A preliminary report on the neuropsychologic sequelae of human immunodeficiency virus.
The neuropsychologic sequelae of acquired immunodeficiency syndrome and human immunodeficiency virus were studied by comparing the results of a neuropsychologic test battery administered to the following three groups of Danish homosexual men: 20 patients with acquired immunodeficiency syndrome, 20 asymptomatic subjects who tested positive for the human immunodeficiency virus, and a matched control group of 20 subjects who tested negative for the human immunodeficiency virus. The group with acquired immunodeficiency syndrome performed significantly worse than the control subjects on the tests measuring concentration, memory, and psychomotor speed. The group with human immunodeficiency virus performed significantly worse than the control subjects on the tests measuring verbal memory and psychomotor speed. On the other tests, their results varied. The study supports the hypothesis that not only patients with acquired immunodeficiency syndrome but also asymptomatic subjects with human immunodeficiency virus may be neuropsychologically impaired early in the course of the disease.


A common DNA-binding site for SZF1 and the BRCA1-associated zinc finger protein, ZBRK1.
More than 220 Kruppel-associated box-zinc finger protein (KRAB-ZFP) genes are encoded in the human genome. KRAB-ZFPs function as transcriptionalrepressors by binding DNA through their tandem zinc finger motifs.Gene silencing is mediated by the highly conserved KRAB domain, which recruits histone deacetylase complexes, histone methylases, and heterochromatin proteins. However, little is known of the biological programs regulated by KRAB-ZFPs, in large part because of the difficulty in identifying DNA-binding sites recognized by long arrays of zinc fingers. In an attempt to identify the natural target genes for a KRAB-ZFP, we chose SZF1, a hematopoietic progenitor-restricted, KRAB-ZFP that contains only four C(2)H(2) zinc finger motifs. Using recombinant SZF1 protein and a PCR-based binding site selection strategy, we identified a 15-bp consensus DNA sequence recognized by SZF1. Remarkably, this sequence is similar to the core DNA-binding site described recently for ZBRK1, a KRAB-ZFP that binds to BRCA1 and is involved in coordinating the cellular DNA damage response. The SZF1 and ZBRK1 proteins bind to both the experimentally derived SZF1 site and the canonical ZBRK1 site. The KRAB domain from SZF1 bound directly to the KAP-1 corepressor and displayed intrinsic silencing activity. Moreover, full-length SZF1 repressed a promoter containing ZBRK1 recognition sequences. Thus, SZF1 and ZBRK1 may regulate a common set of target genes in vivo.


Symptoms of Depression, Positive Symptoms of Psychosis, and Suicidal Ideation Among Adults Diagnosed With Schizophrenia Within the Clinical Antipsychotic Trials of Intervention Effectiveness.
Suicide is among leading causes of death for adults diagnosed with schizophrenia. While symptoms of depression are consistently supported factors involved in suicidal ideation, findings on the role of positive symptoms of psychosis have been mixed with limited understandings of risk. Accordingly, this study aimed to identify the pathways of influence between symptoms of depression, positive symptoms of psychosis (i.e. hallucinations and delusions), and suicidal ideation. Data were obtained from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE; n = 1,460). Suicidal ideation and symptoms of depression were measured by the Calgary Depression Scale (CDRS) and hallucinations and delusions by the Positive and Negative Syndrome Scale (PANSS). The data were analyzed using Structural Equation Modeling (SEM). As symptoms of depression and positive symptoms of psychosis independently increased, on average there were associated increases in suicidal ideation. The present study provides support for the relationship between positive symptoms of psychosis, specifically hallucinations and delusions, and suicidal ideation. Future prospective longitudinal study designs are needed to further increase understandings of the roles that hallucinations, delusions, and additional symptoms of schizophrenia play in both suicidal ideation and attempt to ultimately inform evidence-based interventions aiming to reduce suicidal death.


Dentine caries: take it or leave it?
In modern dentistry the primary aim when excavating carious dentine is to eradicate only the highly infected, irreversibly demineralized and denatured biomass in order to allow effective restoration of the cavity, restoration of the surface anatomy of the tooth and to prevent disease progression. However, the boundary between this superficial zone of dentine requiring excavation and the deeper, affected but repairable tissue is not always obvious either in the clinic or in the research laboratory. The inherent subjectivity in detecting this excavation boundary can result in clinically significant differences in the quality and quantity of dentine removed by different operators and makes the in vitro comparison of newer excavation techniques more difficult. This article discusses the rationale behind carious dentine excavation and the criteria available to the dentist, both clinical and laboratory, to help identify the dentine requiring removal.


Aortitis and periaortic fibrosis.
A 45-year-old man presented with bilateral lower extremity claudication due to aortitis and periaortic fibrosis. This variety of aortitis has been described in the pathologic literature as chronic periaortitis, a subset of idiopathic retroperitoneal fibrosis. The association of this aortitis with abdominal aortic aneurysm has been described in the surgical literature as inflammatory abdominal aortic aneurysms. These entities are thought to be secondary to the same disease process. We review the possible etiology, diagnostic considerations, and management of these aortidites.


Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer.
Women who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer. Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers. However, the risk of subsequent contralateral breast cancer in carriers is markedly increased. Therefore, mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer. Yet, many BRCA carriers forgo this option for fear of harmful effects and choose breast conserving treatment and observation instead. In Israel, BRCA-associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population. In this Institutional Review Board-approved phase II trial, the option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy. The primary end point was contralateral breast cancer. Between May 2007 and October 2017, 162 patients were enrolled. Eighty-one patients opted for standard loco-regional treatment including surgery and radiation to the involved side (control arm) and 81 patients chose additional contralateral breast irradiation (intervention arm). At a median follow-up of 58 months, 10 patients developed contralateral breast cancer in the control arm at a median of 32 months, as compared with 2 patients in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation (log-rank P = 0.011). Among BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation was associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset. Phase II, comparative two-arm trial (NCT00496288).


Transmembrane Pathways and Mechanisms of Rod-like Paclitaxel Nanocrystals through MDCK Polarized Monolayer.
Drug nanocrystals (NCs) appear to be favorable to improving oral bioavailability of poorly water-soluble drugs as evidenced by the great success they have had in the market. However, the pathway and mechanism of drug NCs through epithelial membrane are still unclear. In an attempt to clarify their transport features, paclitaxel nanocrystals (PTX-NCs), and paclitaxel hybrid NCs with lipophilic carbocyanine dyes, were prepared and characterized as the models. The endocytosis, intracellular trafficking, paracellular transport, and transcytosis of PTX-NCs were carefully investigated with Förster resonance energy transfer (FRET) analysis, as well as a colocalization assay, flow cytometry, gene silencing, Western-blot, transepithelial electrical resistance (TEER) study and other approaches on MDCK cells. It was found that rod-like PTX-NCs could transport through the monolayer intact, and the process of endocytosis proved to be time and energy dependent. Endoplasmic reticulum (ER) and Golgi complexes were colocalized with PTX-NCs in cells, so the ER-Golgi complexes/Golgi complexes-basolateral membrane pathway may be involved in the intracellular trafficking and transcytosis of PTX-NCs. It was demonstrated here that cav-1, dynamin, and actin filament modulated the endocytosis process, and Cdc 42 regulated the transcytosis process. In addition, no paracellular transport of PTX-NCs was observed. These findings demonstrated that the rod-like nanocrystals not only enhanced the transcytosis of PTX compared with microparticles of raw drug materials but also changed the pathways of drug delivery. This study certainly provides insight for the oral absorption mechanism of nanocrystals of poorly soluble drugs.


Hierarchical profiles of signaling pathways and networks reveal two complementary pharmacological mechanisms.
Until now the overlapping and diverse pharmacological protective mechanisms of different compounds in the treatment of cerebral ischemia, both on the signaling pathway and network levels have not been revealed. In order to find differential pathway networks from gene expression profiles of hippocampus of ischemic mice treated with baicalin (BA), ursodeoxycholic acid (UA) and jasminoidin (JA), a microarray comprising 16,463 genes, FDA Arraytrack software and Ingenuity Pathway Analysis, was employed. A total of 5, 8, 11, 9 networks and 6, 7, 40, 16 pathways were found in vehicle (vs sham), BA, UA and JA (vs vehicle), respectively. Only 4 and 7 overlapping pathways were shared between BA and UA, UA and JA, accounting for 9.3% and 14.3% of the total number of all pathways, respectively. BA, UA and JA all acted on Ca(2+)-dependent signaling cascades in diverse links. BA intervened in arachidonic acid metabolism. UA affected eicosanoid, cyclin-dependent kinase 5, nuclear factor-kB, and T-helper 1 cell cytokine production. It was found that JA might decrease oxidative damage via nuclear factor erythroid 2-related factor 2-mediated antioxidant response. Compared to vehicle, no overlapping pathways were found among three groups. However, the total of 60 (71.4%) overlapping functions could be approximately divided into diseases and disorders, molecular and cellular functions, physiological system development and function as categories with ratio of 1:1:1. Analysis of network functions and known pathways may be two complementary paradigms for revealing potential pharmacological mechanisms based on the same phenotype variation.


