Drug rash with eosinophilia and systemic symptoms syndrome associated with use of phenytoin, divalproex sodium, and phenobarbital.
A probable case of drug reaction with eosinophilia and systemic symptoms (DRESS) associated with consecutive use of three medications for seizure control is reported. A 36-year-old woman was treated at a community hospital for a mild fever (37.9°C) and diffuse raised maculopapular rash with erythema. Three weeks previously, she had been diagnosed with a seizure disorder and initiated on phenytoin (dose unknown) at that time; about two weeks later, she developed a rash, prompting a switch from phenytoin to extended-release divalproex sodium 250 mg orally twice daily. During the week after discontinuation of phenytoin, the rash was improving, but about five days after the initiation of divalproex therapy, she had worsening rash and pruritus requiring urgent treatment; the divalproex was discontinued, and phenobarbital 30 mg three times daily was initiated for continued seizure control. Despite the discontinuation of phenytoin and divalproex, the patient's hepatic function worsened over five days, and phenobarbital therapy was discontinued. With continued deterioration of the patient's condition to fulminant hepatic failure, a transfer to a liver transplant facility was arranged. The use of the adverse reaction probability scale of Naranjo et al. in this case yielded a score of 8, indicating a probable relationship between DRESS and the serial use of phenytoin, divalproex, and phenobarbital. After receiving phenytoin for treatment of seizure disorder, a 36-year-old woman developed a fever and maculopapular rash with erythema. This reaction continued even after drug therapy was switched to extended-release divalproex and then phenobarbital. The patient's liver function deteriorated despite discontinuation of all seizure medications.


Case Report: Young Adults With Breast Cancer: A Case Series of Fertility Preservation Management and Literature Review.
Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, with 50% adolescent and YAs being diagnosed and 15-44-year-old women showing excellent 5-year survival. Surgical-chemoradiation therapy often results in excellent survivorship with an increased incidence of treatment-induced subfertility. Therefore, adding fertility preservation (FP) to the primary cancer treatment is necessary. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly. To date, the selection of oocytes, embryos and ovarian tissue is widely available as an FP treatment. PGT could reduce the risk of BRCA mutation transmission amongst BRCA carriers before pregnancy planning. Otherwise, gonadotropin-releasing hormone analog has no gonadoprotective effect and thus should not be considered as an FP option.


Advanced oxidation protein products inhibit the autophagy of renal tubular epithelial cells.
It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62. These results suggest that AOPPs may inhibit the autophagic activity of HK-2 cells. Furthermore, the aforementioned changes were mediated by the AOPP-phosphorylated phosphoinositide 3-kinase3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway; this was verified by treatment with LY294002, a PI3K inhibitor, which reversed the AOPP-induced changes. The present study also demonstrated that the activation of autophagy with rapamycin led to an improvement in the AOPP-induced overexpression of kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin, two biomarkers of RTEC injury, whereas inhibiting autophagy with chloroquine further increased their expression during AOPP treatment. Collectively, these results indicate that AOPPs may inhibit autophagy in RTECs via activation of the PI3K/AKT/mTOR pathway and that autophagy inhibition serves a role in AOPP-induced RTEC injury.


A qualitative exploration of the role of NGOs in the recovery support for persons with substance use disorders in a low-income African setting.
In sub-Saharan Africa, most government mental health facilities are under-resourced to cater for the mental health needs of the population, including the provision of treatment and recovery support services for persons with substance use disorders (SUDs). However, in other settings, non-governmental organizations (NGOs) play significant roles by complementing governments' efforts in the provision of care for vulnerable groups. Presently, no study exists that examines the contributions of NGOs in the recovery support of individuals with SUDs in the Ghanaian context. This study sets out to explore the role of NGOs in the recovery of persons with SUDs in Ghana. Using a descriptive qualitative design, eight staff (directors and senior recovery practitioners) from eight NGOs in southern Ghana were purposively selected and interviewed face-to-face using semi-structured interview guide. The interviews were audio-taped, transcribed verbatim, and analyzed using the thematic analysis within an inductive approach. The results showed that NGOs provide three main services: treatment of drug addiction (through psychotherapy and recovery capital), re-integration of recovered individuals into society, and advocacy and awareness creation in schools and communities. These efforts are thwarted by limited qualified professionals and inadequate government support. Our results underscore the need for government agencies to collaborate with NGOs involved in the recovery management of persons with SUDs and other mental disorders to complement their efforts in strategizing, designing, and implementing context-appropriate substance misuse prevention and intervention programs and policies in Ghana.


Congenital third cranial nerve palsy with prenuclear dysinnervation involving otolithic pathways: Underpinnings of a novel congenital cranial dysinnervation disorder.
A 10-year-old boy with unilateral cryptorchidism and renal aplasia displayed features of unilateral congenital pupil sparing third cranial nerve palsy with exotropia manifesting novel dysinnervation encompassing synergistic divergence with upshoot, convergence on attempted upgaze, gaze-evoked phasic conjugate torsion, and gaze-evoked nystagmus. Congenital third nucleus/nerve hypoplasia with secondary dysinnervation is classfied as congenital cranial dysinnervation disorder (CCDD). It is speculated that miswiring between prenuclear structures, otolithic pathways, interstitial nucleus of Cajal (INC), nucleus prepositus hypoglossi, and third and sixth nerve nuclei likely resulted in this novel dysinnervation. Cryptorchidism and renal aplasia if seen may point towards an overlapping phenotype with Duane-radial ray syndrome and acro-renal-ocular/IVIC syndromes.


[The sense of taste].
The taste sense is one of the five human senses. It is essential to our survival because it enables the individual the choice of correct food, which, in turn, is crucial for one's existence, maintenance and function. This is a complicated chemical sense, which operates in conjunction with other senses such as vision, smell and touch, and is also associated with the operation of temperature and consistency receptors. There are five basic tastes: bitter, sweet, sour, salty and "fleshy" (umami), each of which has a role in food selection, being responsible for the recognition of certain chemicals, which may be either necessary or dangerous to our body. The taste cell is located in the taste buds, which, in turn, are situated in the tongue, oral cavity and the proximal third of the esophagus. This translates the chemical signal of tastants in food to electrical stimulation that transfers the signal to higher processing centers in the brain, in a process called transduction, which is explained in this review. Disturbances in the taste sense, as well as effects of industrial exposure on this sense are also described. The accumulated knowledge about the taste sense might enable future breakthroughs in the processed food industry.


Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and H1688 human small-cell lung cancer cells.
The goal of this study was to evaluate the ability of EVO to decrease cell viability and promote cell cycle arrest and apoptosis in small cell lung cancer (SCLC) cells. Lung cancer has the highest incidence and mortality rates among all cancers. Chemotherapy is the primary treatment for SCLC; however, the drugs that are currently used for SCLC are less effective than those used for non-small cell lung cancer (NSCLC). Therefore, it is necessary to develop new drugs to treat SCLC. In this study, the effects of evodiamine (EVO) on cell growth, cell cycle arrest and apoptosis were investigated in the human SCLC cell lines NCI-H446 and NCI-H1688. The results represent the first report that EVO can significantly inhibit the viability of both H446 and H1688 cells in dose- and time-dependent manners. EVO induced cell cycle arrest at G2/M phase, induced apoptosis by up-regulating the expression of caspase-12 and cytochrome C protein, and induced the expression of Bax mRNA and by down-regulating of the expression of Bcl-2 mRNA in both H446 and H1688 cells. However, there was no effect on the protein expression of caspase-8. Taken together, the inhibitory effects of EVO on the growth of H446 and H1688 cells might be attributable to G2/M arrest and subsequent apoptosis, through mitochondria-dependent and endoplasmic reticulum stress-induced pathways (intrinsic caspase-dependent pathways) but not through the death receptor-induced pathway (extrinsic caspase-dependent pathway). Our findings suggest that EVO is a promising novel and potent antitumor drug candidate for SCLC. Furthermore, the cell cycle, the mitochondria and the ER stress pathways are rational targets for the future development of an EVO delivery system to treat SCLC.


[Effect of naloxone on somatosensory evoked potentials in congenital insensitivity to pain].
The somatosensory evoked potentials were recorded (SEP) in a child 11 years old with congenital insensitivity to pain. The records were made before and after naloxone administration (160 mg i.m.) and they were compared with the SEPs from normal children. The place where records were taken was the somatosensory area of the scalp and the site of the stimulation was the contralateral medial nerve of the wrist. The results show that naloxone provokes higher waves of the patient's SEP that before administration of naloxone. On the other hand lower SEPs were observed in the patient with congenital insensitivity to pain than in those from normal children. The results suggest that congenital insensitivity to pain could be related to abnormal activities of morphine-like substances of endogenous production.


