Photochemical properties of mammalian melanopsin.
Melanopsin is the photoreceptor molecule of intrinsically photosensitive retinal ganglion cells, which serve as the input for various nonvisual behavior and physiological functions fundamental to organisms. The retina, therefore, possess a melanopsin-based nonvisual system in addition to the visual system based on the classical visual photoreceptor molecules. To elucidate the molecular properties of melanopsin, we have exogenously expressed mouse melanopsin in cultured cells. We were able to obtain large amounts of purified mouse melanopsin and conducted a comprehensive spectroscopic study of its photochemical properties. Melanopsin has an absorption maximum at 467 nm, and it converts to a meta intermediate having an absorption maximum at 476 nm. The melanopsin photoreaction is similar to that of squid rhodopsin, exhibiting bistability that results in a photosteady mixture of a resting state (melanopsin containing 11-cis-retinal) and an excited state (metamelanopsin containing all-trans-retinal) upon sustained irradiation. The absorption coefficient of melanopsin is 33000 ± 1000 M(-1) cm(-1), and its quantum yield of isomerization is 0.52; these values are also typical of invertebrate bistable pigments. Thus, the nonvisual system in the retina relies on a type of photoreceptor molecule different from that of the visual system. Additionally, we found a new state of melanopsin, containing 7-cis-retinal (extramelanopsin), which forms readily upon long-wavelength irradiation (yellow to red light) and photoconverts to metamelanopsin with short-wavelength (blue light) irradiation. Although it is unclear whether extramelanopsin would have any physiological role, it could potentially allow wavelength-dependent regulation of melanopsin functions.


Endoscopic reconstruction for isolated anterior cruciate ligament rupture.
We treated 90 patients with an isolated injury to the anterior cruciate ligament (ACL) by reconstruction using a patellar tendon autograft and interference screw fixation. Of these, 82 (91%) were available for review at 24 months. Two grafts and two contralateral ACLs had ruptured during sport and there was one case of atraumatic graft resorption. Using the assessment of the International Knee Documentation Committee (IKDC), 86% of the remaining patients were normal or nearly normal. The median Lysholm knee score was 95/100 and 84% of patients were participating in moderate to strenuous activity. All had grade-0 or grade-1 Lachman, pivot-shift and anterior-drawer tests. Measurement with the KT1000 arthrometer gave a side-to-side difference of <3 mm of anterior tibial displacement in 90%. Sixty-six radiographs were IKDC grade A and one was grade B. Pain on kneeling was present in 31% and graft site pain in 44%. At 24 months after operation all patients had excellent knee stability, a high rate of return to sport and minimal radiological evidence of degenerative change. Our series therefore represents a basis for comparison of results using other techniques and after more severe injuries.


Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma.
In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progression-free survival was 83.8% and 5-year disease-specific survival was 95.7% (overall survival 93.0%). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma.


Intraspinal clear cell meningioma without dural attachment: A case report and literature review.
Clear cell meningioma (CCM) is one of the rarest but most aggressive forms of meningioma, with a tendency to occur at a high recurrence rate. Intraspinal CCM, especially the nondura-based type, is even rarer than the intracranial CCM. We report a case of a 45-year-old woman who presented with a 1-month history of episodic pain in the lower back and in both thighs in the front side. Femoral nerve stretch tests were positive on both sides. Magnetic resonance imaging (MRI) demonstrated an intradural tumor at the L3 level, which was isointense on T1- and T2-weighted images (WI) and homogeneously enhanced on gadolinium-contrast T1 WI. The space-occupying lesion was pathologically confirmed as CCM. During surgery, we found that the tumor adhered to a nerve root, without dural attachment. The nerve root was partially removed to achieve complete resection. The pain disappeared after the operation. The 1 year follow-up MRI revealed no evidence of tumor recurrence or metastasis. Nondura-based intraspinal CCM is easier to completely remove, and such complete removal should be achieved during the first operation. Although the recurrence rate of this particular type of meningioma appears to be lower than that of other types, close clinical and radiological follow-up is necessary.


Effective Reaction-Based De Novo Strategy for Kinase Targets: A Case Study on MERTK Inhibitors.
Reaction-based de novo design is the computational generation of novel molecular structures by linking building blocks using reaction vectors derived from chemistry knowledge. In this work, we first adopted a recurrent neural network (RNN) model to generate three groups of building blocks with different functional groups and then constructed an in silico target-focused combinatorial library based on chemical reaction rules. Mer tyrosine kinase (MERTK) was used as a study case. Combined with a scaffold enrichment analysis, 15 novel MERTK inhibitors covering four scaffolds were achieved. Among them, compound 5a obtained an IC50 value of 53.4 nM against MERTK without any further optimization. The efficiency of hit identification could be significantly improved by shrinking the compound library with the fragment iterative optimization strategy and enriching the dominant scaffold in the hinge region. We hope that this strategy can provide new insights for accelerating the drug discovery process.


[Current and perspective treatment of chronic lymphocytic leukemia].
Chronic lymphocytic leukemia represents the most frequent hematological malignancy in the western population. Important role in its pathogenesis has the inhibition of apoptosis, disturbances in differentiation of B-lymphocytes, slightly increased proliferation and induction of angiogenesis. Current treatment options (chemotherapy and immunotherapy) can improve the quality of life and prolong disease-free survival, but the overall survival is not significantly influenced. The only curative treatment alternative is the allogeneic hematopoietic stem cell transplantation. However, this treatment is accompanied by the risk of peritransplantation mortality and its use is limited for younger patients. Number of new compounds is clinically tested. New drugs can influence intracellular events such as induction of apoptosis or inhibition of the transduction cascade. Review summarises treatment alternatives and presents an algorithm for their clinical application.


Vectorized Evidential Learning for Weakly-Supervised Temporal Action Localization.
With the explosive growth of videos, weakly-supervised temporal action localization (WS-TAL) task has become a promising research direction in pattern analysis and machine learning. WS-TAL aims to detect and localize action instances with only video-level labels during training. Modern approaches have achieved impressive progress via powerful deep neural networks. However, robust and reliable WS-TAL remains challenging and underexplored due to considerable uncertainty caused by weak supervision, noisy evaluation environment, and unknown categories in the open world. To this end, we propose a new paradigm, named vectorized evidential learning (VEL), to explore local-to-global evidence collection for facilitating model performance. Specifically, a series of learnable meta-action units (MAUs) are automatically constructed, which serve as fundamental elements constituting diverse action categories. Since the same meta-action unit can manifest as distinct action components within different action categories, we leverage MAUs and category representations to dynamically and adaptively learn action components and action-component relations. After performing uncertainty estimation at both category-level and unit-level, the local evidence from action components is accumulated and optimized under the Subject Logic theory. Extensive experiments on the regular, noisy, and open-set settings of three popular benchmarks show that VEL consistently obtains more robust and reliable action localization performance than state-of-the-arts.


Fabrication and desired properties of conductive hydrogel dressings for wound healing.
Conductive hydrogels are platforms recognized as constituting promising materials for tissue engineering applications. This is because such conductive hydrogels are characterized by the inherent conductivity properties while retaining favorable biocompatibility and mechanical properties. These conductive hydrogels can be particularly useful in enhancing wound healing since their favorable conductivity can promote the transport of essential ions for wound healing via the imposition of a so-called transepithelial potential. Other valuable properties of these conductive hydrogels, such as wound monitoring, stimuli-response etc., are also discussed in this study. Crucially, the properties of conductive hydrogels, such as 3D printability and monitoring properties, suggest the possibility of its use as an alternative wound dressing to traditional dressings such as bandages. This review, therefore, seeks to comprehensively explore the functionality of conductive hydrogels in wound healing, types of conductive hydrogels and their preparation strategies and crucial properties of hydrogels. This review will also assess the limitations of conductive hydrogels and future perspectives, with an emphasis on the development trend for conductive hydrogel uses in wound dressing fabrication for subsequent clinical applications.


Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. The NETWORK Investigators.
Angiotensin converting-enzyme (ACE) inhibitors used for the treatment of heart failure relieve symptoms, increase exercise performance, reduce hospital admissions and prolong life. The large survival studies have used higher doses of ACE inhibitors than those commonly used in clinical practice. NETWORK was set up to compare the effect of dose on the clinical outcome of ACE inhibition. 1532 patients with heart failure drawn from primary care (n = 619) and hospital sources (n = 913) were randomized to receive enalapril 2.5 mg twice daily (n = 506). 5 mg twice daily (n = 510) or 10 mg twice daily (n = 516). The mean age was 70 years and 65% were male. Coronary heart disease was the cause of heart failure in 71%. Sixty-five percent were in NYHA class II and 35% in class III or IV. The mean left ventricular end-diastolic diameter was 59 (SD 11) mm. The incidence of the primary end-point of death, heart failure related hospitalization or worsening heart failure was assessed after follow-up of each patient for 24 weeks. The number of patients reaching the primary end-point was 62 (12.3%) in the 2.5 mg twice daily group, 66 (12.9%) in the 5 mg twice daily group and 76 (14.7%) in the 10 mg twice daily group. Deaths in each group were 21 (4.2%), 17 (3.3%) and 15 (2.9%), respectively. There were no significant differences in the results between the three groups. The crude relative risk for the combined end-point in the 10 mg twice daily group compared to the 2.5 mg twice daily group was 1.20 (95% CI 0.88 to 1.64). NETWORK did not demonstrate a relationship between dose of enalapril and clinical outcome in patients with heart failure selected from both primary care and hospital practice.


Technique for fabrication of an antibiotic-loaded cement hemiarthroplasty (ANTILOCH) prosthesis for infected total hip arthroplasty.
In North America, staged reimplantation is the preferred treatment for infected total hip arthroplasty. A simple technique for implantation of an antibiotic-loaded cement spacer molded in the shape of a hemiarthroplasty prosthesis is described. A Teflon mold was cast in the shape of an Austin Moore hip hemiarthroplasty prosthesis. This mold allows for fabrication of a solid antibiotic-loaded cement spacer that accurately reproduces the shape of a hemiarthroplasty prosthesis. This technique allows for easy insertion, patient comfort, between-stage mobility, and local concentric delivery of antibiotic.