Identification and characterization of an extracellular envelope glycoprotein affecting vaccinia virus egress.
Sequence analysis of the vaccinia virus strain Western Reserve genome revealed the presence of an open reading frame (ORF), SalL4R, which has the potential to encode a transmembrane glycoprotein with homology to C-type animal lectins (G. L. Smith, Y. S. Chan, and S. T. Howard, J. Gen. Virol. 72:1349-1376, 1991). Here we show that the SalL4R gene is transcribed late during infection from a TAAATG motif at the beginning of the ORF. Antisera raised against a TrpE-SalL4R fusion protein identified three glycoprotein species of Mr 22,000 to 24,000 in infected cells. Immunogold electron microscopy demonstrated that SalL4R protein is present in purified extracellular enveloped virus particles but not in intracellular naked virus (INV). A mutant virus was constructed by placing a copy of the SalL4R ORF downstream of an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible vaccinia virus promoter within the thymidine kinase locus and subsequently deleting the endogenous SalL4R gene. The growth kinetics of this virus demonstrated that SalL4R was nonessential for the production of infectious INV but was required for virus dissemination. Consistent with this finding, the formation of wild-type-size plaques by this mutant was dependent on the presence of IPTG. Electron microscopy showed that without SalL4R expression, the inability of the virus to spread is due to a lack of envelopment of INV virions by Golgi-derived membrane, a morphogenic event required for virus egress.


Therapeutic silencing of KRAS using systemically delivered siRNAs.
Despite being among the most common oncogenes in human cancer, to date, there are no effective clinical options for inhibiting KRAS activity. We investigated whether systemically delivered KRAS siRNAs have therapeutic potential in KRAS-mutated cancer models. We identified KRAS siRNA sequences with notable potency in knocking down KRAS expression. Using lung and colon adenocarcinoma cell lines, we assessed antiproliferative effects of KRAS silencing in vitro. For in vivo experiments, we used a nanoliposomal delivery platform, DOPC, for systemic delivery of siRNAs. Various lung and colon cancer models were used to determine efficacy of systemic KRAS siRNA based on tumor growth, development of metastasis, and downstream signaling. KRAS siRNA sequences induced >90% knockdown of KRAS expression, significantly reducing viability in mutant cell lines. In the lung cancer model, KRAS siRNA treatment demonstrated significant reductions in primary tumor growth and distant metastatic disease, while the addition of CDDP was not additive. Significant reductions in Ki-67 indices were seen in all treatment groups, whereas significant increases in caspase-3 activity were only seen in the CDDP treatment groups. In the colon cancer model, KRAS siRNA reduced tumor KRAS and pERK expression. KRAS siRNAs significantly reduced HCP1 subcutaneous tumor growth, as well as outgrowth of liver metastases. Our studies demonstrate a proof-of-concept approach to therapeutic KRAS targeting using nanoparticle delivery of siRNA. This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional "undruggable" targets.


Gravimetric antigen detection utilizing antibody-modified lipid bilayers.
Lipid bilayers containing 5% nitrilotriacetic acid (NTA) lipids supported on SiO2 have been used as a template for immobilization of oligohistidine-tagged single-chained antibody fragments (scFvs) directed against cholera toxin. It was demonstrated that histidine-tagged scFvs could be equally efficiently coupled to an NTA-Ni2+-containing lipid bilayer from a purified sample as from an expression supernatant, thereby providing a coupling method that eliminates time-consuming protein prepurification steps. Irrespective of whether the coupling was made from the unpurified or purified antibody preparation, the template proved to be efficient for antigen (cholera toxin) detection, verified using quartz crystal microbalance with dissipation monitoring. In addition, via a secondary amplification step using lipid vesicles containing GM1 (the natural membrane receptor for cholera toxin), the detection limit of cholera toxin was less than 750 pM. To further strengthen the coupling of scFvs to the lipid bilayer, scFvs containing two histidine tags, instead of just one tag, were also evaluated. The increased coupling strength provided via the bivalent anchoring significantly reduced scFv displacement in complex solutions containing large amounts of histidine-containing proteins, verified via cholera toxin detection in serum.


Evaluation of Venous Structures that Are Involved in Transsylvian Approach Using 3D Rotational Venography.
In the transsylvian (TS) approach, as characterized by clipping surgery, the presurgical visualization of the superficial middle cerebral vein (SMCV) can help change the surgical approach to ensure safe microsurgery. Nevertheless, identifying preoperatively the venous structures that are involved in this approach is difficult. In this study, we investigated the venous structures that are involved in the TS approach using three-dimensional (3D) rotational venography (3D-RV) and evaluated the effectiveness of this method for presurgical simulation. Patients who underwent 3D-RV between August 2018 and June 2020 were involved in this retrospective study. The 3D-RV and partial maximum intensity projection images with a thickness of 5 mm were computationally reconstructed. The venous structures were subdivided into the following three portions according to the anatomic location: superficial, intermediate, and basal portions. In the superficial portion, predominant frontosylvian veins were observed on 31 (41%) sides, predominant temporosylvian veins on seven (9%) sides, and equivalent fronto- and temporosylvian veins on 28 (37%) sides. The veins in the intermediate (deep middle cerebral and uncal veins) and basal portions (frontobasal bridging veins) emptied into the SMCV on 57 (75%) and 34 (45%) sides, respectively. The 3D-RV images were highly representative of the venous structures observed during microsurgery. In this study, 3D-RV was utilized to capture the details of the venous structures from the superficial to the deep portions. Presurgical simulation of the venous structures that are involved in the TS approach using 3D-RV may increase the safety of microsurgical approaches.


The relationship of coffee consumption with mortality.
Coffee consumption has been linked to various beneficial and detrimental health effects, but data on its relation with mortality are sparse. To assess the association between coffee consumption and mortality from cardiovascular disease (CVD), cancer, and all causes during 18 years of follow-up in men and 24 years of follow-up in women. Sex-specific Cox proportional hazard models were used to investigate the association between coffee consumption and incidence of all-cause and disease-specific mortality in a prospective cohort study. Health Professionals Follow-up Study and Nurses' Health Study. 41,736 men and 86,214 women with no history of CVD or cancer at baseline. Coffee consumption was assessed first in 1986 for men and in 1980 for women and then every 2 to 4 years through 2004. Investigators documented 6888 deaths (2049 due to CVD and 2491 due to cancer) among men and 11,095 deaths (2368 due to CVD and 5011 due to cancer) among women. After adjustment for age, smoking, and other CVD and cancer risk factors, the relative risks for all-cause mortality in men across categories of coffee consumption (<1 cup per month, 1 cup per month to 4 cups per week, 5 to 7 cups per week, 2 to 3 cups per day, 4 to 5 cups per day, and >or=6 cups per day) were 1.0, 1.07 (95% CI, 0.99 to 1.16), 1.02 (CI, 0.95 to 1.11), 0.97 (CI, 0.89 to 1.05), 0.93 (CI, 0.81 to 1.07), and 0.80 (CI, 0.62 to 1.04), respectively (P for trend = 0.008). For women, the relative risks were 1.0, 0.98 (CI, 0.91 to 1.05), 0.93 (CI, 0.87 to 0.98), 0.82 (CI, 0.77 to 0.87), 0.74 (CI, 0.68 to 0.81), and 0.83 (CI, 0.73 to 0.95), respectively (P for trend < 0.001). This inverse association was mainly due to a moderately reduced risk for CVD mortality and was independent of caffeine intake. By contrast, coffee consumption was not statistically significantly associated with risk for cancer death after adjustment for potential confounders. Decaffeinated coffee consumption was associated with a small reduction in all-cause and CVD mortality. Coffee consumption was estimated from self-report; thus, some measurement error is inevitable. Regular coffee consumption was not associated with an increased mortality rate in either men or women. The possibility of a modest benefit of coffee consumption on all-cause and CVD mortality needs to be further investigated.


Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr'InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders.
Increases in oxidative stress have been reported to play a central role in the vulnerability to depression, and antidepressant drugs may reduce increased oxidative stress in patients. Among the plants exerting anti-inflammatory and anti-oxidant properties, saffron, a spice derived from the flower of Crocus sativus, is also known for its positive effects on depression, potentially through its SSRI-like properties. However, the molecular mechanisms underlying these effects and their health benefits for humans are currently unclear. Using an original ex vivo clinical approach, we demonstrated for the first time that the circulating human metabolites produced following saffron intake (Safr'InsideTM) protect human neurons from oxidative-stress-induced neurotoxicity by preserving cell viability and increasing BNDF production. In particular, the metabolites significantly stimulated both dopamine and serotonin release. In addition, the saffron's metabolites were also able to protect serotonergic tone by inhibiting the expression of the serotonin transporter SERT and down-regulating serotonin metabolism. Altogether, these data provide new biochemical insights into the mechanisms underlying the beneficial impact of saffron on neuronal viability and activity in humans, in the context of oxidative stress related to depression.


