 mg/L NH4+-N were as follows: sodium succinate supplied as organic carbon (C) source at a C/N ratio of 5, pH 8 and shaking culture at 90 rpm. The N removal rate was 96.0% under these conditions. The SND by Halomonas sp. strain B01 was performed in N removal medium containing 60 g/L NaCl and 4,000 mg/L NH4+-N; after 180 h the residual total inorganic N concentration was 21.7 mg/L and the N removal rate was 99.2%. Halomonas sp. strain B01, with the ability to synthesize the compatible solute ectoine, could simultaneously tolerate high concentrations of NaCl and NH4+-N and efficiently perform N removal by SND.


Measuring overcast colors with all-sky imaging.
Digital images of overcast skies as seen from the earth's surface open new windows onto the angular details of overcast colors and visible-wavelength spectra. After calibration with a spectroradiometer, a commercial CCD camera equipped with a fisheye lens can produce colorimetrically accurate all-sky maps of overcast spectra. Histograms and azimuthally averaged curves of the resulting chromaticities show consistent, but unexpected, patterns in time-averaged overcast colors. Although widely used models such as LOWTRAN7 and MODTRAN4 cannot explain these characteristic patterns, a simple semiempirical model based on the radiative transfer equation does, and it provides insights into the visible consequences of absorption and scattering both within and beneath overcasts.


Adolescent Health: Media Use.
Digital media use has increased rapidly during the past two decades, and media use is now a major issue in adolescent development. Online connections and communities can help foster healthy identity development and provide needed peer support, particularly for adolescents from historically marginalized communities. Online harassment, or cyberbullying, is a common phenomenon. Media use can interfere with sleep hygiene and quality, and screen-based sedentary behaviors have been associated with decreased physical activity, decreased aerobic fitness, and increased adiposity among adolescents. The literature on media use and adolescent mental health still is evolving. Some research suggests a U-shaped association between these two factors, with high and low levels of internet use associated with depression. Social media use may amplify peer pressure to engage in sexual behavior, provide exposure to a greater network of individuals with sexual experience, and increase the risk of sexual behaviors. Counseling adolescent patients about safe and healthy media use is essential. Conversations with patients and their families about media use should begin before adolescence and continue through adolescence in the context of routine preventive care. The American Academy of Pediatrics (AAP) recommends creation and implementation of a Family Media Use Plan.


Smoking cessation delivered by medical students is helpful to homeless population.
The authors pilot a smoking-cessation outreach for the homeless that extends medical students' tobacco cessation education. In this prospective study, second-year medical students administered cognitive behavior therapy or unstructured support to homeless subjects to help them quit smoking. Self-report and biological measures (carbon monoxide) of smoking taken at baseline and follow-up were analyzed using t tests to determine intervention efficacy. Out of 11 enrolled subjects, six completed the protocol and all decreased their smoking frequency. The mean rate of smoking dropped significantly from 19 to nine cigarettes per day when pooling all subjects, and carbon monoxide mean level decreased from 28.0 to 20.2. The homeless subjects who received counseling from medical students significantly reduced their smoking frequency. Subject recruitment and retention were challenges, but a close partnership with local homeless shelters and the addition of pharmacotherapy could improve outcomes and are recommended for future efforts.


A proteomics study of auxin effects in Arabidopsis thaliana.
Many phytohormones regulate plant growth and development through modulating protein degradation. In this study, a proteome study based on multidimensional non-gel shotgun approach was performed to analyze the auxin-induced protein degradation via ubiquitin-proteasome pathway of Arabidopsis thaliana, with the emphasis to study the overall protein changes after auxin treatment (1 nM or 1 µM indole-3-acetic acid for 6, 12, or 24 h). More than a thousand proteins were detected by using label-free shotgun method, and 386 increased proteins and 370 decreased ones were identified after indole-3-acetic acid treatment. By using the auxin receptor-deficient mutant, tir1-1, as control, comparative analysis revealed that 69 and 79 proteins were significantly decreased and increased, respectively. Detailed analysis showed that among the altered proteins, some were previously reported to be associated with auxin regulation and others are potentially involved in mediating the auxin effects on specific cellular and physiological processes by regulating photosynthesis, chloroplast development, cytoskeleton, and intracellular signaling. Our results demonstrated that label-free shotgun proteomics is a powerful tool for large-scale protein identification and the analysis of the proteomic profiling of auxin-regulated biological processes will provide informative clues of underlying mechanisms of auxin effects. These results will help to expand the understanding of how auxin regulates plant growth and development via protein degradation.