A MurF inhibitor that disrupts cell wall biosynthesis in Escherichia coli.
MurF is an essential enzyme of bacterial cell wall biosynthesis. Few MurF inhibitors have been reported, and none have displayed measurable antibacterial activity. Through the use of a MurF binding assay, a series of 8-hydroxyquinolines that bound to the Escherichia coli enzyme and inhibited its activity was identified. To derive additional chemotypes lacking 8-hydroxyquinoline, a known chelating moiety, a pharmacophore model was constructed from the series and used to select compounds for testing in the MurF binding and enzymatic inhibition assays. Whereas the original diverse library yielded 0.01% positive compounds in the binding assay, of which 6% inhibited MurF enzymatic activity, the pharmacophore-selected set yielded 14% positive compounds, of which 37% inhibited the enzyme, suggesting that the model enriched for compounds with affinity to MurF. A 4-phenylpiperidine (4-PP) derivative identified by this process displayed antibacterial activity (MIC of 8 microg/ml against permeable E. coli) including cell lysis and a 5-log(10)-unit decrease in CFU. Importantly, treatment of E. coli with 4-PP resulted in a 15-fold increase in the amount of the MurF UDP-MurNAc-tripeptide substrate, and a 50% reduction in the amount of the MurF UDP-MurNAc-pentapeptide product, consistent with inhibition of the MurF enzyme within bacterial cells. Thus, 4-PP is the first reported inhibitor of the MurF enzyme that may contribute to antibacterial activity by interfering with cell wall biosynthesis.


The side effects of the prostaglandin analogues.
In the last decade topically applied prostaglandin F2alpha analogues (bimatoprost, latanoprost, travoprost and unoprostone) have become widely used as a means to reduce elevated intraocular pressure in patients with glaucoma and ocular hypertension. These molecules all have similar side-effect profiles, which include both side effects that occur frequently (e.g., conjunctiva hyperaemia, increase of iris pigmentation and eyelash changes) and rare adverse reactions (e.g., periocular pigmentation, damage to the blood-aqueous barrier and cystoid macular oedema). Conjunctiva hyperaemia, eyelash changes and cystoid macular oedema are reversible, but certain other side effects, such as increased iris pigmentation, are not. However, the systemic side-effect profile is favourable for all the prostaglandin analogues, and some of the local side effects are only of cosmetic significance. Numerous clinical studies suggest that discontinuing treatment with prostaglandin analogues on account of their side effects is rare in clinical practice.


Antimalarials. 13. 5-Alkoxy analogues of 4-methylprimaquine.
A series of nuclear and side-chain analogues of 4-methylprimaquine incorporating an alkoxy group in the 5-position of the quinoline nucleus has been prepared. The compounds were tested for suppressive antimalarial activity against Plasmodium berghei in mice and for radical curative antimalarial activity against Plasmodium cynomolgi in the rhesus monkey. Although the toxicity problems characteristic of the 8-aminoquinolines were not overcome, several of the compounds, surprisingly, were highly effective as both blood and tissue schizonticidal agents.


Note: theoretical study on the gas pressure dependence of x-ray yield in TE(111) cavity based electron cyclotron resonance x-ray source.
Adopting Langevin methodology, a pressure dependent frictional force term which represents the collisional effect is added to the Lorentz equation. The electrons are assumed to be starting from the uniformly distributed co-ordinates on the central plane. The trajectory of each electron is numerically simulated by solving the modified Lorentz equation for a given pressure. The Bremsstrahlung x-ray energy spectrum for each electron crossing the cavity wall boundary is obtained using the Duane-Hunt law. The total x-ray yield is estimated by adding the spectral contribution of each electron. The calculated yields are compared with the experimental results and a good agreement is found.


Pertussis toxin or phorbol 12-myristate 13-acetate can distinguish between epidermal growth factor- and angiotensin-stimulated signals in hepatocytes.
Epidermal growth factor (EGF) causes rapid increases in free intracellular Ca2+ and stimulates the phosphorylation of 11 cytosolic proteins in hepatocytes. Ten of the 11 cytosolic proteins altered by EGF are identical to those affected by angiotensin II, a hormone that stimulates the breakdown of phosphatidylinositol 4,5-bisphosphate. An increase in the phosphorylation of the other protein, spot c (Mr = 36,000, pI = 5.5), is observed only with EGF. Treatment of intact rats with pertussis toxin to ADP-ribosylate Ni, the inhibitory GTP-binding protein of the adenylate cyclase complex, abolished the effect of EGF on Ca2+ mobilization and on the phosphorylation of the 10 proteins affected in common with angiotensin II. This treatment had minimal effects on the ability of EGF to stimulate the phosphorylation of its unique substrate, spot c. In marked contrast, modification of Ni did not block the ability of angiotensin II to stimulate Ca2+ mobilization or protein phosphorylation. Pretreatment of normal hepatocytes with 4 beta-phorbol 12-myristate 13-acetate blocked all responses to EGF, including the increased phosphorylation of spot c, but had no effect on the responses to angiotensin II. These results imply that Ni or a similar pertussis toxin substrate may mediate the apparent effects of EGF on phosphatidylinositol breakdown and that protein kinase C may regulate a site in the transduction pathway. Angiotensin II appears to use a different signal transduction mechanism to stimulate phosphatidylinositol metabolism in hepatocytes.


Spin Labeling of Potassium Channels.
Potassium channels are the ion channels most extensively studied by structural techniques. Whereas high-resolution crystal structures have provided key insights into the molecular architecture of these channels, spin labeling studies have helped to unveil the dynamic structural aspects underlying their function. From a practical standpoint, the popularity of spin labeling studies of potassium channels lies in their small size and relative ease of overexpression. The inherent fourfold symmetry of most potassium channels has also greatly facilitated spin labeling studies. This chapter focuses on the overexpression, purification, spin labeling, and subsequent reconstitution of modified potassium channels. It will discuss the general methods used to produce a suitable spin-labeled potassium channel sample and highlight some of the common pitfalls that can occur along the way. At the end of the chapter, we provide detailed methods to produce spin-labeled samples of KcsA and KvAP, the two most commonly studied potassium channels.


Effects of Low-Dose Spironolactone Combined with Metformin or Either Drug Alone on Insulin Resistance in Patients with Polycystic Ovary Syndrome: A Pilot Study.
Metformin and spironolactone alone can be used for the management of polycystic ovarian syndrome (PCOS), and their combination could result in even better outcomes. To compare the effects and safety of low-dose spironolactone combined with metformin or either drug alone on insulin resistance (IR) and functional improvement in patients with PCOS, this was a single-center, randomized, open-label, pilot study of patients with PCOS at the Third Affiliated Hospital of Guangzhou Medical University between 01/2014 and 01/2016. The participants were randomized 1 : 1 : 1 to metformin, spironolactone, or metformin + spironolactone. The primary endpoint was the change in the homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. A total of 189 participants were randomized (63 per group); 31 dropped out, and 54, 51, and 53 completed the 12-week treatment in the metformin, spironolactone, and combined groups, respectively. There were no differences in any parameters between the metformin and spironolactone groups (all P > 0.05). In the combined group, after 12 weeks of treatment, HOMA-IR (1.71 ± 0.91) was lower than in the metformin (1.92 ± 1.07, P < 0.05) and spironolactone (2.38 ± 1.14, P < 0.05) groups. In addition, total testosterone (TT), free androgen index (FAI), and area under the curve-insulin (AUCins) were lower in the combined group compared with the metformin group (all P < 0.05), while TT, FAI, HOMA-β, fasting plasma glucose, and AUCins were lower in the spironolactone group (all P < 0.05). Both metformin and spironolactone decreased HOMA-IR in patients with PCOS but without differences between the two monotherapies. The combined therapy decreased HOMA-IR to a greater extent than monotherapy.


Mild hypothermia and vitrification increase the mRNA expression of cold-inducible proteins in bovine oocytes and cumulus cells.
The cold-inducible RNA-binding protein (CIRBP) assists cells in adapting to new environmental conditions stabilizing specific mRNAs and promoting their translation. CIRBP participates in anti-apoptotic and anti-senescence processes, and its expression is induced by mild hypothermia, which may be advantageous to oocytes during vitrification. Several newly discovered small molecules, like zr17-2, mimic the effects of cold temperatures by increasing the expression of CIRBP at normothermia. This study aimed to evaluate the mRNA changes of a group of cold-inducible protein-encoding and apoptotic genes in response to exogenous supplementation of zr17-2 (experiment 1) or CIRBP (experiment 2) in vitro matured bovine oocytes and their cumulus cells. In experiment 1, cumulus-oocyte complexes (COCs) were randomly exposed to three concentrations of zr17-2 (1, 10, and 100 μM) during 24 h of in vitro maturation (IVM) under normothermia (38.5 °C) or mild hypothermia (34 °C) culture conditions. In experiment 2, COCs were randomly exposed to three concentrations of CIRBP (2, 4, and 6 μg/mL) or subjected to mild hypothermia (34 °C), followed by oocyte vitrification/warming after 20 h of IVM. The quantification of the selected gene transcript expression was performed separately in oocytes and cumulus cells by quantitative real-time PCR. We show that oocytes and cumulus cells exhibited similar mRNA expression responses to mild hypothermia and vitrification. However, minor differences were observed when COCs were exposed to exogenous supplementation with zr17-2 and CIRBP. In conclusion, the alterations observed in the mRNA expression in these experimental conditions may impact the quality of the cumulus-oocyte complexes in terms of vitrification and sublethal hypothermia challenges. In this sense, our results should complement other oocyte quality assessments for its application in future assisted reproductive techniques in the bovine species, including improving oocyte cryotolerance to vitrification.