Internal conversion of singlet and triplet states employing numerical DFT/MRCI derivative couplings: Implementation, tests, and application to xanthone.
We present an efficient implementation of nonadiabatic coupling matrix elements (NACMEs) for density functional theory/multireference configuration interaction (DFT/MRCI) wave functions of singlet and triplet multiplicity and an extension of the Vibes program that allows us to determine rate constants for internal conversion (IC) in addition to intersystem crossing (ISC) nonradiative transitions. Following the suggestion of Plasser et al. [J. Chem. Theory Comput. 12, 1207 (2016)], the derivative couplings are computed as finite differences of wave function overlaps. Several measures have been taken to speed up the calculation of the NACMEs. Schur's determinant complement is employed to build up the determinant of the full matrix of spin-blocked orbital overlaps from precomputed spin factors with fixed orbital occupation. Test calculations on formaldehyde, pyrazine, and xanthone show that the mutual excitation level of the configurations at the reference and displaced geometries can be restricted to 1. In combination with a cutoff parameter of tnorm = 10-8 for the DFT/MRCI wave function expansion, this approximation leads to substantial savings of cpu time without essential loss of precision. With regard to applications, the photoexcitation decay kinetics of xanthone in apolar media and in aqueous solution is in the focus of the present work. The results of our computational study substantiate the conjecture that S1 T2 reverse ISC outcompetes the T2 ↝ T1 IC in aqueous solution, thus explaining the occurrence of delayed fluorescence in addition to prompt fluorescence.


Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance.
The pro-inflammatory cytokine, Interleukin-6 (IL-6), has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3) signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4), involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT) phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3). Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore, alantolactone can be a promising candidate for the treatment of inflammation-associated glucose intolerance and insulin resistance.


The Fate of Unused Embryos: Discourses, Action Possibilities, and Subject Positions.
Although in vitro fertilization (IVF) has offered hope to those struggling with infertility, it has also had some unintended consequences, including the fate of embryos that may be "surplus" to requirement following IVF treatment. The number of embryos in storage across the world is high, creating a dilemma for patients who need to make disposal decisions, as well as presenting an administrative and practical dilemma for clinics. Research has suggested that patients' views of the status of their embryo/s may affect their disposal decisions, and yet the nature of the links between views of the embryo and decisions to either donate or discard remain unclear. In this article, we engage in a discursive analysis of literature on disposal decisions. We discuss the range of ways in which embryos may be constructed, and demonstrate how these discourses make available or constrain particular action possibilities, and offer particular subject positions for patients. The analysis highlights the complexity of the relationship between embryo status and decision making, and may assist clinicians in supporting and guiding patients' decisions.


A comparative study of the Bessey method and Hausamen method for serum alkaline phosphatase determination.
The methods of Bessey et al. and Hausamen et al. for serum alkaline phosphatase determination were compared. Determinations were carried out using sera from healthy blood donors and sera from patients suffering from different hepatobiliary diseases. A high reproducibility of values obtained using both methods was noted. The sensitivity of the method of Hausamen et al. is about four times greater than that of the method of Bessey et al., even though the former method employed a lower reaction temperature. A high degree of correlation exists between the two methods and the data reported indicate that both methods are completely valid.


Indocyanine green videoangiography: current status.
Indocyanine-green (ICG) angiography has experienced a rejuvenated interest in the past few years because of improvements in technological systems. After three years of experience with evolving digital technology, we have reviewed our experience to provide an update on potential applications in a variety of choroidopathies. Based on 3,000 cases studied with ICG angiography, we evaluated the diagnostic value of the procedure in choroidal abnormalities including ischemic, tumor, idiopathic, inflammatory, and neovascularized diseases. ICG angiography is still of limited clinical value in ischemic diseases because of a relatively poor imaging potential for the choriocapillaris. The procedure has not yet provided information which is of significant value in the evaluation and management of choroidal tumors. Valuable information has been provided on the fundamental pathogenesis of certain idiopathic diseases. Preliminary experience in inflammatory diseases is very promising. A genuine advance in imaging of "occult"-choroidal neovascularization has been provided by the diagnostic technique. Improved delineation of these vessels offers opportunities for ICG-guided laser treatment.


Early animal model evaluation of an implantable contrast agent to enhance magnetic resonance imaging of arterial bypass vein grafts.
Background Non-invasive monitoring of autologous vein graft (VG) bypass grafts is largely limited to detecting late luminal narrowing. Although magnetic resonance imaging (MRI) delineates vein graft intima, media, and adventitia, which may detect early failure, the scan time required to achieve sufficient resolution is at present impractical. Purpose To study VG visualization enhancement in vivo and delineate whether a covalently attached MRI contrast agent would enable quicker longitudinal imaging of the VG wall. Material and Methods Sixteen 12-week-old male C57BL/6J mice underwent carotid interposition vein grafting. The inferior vena cava of nine donor mice was treated with a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-based contrast agent, with control VGs labeled with a vehicle. T1-weighted (T1W) MRI was performed serially at postoperative weeks 1, 4, 12, and 20. A portion of animals was sacrificed for histopathology following each imaging time point. Results MRI signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significantly higher for treated VGs in the first three time points (1.73 × higher SNR, P = 0.0006, and 5.83 × higher CNR at the first time point, P = 0.0006). However, MRI signal enhancement decreased consistently in the study period, to 1.29 × higher SNR and 2.64 × higher CNR, by the final time point. There were no apparent differences in graft morphometric analyses in Masson's trichrome-stained sections. Conclusion A MRI contrast agent that binds covalently to the VG wall provides significant increase in T1W MRI signal with no observed adverse effects in a mouse model. Further optimization of the contrast agent to enhance its durability is required.


Thermal stress and cellular signaling processes in hemocytes of native (Mytilus californianus) and invasive (M. galloprovincialis) mussels: cell cycle regulation and DNA repair.
In a previous study using hemocytes from native and invasive congeners of Mytilus (Mytilus californianus and Mytilus galloprovincialis, respectively) we showed that DNA damage and cell signaling transduction processes related to the cellular stress response and apoptosis were induced by acute temperature stress. The present study extends this work by examining effects of acute heat- and cold stress on total hemocyte counts (THCs) and expression of key regulatory molecules involved in responding to stress: tumor suppressor factor (p53), cell cycle arrest activator (p21), and a DNA base excision repair enzyme (apurinic/apyrimidinic endonuclease (APE)). Hyperthermia (28 °C, 32 °C) led to significant decreases of THCs in both species. The extent of decrease in THC was temperature-, time-, and species-dependent; lower THC values were found in M. californianus, the more cold-adapted species. Western blot analyses of hemocyte extracts with antibodies specific for p53 protein, several site-specific phosphorylation states of p53, p21 protein, and APE indicated that heat- and cold (2 °C) stress induced a time-dependent activation of stress-related proteins in response to DNA damage; these stress-induced changes could govern cell cycle arrest or DNA damage repair. Our results show that the downstream regulatory response to temperature-induced cell damage may play an important role in deciding cellular fate following heat- and cold stress. Compared to M. californianus, the more warm-adapted M. galloprovincialis appears to have a higher temperature tolerance due to a lesser reduction in THC, faster signaling activation and transduction, and stronger DNA repair ability following heat stress.


Optimised domain-engineered crystals for pure telecom photon sources.
The ideal photon-pair source for building up multi-qubit states needs to produce indistinguishable photons with high efficiency. Indistinguishability is crucial for minimising errors in two-photon interference, central to building larger states, while high heralding rates will be needed to overcome unfavourable loss scaling. Domain engineering in parametric down-conversion sources negates the need for lossy spectral filtering allowing one to satisfy these conditions inherently within the source design. Here, we present a telecom-wavelength parametric down-conversion photon source that operates on the achievable limit of domain engineering. We generate photons from independent sources which achieve two-photon interference visibilities of up to 98.6 ± 1.1% without narrow-band filtering. As a consequence, we reach net heralding efficiencies of up to 67.5%, which corresponds to collection efficiencies exceeding 90%.


Apoptosis, proliferation and differentiation patterns are influenced by Zebularine and SAHA in pancreatic cancer models.
Pancreatic cancer continues to be an urgent clinical problem. We used the novel DNA methyltransferase inhibitor Zebularine and the histone deacetylase inhibitor SAHA to investigate the epigenetic influence on viability and differentiation of the pancreatic cancer cell lines YAP C, DAN G and Panc-89 in vitro and in vivo. Cell vitality, proliferation and expression of PDX-1, cytokeratin 7 and 20, chromogranin A, vimentin, bax and bcl-2 were determined on the protein and mRNA level in vitro and in a subcutaneous xenograft model. A time- and dose-dependent increase of apoptosis, paralleled by decreased proliferation, was observed after incubation with single agents or a combination therapy with lower concentrations. This was associated with up-regulation of pro-apoptotic bax and a phenotypic stabilization by the enhanced expression of cytokeratin 7. In vivo, growth of xenografts was delayed with the most pronounced effect in Panc-89 after 1 week of daily intraperitoneal injections of Zebularine paralleled with CK7 up-regulation and down-regulation of dedifferentiation markers. Epigenetic modulation via inhibition of DNA methyltransferase and histone deacetylase induces apoptosis in human pancreatic cancer cells in vitro and delays xenograft growth in vivo, which is associated with a morphological/molecular phenotypic stabilization. These compounds may therefore be suitable as adjunctive therapeutic agents in the treatment of pancreatic cancer.