Three-year results from a randomised controlled trial comparing prostheses supported by 5-mm long implants or by longer implants in augmented bone in posterior atrophic edentulous jaws.
To evaluate whether 5-mm short dental implants could be an alternative to augmentation with anorganic bovine bone and placement of at least 10-mm long implants in posterior atrophic jaws. Fifteen patients with bilateral atrophic mandibles (5 mm to 7 mm bone height above the mandibular canal) and 15 patients with bilateral atrophic maxillae (4 mm to 6 mm bone height below the maxillary sinus), and bone thickness of at least 8 mm, were randomised according to a split-mouth design to receive one to three 5-mm short implants or at least 10-mm long implants in augmented bone. Mandibles were vertically augmented with interpositional bone blocks and maxillary sinuses with particulated bone via a lateral window. Implants were placed after 4 months, submerged and loaded, after another 4 months, with provisional prostheses. Four months later, definitive provisionally cemented prostheses were delivered. Outcome measures were: prosthesis and implant failures; any complication and peri-implant marginal bone level changes. In five augmented mandibles, the planned 10-mm long implants could not be placed and shorter implants (7 mm and 8.5 mm) had to be used instead. Three years after loading, two patients, one treated in the mandible and one in the maxilla, dropped out. Three prostheses (1 mandibular and 2 maxillary) failed in the short implant group versus none in the long implant group. In mandibles, one long implant failed versus two short implants in 1 patient. In maxillae, one long implant failed versus three short implants in 2 patients. There were no statistically significant differences in the failures. Eight patients had 13 complications at short implants (1 patient accounted for 6 complications) and 11 patients had 13 complications at long implants. There were no statistically significant differences in complications (P = 0.63, difference = 0.10, 95% CI from -0.22 to 0.42). Three years after loading, patients with mandibular implants lost on average 1.44 mm at short implants and 1.63 mm at long implants of peri-implant marginal bone. This difference was not statistically significant (difference = 0.24 mm; 95% CI -0.01, 0.49 P = 0.059). In maxillae, patients lost on average 1.02 mm at short implants and 1.54 mm at long implants. This difference was statistically significant (difference = 0.41 mm; 95% CI 0.21, 0.60, P = 0.001). Three years after loading, 5-mm short implants achieved similar results as longer implants in augmented bone. Short implants might be a preferable choice to vertical bone augmentation, especially in mandibles, since the treatment is faster and cheaper, however there are still insufficient data on the long-term prognosis of short implants.


DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death.
The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.


Growth and health of juvenile barramundi (Lates calcarifer) challenged with DO hypoxia after feeding various inclusions of germinated, fermented and untreated peanut meals.
Peanut (Arachis hypogaea) is mainly grown for oil extraction and the remaining oil-free seed referred as peanut meal (PM) leaves with high protein content which can be a possible substitute for fishmeal in aqua-diets. This study evaluates the suitability of three types of processed peanut seeds, namely untreated PM (UPM), fermented PM (FPM), and germinated PM (GPM) from peanut seeds to replace fishmeal in barramundi (Lates calcarifer) diets cultured under a commercial production environment. Nine formulated diets having 3 inclusion levels from the 3 different peanuts (15%, 30% and 60% fishmeal replacement) were evaluated against a control without PM. The performance of various types and levels of PMs was assessed by examining the growth, gut and liver condition and survival of fish after eight weeks of feeding the test diets. The immunological responses of juvenile barramundi were assessed by exposing the fish to the hypoxic conditions for 4 hours. The results showed that fermentation and germination significantly (P<0.05) reduced the tannins and alkaloid contents in the PMs. The fish fed 15% GPM diet grew faster and had higher survival than fish fed control diet, while fish fed diet including 60% GPM showed a significant reduction in growth and survival, and an increase in food conversion rate (FCR). FPM and UPM at any inclusion levels did not alter the growth, survival and FCR. Histology analysis revealed that fish fed 60% GPM and UPM showed higher amount of lipid droplets in liver, myodigeneration in fish muscle and a decrease number of acidic mucins in distal gut compare to all other test diets. Stress caused by reduced dissolved oxygen did not change the sodium, potassium, chlorides and alanine aminotransferase concentrations of plasma of fish fed any diet. However, the stress did increase plasma cortisol significantly (P<0.05) in fish fed 60% GPM, 30% and 60% UPM diets. These results suggest that the PMs can partly replace the fishmeal in juvenile barramundi diet and the processing further improves the PMs quality by reducing its antinutritional factors which in turn can increase either its inclusion level in the barramundi diets or improved growth and health status of the species.