The effect of face inversion for neurons inside and outside fMRI-defined face-selective cortical regions.
It is widely believed that face processing in the primate brain occurs in a network of category-selective cortical regions. Combined functional MRI (fMRI)-single-cell recording studies in macaques have identified high concentrations of neurons that respond more to faces than objects within face-selective patches. However, cells with a preference for faces over objects are also found scattered throughout inferior temporal (IT) cortex, raising the question whether face-selective cells inside and outside of the face patches differ functionally. Here, we compare the properties of face-selective cells inside and outside of face-selective patches in the IT cortex by means of an image manipulation that reliably disrupts behavior toward face processing: inversion. We recorded IT neurons from two fMRI-defined face-patches (ML and AL) and a region outside of the face patches (herein labeled OUT) during upright and inverted face stimulation. Overall, turning faces upside down reduced the firing rate of face-selective cells. However, there were differences among the recording regions. First, the reduced neuronal response for inverted faces was independent of stimulus position, relative to fixation, in the face-selective patches (ML and AL) only. Additionally, the effect of inversion for face-selective cells in ML, but not those in AL or OUT, was impervious to whether the neurons were initially searched for using upright or inverted stimuli. Collectively, these results show that face-selective cells differ in their functional characteristics depending on their anatomicofunctional location, suggesting that upright faces are preferably coded by face-selective cells inside but not outside of the fMRI-defined face-selective regions of the posterior IT cortex.


Overexpression in Escherichia coli of soluble aristolochene synthase from Penicillium roqueforti.
Aristolochene synthase, a fungal cyclase which has been isolated from Aspergillus terreus and Penicillium roqueforti, catalyzes the cyclization of farnesyl diphosphate to the sesquiterpene hydrocarbon aristolochene. The aristolochene synthase gene (Ari1) of P. roqueforti has previously been cloned and expressed at low levels as a protein A-aristolochene synthase fusion protein in Escherichia coli. We have now used the polymerase chain reaction to amplify the aristolochene synthase coding sequence using engineered primers which produced dsDNA carrying an EcoRI restriction site and the T7 gene 10 ribosome binding site and translational spacer element immediately upstream of the ATG start codon and a BamHI site adjacent to the TAA stop codon. The PCR product was digested with EcoRI and BamHI and inserted into the multiple cloning site of the expression vector pLM1 which carried the promoter and translational leader sequence from T7 gene 10 and the E. coli rrnBT1T2 tandem transcription terminator. Cloning of the resulting construct into E. coli XL1-Blue and subcloning into the expression host E. coli BL21 (DE3) gave transformants which expressed aristolochene synthase at levels up to 40% of soluble protein when induced with isopropyl beta-D-thiogalactoside. Purification of the recombinant protein by ammonium sulfate precipitation, ion-exchange chromatography on Q Sepharose, and affinity dye chromatography on Reactive Blue 4-agarose gave homogenous aristolochene synthase which had the expected N-terminal sequence, ATSTE, mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and steady-state kinetic parameters when compared to native fungal protein.


High circadian stimulus lighting therapy for depression: Meta-analysis of clinical trials.
Although bright light therapy (BLT) has been widely used in the clinical treatment of depression, the antidepressant effect of BLT is not well understood. Considering the connection between depression and disrupted circadian rhythm, we assumed the model of human circadian phototransduction could be more accurate in evaluating the efficacy of BLT for depression compared to light level and spectrum. A systematic review and meta-analysis were conducted and the CS (circadian stimulus) model was used to quantify the efficacy of lighting in BLT. Articles published up to June 2022 were searched in COCHRANE, EMBASE, MEDLINE, and Web of Science. Randomized clinical trials included articles using high circadian stimulus (H-CS, CS > 0.1) as lighting therapy for people with depressive disorder vs. a control group (CS < 0.1). The treatment effect was estimated by calculating the mean difference (MD) with 95% confidence intervals (CIs). Seven trials involving 258 participants met the inclusion criteria. In this sample size, H-CS lighting was associated with a significant reduction in depressive symptoms (MD = -5.56, 95% CI = -9.22 to -1.90, P = 0.003, I 2 = 64%). According to the meta-analysis, CS can be employed for the clinical evaluation of BLT for patients with depressive disorder and exposure to H-CS lighting significantly reduced depressive symptoms among adults. A range of CS > 0.57 was obtained, during which different lighting parameter combinations (e.g., light levels, spectra, duration, and light distribution) could achieve better treatment for depression. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253648.


A Case of Breast Cancer Brain Metastasis with a 16-Year Time Interval without Evidence of Cancer Recurrence.
The median time of brain metastasis from the diagnosis of breast cancer is approximately 3 years. In this case report, a 69-year-old woman demonstrated cerebellar ataxia. Brain magnetic resonance imaging revealed enhanced lesions in bilateral cerebellar hemispheres. She had undergone surgery, radiation, and chemotherapy for uterine and breast cancer 24 years prior and 16 years prior, respectively. Although she had not received any anticancer treatment for 10 years, no recurrences were identified using whole body scans. A partial tumor resection was performed and the histological diagnosis was an adenocarcinoma from breast cancer. As no extracranial lesions were found, gamma-knife irradiation was performed, without additional systemic chemotherapy. One month posttreatment, the tumors dramatically reduced in size and the patient completely recovered from cerebellar ataxia. Systemic chemotherapy is not always required for brain metastasis from breast cancer with a long interval period, as long as no evidence of extracranial recurrence is detected.


iNOS-mediated generation of reactive oxygen and nitrogen species by biomaterial-adherent neutrophils.
Infection due to implanted cardiovascular biomaterials is a serious complication initiated by bacterial adhesion to the surface of the implant. The release of reactive oxygen species by neutrophils, particularly superoxide anion, is a well-known bactericidal mechanism. Additionally, nitric oxide (NO) has also been identified as an important cytotoxic mediator in acute and chronic inflammatory responses with enhanced NO production by upregulation of inducible nitric oxide synthase (iNOS). The interaction of NO and superoxide anion will result in the formation of peroxynitrite (OONO-), a potent cytotoxic oxidant. In this study, we have shown that biomaterial-induced neutrophil activation does not cause upregulation of iNOS and activation of iNOS-mediated pathways. However, NO and O2- production does occur over time upon adhesion to a biomaterial and is modulated by biomaterial surface chemistry. With no stimulus, the polyethylene oxide-modified polyurethane induced greater neutrophil activation than did the control as indicated by the increased production of NO and O2- over time. Adherent-stimulated neutrophils generally produced lower amounts of NO over time in comparison with unstimulated cells. Furthermore, there is no evidence of peroxynitrite activity in unstimulated neutrophils adherent to the Elasthane 80A. However, upon stimulation with adherent Staphylococcus epidermidis, peroxynitrite formation did occur. Our results suggest that bactericidal mechanisms in neutrophils involving NO generation (NOS pathway) are further compromised than O2- producing pathways (NADPH oxidase) upon exposure to biomaterials, resulting in a diminished microbial killing capacity, which can increase the probability of device-centered infections.


[The regional characteristics of endocrine pathology in the Perm kraii].
Nowadays, focus of research is shifted to epidemiology of non-communicable diseases. Hence, actuality of study purpose to investigate epidemiological characteristics of endocrine diseases. The data of population appealability to medical organizations in the Perm region during last 20 years was used. The levels and structure of morbidity were calculated. The dynamic process was evaluated. The trend prognostication was proposed. In 2017, total endocrine system morbidity in the Perm region made up to 88.1 cases per 1000 population. During last 20 years, primary and total morbidity has tripled. In 2006, 2013 and 2015 maximal levels of primary morbidity are conditioned by adoption of a number of legal acts targeted to detection of pathology. The pathology of diseases of the endocrine system is determined by diabetes mellitus, thyroid diseases and obesity in 87.1% of all cases. According the data of population appealability to medical organizations, the rate of prevalence of obesity in 2017 made up to 10.6, diabetes mellitus - 26.6, thyroid diseases - 23.4 per 1000 of population. During last 20 years, incidence of diabetes mellitus increased up to 2 times, and obesity up to 4.8 times. The females suffered of obesity 1.2 times and of thyroid diseases 7.4 times more often than males.


[Exploration of emulsifying material basis of Angelicae Sinensis Radix volatile oil based on partial least squares and hydrophile-lipophile balance value].
This study explores the emulsifying material basis of Angelicae Sinensis Radix volatile oil (ASRVO) based on partial least squares (PLS) method and hydrophile-lipophile balance (HLB) value.The turbidity of ASRVO emulsion samples from Gansu,Yunnan,and Qinghai was determined and the chemical components in the emulsion were analyzed by GC-MS.The PLS model was established with the chemical components as the independent variable and the turbidity as the dependent variable and evaluated with indexes R~2X and R~2Y.The chemical components which were in positive correlation with the turbidity were selected and the HLB values were calculated to determine the emulsification material basis of ASRVO.The PLS models for the 81 emulsion samples had high R~2X and R~2Y values,which showed good fitting ability.Seven chemical components,2-methoxy-4-vinylphenol,trans-ligustilide,3-butylidene-1(3H)-isobenzofuranone,dodecane,1-methyl-4-(1-methylethylidene)-cyclohexene,trans-beta-ocimene,and decane,had positive correlation with turbidity.Particularly,the HLB value of 2-methoxy-4-vinylphenol was 4.4,which was the HLB range of surfactants to be emulsifiers and 2-methoxy-4-vinylphenol was positively correlated with turbidity of the ASRVO emulsion samples from the main producing area.Therefore,2-methoxy-4-vinylphenol was the emulsifying material basis of ASRVO.The selected emulsifying substances can lay a foundation for exploring the emulsification mechanism and demulsification solution of ASRVO.