The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey.
Ever since its first delineation as a distinct clinicopathologic entity in 1957, idiopathic membranous nephropathy (MN) has been the subject of intense laboratory and clinical investigation. The availability of laboratory models (particularly active and passive Heymann nephritis) of this disorder has been a boon to investigators. Concepts regarding the fundamental mechanisms of immune deposit formation, a sine qua non of idiopathic MN, have evolved and now are firmly established. Circulating autoantibodies (immunoglobulin G4 and immunoglobulin G1 subclasses) interacting with antigens native to or planted in the glomerular capillary wall at the podocyte cell membrane-basement membrane interface generally are regarded as the fundamental pathobiological mechanism. Thus, MN now is regarded as a podocytopathy. The immune deposits evoke an alteration in glomerular capillary permeability, probably through complement-mediated injury of the podocyte and its slit-pore membrane; however, cell-mediated immunity also may have a role, and the physical presence of immune deposits and basement membrane alterations also may participate. The exact nature of the autoantibody systems operative in human idiopathic MN is being uncovered rapidly. It is hoped that this 50-year odyssey will culminate in real progress in the diagnosis, prognosis, and therapy for the human disease.


Why I became a home support worker: recruitment in the home health sector.
Home care is considered an essential pillar of the health care systems in many industrialized countries. With an increased demand for home health workers, there has been growing interest in examining recruitment and retention of these workers. With a focus on recruitment of home support workers, in this study we draw on data from interviews with 57 home support workers in three Canadian provinces, to examine the factors that attract individuals to employment in this sector. These factors include: previous experience, financial considerations, and enjoying working with people. Understanding these overlapping factors can aide in the recruitment of future workers.


Detection of later stage breast cancer in First Nations women in Ontario, Canada.
To compare the distribution of stage at breast cancer diagnosis between First Nations (FN) and non-FN women, and to investigate factors associated with later diagnosis in FN women. A case-case design was employed to compare FN women (N = 287) to a frequency-matched random sample of women (N = 671) from the general population diagnosed with breast cancer in the Ontario Cancer Registry. Women were matched (2:1) on period of diagnosis (1995-1999, 2000-2004), age at diagnosis (< 50 vs. > or = 50), and Regional Cancer Centre (RCC). Stage and data relevant to the determinants of stage were collected from medical charts at the RCCs. The association between stage (stage II + vs. I) and FN status was modeled using logistic regression analyses; for FN women, the association between risk factors and stage was examined. FN women (66%) were diagnosed with a later stage significantly more often than non-FN women (56%). FN women with a non-screened cancer (OR 5.03, 95% CI 2.48-10.21) and those who were overweight or obese (OR 2.98, 95% CI 1.27-6.98 and OR 4.46, 95% CI 1.95-10.21, respectively) were significantly more likely to be diagnosed at a later stage. Having a comorbidity reduced the odds of a later stage (OR 0.51, 95% CI 0.27-0.96) in FN women. This study demonstrates the need for FN women, in particular those who are not accessing the health care system, to participate in breast screening programs aimed at detecting breast cancers earlier with a better prognosis. These findings suggest that the cancer care system in Ontario should better target this population through increasing awareness and access to screening.


Role of Regulatory T cells in Airway Inflammation in Asthma.
Asthma is an allergic disease characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), reversibility and remodeling. Inhaled corticosteroids (ICS) are effective in many patients with asthma. However, ICS are a controlling, but not but curative treatment, and there are still many patients with refractory and difficult-to-treat asthma. The evaluation of airway inflammation by induced sputum, non-specific AHR by methacholine, and asthmatic reactions by specific allergen challenge techniques are useful not only to investigate the pathogenesis of asthma but also to help develop new drugs for asthma management. Interactions between inflammation and regulation, such as between regulatory T cells (Tregs), and AHR were investigated using these techniques. The phenotypes are Tregs characterized by expression of the forkhead box P3 (Foxp3) and cytotoxic T-lymphocyte antigen 4 (CTLA4), which are potent mediators of dominant self-tolerance. Foxp3 and CTLA4 interact with each other. In patients with mild asthma, airway Tregs were decreased and airway eosinophilic inflammation was activated with accelerated AHR. Human asthmatic attack models by allergen challenge demonstrated that airway Tregs were decreased from the baseline with late asthmatic response (LAR) in patients with dual-responder asthma, and there was a significant correlation between change in airway Tregs and LAR. Airway Tregs were increased with escalation of interleukin-10 by ICS. The investigation of Tregs may lead to new strategies for management of asthma and other allergic diseases.


Hypnosis as adjunctive therapy for multiple sclerosis: a progress report.
Several reports suggest that hypnosis can facilitate healing in various physical pathologies. This is a preliminary report, supported by three cases. They demonstrate that suggestion by a hypnotist of symptom improvement can be used beneficially in the treatment of the physical impairment caused by Multiple Sclerosis. The first patient, severely affected, had Multiple Sclerosis for over 35 years. He had been wheelchair bound for many years. The second, recently diagnosed and minimally affected, had difficulty with balance and walked with the aid of a cane. The third, also minimally affected, reported pain in her right leg. All three showed improvement either immediately or within several weeks when the hypnotist suggested improvement or displacement of symptoms with the patients in hypnosis. No attempt was made to deal with psychodynamics or to suggest alternative symptoms to the patients. Symptom substitution did not occur. When symptoms improved, even slightly, these patients exhibited increased hopefulness.


Endothelin-1 stimulates expression of cyclin D1 and S-phase kinase-associated protein 2 by activating the transcription factor STAT3 in cultured rat astrocytes.
Brain injury-mediated induction of reactive astrocytes often leads to glial scar formation in damaged brain regions. Activation of signal transducer and activator of transcription 3 (STAT3), a member of the STAT family of transcription factors, plays a pivotal role in inducing reactive astrocytes and glial scar formation. Endothelin-1 (ET-1) is a vasoconstrictor peptide, and its levels increase in brain disorders and promote astrocytic proliferation through ETB receptors. To clarify the mechanisms underlying ET-1-mediated astrocytic proliferation, here we examined its effects on STAT3 in cultured rat astrocytes. ET-1 treatment stimulated Ser-727 phosphorylation of STAT3 in the astrocytes, but Tyr-705 phosphorylation was unaffected, and ET-induced STAT3 Ser-727 phosphorylation was reduced by the ETB antagonist BQ788. ET-1 stimulated STAT3 binding to its consensus DNA-binding motifs. Monitoring G1/S phase cell cycle transition through bromodeoxyuridine (BrdU) incorporation, we found that ET-1 increases BrdU incorporation into the astrocytic nucleus, indicating cell cycle progression. Of note, STAT3 chemical inhibition (with stattic or 5,15-diphenyl-porphine (5,15-DPP)) or siRNA-mediated STAT3 silencing reduced ET-induced BrdU incorporation. Moreover, ET-1 increased astrocytic expression levels of cyclin D1 and S-phase kinase-associated protein 2 (SKP2), which were reduced by stattic, 5,15-DPP, and STAT3 siRNA. ChIP-based PCR analysis revealed that ET-1 promotes the binding of SAT3 to the 5'-flanking regions of rat cyclin D1 and SKP2 genes. Our results suggest that STAT3-mediated regulation of cyclin D1 and SKP2 expression underlies ET-induced astrocytic proliferation.


Echocardiographic oscillating flap in aortic root dissecting aneurysm.
A patient had a history, physical findings, and chest x-ray film suggesting type I aortic dissection. This diagnosis could not be confirmed angiographically. Echocardiographic studies predicted both the presence of dissection and the anatomic findings at surgery. A regularly oscillating echo corresponding to the intimal flap was found in the false lumen. This is suggested as a new echocardiographic finding in dissecting aneurysm.