Host microRNA analysis in cyprinid Herpesvirus-3 (CyHV-3) infected common carp.
The mechanism of latency and the ability of the cyprinid herpesvirus 3 (CyHV-3) to establish life-long infections in carp remains poorly understood. To explain the role of miRNAs in this process we applied a range of molecular tools including high-throughput sequencing of RNA libraries constructed from the blood samples of infected fish followed by bioinformatic and functional analyses which show that CyHV-3 profoundly influences the expression of host miRNAs in vivo. We demonstrated the changed expression of 27 miRNAs in the clinical phase and 5 in the latent phase of infection. We also identified 23 novel, not previously reported sequences, from which 8 showed altered expressions in control phase, 10 in clinical phase and 5 in latent phase of infection. The results of our analysis expand the knowledge of common carp microRNAs engaged during CyHV-3 infection and provide a useful basis for the further study of the mechanism of CyHV-3 induced pathology.


[Estrogen receptors in the brain].
Estrogen plays an important role in changes taking place in the brain through the regulation of growth and differentiation of axons and dendrites, influence on plasticity, support of survival as well cognitive and behavioral functions. The classical mode of estrogen action is through the activation of its receptors, transcription factors. Two such estrogen receptors have been cloned, ER alpha i ER beta. Several isoforms of ER beta have also been characterized, which may be a significant factor in the regulation of estrogen response in the brain. Additionally, actions of estrogens through membrane or intra-cellular receptors, are suggested. The functions played by ER alpha i ER beta in the brain may be explored by studies on ER alpha or ER beta knockout mice. The results of these studies point to the role of ER alpha in reproductive functions, while ER beta seems to be important in cognitive processes. Autoradiography, immunohistochemistry, and in situ hybridization have been employed in the localization of estrogen receptors in the brain. Aside from demonstrating differences in the localization and expression levels of both receptors, these studies have proven, that both ER alpha i ER beta are able to bind estrogen. However, the pattern of expression of estrogen receptors in the brain is not static, but undergoes rapid changes in response to injury. Many studies point to a wide range of estrogen actions in the brain. For that reason, a complementary mechanism of action of estrogen is proposed, based on their interaction with various growth factors, as well as on the synergistic action of this hormone through, both, the estrogen receptors and estrogen-independent pathways.


The beta-hexosaminidase deficiency disorders: development of a clinical paradigm in the mouse.
Tay-Sachs disease and Sandhoff disease are severe neurodegenerative disorders caused by a deficiency of beta-hexosaminidase A and resultant accumulation of its substrate, GM2 ganglioside, in neuronal lysosomes. The three clinical forms of the disorders (infantile, juvenile and adult) are of varying severity and onset, and have been correlated with the amount of residual GM2 ganglioside-degrading activity present in patients' cells. Through targeted disruption of the murine beta-hexosaminidase genes in embryonic stem cells, we have developed a set of mice that vary in their GM2 ganglioside-degrading capacity and exhibit many of the clinical features of the human diseases. These mice are valuable for the study of pathogenic mechanisms and for devising novel therapeutic strategies in these disorders.


The management of equinus deformity in Duchenne muscular dystrophy.
Equinus deformity of the ankle is one of the serious orthopaedic problems associated with Duchenne muscular dystrophy. Sixty-nine patients (age range 4 to 17 years) were treated, 43 conservatively and 26 operatively. They were followed up at six-monthly intervals for a minimum of two years and a maximum of six years. The patients were divided into three groups: independently mobile, mobile in calipers, and wheelchair-bound. It was found that conservative treatment could at best only minimise progression of the deformity. The indications for surgery, the operative procedure and the postoperative management are described; all varied according to the stage of the disease. The postoperative follow-up suggests that, though the deformity recurs, the patients have several years of benefit from the procedure.


Increase in antinociceptive effect of [leu5]enkephalin after intrathecal administration of mixture of three peptidase inhibitors.
Previous in vitro studies have shown that the degradation of [Leu5]enkephalin during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors such as amastatin, captopril, and phosphoramidon. The present in vivo study was performed to examine the antinociceptive effect of [Leu5]enkephalin administered intrathecally under pretreatment with these three peptidase inhibitors. A tail-flick test was used to determine the nociceptive threshold after administration of [Leu5]enkephalin. The time-course profiles of the latency to flick the tail and the area under the time response curve were evaluated for the antinociceptive action of the drug. The antinociceptive effect of [Leu5]enkephalin administered intrathecally on the tail-flick test was increased more than 100-fold under i.t. pretreatment with three peptidase inhibitors. The antinociceptive effect produced by [Leu5]enkephalin in rats pretreated with any single peptidase inhibitor increased antinociception compared to that with saline. The antinociceptive potency of [Leu5]enkephalin under pretreatment with any combination of two peptidase inhibitors was smaller than that in rats pretreated with three peptidase inhibitors together. These results indicate that any residual single peptidase inactivates significant amounts of [Leu5]enkephalin. The present data, together with those of earlier studies, clearly demonstrate that amastatin-, captopril-, and phosphoramidon-sensitive enzymes play an important role in the inactivation of [Leu5]enkephalin administered intrathecally in rat.