[Microbial contamination in dried fruit products in China in 2019].
To investigate the microbial contamination in dried fruit products in China. In 2019, 2917 samples of dried fruit products on the market were collected, and examined for aerobic bacterial count, coliforms, molds, yeasts, Salmonella and Listeria monocytogenes according to the method specified in GB 4789. A total of 34.42%(1004/2917)of the samples had molds above 50 CFU/g and 9.46%(276/2917)of the samples had yeast above 50 CFU/g. The occurrence of aerobic plate count above 10~4 CFU/g and coliforms above 10~2 CFU/g was 5.01%(146/2917)and 2.98%(87/2917), respectively. The detection rate of Salmonella and Listeria monocytogenes were 0.14%(4/2917) and 0.03%(1/2917), respectively. Microbial contamination in different kinds of dried fruit products varied widely, with dried wolfberries and dried durian having the worst overall hygiene. There were differences in microbial contamination of dried fruit products in different regions. In general, samples collected in South China, Southwest China and Central China had more serious microbial contamination. There was no significant difference in microbial contamination between dried fruit products with different packaging and sampling places. The hygienic condition of dried fruit products is generally poor in 2019.


A robust MOF-based trap with high-density active alkyl thiol for the super-efficient capture of mercury.
The first Zr-based metal-organic frameworks (MOFs) with high-density active alkyl thiol were successfully constructed in an aqueous phase. Thanks to the strong affinity between alkyl thiol and Hg2+ ions, the robust MOFs feature high adsorption capacity (734 mg g-1), ultra-fast kinetics (removing 99.99% Hg2+ in 5 min), super-high capture efficiency (dropping Hg2+ concentration from 10 000 ppb to 0.11 ppb), wide working range of pH, high selectivity and good reusability.


Serologic testing for reactive arthritis.
The objective of the study was to determine the sensitivity and specificity of quantitative serum antibody response to Salmonella enteritidis lipopolysaccharide (LPS) as a diagnostic test for post-Salmonella reactive arthritis (ReA). In a single food-source outbreak of Salmonella enteritidis, serum was collected from dysenteric individuals with and without ReA at 6, 12, and 24 months post infection. Serum was also collected from control patients with no prior exposure to Salmonella infection. Quantitative measurements of isotypic antibodies to Salmonella enteritidis LPS were performed by an ELISA. Sensitivity and specificity of quantitative isotypic antibody levels over time were plotted on receiver operator characteristic (ROC) curves. Serum IgG and IgA anti-LPS were found to be present in higher levels in the ReA patients than in controls. Using the optimal cutoff of 0.10 selected from an ROC curve, IgG anti-LPS is 88% sensitive and 94% specific, and IgA anti-LPS is 75% sensitive and 100% specific. We conclude that IgA anti-LPS is both sensitive and specific in distinguishing prior exposure to Salmonella LPS in ReA patients compared to unexposed controls.


Synthesis of Polyynes Using Dicobalt Masking Groups.
Extended triisopropylsilyl end-capped polyynes have been prepared from the corresponding tetracobalt complexes by removing the complexed dicobalt tetracarbonyldiphenylphosphinomethane (Co2(CO)4dppm) moieties. Unmasking of this "masked alkyne equivalent" was achieved under mild conditions with elemental iodine at room temperature, making it possible to obtain fragile polyynes with up to 20 contiguous sp-hybridized carbon atoms. The Co2(CO)4dppm moiety has a strong geometric and steric effect on the polyyne but does not have a marked electronic effect on the terminal alkyne, as indicated by NMR and IR spectroscopy, density functional theory calculations, and X-ray crystallography. An unusual "alkyne hopping" migration of the dicobalt group was noticed as a minor side reaction during copper-catalyzed Eglinton coupling.


[Employment of psychiatrically disabled people. The Lavoro LiberaMente project].
The complexity of giving psychiatrically disabled persons access to work is well known. The percentage of persons thus defined who are on the provincial unemployment lists is constantly increasing. The 'Lavoro Liberamente" ('I work freely') project is aimed not only at enabling a number of psychiatric patients to gain access to work but to do so by experimenting with a network methodology that includes the various agencies that can contribute to a successful outcome. The project was developed in various stages--psychiatric services and company awareness campaigns and task-definition, candidate selection, skills assessment, and work placement--all aimed at finding and maintaining employment. After a thorough preparatory phase, 19 psychiatrically disabled persons were placed in 14 companies. When the apprenticeship was concluded, 13 of them were hired. Considering the short time-frame--about one year between candidates being selected and finally recruited--the ratio between the number of disabled people recruited and those placed was satisfactory. This result should be interpreted positively because, even taking into account some of the most sensitive issues that surfaced and were analysed, it shows that access of the psychiatrically disadvantaged to work is possible if all involved people work synergistically, each according to their responsibilities and knowledge, and on condition that a recognised management of each individual project exists. Within such a network synergism, it is even possible to identify some tasks that are the responsibility of the Occupational Health Physician, therefore further contributing to the overall success of placements.


Orthogeriatric treatment reduces potential inappropriate medication in older trauma patients: a retrospective, dual-center study comparing conventional trauma care and co-managed treatment.
Multimorbidity and polypharmacy are common challenges in the treatment of older trauma patients. Therefore, various integrated care models were developed over the last few years, merging the expertise of geriatricians and trauma surgeons. The aim of this study was to evaluate, if the number of prescriptions of potentially inappropriate medication (PIM) could be reduced in these patients by an interdisciplinary co-managed concept compared to conventional trauma care. We conducted a retrospective, dual-center cohort study, including all patients aged 70 years and older admitted with a fracture of the hip or the proximal humerus within the study period. Patients were treated in the universities department of trauma surgery with two different hospital sites, one with conventional trauma care (CTC) and the other one with a certified orthogeriatric trauma unit (OGC). Based on the STOPP/START criteria by O´Mahony et al., PIMs were defined, which should be avoided in (ortho)geriatric patients. Medical records of each patient were analyzed at discharge. Besides patients basic information, all prescribed drugs, changes in the medication plan and who carried out these changes were collected. For statistical analysis based on the data quality and distribution, the t test, Mann-Whitney U test and the Chi-square test were used. A total of 95 patients were included, 73 of them females, with an average age of 82.59 years (SD ± 6.96). Mean length of hospital stay was 12.98 at CTC and 13.36 days at OGC (p = 0.536). Among conventional care (41 patients), prescription of one or more PIMs was found in 85.4% of the patients, whereas at the orthogeriatric ward (54 patients) only in 22.2% (p < 0.001). Besides that, changes in medication were made for 48.1% of the patients during their stay on the orthogeriatric ward. Our findings show that an integrated care concept can reduce the number of prescriptions of PIMs significantly and potentially avoids adverse drug reactions and additional burdens in older trauma patients.


Secretion of [Met]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine.
Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.


Early pregnancy-related changes in toll-like receptors expression in ovine trophoblasts and peripheral blood leukocytes.
In the present study, we aimed to 1) demonstrate the presence of all 10 toll-like receptors (TLRs) in ovine trophoblasts, and 2) investigate the expression profiles of TLR1-10 mRNAs in peripheral blood leukocytes (PBLs) in ewes during early pregnancy. For those purposes, ovine trophoblasts (n = 6) were collected from pregnant ewes on day 13. PBLs were collected from non-pregnant (n = 6) and pregnant ewes (n = 17) on days of mating (d) 0 and 18. TLR mRNAs in ovine trophoblasts were visualized by free-floating in situ hybridization (ISH). To assess the expression profiles of TLR1-10 in PBLs, total RNA was isolated and transcribed to cDNA. TLR1-10 mRNA levels were determined by real-time PCR in triplicate. The Relative Expression Software Tool (REST 2009) was used for statistical analysis. We detected mRNAs for TLR2, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR10 but not for TLR1, TLR3, and TLR9 in trophoblasts. TLR2, TLR5, TLR6, TLR7, TLR8, and TLR10 mRNAs were expressed by all trophoblasts, whereas TLR4 mRNA and protein in trophoblasts were more limited. In PBLs, TLR expression did not differ between day 0 and day 18 in non-pregnant ewes; however, ewes in early pregnancy exhibited significantly upregulated expression of TLR2 (2.3-fold), TLR4 (3.1-fold), TLR6 (1.7-fold), and TLR8 (2.2-fold) on day 18 compared with day 0. In contrast, TLR10 was downregulated (2-fold) on day 18 by pregnancy. Similar results were also obtained for TLR2, TLR4, TLR6, TLR8 and TLR10 from the comparison between day 18 non -pregnant and day 18 pregnant groups. According to these results, the presence of TLRs in early ovine trophoblasts suggests that these cells play an immunological role at the maternal-fetal interface. The results also suggest that tight regulation of some components of TLRs in PBLs due to embryo- and/or pregnancy-related factors is necessary for successful establishment of early pregnancy in ewes.


A comprehensive review on phenolic compounds from edible mushrooms: Occurrence, biological activity, application and future prospective.
Phenolic compounds are minor metabolites usually present in mushroom species. Because of their potential advantages for human health, such as antioxidant and other biological activities, these bioactive components have been gaining more interest as functional foods, nutraceutical agents for providing better health conditions. This review aims to comprehensively discuss the recent advances in mushroom phenolic compounds, including new sources, structural characteristics, biological activities, potential uses and its industrial applications as well as the future perspectives. Phenolic acids as well as flavonoids are considered the most common phenolics occurring in mushroom species. These are responsible for its bioactivities, including antioxidant, anti-inflammatory, antitumor, antihyperglycaemic, antiosteoporotic, anti-tyrosinase and antimicrobial activities. Several edible mushroom species with good phenolic content and show higher biological activity were highlighted, in a way for its futuristic applications. Trends on mushroom research highlighting new research areas, such as nanoformulation were discussed. Furthermore, the use of phenolic compounds as nutraceutical and cosmeceutical agents as well as the future perspectives and recommendations were made.