[Application of three semi-quantitative risk assessment methods in electroplating enterprises].
Objective: To apply the semi-quantitative risk assessment model in the Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazardous Factors in the Workplace to assess the occupational health risk of electroplating enterprises and explore its applicable conditions and characteristics. Methods: Three electroplating enterprises were selected as the research objects. Occupational hygiene survey and hazard factor detection were conducted on the spot. Three semi-quantitative risk assessment methods were used to assess the risk, and the evaluation results were compared. Results: The consistency between the contact index method and the comprehensive index method was strong. The weighted Kappa value was 0.946 and the P value was less than 0.001, but the consistency between the contact ratio method, the contact index method and the comprehensive index method was poor. The weighted Kappa value was 0.345 and 0.391, and the P value was 0.009 and 0.004, respectively. When the contact concentration is less than 50% OELs, the evaluation results of the contact ratio method are lower than those of the exponential method and the comprehensive exponential method. The consistency of the three methods was the highest when the contact concentration (>50%) and (<OELs). When the contact concentration >OELs, the results of the contact ratio method are higher than those of the index method and the comprehensive index method. Conclusion: Contact ratio method is suitable for occupational health risk assessment under the condition of incomplete occupational health information and for enterprise managers to identify key control points of health risk through self-assessment; Contact index method is suitable for hazard risk assessment of occupational hazards without sampling test conditions or OELs, and pre-assessment of occupational hazards of construction projects without access to analogical test data. The index method is suitable for occupational health risk assessment with available testing data and complete occupational health information.


Well-differentiated adenocarcinoma associated with ulcerative colitis.
Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed.


Socioeconomic barriers to rhegmatogenous detachment surgery in Brazil.
Purpose. To verify access barriers patients with retinal detachment face to arrive at a reference center and to evaluate patients' knowledge about the disease. Methods. Transversal study that applied a questioner to 65 patients of the Clinical Hospital of the University of Sao Paulo with retinal detachment between February and August of 2010. Results. Reasons for not performing the surgery in other services were as follows: 47% were referred because there was not vitreoretinal surgeon at original service; 27% could not afford the surgery, had no health insurance, or had no coverage at health insurance plan for the procedure. Time between the first symptom and the arrival at our service was as follows: 18 patients arrived in up to 7 days; 35 between 8 and 30 days; 8 between 31 and 90 days; 5 in more than 90 days. Reasons for delay were as follows: 70% did not know how serious the pathology was; 56% thought that it had spontaneous cure; 16% did not have money to pay for ophthalmic evaluation, 10% did not know where to go and 24% for other reasons. Conclusion. Educational programs about disease and measures to optimize the referral to specialized services are needed to accelerate the treatment of patients with rhegmatogenous retinal detachment.


Population-based asymmetric margins for moving targets in real-time tumor tracking.
Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.


Glutathione concentration during maturation and after fertilization in pig oocytes: relevance to the ability of oocytes to form male pronucleus.
The present study examined the kinetics of glutathione (GSH) concentration during maturation and after fertilization in pig oocytes and its relevance to the ability of pig oocytes to form a male pronucleus after in vitro fertilization. The GSH concentration was significantly higher in pig oocytes matured in Waymouth medium than in pig oocytes matured in either modified (m) TCM-199 or mTLP media. The addition of 0.04-0.57 mM cysteine (CySH) to mTLP significantly increased both the GSH concentrations in oocytes matured in vitro and the rate of male pronucleus formation as compared to those in oocytes cultured in mTLP alone. When pig oocytes were cultured 12, 24, or 36 h in mTLP plus 0.14 mM CySH, their GSH concentrations were significantly higher than in uncultured oocytes. After fertilization, the GSH concentration in pig oocytes declined significantly. GSH concentrations in oocytes matured in vivo did not differ from those in oocytes matured in mTLP plus 0.14 or 0.57 mM CySH. The results indicate that 1) the composition of maturation medium affects the GSH concentration in pig oocytes; 2) the addition of CySH to maturation medium permits GSH synthesis by the pig oocytes; 3) GSH levels in pig oocytes change during maturation and after fertilization; and 4) GSH synthesis during oocyte maturation is an important factor for promoting their ability to form a male pronucleus after fertilization.


Inefficient neural system stabilization: a theory of spontaneous resolutions and recurrent relapses in psychosis
A striking feature of psychosis is its heterogeneity. Presentations of psychosis vary from transient symptoms with no functional consequence in the general population to a tenacious illness at the other extreme, with a wide range of variable trajectories in between. Even among patients with schizophrenia, who are diagnosed on the basis of persistent deterioration, marked variation is seen in response to treatment, frequency of relapses and degree of eventual recovery. Existing theoretical accounts of psychosis focus almost exclusively on how symptoms are initially formed, with much less emphasis on explaining their variable course. In this review, I present an account that links several existing notions of the biology of psychosis with the variant clinical trajectories. My aim is to incorporate perspectives of systems neuroscience in a staging framework to explain the individual variations in illness course that follow the onset of psychosis.


Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D-Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity.
Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve wound healing in a diabetic mouse model, with increased CD31+ staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.


Teaching evidence-based social work in foundation practice courses: learning from pedagogical choices of allied fields.
The field of social work is attuned to the need to incorporate evidence-based practice education into masters-level curriculum. One question remaining is how to integrate evidence-based practice in the foundation practice courses. Integration of evidence-based practice across the foundation-level curriculum coincides with the Council on Social Work Education's mandate that student's engage in research-informed practice and practice-informed research. Through a discussion of definitions, criticisms, and pedagogy across the allied fields of medicine, nursing, and social work the authors address the current status of evidence-based practice curriculum in foundation-level education. The authors incorporate the lessons learned from allied fields and a Masters of Social Work student's analyses of their experience of evidence-based practice learning to propose an adult-learner model to improve evidence-based practice pedagogy in Social Work.


Nucleus pulposus explant culture model.
Many of the therapeutic interventions for intervertebral disc degeneration attempt to repopulate the nucleus pulposus (NP) tissue; however, NP cells are heterogeneous and not well characterized. To address this, we have investigated the morphology, extracellular gene and protein expression, and apoptosis changes in NP explants cultured in vitro with or without chondrogenic reagents for different periods. We also compared the susceptibility of the explants to different treatments by comparing: treatment of NP explants with GDF5 protein, transfection of NP explants with GDF5 plasmid, and infection of NP explants with GDF5 adenovirus vector. We found that expression levels of two of the major extracellular proteins found in NP tissue, that is, collagen II and aggrecan, could be maintained in an NP explant culture model with a chondrogenic medium up to 7 days, and were significantly higher than that of fresh NP tissue after 14 days of culture in vitro, whether or not chondrogenic medium was used. In addition, the NP explant responded to treatment with growth factor, and could be infected by virus and transfected by plasmid for further evaluation of growth factor gene therapy. NP explant culture could therefore provide an easy in vitro culture model to characterize NP cells and evaluate potential therapeutic reagents.


Study of quantitative interactions of potato and corn starch granules with ions in diluted solutions of heavy metal salts.
Interactions of potato and corn starch granules with ions in diluted solutions of silver, lead, copper or iron salts were investigated. It was shown experimentally that granules accumulated the cations in amounts depending on the granule structure and water content as well as a type of both metal and counter-ions present in solution. Potato starch retained almost three times more cations compared to corn starch what was proportional to the total phosphorous content in these starches. Quantity of milligrams of cations bound by 1g of starch was inversely correlated with the cation hydration. Ag(+), Pb(2+) and Cu(2+) were connected in stoichiometric amounts of moles to semicrystalline and amorphous parts of the granules. Fe(3+) ions were accumulated in higher than stoichiometric quantities mainly in granule amorphous regions. Metal ions penetrated into granules together with anions except nitrates which remained on surface of potato starch granules. Cations facilitated the starch thermal decomposition in accordance with values of their standard redox potentials. Nitrates supported this process only in the presence of base metal cations.