Ontogeny of vascular angiotensin II receptor subtype expression in ovine development.
Angiotensin II (ANG II) increases arterial pressure in fetal sheep and may modulate cardiovascular adaptation before and after birth. The type 1 angiotensin II receptor (AT1R) predominates in adult vascular smooth muscle (VSM) and mediates vasoconstriction. In contrast, AT2R predominate in fetal tissues and are not known to mediate contraction. Although sheep are commonly used to study cardiovascular development, the ontogeny and distribution of VSM ATR subtypes is unknown. We examined ATR binding characteristics and subtype expression across the umbilicoplacental vasculature and in aorta, carotid, and mesenteric arteries from fetal (n = 44; 126-145 d gestation) and postnatal (n = 65; 1-120 d from birth) sheep using plasma membranes from tunica media and tissue autoradiography. Binding density (Bmax) was similar throughout the umbilicoplacental vasculature (p = 0.5), but only external umbilical arteries and veins and primary placental arteries expressed AT1R, whereas subsequent placental branches and fetal placentomes expressed only AT2R. Systemic VSM Bmax and binding affinity did not change significantly during development (p > 0.1). Fetal systemic VSM, however, expressed only AT2R, and binding was insensitive to GTPgammaS. Transition to AT1R in systemic VSM began 2 wk postnatal and was completed by 3 mo. Before birth, umbilical cord vessels are the primary site of AT1R expression in fetal sheep, and AT2R seem to predominate in systemic VSM until 2-4 wk postnatal.


The Ilizarov method for correction of complex deformities. Psychological and functional outcomes.
We reviewed the psychological profile and functional ability of forty-five children (fifty-two extremities) who had had correction of deformities of the lower extremities with the Ilizarov method. Psychological changes were evaluated with the Post-Hospitalization Behavior Questionnaire and the Children's Depression Inventory, and the functional status was measured with the Children Health Information Service Rand Scale. The over-all satisfaction of the patient with regard to the outcome of the operation was assessed as well. The operations were performed between 1988 and 1992. The average age at the time of the operation was twelve years (range, three to eighteen years), and the average duration of follow-up was thirty-six months (range, twenty-four to seventy-two months). The lengthening index, duration of lengthening, and average number of complications were similar to those reported in other studies. All of the children had a normal psychological score, forty-two had no limitations in daily activities, and thirty-seven were satisfied with the over-all result.


Descriptors for binding energies at clusters: The case of nanosilicates as models of interstellar dust grains.
Binding energies of radicals and molecules at dust grain surfaces are important parameters for understanding and modeling the chemical inventory of interstellar gas clouds. While first-principles methods can reliably be used to compute such binding energies, the complex structure and varying sizes and stoichiometries of realistic dust grains make a complete characterization of all adsorption sites exposed by their surfaces challenging. Here, we focus on nanoclusters composed of Mg-rich silicates as models of interstellar dust grains and two adsorbates of particular astrochemical relevance; H and CO. We employ a compressed sensing method to identify descriptors for the binding energies, which are expressed as analytical functions of intrinsic properties of the clusters, obtainable through a single first-principles calculation of the cluster. The descriptors are identified based on a diverse training dataset of binding energies at low-energy structures of nanosilicate clusters, where the latter structures were obtained using a first-principles-based global optimization method. The composition of the descriptors reveals how electronic, electrostatic, and geometric properties of the nanosilicates control the binding energies and demonstrates distinct physical origins of the bond formation for H and CO. The predictive performance of the descriptors is found to be limited by cluster reconstruction, e.g., breaking of internal metal-oxygen bonds, upon the adsorption event, and strategies to account for this phenomenon are discussed. The identified descriptors and the computed datasets of stable nanosilicate clusters along with their binding energies are expected to find use in astrochemical models of reaction networks occurring at silicate grain surfaces.


A Therapeutic Target of Cerebral Hemorrhagic Stroke: Matrix Metalloproteinase- 9.
Cerebral hemorrhagic stroke, including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and hemorrhagic transformation after cerebral infarction, is a major medical emergency in the neurology, neurosurgery, emergency and other clinical departments. The pathophysiological mechanisms of these cerebral hemorrhagic diseases have not been fully elucidated, and there are no effective pharmacological and molecular treatments against these diseases. Matrix metalloproteinase-9 (MMP-9), also known as collagenase B, is one of the most important members of the matrix metalloproteinases (MMPs) family. This article reviews the role of MMP-9 in the pathogenesis of diseases such as brain hemorrhage, hemorrhagic transformation after cerebral infarction, SAH, and brain injury. The expression levels of MMP-9 in brain tissue increased after cerebral hemorrhage and related to the prognosis of brain hemorrhage. MMP-9 is related to post-thrombolytic hemorrhagic transformation after cerebral infarction. Inhibition of MMP-9 can reduce secondary brain injury after brain hemorrhage. MMP-9 aggravates the early brain injury and cerebral vasospasm after SAH. MMP-9 is involved in the pathological process of hemorrhagic stroke through a variety of mechanisms and is closely related to prognosis after cerebral hemorrhagic stroke.


Synthesis and Characterization of Gefitinib and Paclitaxel Mono and Dual Drug-Loaded Blood Cockle Shells (Anadara granosa)-Derived Aragonite CaCO3 Nanoparticles.
Calcium carbonate has slowly paved its way into the field of nanomaterial research due to its inherent properties: biocompatibility, pH-sensitivity, and slow biodegradability. In our efforts to synthesize calcium carbonate nanoparticles (CSCaCO3NP) from blood cockle shells (Anadara granosa), we developed a simple method to synthesize CSCaCO3NP, and loaded them with gefitinib (GEF) and paclitaxel (PTXL) to produce mono drug-loaded GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and dual drug-loaded GEF-PTXL-CSCaCO3NP without usage of toxic chemicals. Fourier-transform infrared spectroscopy (FTIR) results reveal that the drugs are bound to CSCaCO3NP. Scanning electron microscopy studies reveal that the CSCaCO3NP, GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and GEF-PTXL-CSCaCO3NP are almost spherical nanoparticles, with a diameter of 63.9 ± 22.3, 83.9 ± 28.2, 78.2 ± 26.4, and 87.2 ± 26.7 (nm), respectively. Dynamic light scattering (DLS) and N2 adsorption-desorption experiments revealed that the synthesized nanoparticles are negatively charged and mesoporous, with surface areas ranging from ~8 to 10 (m2/g). Powder X-ray diffraction (PXRD) confirms that the synthesized nanoparticles are aragonite. The CSCaCO3NP show excellent alkalinization property in plasma simulating conditions and greater solubility in a moderately acidic pH medium. The release of drugs from the nanoparticles showed zero order kinetics with a slow and sustained release. Therefore, the physico-chemical characteristics and in vitro findings suggest that the drug loaded CSCaCO3NP represent a promising drug delivery system to deliver GEF and PTXL against breast cancer.


The effect of anorectal manometric examination on the surgical treatment plan in chronic anal fissure.
Although lateral internal sphincterotomy (LIS) is the most preferred surgical treatment for chronic anal fissure, In this study, we aimed to investigate the effect of preoperative anorectal manometry on surgical treatment choice in patients presenting with anal fissure. Between January-2015 and August-2017 and whose physical examination revealed chronic anal fissure findings were included in the study. Patients were divided into two groups as Group 1 LIS and Group 2 non-LIS. In addition to the demographic characteristics of the patients, anal manometry findings and its effect on surgical treatment options were examined. 20 patients (M/F:13/7) were included in the study. The mean age was 48.3+17.4 in Group 1 and 45.25 +24.45 in Group 2 (p:0.797). In the preoperative manometric examination, resting pressure(mmHg) range was 93.2+15.9 in Group 1, and44+11.2 in Group 2 (30-57) (p:0.001). Endurance to squeezing time was shorter in Group 2 (p:0.0138). There were no differences between the groups in terms of mean squeezing pressure, rectal sensation, and rectoanal inhibitor reflex (p>0.05). Of the four patients with low sphincter pressures, 3 underwent botulinum toxin injection and 1 underwent advancement flap instead of LIS. There was no significant difference between preoperative and postoperative CCFI scores in the LIS group (0.6±1.8 vs. 1.2±1.85, p>0.05). In the treatment of chronic anal fissure, non-LIS methods were selected in 20% of the patients with the help of preoperative anal manometric examination. Manometric examination is important to minimize the risk of incontinence and to determine the choice of treatment correctly. Anal fissure, Anal incontinence, Anal manometry.