Calorigenic action of circulating epinephrine during pentobarbital, halothane and morphine anesthesia in dogs.
The calorigenic action of circulating epinephrine was analyzed quantitatively in the dog during pentobarbital, halothane and morphine anesthesia. The whole body oxygen consumption (VO2) was measured by an on-line analysis of breath-by-breath respiratory gas exchange. Epinephrine was infused at various doses and the plasma concentrations of epinephrine were measured by semiautomated fluorimetric analysis. During pentobarbital anesthesia, the basal VO2 was 5.26 ml/kg/min and was increased by epinephrine in a dose dependent manner at plasma concentrations between 3.9 ng/ml (VO2 = 5.68 ml/kg/min) and 36.5 ng/ml (VO2 = 6.47 ml/kg/min). Epinephrine exerted a similar effect during halothane anesthesia, but it failed to affect VO2 during morphine anesthesia. Morphine also inhibited dibutyryl cyclic AMP-induced increase in VO2, suggesting that morphine inhibits the calorigenic action of epinephrine at the intracellular site distal to beta-receptors.


Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation.
Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell cancer exhibiting a wide spectrum of disease courses and treatment responses. Molecular characterization of RNA and DNA from CLL cases has led to the identification of important driver mutations and disease subtypes, but the precise mechanisms of disease progression remain elusive. To further our understanding of CLL biology we performed isobaric labeling and mass spectrometry proteomics on 14 CLL samples, comparing them with B-cells from healthy donors (HDB). Of 8694 identified proteins, ∼6000 were relatively quantitated between all samples (q<0.01). A clear CLL signature, independent of subtype, of 544 significantly overexpressed proteins relative to HDB was identified, highlighting established hallmarks of CLL (e.g. CD5, BCL2, ROR1 and CD23 overexpression). Previously unrecognized surface markers demonstrated overexpression (e.g. CKAP4, PIGR, TMCC3 and CD75) and three of these (LAX1, CLEC17A and ATP2B4) were implicated in B-cell receptor signaling, which plays an important role in CLL pathogenesis. Several other proteins (e.g. Wee1, HMOX1/2, HDAC7 and INPP5F) were identified with significant overexpression that also represent potential targets. Western blotting confirmed overexpression of a selection of these proteins in an independent cohort. mRNA processing machinery were broadly upregulated across the CLL samples. Spliceosome components demonstrated consistent overexpression (p = 1.3 × 10-21) suggesting dysregulation in CLL, independent of SF3B1 mutations. This study highlights the potential of proteomics in the identification of putative CLL therapeutic targets and reveals a subtype-independent protein expression signature in CLL.


Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin.
A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentrations (anti-Factor Xa) and clotting times (APTT). Using one of the most effective delivery agents in this series, an estimated relative bioavailability of 8% can be achieved following oral administration to cynomolgus monkeys. To establish a correlation between the in vivo data and an in vitro parameter, immobilized artificial membrane (IAM) chromatography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.


Face to face: visual scanpath evidence for abnormal processing of facial expressions in social phobia.
Cognitive models of social phobia propose that cognitive biases and fears regarding negative evaluation by others result in preferential attention to interpersonal sources of threat. These fears may account for the hypervigilance and avoidance of eye contact commonly reported by clinicians. This study provides the first objective examination of threat-related processing in social phobia. It was predicted that hyperscanning (hypervigilance) and eye avoidance would be most apparent in social phobia for overt expressions of threat. An infrared corneal reflection technique was used to record visual scanpaths in response to angry, sad, and happy vs. neutral facial expressions. Twenty-two subjects with social phobia were compared with age- and sex-matched normal controls. As predicted, social phobia subjects displayed hyperscanning, (increased scanpath length) and avoidance (reduced foveal fixations) of the eyes, particularly evident for angry faces. The results could not be explained by either medication or co-morbid depression. These findings are consistent with theories emphasising the role of information processing biases in social phobia, and show promise in the application to treatment evaluation in this disorder.


Histochemical investigations of thyrosine in normal and pathological glia cells.
Investigations on thyrosine content in normal and pathological glia cells are the continuation of researches on occurrence of protein functional groups in abnormal glia cells (Szydlowska, 1970a, 1970b). The investigations carried out with the use of Caselli, Glenner and Lille methods have shown that fluctuations of thyrosine level in nuclea and cytoplasm of glia cells pathologically changed correspond to quantitative changes of other functional groups of proteins. Hence it may be assumed that the observed increase of thyrosine in pathologically changed glia cells is not connected with the change of protein composition of a cell but with the general increase of proteins in its nucleus or cytoplasm.


Endovascular treatment of blister aneurysms.
Blister aneurysms are rare cerebrovascular lesions for which the treatment methods are reviewed here, with a focus on endovascular options. The reported pathogenesis of blister aneurysms varies, and hemodynamic stress, arterial dissection, and arteriosclerotic ulceration have all been described. There is consensus on the excessive fragility of blister aneurysms and their parent vessels, which makes clipping technically difficult. Open surgical treatment is associated with high rates of complications, morbidity, and mortality; endovascular treatment is a promising alternative. Among endovascular treatment options, deconstructive treatment has been associated with higher morbidity compared with reconstructive methods such as direct embolization, stent- or balloon-assisted direct embolization, stent monotherapy, and flow diversion. Flow diversion has been associated with higher technical success rates and similar clinical outcomes compared with non-flow diverting treatment methods. However, delayed aneurysm occlusion and the need for antiplatelet therapy are potential drawbacks to flow diversion that must be considered when choosing among treatment methods for blister aneurysms.


Comparison of echocardiography with tissue Doppler imaging and magnetic resonance imaging with delayed enhancement in the assessment of children with hypertrophic cardiomyopathy.
In children with hypertrophic cardiomyopathy (HCM) there often occurs a non-ischemic pattern of myocardial fibrosis, which could be the cause of impaired left ventricular (LV) diastolic function assessed by tissue Doppler imaging (TDI). The aim of the study was to determine the prevalence of myocardial fibrosis in children with HCM, and to evaluate its relationship with echocardiographic parameters including LV diastolic dysfunction. Sixty-three children with HCM, mean age 12.2 ±4.5 years, underwent magnetic resonance imaging (MRI) and echocardiographic study from January 2010 to April 2014. The results of MRI, echocardiography, and TDI velocities were analyzed and compared between children with and without myocardial fibrosis. Moreover, correlations between the results of echocardiography and MRI were assessed. Our results showed a significant correlation between magnetic resonance and echocardiographic measurements of septal wall thickness, posterior wall thickness, LV mass and left atrial dimension. Children with myocardial fibrosis (60%) had a significantly thicker interventricular septum (21.3 vs. 1.8 mm; p < 0.0001) and larger left atrial dimension (36.7 vs. 27.8 mm; p = 0.0004) and volume index (42.0 vs. 26.6 ml/m²; p = 0.0011). Tissue Doppler imaging demonstrated significantly decreased lateral E' (9.02 vs. 13.53 cm/s; p < 0.0001) and septal E' (7.05 vs. 9.36 cm/s; p = 0.0082) velocities and a significantly increased transmitral lateral (10.34 vs. 6.68; p = 0.0091) and septal (13.1 vs. 9.8; p = 0.046) E/E' ratio in children with myocardial fibrosis. Myocardial fibrosis in children with hypertrophic cardiomyopathy was associated with markers for disease severity such as larger septum thickness, enlargement of the left atrium as well as impairment of left ventricular diastolic function. Tissue Doppler imaging is a helpful tool to detect the presence of left ventricular diastolic dysfunction in children with hypertrophic cardiomyopathy and myocardial fibrosis.


Prenatal diagnosis of trisomy 21 by quantitatively pyrosequencing heterozygotes using amniotic fluid as starting material of PCR.
Allelic ratio of an SNP has been used for prenatal diagnosis of fetal trisomy 21 by MALDI-TOF mass spectrometry (MS). Because MALDI-TOF MS is challenging in quantification performance, pyrosequencing was proposed to replace MS by better quantification of allelic ratios. To achieve a simple and rapid clinical diagnostic, PCR with "HpH Buffer" (a buffer with a high pH) was developed to directly amplify amniotic fluid. By the established assay, 114 samples of amniotic fluid were analyzed by pyrosequencing five SNPs of each sample; the allelic ratios of euploid heterozygotes were thus calculated to determine the cut-off values for prenatal diagnosis of trisomy 21. The panel of five SNPs were high in heterozygosity so that at least one heterozygote was found in each sample, and 86% of the samples had at least two heterozygotes, giving a nearly 100% sensitivity (population coverage) of the assay. By using the cut-off values of each SNP, 20 pre-diagnosed clinical samples were detected as trisomy 21 carriers with a confidence level over 99%, indicating that our method and karyotyping analysis were consistent in results. In conclusion, this pyrosequencing-based approach, coupled with direct amplification of amniotic fluid, is accurate in quantitative genotyping and simple in operation. We believe that the approach could be a promising alternative to karyotyping analysis in prenatal diagnosis.


Testing multiple means of self-affirmation.
The effects of self-affirmation manipulations are not yet well understood because several different affirmation manipulations have been tested using multiple dependent variables. The aim of the present research was to establish whether global self-feelings and self-esteem, or interpersonal positive feelings are affected by affirming the self. Experiment 1 showed that completing a kindness questionnaire led to adolescent girls reporting more positive interpersonal feelings, but no greater self-feelings or self-esteem than completing an opinions (control) questionnaire. Experiment 2 showed again that self-affirmation did not affect self-esteem, and that there were few differences between writing an essay about a cherished value, writing an essay about kindness, or completing a questionnaire about kindness in boosting positive interpersonal feelings. The findings are discussed in relation to self-affirmation theory and the possible practical implications of self-affirmation for aiding the delivery of social and health messages.