New therapeutic strategies in chronic heart failure: challenge of long-term beta-blockade.
It is claimed that long-term treatment with beta-blockers improves cardiac function and exercise capacity in patients with various forms of congestive heart failure. This was first reported by Waagstein and coworkers in patients with idiopathic dilated cardiomyopathy in 1975 and was later confirmed in 8 further studies in this type of patient. A total of 211 patients with idiopathic dilated cardiomyopathy were treated for 12-19 months. About two thirds of the patients have improved to some extent. Seven other studies reported favourable long-term effects of beta-blockers in 120 patients with other forms of dilated cardiomyopathy, e.g. caused by coronary artery disease, adriamycin, diabetes, or valvular heart disease. Pooled data from 10 studies on 153 patients with various forms of cardiomyopathy, showed that ejection fraction was improved by 40% from 27 to 38%. Only two studies were inconclusive, both with only one month's treatment. In all studies with favourable effects of long-term beta-blockade, treatment was given for more than 2 months and in most cases for about 6 months. A number of beta-blockers have been used in the studies, including acebutulol, alprenolol, bucindolol, labetalol, metoprolol, practolol and propranolol. In most cases, a rather low dose was given initially and there was a stepwise increase in the dosages. After 6-8 weeks most patients were given beta-blockers in daily doses comparable to those given in patients with angina pectoris and hypertension. There is at present no indication that one beta-blocker is superior to others. It therefore seems reasonable to believe that the effects are due to beta 1-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)


Physicochemical Approach to Understanding the Structure, Conformation, and Activity of Mannan Polysaccharides.
Extracellular polysaccharides are widely produced by bacteria, yeasts, and algae. These polymers are involved in several biological functions, such as bacteria adhesion to surface and biofilm formation, ion sequestering, protection from desiccation, and cryoprotection. The chemical characterization of these polymers is the starting point for obtaining relationships between their structures and their various functions. While this fundamental correlation is well reported and studied for the proteins, for the polysaccharides, this relationship is less intuitive. In this paper, we elucidate the chemical structure and conformational studies of a mannan exopolysaccharide from the permafrost isolated bacterium Psychrobacter arcticus strain 273-4. The mannan from the cold-adapted bacterium was compared with its dephosphorylated derivative and the commercial product from Saccharomyces cerevisiae. Starting from the chemical structure, we explored a new approach to deepen the study of the structure/activity relationship. A pool of physicochemical techniques, ranging from small-angle neutron scattering (SANS) and dynamic and static light scattering (DLS and SLS, respectively) to circular dichroism (CD) and cryo-transmission electron microscopy (cryo-TEM), have been used. Finally, the ice recrystallization inhibition activity of the polysaccharides was explored. The experimental evidence suggests that the mannan exopolysaccharide from P. arcticus bacterium has an efficient interaction with the water molecules, and it is structurally characterized by rigid-rod regions assuming a 14-helix-type conformation.


Rotational bed therapy to prevent and treat respiratory complications: a review and meta-analysis.
Immobility is associated with complications involving many body systems. To review the effect of rotational therapy (use of therapeutic surfaces that turn on their longitudinal axes) on prevention and/or treatment of respiratory complications in critically ill patients. Published articles evaluating prophylaxis and/or treatment were reviewed. Prospective randomized controlled trials were assessed for quality and included in meta-analyses. A literature search yielded 15 nonrandomized, uncontrolled, or retrospective studies. Twenty prospective randomized controlled trials on rotational therapy were published between 1987 and 2004. Various types of beds were studied, but few details on the rotational parameters were reported. The usual control was manual turning of patients by nurses every 2 hours. One animal investigation and 12 clinical trials addressed the effectiveness of rotational therapy in preventing respiratory complications. Significant benefits were reported in the animal study and 4 of the trials. Significant benefits to patients were reported in 2 of another 4 studies focused on treatment of established complications. Researchers have examined the effects of rotational therapy on mucus transport, intrapulmonary shunt, hemodynamic effects, urine output, and intracranial pressure. Little convincing evidence is available, however, on the most effective rotation parameters (eg, degree, pause time, and amount of time per day). Meta-analysis suggests that rotational therapy decreases the incidence of pneumonia but has no effect on duration of mechanical ventilation, number of days in intensive care, or hospital mortality. Rotational therapy may be useful for preventing and treating respiratory complications in selected critically ill patients receiving mechanical ventilation.


Simultaneous Isolation of High Quality Cardiomyocytes, Endothelial Cells, and Fibroblasts from an Adult Rat Heart.
The rat is an important animal model used in cardiovascular research, and rat cardiac cells are used routinely for in vitro analysis of the molecular mechanisms of cardiovascular disease progression such as cardiac hypertrophy, fibrosis, and atherosclerosis. Although several attempts with variable success have been made to develop immortalized cell lines from the cardiovascular system to understand these cellular mechanisms, primary cells offer a more natural and close to in vivo environment for such studies. Therefore, different laboratories working on a particular cell type have developed protocols to isolate individual types of rat cardiac cells of interest. A protocol that allows the isolation of more than one cell type, however, is missing. Here an optimized protocol is described that allows the isolation of high-quality major cardiac cell types (cardiomyocytes, endothelial cells, and fibroblasts) from a single preparation and enables their use for cellular analyses. This permits the most efficient use of available resources, which may save time and reduce research costs.


Operational cost minimization of heat pump for milk pasteurization in dairy.
A thermo economic optimization analysis is presented yielding simple algebraic formula for estimating the optimum operating conditions of interconnected heat pump assisted milk pasteurizing systems. The overall operational cost method including the cost of auxiliary heater is used in the present study, together with the thermal analyses of all system components, for thermo economic analysis of the system.


Functional classification and mutation analysis of a synpolydactyly kindred.
The aim of the present study was to analyze a congenital syndactyly/polydactyly kindred and propose a new functional classification method of clinical significance. The modes of inheritance and mutational mechanisms were also determined using genetic analyses. Hand and foot anatomy and functions were measured using photographic images, X-ray imaging and grip ability tests. Genetic analysis comprised the genotyping of polymorphic microsatellite markers at known polydactyly-associated loci and the sequencing of the candidate gene. A functional classification system was devised to divide the clinical features into three types, which included mild, moderate or severe deformity. The family was concluded to have syndactyly type II with autosomal dominant inheritance. The microsatellites, D2S2310 and D2S2314, at the 2q31-32 chromosome, which have previously been associated with synpolydactyly type I, were found to be associated with the disorder in the current family. A 27-bp insertion mutation was identified in the affected individuals in the HOXD13 gene at this locus. The insertion added a further nine alanine residues to the polyalanine stretch within the encoded protein. In conclusion, the functional classification method described in the present study may be used to guide surgical approaches to treatment. A family was identified in whom expansion of the polyalanine tract in the HOXD13 gene causes autosomal dominant hereditary synpolydactyly.


The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.
Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c.


Cognitive Impairment in Tuberculous Meningitis.
Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described. A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. Of 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19). Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.


Synthesis and solution- and solid-state characterization of gold(I) rings with short Au...Au interactions. Spontaneous resolution of a gold(I) complex.
We report the synthesis and solution- and solid-state characterization of gold(I) rings with short 1,9-transannular Au...Au interactions. The 9- and 16-membered gold(I) rings were prepared by reacting 9,9-dimethyl-4,5-bis(diphenylphosphino)-xanthene and (Me2S)AuCl in the presence of AgNO3 in the molar ratio of 1:0.5:1 and 1:1:1, respectively. X-ray crystallographic measurements in conjunction with solution X-ray diffraction and NMR methods have been used to determine the structure of gold(I) rings, and we also gained insight into the dynamics. The nine-membered gold(I) ring is chiral, and the crystal contains only one of the two enantiomers, either right- or left-handed. To the best of our knowledge this represents the first example of crystallization-induced spontaneous resolution of a binuclear gold(I) cycle. The 16-membered ring with 1,9-transannular Au...Au interaction is in a figure-eight conformation.


Encapsulation of Sericin-Decorated Efficient Agents in Silk Hydrogels for Wound Dressings.
Excessive oxidative stress, bacterial infections, and inflammation are the primary factors impeding the healing of skin wounds. Bioactive hydrogels are commonly employed in the treatment of skin injuries. However, the limited solubility of many drugs and active agents in water significantly hampers their effectiveness in hydrogel dressings. In this research, prior to incorporation into the silk fibroin (SF) hydrogel matrix, two active agents curcumin and silver nanoparticles (Ag NPs) were decorated by silk sericin to improve their dispersibility and stability in water. The resultant SF/Ag/C hydrogels combined the biological safety and nontoxicity of SF, the antioxidant and anti-inflammatory efficacy of curcumin, and the antibacterial effect of Ag NPs. These properties effectively enhanced wound repair by reducing bacterial infections, mitigating oxidative stress, suppressing the expression of pro-inflammatory factors, and promoting angiogenesis. This study presented a straightforward approach for constructing bioactive hydrogels for the promotion of the wound healing process.


The highways and byways of the brain.
Brain functions rely on the communication network formed by axonal fibers. However, the number of axons connecting different brain regions is unknown. A study in PLoS Biology addresses this question and finds that most areas of the human cerebral cortex are linked by an astoundingly small number of fibers.


Benchmarking in the process of donation after brain death: a methodology to identify best performer hospitals.
A benchmarking approach was developed in Spain to identify and spread critical success factors in the process of donation after brain death. This paper describes the methodology to identify the best performer hospitals in the period 2003-2007 with 106 hospitals throughout the country participating in the project. The process of donation after brain death was structured into three phases: referral of possible donors after brain death (DBD) to critical care units (CCUs) from outside units, management of possible DBDs within the CCUs and obtaining consent for organ donation. Indicators to assess performance in each phase were constructed and the factors influencing these indicators were studied to ensure that comparable groups of hospitals could be established. Availability of neurosurgery and CCU resources had a positive impact on the referral of possible DBDs to CCUs and those hospitals with fewer annual potential DBDs more frequently achieved 100% consent rates. Hospitals were grouped into each subprocess according to influencing factors. Hospitals with the best results were identified for each phase and hospital group. The subsequent study of their practices will lead to the identification of critical factors for success, which implemented in an adapted way should fortunately lead to increasing organ availability.