The dilemma of an incidental preoperative electrocardiogram showing a Brugada phenotype.
A Brugada pattern on routine electrocardiography is one of several features that can indicate the potential for life threatening rhythm disturbances. The authors describe such a scenario in an asymptomatic 38-year-old woman who required significant surgery under anaesthesia. The diagnosis and possible management routes are outlined with an emphasis on the incumbent psychosocial and familial issues that are encountered. The patient underwent her surgery and was then further investigated to 'prove' the diagnosis. Ultimately, the patient declined further investigations and interventions. This case highlights the dilemma faced by anaesthetists and clinicians, not to mention the patients and their family when a Brugada phenotype is identified on a routine ECG. Clinicians should seek an expert opinion but ultimately, as in this case, the patient should be positioned to make an informed decision on what route to follow.


Leadership through an occupational lens: celebrating our territory.
This paper addresses key qualities of leadership and describes leadership through an occupational lens. It aims to encourage individuals to identify themselves as leaders wherever they are positioned within organisations or in their professional lives. Leadership vignettes are used to highlight and celebrate how occupational therapy philosophies, as well as our theoretical and practical knowledge assisted these leaders in their current and emerging leadership roles. A number of issues that are affecting us as global citizens, including natural disasters and humanitarian crises in third world contexts are highlighted. The potential for our profession to take a leadership role in these issues is proposed. Finally, there is a call to action for all occupational therapists whatever their professional roles, recommending that all members of the profession embrace leadership opportunities no matter how big or small. In so doing it is argued that leadership will be recognised and celebrated as being very much part of our profession's territory.


Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.
Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.


Association between children's dental behavior and play behavior.
The results of this study showed that clinical distinctions can be made regarding the behavior of children in the dental setting and that these distinctions are reflected in the behavior of these children in an easily-arranged play situation. The existence of such associations of behavior presents the possibility that play behavior may be a reliable predictor of maladaptive dental behavior. If so, the incorporation of a play dental area into a dental office would be an inexpensive and convenient method of intercepting potential problem dental patients. If the results of this study can be replicated, they would support the initiation of a study to predict the behavior of children in the dental setting by means of easily scorable aspects of their play behavior in a simulated dental environment. Special management considerations could then be made to prevent disruptive behavior at subsequent appointments. The results also point up the tendency of problem patients to avoid certain aspects of the play dental experience. This suggests a possible treatment potential for the dental play area, using it as an instrument to desensitize appropriate patients to those aspects of dental treatment which distress them, and thereby reduce their anxieties, prior to actual dental treatment.


Direct Optical Patterning of Quantum Dots: One Strategy, Different Chemical Processes.
Patterning, stability, and dispersion of the semiconductor quantum dots (scQDs) are three issues strictly interconnected for successful device manufacturing. Recently, several authors adopted direct optical patterning (DOP) as a step forward in photolithography to position the scQDs in a selected area. However, the chemistry behind the stability, dispersion, and patterning has to be carefully integrated to obtain a functional commercial device. This review describes different chemical strategies suitable to stabilize the scQDs both at a single level and as an ensemble. Special attention is paid to those strategies compatible with direct optical patterning (DOP). With the same purpose, the scQDs' dispersion in a matrix was described in terms of the scQD surface ligands' interactions with the matrix itself. The chemical processes behind the DOP are illustrated and discussed for five different approaches, all together considering stability, dispersion, and the patterning itself of the scQDs.


The Real Experience and Management Strategies Analysis of Chinese Nurses Aiding COVID-19 Epidemic: A Qualitative Study.
Emergent public health events, such as coronavirus disease 2019 (COVID-19), have been the focus of attention of researchers at home and abroad. In China, nurses are an important group contributing to the prevention and control of the COVID-19 pneumonia epidemic. Using semi-structured interviews, qualitative interviews were conducted with 23 nurses who supported the novel coronavirus pneumonia epidemic, and the data were collated and analyzed using Colaizzi analysis. The work experience of Chinese nurses can be summarized into 4 major themes: they had different emotional experiences during aiding periods, aiding work had a double impact on the nurses, there were certain difficulties in aiding work, and there were significant age differences in aiding work experience. It is necessary to strengthen the psychological construction of nurses. All hospitals must coordinate and manage various safety tasks, and ensure the precise, scientific, and streamlined deployment of rescue work. Humanized management, shift adjustment, performance allocation weight, and organizational care are also the top priorities of human resource management.