Peritumoral Clefting and Expression of MMP-2 and MMP-9 in Basal Cell Carcinoma of the Skin.
Peritumoral clefting is one of the main histologic features of basal cell carcinoma of the skin (BCC). The aim of the study was to analyze the expression of MMP-2 and MMP-9 both in cells of basal cell carcinoma and in the adjacent stroma and to correlate the findings of immunohistochemical analysis with the presence of peritumoral clefting. The study was made on archival material comprising 48 cases of BCC. These were scanned for the presence of peritumoral clefts. The results of immunohistochemical staining for MMP-2 and MMP-9 were determined semiquantitatively using immunohistochemical staining index (ISI). Peritumoral retractions were found in 40 BCC cases. Positive immunohistochemical reaction for MMP-2 in tumor cells was found in 47 cases and in all cases in the adjacent stroma. Positive immunostaining for MMP-9 in BCC tumor cells was observed in 37 cases and in all cases in the adjacent stroma. There was no statistically significant association between peritumoral retractions and expression of MMPs. A statistically significant correlation was found in the expression of both MMP-2 and MMP-9 between the tumor and the stroma. Tumor cells elaborate MMP-2 and -9, but they also produce some other factors that may induce production of MMPs in adjacent stromal cells. The role of MMPs in the development of peritumoral clefts could not be confirmed.


Efficacy and Safety of a Traditional Chinese Herbal Formula Xuefu Zhuyu Decoction for Hypertension: A Systematic Review and Meta-Analysis.
The cardioprotective role of xuefu zhuyu decoction (XZD), a well-known classical herbal formula, has been documented for hypertension treatment recently. This study aims to summarize the efficacy and safety of XZD in treating hypertension.Seven databases were searched to identify randomized controlled trials evaluating the efficacy of XZD in hypertensive patients. Fifteen studies involving 1364 hypertensive patients were included. All studies compared XZD and antihypertensive drugs with antihypertensive drugs used alone.In all, 15 studies reported significant effects of XZD for lowering blood pressure compared with the control group (P < 0.05), and 7 studies reported significant effects of XZD for improving symptoms compared with the control group (P < 0.00001). Meanwhile, studies reported XZD was more efficacious than antihypertensive drugs in improving total cholesterol, triglycerides, low-density lipoprotein cholesterol, homocysteine, hemorheology, carotid intima-media thickness, and left ventricular mass index (P < 0.05). No severe adverse event was reported.This meta-analysis provides evidence that XZD is beneficial for hypertension. Although concerns regarding selective bias and methodologic flaws were raised, our findings suggests XZD as a new candidate cardioprotective drug for hypertension, which should be given priority for future preclinical and clinical studies.


Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder.
The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger's Diagnostic Scale-Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water's relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.


A SPECT study in internal carotid artery occlusion: discrepancies between flow image and neurologic deficits.
A SPECT (single photon emission computed tomography) study in internal carotid artery (ICA) occlusion was performed in 6 patients. The validity of iodoamphetamine (IMP) SPECT study in the evaluation of cerebral blood flow (CBF) or neurologic function is still controversial. In this study, the authors showed several cases in whom SPECT images of brain were not compatible with their neurologic deficits. In 2 typical cases, a large low-density area was observed in the non-dominant hemisphere in computed tomography (CT) scan, but no apparent motor-sensory deficits in left limbs were present. In these patients, SPECT study also revealed flow reduction in the affected side of the brain. So there was a possibility that an IMP brain image could not always reflect CBF, which maintains neurologic function of the brain.


[Preventive and therapeutic effects of Icariside Ⅱ on radiation injury-induced erectile dysfunction in rats].
To explore the preventive and therapeutic effects of Icariside Ⅱ (ICAⅡ) on radiation injury-induced ED (Ri-ED) in rats. Twenty-four 10-week-old male SD rats received exposure of the prostate to single X-ray irradiation of 20 Gy, and were randomly equally divided into an Ri-ED group (6 survived and 6 died) and a treatment group treated with ICAⅡ at 4.5 mg/kg/d (9 survived and 3 died). Another 6 SD rats were taken as negative controls. After 4 weeks of continuous intragastric administration and 2 weeks of drug elution, the erectile function of the rats was evaluated by measurement of the maximum intracavernous pressure / mean arterial pressure (ICPmax/MAP), and the penile tissues were subjected to immunofluorescence staining, immunohistochemistry, Masson's trichrome staining, Western blot and detection of oxidative stress indicators. Compared with the negative controls, the rats in the Ri-ED group showed significant decreases in ICPmax/MAP (0.76 ± 0.09 vs 0.42 ± 0.06, P < 0.01), the number of nNOS-positive nerve fibers in the corpus cavernosum (10.17 ± 2.64 vs 3.17 ± 1.72, P < 0.01), the content of endothelial cells (1.39 ± 0.30 vs 0.35 ± 0.12, P < 0.01), the expressions of nNOS (0.42 ± 0.08 vs 0.08 ± 0.01, P < 0.01) and eNOS (0.99 ± 0.24 vs 0.12 ± 0.08, P < 0.01) and the activity of superoxide dismutase (SOD) ([343.73 ± 58.57] vs [153.50 ± 34.06] U/mg prot, P < 0.01), but an increase in the malondialdehyde (MDA) level ([1.80 ± 0.31] vs [3.25 ± 0.21] nmol/mg prot, P < 0.01). In comparison with the Ri-ED group, the animals treated with ICAⅡ exhibited remarkably increased ICP/MAP (0.42 ± 0.06 vs 0.66 ± 0.07, P < 0.01), number of nNOS-positive nerve fibers (3.17 ± 1.72 vs 7.33 ± 1.75, P < 0.05), content of endothelial cells (0.35 ± 0.12 vs 1.07 ± 0.36, P < 0.01), and expressions of nNOS (0.08 ± 0.01 vs 0.16 ± 0.05, P < 0.05) and eNOS (0.12 ± 0.08 vs 0.86 ± 0.30, P < 0.01) in the corpus cavernosum, but a decreased level of MDA ([3.25 ± 0.21] vs [2.17 ± 0.55] nmol/mg prot, P < 0.05). In addition, ICAⅡ effectively reduced radiation injury-induced mortality of the rats. IcarisideⅡ can significantly improve ED and pathological changes and reduce mortality caused by radiation injury in rats, which may be related to its ability of improving radiation-induced oxidative stress.


A descriptive online survey about the knowledge of palliative care residents of Saudi Arabia has compared to the general worldwide population.
To assess communities' basic knowledge of palliative care by developing a questionnaire. This prevalence study, an anonymous online questionnaire, was answered by 326 individuals living throughout Saudi Arabia over one month. The questions concerned the basic principles and knowledge of palliative care. We collected the data between February and May 2019. The results showed that 72% of the respondents had neither heard nor knew about palliative care. Those who know about palliative care assess their knowledge as the following: 17.8% of the respondents reported that they knew the meaning and could explain it to others. As well, 10.5% knew the meaning but could not explain it to others; 9.3% had heard of it but did not know the meaning, and 62.4% had never heard of it. The research showed that there is a lack of knowledge about palliative-care among the population of Saudi Arabia. Data shows that there should be more efforts toward providing the community with better knowledge about palliative care.


Dynamic Investigation of Battery Materials via Advanced Visualization: From Particle, Electrode to Cell Level.
Li-ion batteries, the most-popular secondary battery, are typically electrochemical systems controlled by ion-insertion dynamics. The battery dynamics involve mass transport, charge transfer, ion-electron coupled reactions, electrolyte penetration, ion solvation, and interfacial evolution. However, it is difficult for the traditional electrochemical methods to capture the accurate and individual details of the dynamic processes in "black box" batteries; instead, only the net result of multi-factors on the whole scale. Recently, different advanced visualization techniques have been developed, which provide powerful tools to track and monitor the internal real-time dynamic processes, giving intuitive details and fine information at various scales from crystal lattice, single particle, electrode to cell level. Here, the recent progress on the investigation of electrochemical dynamics in battery materials are reviewed, via developed techniques across wide timescales and space-scales, including the dynamic process inside the active particle, kinetics issues at the electrode/electrolyte interface, dynamic inhomogeneity in the electrode, and dynamic transportation at the cell level. Finally, the fundamental principles to improve the battery dynamics are summarized and new technologies for future more stringent conditions are highlighted. In prospect, this review opens sight on the battery interior for a clearer, deeper, and more thorough understanding of the dynamics.


Mapping resistance responses to Sclerotinia infestation in introgression lines of Brassica juncea carrying genomic segments from wild Brassicaceae B. fruticulosa.
Sclerotinia stem rot (Sclerotinia sclerotiorum) is a major disease of Brassica oilseeds. As suitable donors to develop resistant cultivars are not available in crop Brassicas, we introgressed resistance from a wild Brassicaceae species, B. fruticulosa. We produced 206 B. juncea-B. fruticulosa introgression lines (ILs). These were assessed for pollen grain fertility, genome size variations and resistance responses to Sclerotinia following stem inoculations under disease-conducive conditions. Of these, 115 ILs showing normal fertility and genome size were selected for cytogenetic characterization using florescent genomic in situ hybridization (Fl-GISH). B. fruticulosa segment substitutions were indicated in 28 ILs. These were predominantly terminal and located on B-genome chromosomes. A final set of 93 highly fertile and euploid (2n = 36) ILs were repeat-evaluated for their resistance responses during 2014-15. They were also genotyped with 202 transferable and 60 candidate gene SSRs. Association mapping allowed detection of ten significant marker trait associations (MTAs) after Bonferroni correction. These were: CNU-m157-2, RA2G05, CNU-m353-3, CNU-m442-5, ACMP00454-2, ACMP00454-3, EIN2-3-1, M641-1, Na10D09-1 and Na10D11-1. This is the first time such a molecular mapping technique has been deployed with introgression lines carrying genomic segments from B. fruticulosa, and the first to show that they possess high levels of resistance against S. sclerotiorum.