Hepatic inflammatory myofibroblastic tumor: A case report.
Hepatic inflammatory myofibroblastic tumor (HIMT) is a rare type of hepatic tumor. It is always misdiagnosed and mistreated because it is primarily found with no obvious specific manifestation, and its imaging findings are diverse. Here, we report a case of HIMT that was initially diagnosed as liver malignancy but was confirmed as HIMT by histopathology after hepatectomy. Mostly, HIMTs are infiltrated with plasma cells and stain positively for anaplastic lymphoma kinase on immunohistochemistry as well as for some other kinases. HIMT can be treated with single nonsteroidal anti-inflammatory drugs and without surgery when it is diagnosed accurately. Because the etiology of HIMT is unknown and the diagnosis is difficult, the pathogenesis and clinical process need to be further studied.


Facial soft tissue thickness among various vertical facial patterns in adult Pakistani subjects.
Facial reconstruction techniques are used to obtain an approximation of an individual's appearance thus helping identification of unidentified decedents from their dried skeletal remains. Many of these techniques rely on the sets of average facial soft tissue thickness (FST) values at different anatomical landmarks provided by the previous studies. FST is influenced by the age, sex, ethnicity and the body mass index of the individual. Recent literature has shown that the anthropological variations of the skull may also affect FST at certain points. This study was designed to evaluate the effect of such variations in vertical skull morphology on FST as around one third of different population groups have either a long or short facial pattern as compared to the average facial pattern. Moreover, this study also provides a FST database for the adult Pakistani subjects that may have potential implications in the facial reconstruction of the local subjects. A retrospective analysis of 276 lateral cephalograms of adult subjects having normal sagittal facial pattern was performed. Subjects were categorized into three vertical facial patterns (long face=95, average face=102, short face=79) according to the vertical dimensions of the skull and the FST was measured at 11 midline points. To compare the FST between males and females Mann-Whitney U test was used. Kruskal-Wallis test was applied to compare FST among three vertical facial patterns. The results of our study revealed significant differences in FST at nine landmarks between males and females. These sex-based differences were more pronounced in the long and short facial patterns as compared to the average facial pattern. FST at stomion, pogonion, gnathion and menton was significantly greater in the short facial pattern as compared to the long facial pattern in both the sexes. The results of the present study highlight the importance of anthropological analysis of the skull and taking the vertical skeletal dimension into consideration while performing facial reconstruction.


Polymorphic organization of constitutive heterochromatin in Equus asinus (2n = 62) chromosome 1.
In the karyotype of Equus asinus (domestic donkey, 2n = 62), non-centromeric heterochromatic bands have been described in subcentromeric and telomeric positions. In particular, chromosome 1 is characterised by heterochromatic bands in the proximal region of the long arm and in the short arm; it has been shown that these regions are polymorphic in size. Here we investigated the variation in the intensity and distribution of fluorescence signals observed on donkey chromosome 1 after in situ hybridization with two DNA probes containing fragments from the two major equine satellite DNA families. Our results show that, in Equus asinus chromosome 1, the amount and distribution of large clusters of satellite DNA can define at least nine polymorphic variants of the constitutive heterochromatin that cannot be detected by C-banding alone.


Cherubism with multiple dental abnormalities: a rare presentation.
Cherubism is a progressive, hereditary fibro-osseous lesion exclusively affecting the jaw bones. It is caused by the abnormal functioning of osteoblasts and osteoclasts, leading to replacement of normal bone by cellular fibrous tissue and immature bone, which produces painless progressive growth of the jaw, with a round facial appearance. It was first described in 1933 by Jones as 'familial multilocular cystic disease of the jaws'. The term 'cherubism' was later coined to describe the rounded facial appearance resulting from jaw hypertrophy that was reminiscent of cherubs depicted throughout Renaissance art. The bony lesions generally occur at an early age, affect one or both jaws symmetrically, and grow progressively until puberty. Spontaneous regression is seen in most cases, although surgical re-contouring may be required for others for aesthetic reasons.


Opening Pandora's box: parental anxiety and the assessment of childhood murmurs.
Most family physicians and pediatricians recognize the induction of parental anxiety when a newly diagnosed childhood murmur is discussed with a child's parent. To assess parental anxiety before and after consultation with a pediatric cardiologist for assessment of a childhood murmur. The study investigated the relationship between anxiety and parental understanding of murmurs, and assessed the possible role of the primary physician's initial diagnosis of the child's murmur on the anxiety level of parents. One hundred ninety-five consecutive parents who presented with their child to the Alberta Children's Hospital Cardiology Clinic, Calgary, Alberta, were recruited. The children were referred for an initial consultation with a pediatric cardiologist for assessment of a heart murmur noted previously by the referring physicians. Before consultation, the patients were divided into three murmur groups for diagnosis: innocent, pathological and unknown. Anxiety questionnaires, as well as questionnaires assessing basic parent understanding of childhood murmurs, were administered to one of the parents pre- and postconsultation. The initial diagnosis given to the caregiver by the primary care physician as the reason for referral did not seem to affect the level of parental anxiety within groups. As expected, postconsultation anxiety levels were significantly higher in parents whose children received a pathological diagnosis from the pediatric cardiologist. A significant drop in parental anxiety post-consultation was seen in all parent groups, including parents of a child diagnosed with a significant cardiac problem or pathology requiring further investigation and/or cardiac follow-up. There was a consistent correlation between higher scores on parental understanding and lower levels of parental anxiety. The present study confirms that the finding of a childhood murmur by the family doctor or pediatrician induces significant parental anxiety, even when the presumptive diagnosis is that of an 'innocent' murmur. Pediatric cardiology consultation decreases parental anxiety, even in parents whose child has been given a diagnosis of pathology. The correlation between poor understanding of murmurs and high parental anxiety suggests that further study is required on the role of the referring physician in augmenting parental understanding of the term 'heart murmur' and the referral process.


Neferine attenuates doxorubicin-induced fibrosis and hypertrophy in H9c2 cells.
Doxorubicin (DOX), an anthracycline antineoplastic candidate is used to treat various malignancies. Around 41% of patients undergoing DOX treatment develop acute cardiotoxicity. Preventing DOX-induced cardiac fibrosis and hypertrophy helps in evading cardiac remodeling leading to cardiomyopathy and heart failure. Neferine, an alkaloid from the lotus has numerous pharmacological activities. The present study was designed to evaluate the protective effect of neferine on DOX-mediated fibrosis and hypertrophy. DOX-induced fibrosis involves activation of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase 2 (MMP-2), and MMP-9 with concomitant downregulation of tissue inhibitors of MMPs (TIMP)-1 and TIMP-2 expressions in H9c2 cardiomyoblasts. Furthermore, DOX treatment also resulted in hypertrophy with the increased cell volume and overexpression of hypertrophy markers calcineurin, brain natriuretic peptide, and atrial natriuretic peptide. Finally, DOX treatment resulted in apoptosis through activation of p53. Pretreatment with neferine markedly activated SIRT1 expression and modulated the expression levels of TGF-β1 and p53, thereby significantly reducing DOX-induced fibrosis, hypertrophy, and apoptosis in H9c2 cardiomyoblasts.


Asymmetric Total Synthesis of Clionastatins A and B.
Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland-Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.


Engineering Carboxylic Acid Reductase (CAR) through a Whole-Cell Growth-Coupled NADPH Recycling Strategy.
Rapid evolution of enzyme activities is often hindered by the lack of efficient and affordable methods to identify beneficial mutants. We report the development of a new growth-coupled selection method for evolving NADPH-consuming enzymes based on the recycling of this redox cofactor. The method relies on a genetically modified Escherichia coli strain, which overaccumulates NADPH. This method was applied to the engineering of a carboxylic acid reductase (CAR) for improved catalytic activities on 2-methoxybenzoate and adipate. Mutant enzymes with up to 17-fold improvement in catalytic efficiency were identified from single-site saturated mutagenesis libraries. Obtained mutants were successfully applied to whole-cell conversions of adipate into 1,6-hexanediol, a C6 monomer commonly used in polymer industry.


[Comorbidity in connection with psoriasis is more than psoriatic arthritis].
Psoriasis is a common chronic inflammatory disease which is associated with extensive comorbidity, including psoriatic arthritis, cardiovascular and cardiometabolic disease, inflammatory bowel disease, malignancy, chronic kidney disease and depression. Clinical guidelines have been developed to target some of these comorbid diseases in patients with psoriasis and should be used by the treating physician.