[Assessment of efficacy of endarterectomy of coronary arteries].
Results of coronary artery bypass grafting (CABG) with coronary endarterectomy (CE) are analyzed. The study group consisted of 97 patients who has undergone ACB with CE, control group--102 patients after ACB without CE. There were no differences in clinical state of the patients early (30 days) and late (1-2 years) after surgery. Computed tomography was used for detection of coronary bypass patency. In long-term period of follow-up (60 patients) autoarterial shunts were occluded in 3% cases in the study group and in 5% cases in the control one. Autovenous shunts were occluded in 36 and 27% cases respectively. These results demonstrate necessity of CE in CABG.


[Prognosis of mild dementia based on catamnestic study of the population].
A clinico-catamnestic investigation of a group of patients with initial psychoorganic changes qualified at first examination as the "soft" dementia and "accelerated mental aging", attributed the states of "soft" dementia a high value in prediction of manifested senile dementia. Predictive value of a complex of signs classified as "accelerated mental aging" was ambiguous.


Laboratory-based investigation of the materials' water activity and pH relative to fungal growth in internally insulated solid masonry walls.
This project investigated fungal growth conditions in artificially contaminated interfaces between solid masonry and adhesive mortar for internal insulation. The project comprised several laboratory experiments: test of three fungal decontamination methods; investigation of development of fungal growth in solid masonry walls fitted with five internal insulation systems; and investigation of volatile organic compounds (VOC) diffusion through materials and whole insulation systems. One aim was to examine whether the alkaline environment (pH > 9) in the adhesive mortars could prevent fungal growth despite the water activity (aw ) in the interface exceeds the level (aw > 0.75) commonly considered critical for fungal growth. The findings indicate that do-it-yourself decontamination solutions were inadequate for removal of fungal growth, while professional solutions were successful. However, the choice of decontamination method was of minor importance in the case of application of internal insulation with high pH adhesive mortar, as the high pH adhesive mortars were found to inactivate existing growth and prevented spore germination during the experimental period. The three tested VOCs were capable of diffusing through most of the examined products and could potentially affect the indoor air quality.


Comparison of Treatment Modalities for Locally Advanced Gastric Cancer: A Propensity Score Matching Analysis.
Background: A consensus regarding optimum treatment strategies for locally advanced gastric cancer (LAGC) has not yet been reached. We aimed to evaluate the efficacy of various treatment modalities for LAGC and provided clinicians salvage options under real-world situation. Methods: Medical charts of patients with LAGC who underwent radical resection plus adjuvant chemotherapy or chemoradiotherapy from July 2003 to December 2014 were included. Validation cohort were selected from SEER database between 2004 and 2014. Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results: A total of 350 patients were included and divided into D1 dissection plus chemotherapy group (D1CT, n = 74), D1 dissection plus adjuvant chemoradiotherapy group (D1CRT, n = 69), D2 dissection plus adjuvant chemotherapy group (D2CT, n = 134), and D2 dissection plus adjuvant chemoradiotherapy group (D2CRT, n = 73). PSM identified 50 patients in each group. After PSM, better DFS (P for D2CRT vs. D1CT, D1CRT, and D2CT was 0.001, 0.006, and 0.001, respectively) and OS (P for D2CRT vs. D1CT, D1CRT, and D2CT was 0.001, 0.011, and 0.022, respectively) were found for the D2CRT group (mean, OS = 110.7months, DFS = 95.2 months) than the other groups. Similar findings were further validated in the Surveillance, Epidemiology, and End Results database (SEER) cohort. In addition, patients in the D1CRT group achieved similar survival outcomes to those in the D2CT group (mean OS, 72.8 vs. 59.1 months, P = 0.86; mean DFS, 54.4 vs. 34.1 months, P = 0.460). Conclusions: The results of the study indicated the better role for D2CRT in treating the LAGC, meanwhile, the patients treated with D1CRT might achieve similar survival as that of D2CT patients.


Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit.
This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). The most important risks of hypnotics include excess mortality, especially overdose deaths, quiet deaths at night, infections, cancer, depression and suicide, automobile crashes, falls, and other accidents, and hypnotic-withdrawal insomnia. Short-term use of one-two prescriptions is associated with greater risk per dose than long-term use. Hypnotics have usually been prescribed without approved indication, most often with specific contraindications, but even when indicated, there is little or no benefit. The recommended doses objectively increase sleep little if at all, daytime performance is often made worse, not better, and the lack of general health benefits is commonly misrepresented in advertising. Treatments such as the cognitive behavioral treatment of insomnia and bright light treatment of circadian rhythm disorders offer safer and more effective alternative approaches to insomnia.


Quantitative assessment of lung microstructure in healthy mice using an MR-based 3He lung morphometry technique.
The recently developed technique of lung morphometry using hyperpolarized (3)He diffusion magnetic resonance (MR) (Yablonskiy DA, Sukstanskii AL, Woods JC, Gierada DS, Quirk JD, Hogg JC, Cooper JD, Conradi MS. J Appl Physiol 107: 1258-1265, 2009) permits in vivo study of lung microstructure at the alveolar level. Originally proposed for human lungs, it also has the potential to study small animals. The technique relies on theoretical developments in the area of gas diffusion in lungs linking the diffusion attenuated MR signal to the lung microstructure. To adapt this technique to small animals, certain modifications in MR protocol and data analysis are required, reflecting the smaller size of mouse alveoli and acinar airways. This is the subject of the present paper. Herein, we established empirical relationships relating diffusion measurements to geometrical parameters of lung acinar airways with dimensions typical for mice and rats by using simulations of diffusion in the airways. We have also adjusted the MR protocol to acquire data with much shorter diffusion times compared with humans to accommodate the substantially smaller acinar airway length. We apply this technique to study mouse lungs ex vivo. Our MR-based measurements yield mean values of lung surface-to-volume ratio of 670 cm(-1), alveolar density of 3,200 per mm(3), alveolar depth of 55 μm, and mean chord length of 62 μm, all consistent with published data obtained histologically in mice by unbiased methods. The proposed technique can be used for in vivo experiments, opening a door for longitudinal studies of lung morphometry in mice and other small animals.


Evaluation of an automated method for analysing the electromyogram.
An automated system, incorporating the ANOPS-101 mini-computer, has been used to analyse the EMG. The vastus medialis (VM) and biceps brachii (BB) muscles were studied in 28 controls, 16 patients with myopathies, and in 26 patients with denervating disorders. For each muscle mean values were computed for the durations and numbers of phases of muscle action potentials; the mean density and amplitude of the deflections in the interference pattern were also measured. A higher incidence of abnormalities could be detected in myopathic than in neuropathic disorders; for both conditions the incidence was significantly greater in BB than in VM. For the diagnosis of denervation the most useful measurement was that of potential duration; for the detection of myopathies amplitude determinations were also very useful. The present results have been compared with those of other published studies in which automatic EMG analysis has been employed.


Validation of a simple spectrophotometric method for the rapid determination of salicylates in plasma.
The determination of salicylate concentrations constitutes a critical aspect of medical diagnostics, particularly in emergency settings. High-performance liquid chromatography (HPLC) and spectrophotometry are efficient methods commonly utilized for this purpose. In emergency laboratories with limited resources, the validation of a cost-effective and reliable spectrophotometric method for salicylates in plasma becomes imperative. The present study aims to validate such a method, ensuring its applicability in toxicological emergencies within resource-constrained laboratories. The proposed spectrophotometric analysis relies on detecting salicylic ions amidst the presence of ferric salts, resulting in the formation of a distinct purple chelate complex. To ascertain the method's credibility, the validation guidelines established by the European Medicines Agency (EMA) were employed as a benchmark. A comprehensive validation process was conducted over a three-day period, with three levels of validation standards being considered. Following the EMA protocol, the spectrophotometric method demonstrated commendable fidelity, accuracy, and linearity over a concentration range of 50 to 500 mg/L. The limit of detection and quantification was found to be 10 and 50 mg/L, respectively, and the correlation coefficient was determined to be R2 = 0.998. However, it is essential to acknowledge that interference with phenothiazines occurred at concentrations ranging from 50 to 100 mg/L. Despite this, the method's average sensitivity remains viable for practical use in cases of poisoning. The accuracy per concentration level proved satisfactory, with relative biases remaining below 15%, and the confidence intervals of mean recovery closely approximating the desired target value of 100%. In conclusion, the presented spectrophotometric method stands out as an economical, straightforward, and user-friendly approach, ideally suited for toxicological emergencies when resources are limited. The method delivers satisfying results, establishing its practical utility in critical medical scenarios. This validated method holds immense promise for emergency laboratories facing resource constraints.