Coup de sabre presenting with worsening diplopia and enophthalmos.
A middle-aged woman with a diagnosis of linear scleroderma and systemic sclerosis presented with an atrophic skin lesion of the forehead extending in the right orbit and progressive diplopia in the right gaze. On exam, she had enophthalmos with a small, manifest esotropia in the right gaze. Orbital MRI revealed fat atrophy of the right upper eyelid and orbit not previously described. Inflammation and progressive collagen fibrosis involving subcutaneous tissue, fat, and muscle secondary to linear scleroderma may result in enophthalmos and diplopia.


Epidermal cell kinetics in hairless mice after bleomycin. II. Perturbations after multiple doses.
Bleomycin (BLM) at doses of 0.1 mg/animal was injected into hairless mice every 4 hours for 4 days. Epidermal cell cycle phase distributions were determined by flow cytofluorometric DNA measurements. Labeling indices and mean grain counts were determined by means of autoradiography, and mitotic rates were determined by demecolcine arrest of metaphases. A small, partially reversible accumulation of cells with G2 phase DNA content was observed subsequent to BLM administration. Most of the cells accumulated in G2 phase, however, seemed to stop proliferation and die in this phase. Thus, BLM does not fulfill the criteria for a good synchronizing agent in the hairless mouse epidermis. Flow cytofluorometry alone cannot determine whether piling up of cells in a particular cell cycle phase is true synchrony or an accumulation of lethally damaged cells. Several cell kinetic methods should be used to demonstrate real synchrony.


Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter.
According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.


Local calcium release activation by DHPR calcium channel openings in rat cardiac myocytes.
The principal role of calcium current in the triggering of calcium release in cardiac myocytes is well recognized. The mechanism of how calcium current (I(Ca)) controls the intensity of calcium release is not clear because of the stochastic nature of voltage-dependent gating of calcium channels (DHPRs) and of calcium-dependent gating of ryanodine receptors (RyRs). To disclose the relation between DHPR openings and the probability of calcium release, local calcium release activation by I(Ca) was investigated in rat ventricular myocytes using patch-clamp and confocal microscopy. Calcium spikes were activated by temporally synchronized DHPR calcium current triggers, generated by instantaneous 'tail' I(Ca) and modulated by prepulse duration, by tail potential, and by the DHPR agonist BayK 8644. The DHPR-RyR coupling fidelity was determined from the temporal distribution of calcium spike latencies using a model based on exponentially distributed DHPR open times. The analysis provided a DHPR mean open time of approximately 0.5 ms, RyR activation time constant of approximately 0.6 ms, and RyR activation kinetics of the 4th order. The coupling fidelity was low due to the inherent prevalence of very short DHPR openings but was increased when DHPR openings were prolonged by BayK 8644. The probability of calcium release activation was high, despite low coupling fidelity, due to the activation of many DHPRs at individual release sites. We conclude that the control of calcium release intensity by physiological stimuli can be achieved by modulating the number and duration of DHPR openings at low coupling fidelity, thus avoiding the danger of inadvertently triggering calcium release events.


The effect of platelet-rich plasma on the bone healing around calcium phosphate-coated and non-coated oral implants in trabecular bone.
The effect of local application of autologous platelet-rich plasma (PRP) on bone healing in combination with the use of titanium implants with 2 different surface configurations was investigated. PRP fractions were obtained from venous blood sample of 6 goats and applied via gel preparation and subsequent installation in the implant site or via dipping of the implant in PRP liquid before insertion. Thirty-six implants (18 non-coated and 18 calcium phosphate (CaP) coated) were placed into the goat femoral condyles (trabecular bone). The animals were sacrificed at 6 weeks after implantation, and implants with surrounding tissue were processed for light microscopical evaluation. In addition to subjective description of the histological findings, histomorphometrical variables were also evaluated (the bone-implant contact and the bone mass adjacent to the implant). Significantly more interfacial bone-to-implant contact was observed for all 3 groups of CaP-coated implants and the titanium / liquid group (non-coated implant with PRP liquid) than for the other 2 non-coated titanium groups (with PRP gel or without PRP). The evaluation of the bone mass close to implant surface indicated that all the groups induced a significant increase of the bone mass except the PRP gel groups. On the basis of the observations, it was concluded that magnetron-sputtered CaP coatings can improve the integration of oral implants in trabecular bone. The additional use of PRP did not offer any significant effect on the bone response to the CaP-coated implants, whereas PRP in a liquid form showed a significant effect on bone apposition to roughened titanium implants during the early post-implantation healing phase.


Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases.
The relationship between infection and autoimmunity has been increasingly defined over the last 20 years. The systemic rheumatic diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to self-antigen. The exact etiology for the majority of these diseases is unknown; however, a complex combination of host and environmental factors are believed to play a pivotal role. Helicobacter pylori (H. pylori) is one of the most widely studied infectious agents proposed as agents triggering autoimmune response. The persistent presence of H. pylori in the gastric mucosa results in chronic immune system activation with ongoing cytokine signaling, infiltration of gastric mucosa by neutrophils, macrophages, lymphocytes, as well as production of antibodies and effector T-cells. Various mechanisms have been proposed in an attempt to explain the extra-intestinal manifestations of H. pylori infections. These include: molecular mimicry, endothelial cell damage, superantigens and microchimerism. I performed a systematic literature review using the keywords "rheumatoid arthritis", "Sjögren's syndrome", "systemic sclerosis", "systemic lupus erythematosus", "Helicobacter pylori" and "pathogenesis". A systematic literature search was carried out in MEDLINE; EMBASE; Cochrane Library and ACR/EULAR meeting abstracts. In systemic rheumatic diseases H. pylori infection prevalence alone should not be expected to provide sufficient evidence for or against a pathologic role in the disease. In this article I review studies examining the potential involvement of H. pylori infection in autoimmune systemic rheumatic diseases. Further studies of the immunological response to H. pylori and its role in the pathogenesis of systemic rheumatic diseases are warranted.


[Prevention and screening of HIV infection ].
The prevention of the HIV infection remains relevant considering the dynamics of the epidemic and the slackening of the preventive behavior of certain populations. The strategies associate initiatives of universal prevention: information, education, communication, screening; and specific actions in the direction of the most exposed populations. The paradigms of prevention evolved a lot these last years to take into account the preventive efficiency of antiretrovirals. If the condom remains the reference method, it is advisable for the populations the most exposed today to associate all the tools of prevention: behavioral methods, screening and antiretroviral. The possibility given to non-governmental organizations to realize test of fast screening allowed to go to closer of the most exposed populations.The arrival on the market of the autotests must be supervised to touch the people who do not turn to the screening.


Prevalence of Lower Urinary Tract Symptoms in China, Taiwan, and South Korea: Results from a Cross-Sectional, Population-Based Study.
Few population-based data are available evaluating the prevalence of lower urinary tract symptoms (LUTS) in Asia. The objective of our study was to determine LUTS prevalence in China, Taiwan, and South Korea using International Continence Society (ICS) 2002 criteria. An Internet-based self-administered survey among individuals aged at least 40 years with the ability to use a computer and to read the local language. Survey questions included ICS symptom definitions and the international prostate symptom score (IPSS). Data analysis was based on descriptive statistics and post hoc significance testing. There were 8284 participants, of whom 51% were women and 34% were aged at least 60 years. LUTS prevalence was slightly higher in men than women (62.8% vs. 59.6%; p = 0.004), increasing significantly with age (p = 0.001). All three ICS symptom groups (voiding, storage, and post-micturition) were present in 35% of individuals with LUTS. Symptoms with the highest overall prevalence were nocturia, frequency, incomplete emptying, and terminal dribble. The most bothersome symptoms were terminal dribble, nocturia, and urgency. According to IPSS scores, 87% of participants had at least mild symptoms; 43% of those aged over 60 years had moderate/severe symptoms. The percentage of participants with any LUTS who had visited healthcare professionals because of urinary symptoms was 26%, rising to 45% amongst individuals with all three symptom groups (p = 0.001 vs. other ICS symptom groups). LUTS are highly prevalent in men and women aged at least 40 years who participated in this study in China, Taiwan, and South Korea and increases with increasing age. A minority of individuals with LUTS seek healthcare and our results suggest an increased patient awareness of LUTS is required. Astellas Pharma Singapore Pte. Ltd. ClinicalTrials.gov identifier, NCT02618421.


Inexpensive, rapid fabrication of polymer-film microfluidic autoregulatory valve for disposable microfluidics.
This work presents the fabrication of a microfluidic autoregulatory valve which is composed of several layers of thin polymer films (i.e., polyvinyl chloride (PVC), polyethylene terephthalate (PET) double-sided tape, and polydimethylsiloxane (PDMS)). Briefly, pulsed UV laser is employed to cut the microstructures of through grooves or holes in the thermoplastic polymer films, and then the polymer-film valves are precisely assembled through laminating the PDMS membranes to the thermoplastic polymer films through the roll-lamination method. The effective bonding between the PVC film and the PDMS membrane is realized using the planar seal method, and the valve is sandwiched and compressed by a home-made housing to achieve the good seal effect. Then, the flow performances of the prototype valve are examined, and constant flow autoregulation is realized under the static or dynamic test pressures. The long-term response of the valve is also studied and minimum flow-rate decrements are found over a long actuation time. The fabrication method proposed in this work is successful for the low-cost and fast prototyping of the polymer-film valve. We believe our method will also be broadly applicable for fabrication of other low-cost and disposable polymer-film microfluidic devices.