Engineering immunomodulatory biomaterials for type 1 diabetes.
A cure for type 1 diabetes (T1D) would help millions of people worldwide, but remains elusive thus far. Tolerogenic vaccines and beta cell replacement therapy are complementary therapies that seek to address aberrant T1D autoimmune attack and subsequent beta cell loss. However, both approaches require some form of systematic immunosuppression, imparting risks to the patient. Biomaterials-based tools enable localized and targeted immunomodulation, and biomaterial properties can be designed and combined with immunomodulatory agents to locally instruct specific immune responses. In this Review, we discuss immunomodulatory biomaterial platforms for the development of T1D tolerogenic vaccines and beta cell replacement devices. We investigate nano- and microparticles for the delivery of tolerogenic agents and autoantigens, and as artificial antigen presenting cells, and highlight how bulk biomaterials can be used to provide immune tolerance. We examine biomaterials for drug delivery and as immunoisolation devices for cell therapy and islet transplantation, and explore synergies with other fields for the development of new T1D treatment strategies.


Selected metabolic and morphologic complications associated with highly active antiretroviral therapy.
Metabolic and morphologic changes have been described in patients with human immunodeficiency virus (HIV) infection. In the short term, these disorders can be debilitating and may require medical intervention, including alterations in antiretroviral therapy regimens. The long-term consequences have not been fully realized, but are important, particularly in the era of durable HIV disease management with highly active antiretroviral therapy. This review focuses on 3 of the important morphologic or metabolic changes, namely alterations in body fat distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these disorders remains unknown due to varied definitions and difficulty in recognition of the conditions for both the patient and the clinician. Treatment regimens directed at these abnormalities are being developed, but clinical trials are needed to fully ascertain the efficacy and safety of such interventions.


Testing their metal.
Metals continually rank at the top of the U.S. Environmental Protection Agency's annual list of agents that pose the greatest hazard to the people of the United States. Metals aren't going away, either. They do not biodegrade, and they often concentrate in human and animal cells and tissue. Many metals are known human and animal carcinogens, while many others are suspected to play a role in cancer. Little is known, however, about the mechanisms by which metals cause cancer.


Extreme ultra-violet movie camera for imaging microsecond time scale magnetic reconnection.
An ultra-fast extreme ultra-violet (EUV) movie camera has been developed for imaging magnetic reconnection in the Caltech spheromak/astrophysical jet experiment. The camera consists of a broadband Mo:Si multilayer mirror, a fast decaying YAG:Ce scintillator, a visible light block, and a high-speed visible light CCD camera. The camera can capture EUV images as fast as 3.3 × 10(6) frames per second with 0.5 cm spatial resolution. The spectral range is from 20 eV to 60 eV. EUV images reveal strong, transient, highly localized bursts of EUV radiation when magnetic reconnection occurs.


Laboratory evaluation of extrinsic stain removal by a specially engineered sonic powered toothbrush with unique sensing and control technologies.
The purpose of this laboratory study was to evaluate extrinsic stain removal from teeth by a specially engineered sonic powered toothbrush with unique sensing and control technologies, using the Triple Clean and the Sensitive refill brush heads, in comparison to a manual flat-trim toothbrush. Twelve (12) artificially stained bovine teeth were tested with each product. The percentage of stain removed by each product was calculated by taking the ratio of the amount of stain removed by brushing for 800 strokes to the total amount of stain removed by subsequent application of a dental prophylaxis. The stain was quantified by measuring the light reflected by the stained teeth with a spectrophotometer. Data were reported as L*, lightness of the stain, and as W*, a whiteness index comprising the lightness, hue, and chroma of reflected light. Statistical analyses were performed separately for the AL* and AW* scores. Comparisons of the toothbrushes with respect to baseline-adjusted deltaL* and deltaW* scores were performed using an analysis of covariance (ANCOVA). Post-ANCOVA pair-wise comparisons of the study toothbrushes were performed using Tukey's test for multiple comparisons. All statistical tests of hypotheses were two-sided, and employed a minimum level of significance of 0.05. The percentage of stain removed by the sonic powered toothbrush, using either the Triple Clean brush head or the Sensitive brush head under laboratory test conditions, is superior (p < 0.05) to the percentage of stain removed by the manual flat-trim toothbrush when analyzed for both the deltaL* and deltaW* scores. The mean percentage of stain removed was 62.10 for the power toothbrush with the Triple Clean brush head, 49.01 for the power toothbrush with the Sensitive brush head, and 30.56 for the manual flat-trim toothbrush when calculated using deltaL* scores. The mean percentage of stain removed was 59.89 for the power toothbrush with the Triple Clean brush head, 46.83 for the power toothbrush with the Sensitive brush head, and 29.25 for the manual flat-trim toothbrush when calculated using deltaW* scores. This new specially engineered sonic powered toothbrush with unique sensing and control technologies effectively removes extrinsic stains from the surface of teeth under laboratory test conditions with both the Triple Clean and the Sensitive brush heads. The effectiveness of stain removal with either brush head is significantly greater than the effectiveness of stain removal of a manual flat-trim toothbrush under these conditions.