[Effects of the combined therapy of the auricular-point pressure at the free position and the unprotected perineal delivery technique during the second stage of labor in the primiparas].
To observe the effects of the combined therapy of the auricular-point pressure at the free position and the unprotected perineal delivery technique during the 2nd stage of labor in the primiparas so as to improve the clinical delivery quality. A total of 146 primiparas who accepted the natural delivery willingly were collected. According to the visit sequence, they were divided into an observation group (72 cases) and a control group (74 cases). The free position and the unprotected perineal delivery were adopted in combination during the labor in both of the two groups. Additionally, in the observation group, the auricular-point pressure with semen vaccariae was intervened when entering the active phase. The points were pengqiang (TF5), zigong (uterus), neishengzhiqi (TF2), pizhixia (AT4), shenmen (TF4), jiaogan (AH6a), pi (CO13) and wei (CO4). Each point was pressed for 1 to 2 min each time, repeated once every 10 to 20 min until the end of the 2nd stage of labor. The episiotomy rate, perineal laceration degree, perineal pain degree, the duration of the 2nd labor stage, postpartum hemorrhage, postpartum urine retention and neonatal asphyxia rate were recorded and compared in the primiparas between the two groups. The perineal laceration of the degree Ⅲ and Ⅳ did not occur in the two groups. Compared with the control group, the effect on the perineal laceration was better in the observation group (P<0.05). The episiotomy rate was 5.6% (4/72) in the observation group, lower than that in the control group (P<0.05). The total perineal laceration rate was 68.1% (48/72) in the observation group, similar to the control group (P>0.05). In the observation group, the neonatal asphyxia rate was 1.4% (1/72), the postpartum hemorrhage 6.9% (5/72) and the incidence of urine retention 5.6% (4/72), all lower than 10.8% (8/74), 18.9% (14/74) and 17.6% (13/74) in the control group respectively (all P<0.05). In the observation group, on the 1st, 2nd and 3rd days after labor, the perineal pain degree and the duration of the 2nd stage of labor were superior to the control group (all P<0.001). The combined therapy of the auricular-point pressure intervention at the free position and the unprotected perineal delivery technique effectively reduces the episiotomy rate and perineal laceration degree, relieves the perineal pain, reduces the neonatal asphyxia rate and improves the delivery quality during the 2nd stage of labor in the primiparas.


Cognitive performance and neural correlates of detecting driving hazards in healthy older adults.
In spite of the growing number of seniors who drive and their relatively frequent involvement in accidents, little is known about the cognitive substrates of road hazard recognition and their relationship with general cognitive performance in this population. We aimed to investigate, using a combination of functional MRI (fMRI) and a comprehensive neuropsychological battery, the anatomical and cognitive components of driving hazard recognition. Fourteen healthy active drivers aged between 65 and 87 years underwent neuropsychological evaluation and fMRI scanning. fMRI was performed while subjects watched a video composed of clips of driving hazards randomly interspersed with uneventful driving clips. We investigated brain areas that are recruited for hazard detection, in contrast to brain areas responding to driving without a hazard. The performance on neuropsychological tests was then regressed with the degree of activation of cortical areas related exclusively to detecting hazards. Driving hazards generated significant activations, compared to non-hazards, in the lateral associative occipital cortex and in the right prefrontal cortex. Intensity of brain activation was correlated on performance on memory and cognitive control neuropsychological tests. Future studies can possibly address the same relationship in early dementia, as a preliminary form of investigation for driving safety.


Models of man and models of policy: reflections of "Exit, Voice, and Loyalty" ten years later.
The challenge of health care policy is how to combine sensitivity to both consumer preferences (the economic model) and citizen wishes (the political model): what either wants the other may wish to deny him. Competing economic (exit) and political (voice) activities in response to deterioration in the quality of a service, however, may be an inadequate framework to encompass discontent with the complex mix of types of services offered. The "political market" in which decisions about health care are made is suggested for further exploration.


Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: study of their in vitro immunological interactions.
Many studies have suggested that the immune response may play a crucial role in the progression of hepatocellular carcinoma (HCC). Therefore, our aim was to establish a (i) functional culture of primary human tumor hepatocytes and non-tumor from patients with hepatocellular carcinoma (HCC) and (ii) a co-culture system of HCC and non-HCC hepatocytes with autologous peripheral blood mononuclear cells (PBMCs) in order to study in vitro cell-to-cell interactions. Tumor (HCC) and non-tumor (non-HCC) hepatocytes were isolated from the liver resection specimens of 11 patients operated for HCC, while PBMCs were retrieved immediately prior to surgery. Four biopsies were obtained from patients with no liver disease who had surgery for non malignant tumor (normal hepatocytes). Hepatocytes were either cultured alone (monoculture) or co-cultured with PBMCs. Flow cytometry measurements for MHC class II expression, apoptosis, necrosis and viability (7AAD) were performed 24 h, 48 h and 72 h in co-culture and monocultures. HCC and non-HCC hepatocytes exhibited increased MHC-II expression at 48h and 72h in co-culture with PBMCs as compared to monoculture, with MHC II-expressing HCC hepatocytes showing increased viability at 72 h. PBMCs showed increased MHC-II expression (activation) in co-culture with HCC as compared to non-HCC hepatocytes at all time points. Moreover, CD8+ T cells had significantly increased apoptosis and necrosis at 48h in co-culture with HCC hepatocytes as compared to monocultures. Interestingly, MHC-II expression on both HCC and non-HCC hepatocytes in co-culture was positively correlated with the respective activated CD8+ T cells. We have established an in vitro co-culture model to study interactions between autologous PBMCs and primary HCC and non-HCC hepatocytes. This direct interaction leads to increased antigen presenting ability of HCC hepatocytes, activation of PBMCs with a concomitant apoptosis of activated CD8+ T cells. Although, a partially effective immune response against HCC exists, still tumor hepatocytes manage to escape.


Extended spectrum beta-lactamase mediated resistance to third generation cephalosporins in Klebsiella pneumoniae in Nagpur, central India.
Out of 66 clinical isolates of Klebsiella pneumoniae, 17 showed resistance or decreased susceptibility to third generation cephalosporins (17 to cefotaxime, 16 to ceftriaxone, and 9 to ceftazidime) while the remaining 49 were sensitive by the disc diffusion method. The minimum inhibitory concentrations (MICs) of the third generation cephalosporins (3GC) for the strains ranged from 2-128 micrograms/ml by agar dilution method. Their sensitive phenotypes had zone diameters smaller (mean difference 3. 1 mm for ceftriaxone, and 6.5 mm for ceftazidime), and MICs > 10 fold higher than the corresponding values in the fully sensitive isolates. Resistance to cefotaxime was transferred to recipient Escherichia coli K12 strain in 15 isolates. All the resistant isolates were sensitive to imipenem but were variably sensitive to aminoglycosides, and quinolones. In all 17 resistant isolates extended spectrum beta-lactamase (ES beta L) was detected. The sensitivity testing systems may fail to recognise the potential ES beta L mediated resistance to 3GC. Hence ES beta L detection should be routinely undertaken.


Applying human factors and ergonomics to the misuse of nonsterile clinical gloves in acute care.
Health care workers (HCWs) are recommended to wear nonsterile clinical gloves (NSCG) for direct contact with blood and body fluids. However, there is evidence of extensive inappropriate NSCG use. A mixed-methods study comprising observation of NSCG use in 2 acute hospitals and semistructured HCW interviews. Qualitative data were categorized using thematic analysis. Findings were mapped to the Systems Engineering Initiative for Patient Safety model and used to develop a strategy for improving NSCG use. Two hundred seventy-eight procedures performed in 178 episodes of care involved the use of NSCG. NSCG were inappropriate for 59% of procedures (165 out of 278). Risk of cross-contamination occurred in 49% (87 out of 178) episodes. Twenty-six HCWs were interviewed; emotion and socialization were key factors influencing decisions to use NSCG. Data from observation and thematic analysis were mapped to 6 interacting components of the Systems Engineering Initiative for Patient Safety work system. Interventions targeting each component informed quality improvement strategies CONCLUSIONS: Despite intense promotion of hand hygiene as the key measure to protect patients from health care-associated infection, NSCG dominate routine clinical practice and potential cross-contamination occurs in 50% of care episodes. Such practice is associated with significant environmental and financial costs and adversely affects patient safety. The application of human factors and ergonomics to the complex drivers of inappropriate NSCG behavior may be more effective than conventional approaches of education and policy in achieving the goal of preventing health care-associated infection and improving patient safety.