Direct determination of rosmarinic acid in Lamiaceae herbs using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and chemometrics.
For the determination of rosmarinic acid (RA) directly in pulverized plant material, a method is developed using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) without any physicochemical pretreatment of samples. The RA content of 11 samples of eight different Lamiaceae herbs, as determined by high performance liquid chromatography (HPLC), varied between 86 ± 1 mg/g (in lemon balm) and 12.0 ± 0.8 mg/g (in hyssop) of dried plant material. The 11 samples and 50 other additional samples, which were prepared by mixing initial samples with KBr, were measured using DRIFTS. The second derivative of the spectral region 1344-806 cm(-1) was used and the corresponding data were analyzed using partial least squares (PLS) regression. The correlation between infrared spectral analysis and HPLC measurements shows that the DRIFTS method is sufficiently accurate, simple, and rapid. The RA content of the 11 Lamiaceae samples determined by DRIFTS ranged from 81 ± 4 mg/g (in lemon balm) to 12 ± 3 mg/g (in hyssop) of dried plant material.


[Experience of cooperation between Occupational Diseases Department in the Rostov State Medical University and Occupational Diseases Center with Health Ministry Department of the Rostov region].
Over 35 years Occupational Diseases Department in Rostov State Medical University works cooperatively with Occupational Diseases Center with Health Ministry Department of Rostov region. The article deals with experience of this cooperation in occupational therapists training, in qualification courses for professional improvement, in writing scientific and methodic materials, in carrying research work based on the Occupational Center facilities.


Effects of treatment with pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.
Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte function and inhibits tumor necrosis factor (TNF)-alpha release. As TNF-alpha is considered a proximal mediator in the cascade leading to septic shock, we evaluated the ability of PTXF to attenuate the cardiovascular manifestations of sepsis secondary to an infusion of group B beta-hemolytic streptococci (GBS). Fifteen anesthetized, mechanically ventilated piglets (weight, 2815 +/- 552 g) were randomly assigned to a treatment group which received a continuous infusion of PTXF (5 mg/kg/h) beginning 30 min after GBS (7.5 x 10(8) colony-forming units/kg/min) administration was started or to a control group which received GBS plus saline as placebo. Comparison of the hemodynamic measurements and arterial blood gases over the first 120 min of bacterial infusion for treatment and control groups revealed the following statistically significant differences (120-min values presented): cardiac output was significantly higher in the PTXF group (0.159 +/- 0.035 versus 0.09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and systemic vascular resistances remained lower in the PTXF-treated animals (167 +/- 45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versus 828 +/- 426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an additional group of animals, PTXF administration before GBS infusion revealed no attenuation in the rise of TNF-alpha, accompanying sepsis. These data demonstrate that treatment with PTXF may ameliorate some of the deleterious hemodynamic manifestations of GBS sepsis and result in improved survival in a young animal model without significantly modifying plasma TNF-alpha levels.


Highlights from the Innovations in Cardiovascular Interventions Meeting: in favor of creativity and ingenuity.
The annual Innovations in Cardiovascular Interventions Meeting was organized in close collaboration with the Cardiovascular Research Foundation and was co-sponsored by the Society for Coronary Angiography and Interventions. The meeting was co-chaired by Rafael Beyar and Chaim Lotan, and took place in Tel Aviv, Israel, on 6-8 December 2009. It was a continuation of the series of international conferences in interventional cardiology held in Israel since 1995. The meeting is distinctive in that it provides a wide perspective on the innovative technologies and therapies for cardiovascular applications. Unique sessions covering emerging technologies, relationships between academia and industry, as well as regulatory aspects of medical devices provided participants with a wide perspective on current and future technologies. The Innovations in Cardiovascular Interventions Meeting was attended by over 700 participants from over 40 countries, including cardiologists, surgeons, nurses, pharmacists and allied health professionals. The world's leading experts in the field of interventional cardiology, cardiac surgery and radiology presented the latest information on innovative diagnostic and treatment modalities for cardiovascular pathology, and delivered expert lectures and clinical overviews, as well as presentations on the advances and controversies in basic, translational and clinical research. The meeting was accompanied by thematic live cases and a parade of new technology companies. Innovations in Cardiovascular Interventions Meeting 2009 presentations are available to watch and download at www.congress.co.il/ici2009 .


Sex attraction in paper wasp,Polistes exclamans viereck (Hymenoptera: Vespidae), in a wind tunnel.
A wind-tunnel bioassay was developed to test for the presence of sex attractants in the paper wasp,Polistes exclamans Viereck (Hymenoptera: Vespidae). Males exhibited significant upwind flight and attraction (chemoanemotaxis) in response to airflow passed over unmated females, and to hexane extracts of whole bodies and thoraces of unmated females. Unmated females were attracted to hexane extracts of males and to hexane extracts of each body tagma of males, suggesting distribution of the pheromone over the cuticle by grooming. The ectal mandibular and seventh sternal glands are the likely sources of the male-produced sex attractant(s) since extracts of each elicited female attraction in the flight tunnel. These glands are associated with gastral and mandibular rubbing of perch sites by territorial males ofPolistes species.


Different menopausal hormone regimens and risk of breast cancer.
There are considerable knowledge gaps concerning different estrogen and progestin formulations, regimens, and modes of administration of menopausal hormone therapy (HT) and the risk of breast cancer. Our objective was to assess the different treatment options for menopausal HT and the risk of breast cancer. This Swedish prospective nationwide cohort study included all women who received ≥1 HT prescription during the study period 2005-2012 (290 186 ever-users), group-level matched (1 : 3) to 870 165 never-users; respectively, 6376 (2.2%) and 18 754 (2.2%) developed breast cancer. HT, ascertained from the Swedish Prescribed Drug Register, was subdivided by estrogen and progestogen formulation types, regimens (continuous versus sequential) and modes of administration (oral versus transdermal). The risk of invasive breast cancer was presented as adjusted odds ratios (OR) and 95% confidence intervals. Current use of estrogen-only therapy was associated with a slight excess breast cancer risk [odds ratio (OR) = 1.08 (1.02-1.14)]. The risk for current estrogen plus progestogen therapy was higher [OR = 1.77 (1.69-1.85)] and increased with higher age at initiation [OR = 3.59 (3.30-3.91) in women 70+ years]. In contrast, past use was associated with reduced breast cancer risk. Current continuous estrogen/progestin use was associated with higher risk [OR = 2.18 (1.99-2.40) for progesterone-derived; OR = 2.66 (2.49-2.84) for testosterone-derived] than sequential use [OR = 1.37 (0.97-1.92) for progesterone-derived; OR = 1.12 (0.96-1.30) for testosterone-derived]. The OR for current use was 1.12 (1.04-1.20) for estradiol, 0.76 (0.69-0.84) for estriol, 4.47 (2.67-7.48) for conjugated estrogens, and 1.68 (1.51-1.87) for tibolone. Oral and cutaneous HT showed similar associations. Different HT regimens have profoundly different effects on breast cancer risk. Because of registry limitations some confounders could not be assessed. This knowledge may guide clinical decision-making when HT is considered.


Aspiration cytology of primary thyroid paraganglioma.
Thyroid paragangliomas are extremely rare tumors arising from the inferior laryngeal paraganglia. Most patients are female and present as asymptomatic thyroid nodule. Diagnosing thyroid paraganglioma can be difficult on fine-needle aspiration (FNA) since it could be misdiagnosed as medullary thyroid carcinoma, calcitonin-negative neuroendocrine tumor of the thyroid gland (CNNETT), metastatic neuroendocrine tumor, and intrathyroid parathyroid proliferation. We describe the cytologic features and immunohistochemical staining pattern of thyroid paraganglioma from a 60-year-old woman with a gradually enlarging neck mass for several months. An ultrasound guided fine-needle aspiration was performed which revealed epithelioid, plasmacytoid to occasionally spindle-shaped cells with ovoid to elongated nuclei, fine chromatin pattern and inconspicuous nucleoli. The cells were arranged singly, in sheets, and focally in acinar pattern. Occasional nuclear overlapping, crush artifact, and binucleated cells were identified. Neither colloid nor amyloid was seen. Immunohistochemical stains performed on the cell block showed the tumor cells were positive for neuroendocrine markers and negative for cytokeratin (AE1/AE3), calcitonin, CEA, thyroglobulin, and TTF-1. There were rare S-100 positive cells. Given the difference in management of paragangliomas compared to its cytology mimics and association with familial cancer syndromes in some cases, awareness of this rare tumor, and use of immunohistochemical stains are critical in arriving at the diagnosis.