Lattice theory for low energy fermions at nonzero chemical potential.
We construct a lattice theory describing a system of interacting nonrelativistic spin s=1/2 fermions at nonzero chemical potential. The theory is applicable whenever the interparticle separation is large compared to the range of the two-body potential and does not suffer from a sign problem. In particular, the theory could be useful in studying the thermodynamic limit of fermion systems for which the scattering length is much larger than the interparticle spacing, with applications to realistic atomic systems and dilute neutron gases.


Fruit-Induced Anaphylaxis: Clinical Presentation and Management.
Data are sparse regarding the clinical characteristics and management of fruit-induced anaphylaxis. To assess clinical characteristics and management of patients with fruit-induced anaphylaxis and determine factors associated with severe reactions and epinephrine use. Over 9 years, children and adults presenting with anaphylaxis to seven emergency departments in four Canadian provinces and patients requiring emergency medical services in Outaouais, Quebec were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting symptoms, triggers, and management was collected. Multivariate logistic regression was used to identify factors associated with severe reactions and epinephrine treatment in the pre-hospital setting. We recruited 250 patients with fruit-induced anaphylaxis, median age 10.2 years (interquartile range, 3.6-23.4 years); 48.8% were male. The most common fruit triggers were kiwi (15.6%), banana (10.8%), and mango (9.2%). Twenty-three patients reported having eczema (9.3%). Epinephrine use was low in both the pre-hospital setting and the emergency department (28.4% and 40.8%, respectively). Severe reactions to fruit were more likely to occur in spring and among those with eczema (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI], 1.03-1.23; and 1.17, 95% CI, 1.03-1.34, respectively). Patients with moderate and severe reactions (aOR = 1.23; 95% CI, 1.06-1.43) and those with a known food allergy (aOR = 1.38; 95% CI, 1.24-1.54) were more likely to be treated with epinephrine in the pre-hospital setting. Severe anaphylaxis to fruit is more frequent in spring. Cross-reactivity to pollens is a potential explanation that should be evaluated further.


Formally Copper(III)-Alkylperoxo Complexes as Models of Possible Intermediates in Monooxygenase Enzymes.
Reaction of [NBu4][LCuIIOH] with excess ROOH (R = cumyl or tBu) yielded [NBu4][LCuIIOOR], the reversible one-electron oxidation of which generated novel species with [CuOOR]2+ cores (formally CuIIIOOR), identified by spectroscopy and theory for the case R = cumyl. This species reacts with weak O-H bonds in TEMPO-H and 4-dimethylaminophenol (NMe2PhOH), the latter yielding LCu(OPhNMe2), which was also prepared independently. With the identification of [CuOOR]2+ complexes, the first precedent for this core in enzymes is provided, with implications for copper monooxygenase mechanisms.


Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats.
Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1β, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1β, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.


Plasminogen activation by normal B lymphocytes, a function associated with the cell membrane.
When purified murine plasminogen was added to cultures of mouse spleen B cells, active plasmin progressively appeared in the supernatants. This reaction, resulting from the specific cleavage of the plasminogen by lymphocyte plasminogen activator (LPA), was measured in a fibrinolysis assay using 125I-fibrinogen. T cells were totally ineffective; under certain conditions, they could even antagonize the B cell action. Of the various B populations studied, i.e., obtained from spleen, lymph nodes, or blood of various mouse strains, all expressed the same property of plasminogen activation, which concerned mainly medium-sized B cells. Since only slight activities were detected in extracellular or intracellular compartments, a membrane-associated proteolytic enzyme may be responsible for plasminogen activation. Submitted to a series of group-specific antiproteases, the lymphocyte plasminogen activator essentially behaved as a serine-protease, with sensitivity to diisopropyl fluorophosphate, phenyl methyl sulfonyl fluoride, and nitro phenyl guanidino benzoate. The fast renewal of the enzyme in the membrane was also demonstrated by different techniques, using modifiers of cell physiology, like cycloheximide and dexamethasone, or following the reexpression of the enzyme by the cell kinetically.


Drug-induced musculoskeletal disorders.
Drug-induced musculoskeletal disorders represent a broad clinical spectrum, from asymptomatic biological abnormalities to severe and even life-threatening diseases. Since an increasing number of drugs have been implicated in inducing rheumatic symptoms and/or syndromes, this review is not meant to be exhaustive, bearing in mind that the development of any musculoskeletal disorder should be considered as possibly related to a medication. The purpose of this article is to provide an overview of the more frequent drug-induced musculoskeletal disorders. These include: (i) arthralgias and arthropathies, including chondropathies and inflammatory arthritis; (ii) connective tissue diseases, especially lupus-like syndromes; (iii) periarticular disorders, including tendinopathies, enthesopathies and frozen shoulder; (iii) bone diseases, such as osteoporosis, osteomalacia and osteonecrosis; and (iv) myopathies. Although virtually all drug classes may induce musculoskeletal disorders, a significant part of them are related to corticosteroids, vaccines, antibacterials and lipid-lowering agents. Knowledge of drug-induced musculoskeletal disorders avoids carrying out unnecessary investigations, and allows optimal management of the patients, i.e. early discontinuation of the offending agent, adequate treatment monitoring and/or intervention with appropriate preventive actions.