[Difficulties in diagnosing idiopathic hypereosinophilic syndrome in Black Africa. A case report observed in Senegal].
A combination of febrile malaise with adenopathy, massive hypereosinophilia (62678 components/mm3) and visceral, cutaneous, central nervous and digestive infiltration suggesting essential hypereosinophilic syndrome was observed in a 42-year-old male Senegalese. Diagnosis was confirmed after excluding all other possible causes in particular parasitic infection and by the rapidly fatal outcome. To our knowledge, this is the first reported case of essential hypereosinophilic syndrome in West Africa. Because of the high incidence of parasitic hypereosinophilia in this region and the non-specific nature of the symptoms, diagnosis of this syndrome can be difficult. In Africa more than elsewhere, diagnosis must be made after elimination of all other possible causes based on the criteria of Chusid. Although uncommon, essential hypereosinophilic syndrome has an unfavorable prognosis even when immunosuppressor therapy is administered.


Catalytic N-Alkylation of Amines Using Carboxylic Acids and Molecular Hydrogen.
A convenient, practical and green N-alkylation of amines has been accomplished by applying readily available carboxylic acids in the presence of molecular hydrogen. Applying an in situ formed ruthenium/triphos complex and an organic acid as cocatalyst, a broad range of alkylated secondary and tertiary amines are obtained in good to excellent yields. This novel method is also successfully applied for the synthesis of unsymmetrically substituted N-methyl/alkyl anilines through a direct three-component coupling reaction of the corresponding amines, carboxylic acids, and CO2 as a C1 source.


[A case of pneumatosis intestinalis associated with sunitinib treatment for renal cell carcinoma].
Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.


Reflex and dilatation: a clinical epidemiological evaluation.
The recent controversy surrounding the use of the reflex anal dilatation (RAD) sign in cases of suspected sexual abuse is a general illustration of the difficulties clinicians face in determining which symptoms, signs or laboratory tests to use in their daily practice. The evidence required fully to evaluate RAD is incomplete. The specificity in particular is uncertain. Sufficient evidence is, however, available to permit a quantitative examination of the test's performance under various circumstances. Our analysis suggests that, at the prevalence of anal abuse reported in one large series of children referred to paediatricians with suspected sexual abuse (13%), only if the specificity of the test is 99% or greater, may the positive predictive value of RAD be as high as 90%. At the likely prevalence of anal abuse in the general child population (less than 0.5%), however, an even higher specificity of 99.99% would be necessary to achieve a similar positive predictive value.


Inclusion of lateral pressure/curvature stress effects in implicit membrane models.
Implicit membrane models usually treat the membrane as a hydrophobic slab and neglect lateral pressure/curvature stress effects. As a result, they cannot distinguish, for example, PE from PC lipids. Here, the implicit membrane model IMM1 is extended to include these effects using a combination of classical thermodynamics and membrane elasticity theory. The proposed model is tested by molecular dynamics simulation of the peptides alamethicin, melittin, cyclotide kalata B1, 18A, and KKpL15. The lateral pressure term stabilizes interfacial binding due to the negative pressure at the hydrocarbon-water interface. In agreement with experiment, increase in the peptide/lipid molar ratio shifts the equilibrium from the interfacial to the transmembrane orientation. Simulations of mixed DOPC/DOPE bilayers show that increase of the DOPE mole fraction in general stabilizes interfacial orientations and destabilizes transmembrane orientations. The extent of the stabilization or destabilization varies depending on the exact position of the peptides. The computational results are in good agreement with experiments.


The 'Herbivory Uncertainty Principle': application in a cerrado site.
Researchers may alter the ecology of their studied organisms, even carrying out apparently beneficial activities, as in herbivory studies, when they may alter herbivory damage. We tested whether visit frequency altered herbivory damage, as predicted by the 'Herbivory Uncertainty Principle'. In a cerrado site, we established 80 quadrats, in which we sampled all woody individuals. We used four visit frequencies (high, medium, low, and control), quantifying, at the end of three months, herbivory damage for each species in each treatment. We did not corroborate the 'Herbivory Uncertainty Principle', since visiting frequency did not alter herbivory damage, at least when the whole plant community was taken into account. However, when we analysed each species separately, four out of 11 species presented significant differences in herbivory damage, suggesting that the researcher is not independent of its measurements. The principle could be tested in other ecological studies in which it may occur, such as those on animal behaviour, human ecology, population dynamics, and conservation.


Data-driven discovery of 3D and 2D thermoelectric materials.
In this work, we first perform a systematic search for high-efficiency three-dimensional (3D) and two-dimensional (2D) thermoelectric materials by combining semiclassical transport techniques with density functional theory (DFT) calculations and then train machine-learning models on the thermoelectric data. Out of 36 000 three-dimensional and 900 two-dimensional materials currently in the publicly available JARVIS-DFT database, we identify 2932 3D and 148 2D promising thermoelectric materials using a multi-steps screening procedure, where specific thresholds are chosen for key quantities like bandgaps, Seebeck coefficients and power factors. We compute the Seebeck coefficients for all the materials currently in the database and validate our calculations by comparing our results, for a subset of materials, to experimental and existing computational datasets. We also investigate the effect of chemical, structural, crystallographic and dimensionality trends on thermoelectric performance. We predict several classes of efficient 3D and 2D materials such as Ba(MgX)2 (X = P, As, Bi), X2YZ6 (X = K, Rb, Y=Pd, Pt, Z = Cl, Br), K2PtX2 (X = S, Se), NbCu3X4 (X = S, Se, Te), Sr2XYO6 (X = Ta, Zn, Y=Ga, Mo), TaCu3X4 (X = S, Se, Te), and XYN (X = Ti, Zr, Y=Cl, Br). Finally, as high-throughput DFT is computationally expensive, we train machine learning models using gradient boosting decision trees and classical force-field inspired descriptors for n-and p-type Seebeck coefficients and power factors, to quickly pre-screen materials for guiding the next set of DFT calculations. The dataset and tools are made publicly available at the websites: https://www.ctcms.nist.gov/~knc6/JVASP.html, https://www.ctcms.nist.gov/jarvisml/and https://jarvis.nist.gov/.


Lipophilic Environmental Chemical Mixtures Released During Weight-Loss: The Need to Consider Dynamics.
Intentional weight loss can increase health risk in the long-term, despite short-term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs.


[Rolandic epilepsy. An analysis of the clinical and electrophysiological characteristics, treatment and prognosis in 87 patients].
Rolandic epilepsy is the most common epileptic syndrome in infancy. It usually has a favourable prognosis and seizures disappear during the teenage years. The aim of this study was to describe a sample of children diagnosed with rolandic epilepsy in clinical, electrophysiological and imaging terms. We also intend to compare the results obtained with those described in the literature. We conducted a retrospective, descriptive study of the children diagnosed with rolandic epilepsy who had been submitted to a follow-up at the Neuropaediatrics Unit at the HGSA since 1989. Children who were less than 2 years old when they suffered their first seizures or who had abnormal neurological/imaging examinations were excluded. Two groups were defined (typical and atypical), several variables were characterised and these were then analysed statistically. A total of 87 children (51 males) were included in this study, their mean age being 13.6 years. The population was divided into two groups: A (typical cases; n = 69) and B (atypical cases; n = 18). The mean age at the onset of seizures was 6.2 and 6 years for groups A and B, respectively. The predominant type of seizures was simple partial for group A and complex partial for group B; they were mainly sporadic and nocturnal in both groups. Medication was administered to 51 (73.9%) of the children in group A, with a good response in 78.4% of them; 13 members of group B (72.2%) received medication, with a positive response in 76.9% of them. Rolandic epilepsy has a broad clinical spectrum and usually courses with normal psychomotor development, but may coexist with learning disabilities. In this study, no significant differences were found between the typical and atypical forms of presentation, as far as their progress and response to treatment are concerned.


Filtering of nanoparticles with tunable semiconductor membranes.
Translocation dynamics of nanoparticles permeating through the nanopore in an n-Si semiconductor membrane is studied. With the use of Brownian Dynamics to describe the motion of the charged nanoparticles in the self-consistent membrane-electrolyte electrostatic potential, we asses the possibility of using our voltage controlled membrane for the macroscopic filtering of the charged nanoparticles. The results indicate that the tunable local electric field inside the membrane can effectively control interaction of a nanoparticle with the nanopore by either blocking its passage or increasing the translocation rate. The effect is particularly strong for larger nanoparticles due to their stronger interaction with the membrane while in the nanopore. By extracting the membrane permeability from our microsopic simulations, we compute the macroscopic sieving factors and show that the size selectivity of the membrane can be tuned by the applied voltage.


Transcriptional modulation of heat-shock protein gene expression.
Heat-shock proteins (Hsps) are molecular chaperones that are ubiquitously expressed but are also induced in cells exposed to stressful stimuli. Hsps have been implicated in the induction and propagation of several diseases. This paper focuses on regulatory factors that control the transcription of the genes encoding Hsps. We also highlight how distinct transcription factors are able to interact and modulate Hsps in different pathological states. Thus, a better understanding of the complex signaling pathways regulating Hsp expression may lead to novel therapeutic targets.