Beliefs About the Direct Comparison of E-Cigarettes and Cigarettes.
Recent data suggests that positive beliefs about electronic cigarettes (e-cigs) use can lead to later e-cig use. Considering that many advertisements claim that e-cigs are superior to cigarettes, individuals' likelihood to view e-cigs more favorably than cigarettes can also influence subsequent e-cig use; however, no studies have directly assessed such a comparison. The present study created and validated the Comparing E-Cigarettes and Cigarettes questionnaire (CEAC), which asks individuals to directly compare e-cigs and cigarettes on a number of dimensions, in two independent samples. In sample 1 (451 undergraduates; mean age = 20.35, SD = 5.44, 72.4% female, 73.4% Caucasian) we explored the factor structure of the CEAC and in sample 2 (699 community adults collected via Amazon's Mechanical Turk; mean age = 34.04, SD = 10.9, 47.7% female, 83.3% Caucasian) we replicated the factor structure. Exploratory factor analysis suggested a three-factor structure: General Benefits (α = 0.80), General Effects (α = 0.86), and Health Benefits (α = 0.88), which was replicated via confirmatory factor analysis, χ2 = 4.36; RMSEA = 0.07, 90% CI = 0.06-0.08; TLI = 0.99; CFI = 0.99, and was relatively invariant across product use and gender. Individuals reported viewing e-cigs as safer and more beneficial than cigarettes and these beliefs were higher in e-cig users. Future work should establish how these comparative beliefs are influenced by e-cig use and/or influence subsequent transition to and increases in e-cig use. Although e-cigs are likely less harmful than cigarettes, and thus these comparative beliefs represent that state of nature, e-cigs are not completely without risk.


New life after prostate brachytherapy? Considering the fertile female partner of the brachytherapy patient.
To examine several cases of unusual and unexpected pregnancy in the female partners of men treated with brachytherapy for cancer of the prostate. Self-reported pregnancy of partners of patients who had had prostate brachytherapy was assessed. The dosimetry to the testicles and sperm counts were used to examine the feasibility of pregnancy in the partners. Three reported cases of pregnancy showed the men to have viable counts of within several or all of the parameters of the World Health Organisation criteria for normal semen analysis. These cases provide a cautionary tale and suggest that all men being treated with prostate brachytherapy should be counselled about the possibility of continued fertility. Documentation of this 'risk' on the consent form will allow for proper discussion of this issue in a clinical and medicolegal context. The key to addressing this problem is to propagate much better patient information. The topic should be addressed clearly in information booklets for the patients. Prostate brachytherapy may allow for pregnancy to be achieved in the fertile partners of patients, even after full radiation treatment of the patient.


Repression of IL-4-induced gene expression by IFN-gamma requires Stat1 activation.
IFN-gamma antagonizes many physiological responses mediated by IL-4, including the inhibition of IL-4-induced IgE production. This event is largely mediated at the level of transcription. We observed that the IL-4 response element of the germline epsilon promoter is sufficient to confer IFN-gamma-mediated repression onto a reporter construct. The inhibitory effects were observed in both lymphoid and nonlymphoid cell lines. Stat1, which is activated by IFN-gamma, cannot recognize the Stat6-specific IL-4 response element in the epsilon promoter. Hence, competitive DNA binding does not seem to be the underlying mechanism for the inhibitory effect. This is supported by the observation that inhibition is not seen at early time points, but requires prolonged IFN-gamma treatment. IFN-gamma stimulation results in a loss of IL-4-induced Stat6 tyrosine phosphorylation, nuclear translocation, and DNA binding. Using the fibrosarcoma cell line U3A, which lacks Stat1, we demonstrated that the transcription activation function of Stat1 is required for the IFN-gamma-mediated repression. Repression was restored by overexpression of Stat1alpha, but not Stat1beta, in U3A cells. Treatment with IFN-gamma, but not IL-4, specifically up-regulates the expression of SOCS-1 (silencer of cytokine signaling), a recently characterized inhibitor of cytokine signaling pathways, such as IL-6 and IFN-gamma. Overexpression of SOCS-1 effectively blocks IL-4-induced Stat6 phosphorylation and transcription. This suggests that IFN-gamma-mediated repression of IL-4-induced transcription is at least in part mediated by SOCS-1.


Strong Correlation Between Superconductivity and Ferromagnetism in an Fe-Chalcogenide Superconductor.
The interplay among topology, superconductivity, and magnetism promises to bring a plethora of exotic and unintuitive behaviors in emergent quantum materials. The family of Fe-chalcogenide superconductors FeTexSe1-x are directly relevant in this context due to their intrinsic topological band structure, high-temperature superconductivity, and unconventional pairing symmetry. Despite enormous promise and expectation, the local magnetic properties of FeTexSe1-x remain largely unexplored, which prevents a comprehensive understanding of their underlying material properties. Exploiting nitrogen vacancy (NV) centers in diamond, here we report nanoscale quantum sensing and imaging of magnetic flux generated by exfoliated FeTexSe1-x flakes, demonstrating strong correlation between superconductivity and ferromagnetism in FeTexSe1-x. The coexistence of superconductivity and ferromagnetism in an established topological superconductor opens up new opportunities for exploring exotic spin and charge transport phenomena in quantum materials. The demonstrated coupling between NV centers and FeTexSe1-x may also find applications in developing hybrid architectures for next-generation, solid-state-based quantum information technologies.


Smartphone-based mobile thermal imaging technology to assess limb perfusion and tourniquet effectiveness under normal and blackout conditions.
Over the past decade, there has been a resurgence of tourniquet use in civilian and military settings. Several key challenges include assessment of limb perfusion and adequacy of tourniquet placement, particularly in the austere or prehospital environments. We investigated the utility of thermal imaging to assess adequacy of tourniquet placement. The FLIR ONE smartphone-based thermal imager was utilized. Ten swine underwent tourniquet placement with no associated hemorrhage (n = 5) or with 40% hemorrhage (n = 5). Experiment 1 simulated proper tourniquet application, experiment 2 had one of two tourniquets inadequately tightened, and experiment 3 had one of two tourniquets inadequately tightened while simulating blackout-combat conditions. Static images were taken at multiple time points up to 30 minutes. Thermal images were then presented to blinded evaluators who assessed adequacy of tourniquet placement. The mean core temperature was 38.3 °C in non-hemorrhaged animals versus 38.2 °C in hemorrhaged animals. Hemorrhaged animals were more hypotensive (p = 0.001), anemic (p < 0.001), vasodilated (p = 0.008), and had a lower cardiac output (p = 0.007) compared to non-hemorrhaged animals. The thermal imaging temperature reading decreased significantly after proper tourniquet placement in all animals, with no difference between hemorrhaged and non-hemorrhaged groups at 30 minutes (p = 0.23). Qualitative thermal image analysis showed clearly visible perfusion differences in all animals between baseline, adequate tourniquet, and inadequate tourniquet in both hemorrhaged and non-hemorrhaged groups. Ninety-eight percent of blinded evaluators (n = 62) correctly identified adequate and inadequate tourniquet placement at 5 minutes. Images in blackout conditions showed no adverse impact on thermal measurements or in the ability to accurately characterize perfusion and tourniquet adequacy. A simple handheld smartphone-based forward looking infrared radiometry device demonstrated a high degree of accuracy, reliability, and ease of use for assessing limb perfusion. Forward looking infrared radiometry also allowed for rapid and reliable identification of adequate tourniquet placement that was not affected by major hemorrhage or blackout conditions.


Easy harvesting of radial artery with ultrasonically activated scalpel.
The radial artery was proposed and then abandoned as a coronary artery bypass graft in the 1970s. Development of new pharmacologic antispasmodic agents and minimally traumatic harvesting techniques has led to a revival of the use of the radial artery in coronary artery bypass surgery. Usually the main reasons for the spasm are thermal injury caused by electrocautery and traumatic harvesting technique. In our technique an ultrasonically activated scalpel (Harmonic Scalpel; Ultracision Inc, Smithfield, RI) was used for radial artery harvesting without using hemostatic clips for vessel side branches. The patients in the study were divided into two groups of 10 patients each. In the first group radial arteries were harvested with this technique, and in the second group with hemostatic clips, scissors, and minimal electrocautery. Harvesting time, frequency of spasm, and use of hemostatic clips were compared between the two groups. The Harmonic Scalpel decreased the harvesting time, frequency of spasm, and excessive use of hemostatic clips. Good coagulation capacity with markedly decreased use of hemostatic clips and minimized thermal injury offers the surgeon the ability to perform less traumatic, spasm free, and rapid radial artery harvesting.


Clinical nurses' attitudes towards death and caring for dying patients in China.
To examine Chinese clinical nurses' attitudes towards death and caring for dying patients, and to examine the relationships between clinical nurses' attitudes towards death and caring for dying patients. A convenience sample of 770 clinical nurses from 15 hospitals in China. All participants completed the Chinese version of the Frommelt Attitude Toward Care of the Dying Scale, Form B (FATCOD-B-C), the Chinese version of the Death Attitude Profile-Revised (DAP-R-C), and a demographic questionnaire. The mean score of the FATCOD-B-C items was 95.62 (SD = 7.45). The majority of Chinese clinical nurses were likely to provide care for the dying person's family (mean = 3.77), but did not have a positive attitude towards communication with the dying person(mean = 2.62). The majority of Chinese clinical nurses showed low scores on death avoidance (mean=1.96) and natural acceptance (mean = 1.61), and most of them viewed death as a passageway to a happy afterlife (mean = 4.33). Attitudes towards caring for dying patients were significantly negatively correlated with fear of death (r = -0.120) and positively correlated with approach acceptance (r = 0.127) and natural acceptance (r = 0.117). Factors that predicted clinical nurses' attitudes towards the care of dying patients included education level, fear of death, approach acceptance, religious beliefs, previous education on death and dying, natural acceptance, professional title, and experience with death or dying patients, which accounted for 18.7% of the variance. Nurses' personal attitudes towards death were associated with their attitudes towards the care of dying patients. Training and educational programmes for clinical nurses should take into consideration nurses' personal attitudes towards death as well as their cultural backgrounds and religious beliefs.