Autophagy and Longevity.
Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.


Aerosols generated by accidents: pressurized liquid release experiments.
Safety assessments and environmental impact statements for facilities require an estimation of airborne releases from accidents. Aerosols generated by accidents are being investigated to develop the source terms for these releases. One example of a severe accidental release event is a pressurized liquid release. Pressurized liquid release experiments performed in static air measured the mass airborne as a function of source size and containment pressure. Pressurized releases with the containment breach above the liquid level were investigated. For this configuration, only containment pressure at the time of release was found to be a significant parameter. Releases in static air can be estimated using the relationships developed in this work. Weight percent of the airborne source ranged from 4 X 10(-4) to 0.15%. All of the pressurized releases produced a significant fraction of respirable particles.


BiNoM 2.0, a Cytoscape plugin for accessing and analyzing pathways using standard systems biology formats.
Public repositories of biological pathways and networks have greatly expanded in recent years. Such databases contain many pathways that facilitate the analysis of high-throughput experimental work and the formulation of new biological hypotheses to be tested, a fundamental principle of the systems biology approach. However, large-scale molecular maps are not always easy to mine and interpret. We have developed BiNoM (Biological Network Manager), a Cytoscape plugin, which provides functions for the import-export of some standard systems biology file formats (import from CellDesigner, BioPAX Level 3 and CSML; export to SBML, CellDesigner and BioPAX Level 3), and a set of algorithms to analyze and reduce the complexity of biological networks. BiNoM can be used to import and analyze files created with the CellDesigner software. BiNoM provides a set of functions allowing to import BioPAX files, but also to search and edit their content. As such, BiNoM is able to efficiently manage large BioPAX files such as whole pathway databases (e.g. Reactome). BiNoM also implements a collection of powerful graph-based functions and algorithms such as path analysis, decomposition by involvement of an entity or cyclic decomposition, subnetworks clustering and decomposition of a large network in modules. Here, we provide an in-depth overview of the BiNoM functions, and we also detail novel aspects such as the support of the BioPAX Level 3 format and the implementation of a new algorithm for the quantification of pathways for influence networks. At last, we illustrate some of the BiNoM functions on a detailed biological case study of a network representing the G1/S transition of the cell cycle, a crucial cellular process disturbed in most human tumors.


MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.


Solar Thermal Energy Storage in a Photochromic Macrocycle.
The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring-closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release.


[Clinical study on the contact between the partial denture and the alveolar process].
53 clinically prepared bridges were examined with regard to the resting position of the bridge body on the alveolar ridge, before they were finally cemented. It was to be tested whether the ideal requirements of punctate or linear pressure-less resting was met and if not, how big the portion of the base resting on the gingiva was as compared to the total base. All bridge bodies were resting on the alveolar ridge without exerting pressure but with a more or less broad base. In 42 out of the 66 examined cases, the bridge body was in a 50 to 100% contact with the mucosa.


Dynamics of the solvent around a solute: generalized Langevin theory.
The generalized Langevin theory for a solution has been derived as the infinite dilution limit of the theory for a two component mixture. Following a similar formalism, the mode coupling approximations of the memory kernel have been also obtained. We have applied this method for one component bulk liquid of Lennard-Jones spheres and proved this approximation theoretically. The analysis of the space and time pair correlation proposed by Van Hove has been carried out as a function of solute particle sizes. It is found that the size of the solute particle is deeply related to the relaxation process of the solvation structure characterized around a solute particle at equilibrium. We have also investigated the relation between the different thermodynamic environments and relaxation process. From these studies, we have obtained the useful information about the rapidity of the relaxation of the solvation structure around a solute at equilibrium.


Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk.
Although numerous genetic loci have been associated with coronary artery disease (CAD) with genome wide association studies, efforts are needed to identify the causal genes in these loci and link them into fundamental signaling pathways. Recent studies have investigated the disease mechanism of CAD associated gene SMAD3, a central transcription factor (TF) in the TGFβ pathway, investigating its role in smooth muscle biology. In vitro studies in human coronary artery smooth muscle cells (HCASMC) revealed that SMAD3 modulates cellular phenotype, promoting expression of differentiation marker genes while inhibiting proliferation. RNA sequencing and chromatin immunoprecipitation sequencing studies in HCASMC identified downstream genes that reside in pathways which mediate vascular development and atherosclerosis processes in this cell type. HCASMC phenotype, and gene expression patterns promoted by SMAD3 were noted to have opposing direction of effect compared to another CAD associated TF, TCF21. At sites of SMAD3 and TCF21 colocalization on DNA, SMAD3 binding was inversely correlated with TCF21 binding, due in part to TCF21 locally blocking chromatin accessibility at the SMAD3 binding site. Further, TCF21 was able to directly inhibit SMAD3 activation of gene expression in transfection reporter gene studies. In contrast to TCF21 which is protective toward CAD, SMAD3 expression in HCASMC was shown to be directly correlated with disease risk. We propose that the pro-differentiation action of SMAD3 inhibits dedifferentiation that is required for HCASMC to expand and stabilize disease plaque as they respond to vascular stresses, counteracting the protective dedifferentiating activity of TCF21 and promoting disease risk.


A Confucian reflection on genetic enhancement.
This essay explores a proper Confucian vision on genetic enhancement. It argues that while Confucians can accept a formal starting point that Michael Sandel proposes in his ethics of giftedness, namely, that children should be taken as gifts, Confucians cannot adopt his generalist strategy. The essay provides a Confucian full ethics of giftedness by addressing a series of relevant questions, such as what kind of gifts children are, where the gifts are from, in which way they are given, and for what purpose they are given. It indicates that Confucians should sort out different types of enhancement and bring them to the test of the Confucian values in terms of both Confucian virtue principles and specific ritual rules. It concludes that Confucians can accept some types of enhancement but must reject others.


Current problems with intrahepatic bile duct stones in Japan--congenital biliary malformations as a cause.
In patients with primary intrahepatic bile duct stones, strictures of the biliary duct are often present, but the relationship between these strictures and the formation of the stones remains controversial. Intrahepatic bile duct carcinoma in association with intrahepatic bile duct stones has recently been reported. The present study attempted to ascertain whether bile stasis induced by congenital biliary strictures is the basis for the formation of stones and occurrence of carcinoma. We analyzed the location of strictures in 58 patients with strictures in the upper portion of the biliary tract including 38 patients with intrahepatic bile duct stones and 9 with intrahepatic bile duct carcinoma. The cell cycle of epithelial cells from the intrahepatic bile duct were analyzed with using proliferating cell nuclear antigen, which is a immunohistochemical staining method. Fifty six of 58 patients had congenital cystic dilatation of the common bile duct (two infant type and 54 adult type). Thirty eight patients had intrahepatic bile duct stones proximal to the strictures at the hepatic hilum. The location of the strictures were classified into four types. Nine patients had intrahepatic bile duct carcinoma and eight of the 9 carcinomas coexisted with intrahepatic bile duct stones. In the nine patients with intrahepatic bile duct carcinoma, the expression of proliferating cellular nuclear antigen (PCNA) in the carcinoma and the normal bile duct epithelium adjacent to the carcinoma was higher than that of patients with hepatocellular carcinoma without anomaly of the biliary duct. Considering the location of the strictures and clinical features, the strictures may have been formed congenitally. Furthermore, adult type cysts of the common bile duct with strictures in the upper portion of the biliary tract are thought to be the basis for the formation of primary intrahepatic bile duct stones. The most appropriate treatment for intrahepatic bile duct stones is thus suggested to be removal of the affected hepatic segment including the region of strictures, combined eventually with hepaticoenterostomy.


A genome-screen experiment to detect quantitative trait loci affecting resistance to facial eczema disease in sheep.
Facial eczema (FE) is a secondary photosensitization disease arising from liver cirrhosis caused by the mycotoxin sporidesmin. The disease affects sheep, cattle, deer and goats, and costs the New Zealand sheep industry alone an estimated NZ$63M annually. A long-term sustainable solution to this century-old FE problem is to breed for disease-resistant animals by marker-assisted selection. As a step towards finding a diagnostic DNA test for FE sensitivity, we have conducted a genome-scan experiment to screen for quantitative trait loci (QTL) affecting this trait in Romney sheep. Four F(1) sires, obtained from reciprocal matings of FE resistant and susceptible selection-line animals, were used to generate four outcross families. The resulting half-sib progeny were artificially challenged with sporidesmin to phenotype their FE traits measured in terms of their serum levels of liver-specific enzymes, namely gamma-glutamyl transferase and glutamate dehydrogenase. In a primary screen using selective genotyping on extreme progeny of each family, a total of 244 DNA markers uniformly distributed over all 26 ovine autosomes (with an autosomal genome coverage of 79-91%) were tested for linkage to the FE traits. Data were analysed using Haley-Knott regression. The primary screen detected one significant and one suggestive QTL on chromosomes 3 and 8 respectively. Both the significant and suggestive QTL were followed up in a secondary screen where all progeny were genotyped and analysed; the QTL on chromosome 3 was significant in this analysis.