Differences in CuZn superoxide dismutase induction in lungs of neonatal and adult rats.
The failure of adult rats to survive prolonged exposure to greater than 95% O2 is generally ascribed to the inability of their lungs to increase antioxidant enzyme synthesis in response to the oxidant challenge. We studied the synthesis rate of the antioxidant enzyme CuZn superoxide dismutase (CuZn SOD) in lungs of adult and neonatal rats exposed to conditions that alter the lung's oxidant-to-antioxidant balance. Lung CuZn SOD synthesis in the adult was significantly increased after 24 h of hyperoxia but fell to control levels after further exposure, whereas in neonatal lungs an increased rate of synthesis of CuZn SOD was found only after 72 h of hyperoxia. The adult lung responded to two in vitro oxidant stresses, [diethyldithiocarbamate exposure and heat (42 degrees C)] with increases in CuZn SOD synthesis twice the magnitude of those in the neonatal lung. These data indicate that the adult lung is at least as capable as the neonatal lung of increasing its synthesis of CuZn SOD in response to an oxidative stress. However, the inability of the adult lung to maintain an increased rate of CuZn SOD synthesis during in vivo hyperoxia may contribute to the poor tolerance of the adult lung to greater than 95% O2.


Laser-Induced MoOx/Sulfur-Doped Graphene Hybrid Frameworks as Efficient Antibacterial Agents.
Rational design and scalable construction of antibacterial mediators based on unique graphene architectures with highly efficient antibacterial ability and significant biocompatibility are challenging. Herein, sulfur-doped graphene skeletons uniformly decorated with metal oxide nanoparticles were designed and constructed via one-step laser-induced microexplosive techniques and demonstrated for the first time as highly efficient antibacterial agents. The optical density and flat colony counting methods demonstrated that the as-designed laser-induced MoOx/sulfur-doped graphene hybrids exhibited exceptional activity inhibition of Escherichia coli and Staphylococcus aureus. Moreover, the bacteria were treated with an impressive laser-induced MoOx/sulfur-doped graphene colloidal solution of concentration as low as 1 mg/mL for 4 h, leading to an excellent viability loss of 85% for the two bacteria. Cell toxicity experiments proved that the biological toxicity of laser-induced MoOx/sulfur-doped graphene to pig sperm cells was negligible. The molecular dynamics calculations proposed that the intrinsic interaction with N-acetylglucosamine at the cell wall and the high-efficiency synergistic effect of sulfur-doped graphene and MoOx played the key role in inhibiting the viability of bacteria. This work provides new insights for a novel structure design and opens up a potential route to construct antibacterial agents with high efficiency for clinical application.


The evolution from life insurance to financial engineering.
Since the mid-1980s, the share of household net worth intermediated by US financial institutions has shifted from defined benefit plans to life insurers and defined contribution plans. Life insurers have primarily grown through variable annuities, which are mutual funds with longevity insurance, a potential tax advantage, and minimum return guarantees. The minimum return guarantees change the primary function of life insurers from traditional insurance to financial engineering. Variable annuity insurers are exposed to interest and equity risk mismatch and their stock returns were especially low during the COVID-19 crisis. We consider regulatory changes, such as more detailed financial disclosure and standardized stress tests, to monitor potential risk mismatch and to ensure stability of the insurance sector.


Limited haplotype diversity underlies polygenic trait architecture across 70 years of wheat breeding.
Selection has dramatically shaped genetic and phenotypic variation in bread wheat. We can assess the genomic basis of historical phenotypic changes, and the potential for future improvement, using experimental populations that attempt to undo selection through the randomizing effects of recombination. We bred the NIAB Diverse MAGIC multi-parent population comprising over 500 recombinant inbred lines, descended from sixteen historical UK bread wheat varieties released between 1935 and 2004. We sequence the founders' genes and promoters by capture, and the MAGIC population by low-coverage whole-genome sequencing. We impute 1.1 M high-quality SNPs that are over 99% concordant with array genotypes. Imputation accuracy only marginally improves when including the founders' genomes as a haplotype reference panel. Despite capturing 73% of global wheat genetic polymorphism, 83% of genes cluster into no more than three haplotypes. We phenotype 47 agronomic traits over 2 years and map 136 genome-wide significant associations, concentrated at 42 genetic loci with large and often pleiotropic effects. Around half of these overlap known quantitative trait loci. Most traits exhibit extensive polygenicity, as revealed by multi-locus shrinkage modelling. Our results are consistent with a gene pool of low haplotypic diversity, containing few novel loci of large effect. Most past, and projected future, phenotypic changes arising from existing variation involve fine-scale shuffling of a few haplotypes to recombine dozens of polygenic alleles of small effect. Moreover, extensive pleiotropy means selection on one trait will have unintended consequences, exemplified by the negative trade-off between yield and protein content, unless selection and recombination can break unfavorable trait-trait associations.


Are telehealth technologies for hypertension care and self-management effective or simply risky and costly?
Hypertension is a prevalent chronic disease that requires ongoing management and self-care. The disease affects 31% of American adults and contributed to or caused the deaths of 348,000 Americans in 2008, fewer than 50% of whom effectively self-managed the disease. However, self-management is complex, with patients requiring ongoing support and easy access to care. Telehealth may help foster the knowledge and skills necessary for those with hypertension to engage in successful self-management. This paper considers the applicability, efficacy, associated risks, and cost-effectiveness of telehealth for individuals and populations with hypertension. Telehealth is a broad term, encompassing telemedicine and mobile health that is used for physician-patient interactions, diagnostics, care delivery, education, information sharing, monitoring, and reminders. Telemedicine may have considerable utility for people diagnosed with hypertension who have poor access or social barriers that constrain access, but potential risks exist. Telehealth technology is evolving rapidly, even in the absence of fully proven cost-effectiveness and efficacy. Considering the cost of inpatient and emergency department care for patients with hypertension, telehealth is a highly attractive alternative, but there are risks to consider. Incorporating telehealth, which is increasingly characterized by mobile health, can increase both the capacity of health care providers and the reach of patient support, clinical management, and self-care. Telehealth studies need improvement; long-term outcome data on cardiovascular events must be obtained, and robust risk analyses and economic studies are needed to prospectively evaluate the safety and cost savings for hypertension self-management.


Quality of work life and its association with workplace violence of the nurses in emergency departments.
Nurses as the major group of health service providers need to have a satisfactory quality of work life in order to give desirable care to the patients. Workplace violence is one of the most important factors that cause decline in the quality of work life. This study aimed to determine the quality of work life of nurses in selected hospitals of Isfahan University of Medical Sciences and its relationship with workplace violence. This was a descriptive-correlational study. A sample of 186 registered nurses was enrolled in the study using quota sampling method. The research instrument used was a questionnaire consisting of three parts: Demographic information, quality of work life, and workplace violence. Collected data were analyzed using descriptive and inferential statistics by SPSS version 16. The subjects consisted of 26.9% men and 73.1% women, whose mean age was 33.76 (7.13) years. 29.6% were single and 70.4% were married. About 76.9% of the subjects were exposed to verbal violence and 26.9% were exposed to physical violence during past year. Mean score of QNWL was 115.88 (30.98). About 45.7% of the subjects had a low level of quality of work life. There was an inverse correlation between the quality of work and the frequency of exposures to workplace violence. According to the results of this study, it is suggested that the managers and decision makers in health care should plan strategies to reduce violence in the workplace and also develop a program to improve the quality of work life of nurses exposed to workplace violence.


Optimization of ex vivo inducible nitric oxide synthase gene transfer to vein grafts.
Vein graft failure as the result of intimal hyperplasia (IH) remains a significant clinical problem. Ex vivo modification of vein grafts using gene therapy is an attractive approach to attenuate IH. Gene transfer of the inducible nitric oxide synthase (iNOS) gene effectively reduces IH. However, iNOS activity after gene transfer may be impaired by the availability of cofactor, such as tetrahydrobiopterin (BH4). The purpose of this study is to determine the optimal conditions for ex vivo adenoviral-mediated iNOS gene transfer into arterial and venous vessels. Porcine internal jugular veins and carotid arteries were infected ex vivo with the adenoviral iNOS vector (AdiNOS) and with an adenovirus carrying the cDNA encoding guanosine triphosphate cyclohydrolase I (AdGTPCH), the rate-limiting enzyme for BH4 synthesis. The production of nitrite, cyclic guanosine monophosphate (cGMP), and biopterin were assessed daily. Nitric oxide (NO) production after iNOS gene transfer was maximal when vessels were cotransduced with AdGTPCH. NO production in these vessels persisted for more than 10 days. Vein segments generated approximately 2-fold more nitrite, cGMP, and biopterin than arterial segments infected with AdiNOS/AdGTPCH. Submerging vein segments into adenoviral solution resulted in improved gene transfer with greater nitrite and cGMP release compared with infections carried out under pressure intraluminally. Similarly, injury to the vein segments before infection with AdiNOS resulted in less nitrite production. These data demonstrate that AdiNOS can efficiently transduce vein segments ex vivo and that the cotransfer of GTPCH can optimize iNOS enzymatic activity. This cotransfer technique may be used to engineer vein grafts before coronary artery bypass to prevent IH.


RegR virulence regulon of rabbit-specific enteropathogenic Escherichia coli strain E22.
AraC-like regulators play a key role in the expression of virulence factors in enteric pathogens, such as enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli, enteroaggregative E. coli, and Citrobacter rodentium. Bioinformatic analysis of the genome of rabbit-specific EPEC (REPEC) strain E22 (O103:H2) revealed the presence of a gene encoding an AraC-like regulatory protein, RegR, which shares 71% identity to the global virulence regulator, RegA, of C. rodentium. Microarray analysis demonstrated that RegR exerts 25- to 400-fold activation on transcription of several genes encoding putative virulence-associated factors, including a fimbrial operon (SEF14), a serine protease, and an autotransporter adhesin. These observations were confirmed by proteomic analysis of secreted and heat-extracted surface-associated proteins. The mechanism of RegR-mediated activation was investigated by using its most highly upregulated gene target, sefA. Transcriptional analyses and electrophoretic mobility shift assays showed that RegR activates the expression of sefA by binding to a region upstream of the sefA promoter, thereby relieving gene silencing by the global regulatory protein H-NS. Moreover, RegR was found to contribute significantly to virulence in a rabbit infection experiment. Taken together, our findings indicate that RegR controls the expression of a series of accessory adhesins that significantly enhance the virulence of REPEC strain E22.


[Hepatoprotectors in treatment of alcoholic liver disease].
The best hepatoprotective effect has combined appointment Essentiale forte N, Heptral and Apilak at rats with chronic alcohol intoxication. Use of these drugs is characterized by minor morphological changes in structure of liver and constant biochemical parameters.


Intracellular Transport Routes for MHC I and Their Relevance for Antigen Cross-Presentation.
Cross-presentation, in which exogenous antigens are presented via MHC I complexes, is involved both in the generation of anti-infectious and anti-tumoral cytotoxic CD8(+) T cells and in the maintenance of immune tolerance. While cross-presentation was described almost four decades ago and while it is now established that some dendritic cell (DC) subsets are better than others in processing and cross-presenting internalized antigens, the involved molecular mechanisms remain only partially understood. Some of the least explored molecular mechanisms in cross-presentation concern the origin of cross-presenting MHC I molecules and the cellular compartments where antigenic peptide loading occurs. This review focuses on MHC I molecules and their intracellular trafficking. We discuss the source of cross-presenting MHC I in DCs as well as the role of the endocytic pathway in their recycling from the cell surface. Next, we describe the importance of the TAP peptide transporter for delivering peptides to MHC I during cross-presentation. Finally, we highlight the impact of innate immunity mechanisms on specific antigen cross-presentation mechanisms in which TLR activation modulates MHC I trafficking and TAP localization.


Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.
To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.


Proteomics to unravel platelet-related diseases and identify novel anti-platelet drugs.
Blood platelets play a fundamental role in primary haemostasis and wound repair, but are also involved in several thrombotic and bleeding disorders for which the underlying mechanisms are still largely unknown. Elucidating platelet biology would help in finding novel disease biomarkers and drug targets in complex and/or genetically unknown platelet-related disorders. Proteomics, which allows studying thousands of gene products at once, represents an efficient tool to quali-quantitatively analyze and compare the platelet protein patterns of different samples (i.e. control/patient, treated/untreated, drug sensitive/resistant), to investigate post-translation modifications, protein-protein interactions and the underlying molecular pathways. This review gives an overview of the applications of proteomic strategies to study platelet biology and function, as well as to unravel differences in protein expression according to specific platelet conditions (i.e. basic versus activated), compartments (i.e. membrane or granules) and fractions (i.e. phosphoproteins and glycoproteins). The use of innovative powerful proteomic technologies can lead to the identification of proteins whose expression is altered in pathological conditions, allowing the identification of candidate biomarkers for: i) understanding the molecular defects underlying platelet disorders, ii) obtaining novel insights in more complex diseases that involve platelets, iii) unraveling the drug mode of action or identifying the mechanisms of drug resistance and iv) detecting novel therapeutic antiplatelet targets based on fundamental platelet research studies. Several studies on how proteomics proved to be useful in our understanding of platelet function and its diseases are discussed. Eventually, this could result in the discovery of novel drug targets for antiplatelet therapy.


Power of confinement: adsorbate dynamics on nanometer-scale exposed facets.
The diffusion and arrangements of CO adsorbates within nanometer-scale pores on a copper surface are investigated by low-temperature scanning tunneling microscopy. In contrast to extended terraces, confinement stabilizes dislocation lines that expose more than one-fourth of the adsorbate population to potentially more reactive adsorption configurations. Confinement allows correlation between adsorbate diffusivity and the number of adsorbates in the pore. A marked increase is found that coincides with the absence of dense films on the exposed facets. In combination, we find that in confinement CO molecules are much more likely to be at adsorption sites that allow lateral access, in contrast to the dense and uniform films on extended terraces.


Multilevel drivers of human immunodeficiency virus/acquired immune deficiency syndrome among Black Philadelphians: exploration using community ethnography and geographic information systems.
Unequal human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) distribution is influenced by certain social and structural contexts that facilitate HIV transmission and concentrate HIV in disease epicenters. Thus, one of the first steps in designing effective community-level HIV/AIDS initiatives is to disentangle the influence of individual, social, and structural factors on HIV risk. Combining ethnographic methodology with geographic information systems mapping can allow for a complex exploration of multilevel factors within communities that facilitate HIV transmission in highly affected areas. We present the formative comparative community-based case study findings of an investigation of individual-, social-, and structural-level factors that contribute to the HIV/AIDS epidemic among Black Philadelphians. Communities were defined using census tracts. The methodology included ethnographic and geographic information systems mapping, observation, informal conversations with residents and business owners, and secondary analyses of census tract-level data in four Philadelphia neighborhoods. Factors such as overcrowding, disadvantage, permeability in community boundaries, and availability and accessibility of health-related resources varied significantly. Furthermore, HIV/AIDS trended with social and structural inequities above and beyond the community's racial composition. This study was a first step to disentangle relationships between community-level factors and potential risk for HIV in an HIV epicenter. The findings also highlight stark sociodemographic differences within and across racial groups and further substantiate the need for comprehensive, community-level HIV prevention interventions. These findings from targeted U.S. urban communities have potential applicability for examining the distribution of HIV/AIDS in broader national and international geosocial contexts.


Hybrids between the Florida amphioxus (Branchiostoma floridae) and the Bahamas lancelet (Asymmetron lucayanum): developmental morphology and chromosome counts.
The cephalochordate genera Branchiostoma and Asymmetron diverged during the Mesozoic Era. In spite of the long separation of the parental clades, eggs of the Florida amphioxus, B. floridae, when fertilized with sperm of the Bahamas lancelet, A. lucayanum (and vice versa), develop through embryonic and larval stages. The larvae reach the chordate phylotypic stage (i.e., the pharyngula), characterized by a dorsal nerve cord, notochord, perforate pharynx, and segmented trunk musculature. After about 2 weeks of larval development, the hybrids die, as do the A. lucayanum purebreds, although all were eating the same algal diet that sustains B. floridae purebreds through adulthood in the laboratory; it is thus unclear whether death of the hybrids results from incompatible parental genomes or an inadequate diet. The diploid chromosome count in A. lucayanum and B. floridae purebreds is, respectively, 34 and 38, whereas it is 36 in hybrids in either direction. The hybrid larvae exhibit several morphological characters intermediate between those of the parents, including the size of the preoral ciliated pit and the angles of deflection of the gill slits and anus from the ventral midline. Based on the time since the two parent clades diverged (120 or 160 million years, respectively, by nuclear and mitochondrial gene analysis), the cross between Branchiostoma and Asymmetron is the most extreme example of hybridization that has ever been unequivocally demonstrated among multicellular animals.


Work addiction: An organizational behavior as well as an addictive behavior?
In their critical review, Griffiths et al. (2018) discussed 10 myths in the study of work addiction, and addressed the need to conceptualize and investigate this area of research more carefully. In this commentary, we expand their arguments, suggesting that indeed some of the popular myths have solid evidence-based results in the organizational literature. Yet, some of the arguments are only indirectly related to previous organizational findings. Therefore, we emphasize the need to resolve the ambiguities of work addiction, as well as to develop a comprehensive and interdisciplinary understanding of the well-known phenomenon of addictive work behavior.


Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress.
Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model. The safflower seed extract was orally administered at a dose of 100 mg kg-1 day-1, and then behavior tests (such as T-maze and novel object recognition tests) were conducted. Acetyl cholinesterase (AChE) activity, reactive oxygen species (ROS) production, and antioxidant enzymes in the brain were measured. In behavior tests, the novel route exploration and object recognition were improved by the administration of the safflower seed extract, which suggests that the safflower seed extract improves memory function in the scopolamine-treated mouse model. In addition, the safflower seed extract-administered group showed inhibition of the AChE activity and improved cholinergic dysfunction. Furthermore, the administration of the safflower seed extract resulted in lower ROS production and higher antioxidant enzyme levels as compared to the scopolamine-treated group, suggesting the protective role of the safflower seed extract against oxidative stress. The results of the present study suggest that the safflower seed extract improves scopolamine-induced memory deficits via the inhibition of cholinergic dysfunction and oxidative stress. Therefore, safflower seeds might become a promising agent for memory improvement in AD patients.


Assessment of the Abbreviated National Eye Institute Visual Function Questionnaire (NEI VFQ 9) in blepharoptosis and dermatochalasis.
To evaluate the Abbreviated National Eye Institute Visual Function Questionnaire (NEI VFQ 9), which is shorter than those previously published, as a tool for assessing vision-related quality of life in patients with ptosis and dermatochalasis. This is a cohort study of 46 patients who underwent blepharoptosis and/or upper eyelid blepharoplasty surgery by a single surgeon (CN) in 2013 in a public, academic, ambulatory care referral center. Patients included 29 who underwent blepharoplasty, 11 who underwent ptosis surgery, and 6 who underwent combined surgery. The NEI-VFQ 9 was administered pre- and postoperatively, and the composite scores were compared using Student's t-test. Survey duration was timed in a subset of patients. The hypothesis was that the NEI VFQ 9 could detect a statistically significant improvement in composite score after surgical intervention. The mean pre- and postoperative NEI VFQ 9 composite scores were 74.9 and 86.8, respectively, in the blepharoplasty-only group (P<0.0001), 72.07 and 86.41, respectively, in the ptosis-only group (P=0.004), and 75.8 and 87.2, respectively, in the combined group (P=0.022). There was no correlation between the gain in composite score and the change in upper eyelid margin to reflex distance. Twenty-five patients were timed filling out the survey, and the mean was 2.3 min. The NEI VFQ 9 consistently demonstrates a significant increase in visual function for blepharoptosis and dermatochalasis patients. Thus, it may be a useful tool for assessing vision-related quality of life in patients with ptosis and dermatochalasis.


On the accurate estimation of intermolecular interactions and charge transfer: the case of TTF-CA.
High-resolution X-ray diffraction experiments and state-of-the-art density functional theory calculations have been performed. The validity of the atoms-in-molecules approach is tested for the neutral-ionic transition of TTF-CA which involves a transfer of less than one electron between the donor and acceptor molecules. Foremost, crystallographical data have been reassessed along the temperature-induced neutral-ionic phase transition undergone by this charge transfer complex. Based on accurate X-ray structures at 105 and 15 K, topological analysis of both DFT and the experimental multipolar electron densities allowed detailed characterization of intra- and interstack intermolecular interactions. Direct quantification of the intermolecular charge transfer and the dipole moment are discussed.


Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial.
Persistent tachycardia in patients with septic shock predicts poor outcome. This study sought to investigate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and cardio-circulatory function in patients with septic shock. After informed consent, 60 patients with septic shock and persistent tachycardia (heart rate >95 /minute) were prospectively randomly assigned to receive either standard therapy for septic shock (group S) or standard therapy along with enteral ivabradine (group I) for the initial 96 hours after enrolment. Primary outcome was the difference in heart rate between the two groups during the first 96 hours. Secondary outcomes included the effect of ivabradine on haemodynamic, oxygenation, myocardial function and organ function parameters, incidence of adverse events and 30-day overall survival. Heart rate was lower in group I compared to group S (median difference in area under the curve -25.6 (95% confidence intervals -31.4 to -15.9) /minute; P <0.001). Vasopressor requirements, blood lactate levels, Sequential Organ Failure Assessment scores and E/e' ratio were lower in group I compared to group S. Stroke volume index and ejection fraction were higher in group I while cardiac index and oxygen delivery parameters were maintained similar to group S. There was no difference in 30-day mortality or in the incidence of serious adverse events. Enteral ivabradine is effective in reducing heart rate, and improving haemodynamic parameters and cardiac function in patients with septic shock and persistent tachycardia, without increasing the incidence of adverse events.


Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy.
To assess the efficacy and tolerability of adjunctive levetiracetam in patients with uncontrolled generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsies (IGE). This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults and children (4 to 65 years) with IGE experiencing >or=3 GTC seizures during the 8-week baseline period (4-week retrospective and 4-week prospective), despite receiving stable doses of one or two antiepileptic drugs (AEDs). Patients were randomized to levetiracetam (target dose 3,000 mg/day for adults; 60 mg/kg/day for children) or placebo and a 4-week titration period was followed by a 20-week evaluation period. Of 229 patients screened, 164 were randomized (levetiracetam, n = 80; placebo, n = 84). Levetiracetam produced a greater mean reduction in GTC seizure frequency per week over the treatment period (56.5%) than placebo (28.2%; p = 0.004). The percentage of patients who had >or=50% reduction of GTC seizure frequency per week (responders) during the treatment period was 72.2% for levetiracetam and 45.2% for placebo (p < 0.001; OR 3.28; 95% CI 1.68 to 6.38). During the first 2-week treatment 64.6% of patients on levetiracetam and 45.2% on placebo (p = 0.018) were classified as responders. During the evaluation period the percent of patients free of GTC seizures (34.2% vs 10.7%; p < 0.001) and all seizure types (24.1% vs 8.3%; p = 0.009) was greater for levetiracetam than placebo. Levetiracetam was well tolerated with 1.3% of patients discontinuing therapy due to adverse events vs 4.8% on placebo. Adjunctive levetiracetam is an effective and well-tolerated antiepileptic drug for treating generalized tonic-clonic seizures in patients with idiopathic generalized epilepsies.


Prenatal development of cat retinogeniculate axon arbors in the absence of binocular interactions.
During prenatal development of the cat's retinogeniculate projection, inputs from the ganglion cell axons of the two eyes are initially intermixed with each other within the lateral geniculate nucleus (LGN). As development proceeds, the inputs sort out to give rise to the eye-specific layers characteristic of the adult. During this sorting out process, individual axons undergo a stereotyped sequence of morphological changes that ultimately produce the characteristic pattern of arborization in which axon arbors are restricted in extent only to those layers of the LGN appropriate for the eye of origin (Sretavan and Shatz, 1984, 1986). Here, we examine whether binocular interactions between retinal ganglion cell axons from the two eyes are required for the formation of this restricted pattern of terminal arborization. To examine this question, one eye was removed at embryonic day 23 (E23), when ganglion cell axons have not yet reached the optic chiasm, and the ganglion cell axons from the remaining eye were allowed to develop in the complete absence of binocular interactions. At E59, when segregation into eye-specific layers is normally almost complete, the retinogeniculate projection from the remaining eye was then examined both by anterograde transport following intraocular injections of 3H-leucine and by the in vitro filling of individual ganglion cell axons with HRP. Results from the intraocular injections showed that in the absence of one eye, the remaining eye is still capable of forming both ipsilateral and contralateral optic tracts; however, the projection was distributed diffusely throughout each LGN, rather than being confined to normal eye-specific territories. When individual HRP-filled axons were reconstructed and examined, it was remarkable to find that the pattern of terminal arborization was virtually indistinguishable from normal axons. As usual, arbors were restricted to the distal portion of each axon trunk, and measurements showed that the total linear length of axon contributing to each arbor was within the normal range (enucleated, 2310 +/- 920 microns; normal, 2520 +/- 810 microns). Furthermore, the terminal arborizations of axons appeared to be organized into a series of tiers within the LGN in a pattern surprisingly similar to the pattern of eye-specific layers normally present by E59. Also unchanged was the normally occurring loss of axons from the remaining optic nerve: Counts at E59 showed that about 2.3 X 10(5) axons were present in enucleated animals as compared to 2.5 X 10(5) axons in controls.(ABSTRACT TRUNCATED AT 400 WORDS)


Fluorescence quenching of human orosomucoid. Accessibility to drugs and small quenching agents.
The fluorescence behaviour of human orosomucoid was investigated. The intrinsic fluorescence was more accessible to acrylamide than to the slightly larger succinimide, indicating limited accessibility to part of the tryptophan population. Although I- showed almost no quenching, that of Cs+ was enhanced, and suggested a region of negative charge proximal to an emitting tryptophan residue. Removal of more than 90% of sialic acid from the glycan chains led to no change in the Cs+, I-, succinimide or acrylamide quenching, indicating that the negatively charged region originates with the protein core. Quenching as a function of pH and temperature supported this view. The binding of chlorpromazine monitored by fluorescence quenching, in the presence and in the absence of the small quenching probes (above), led to a model of its binding domain on orosomucoid that includes two tryptophan residues relatively shielded from the bulk solvent, with the third tryptophan residue being on the periphery of the domain, or affected allotopically and near the negatively charged field.


Measurement of sap flow in roots of woody plants: a commentary.
Measurements of sap flow in roots have recently been used to study patterns of resource acquisition by woody plants; however, the various thermometric methods employed have yielded disparate findings. These findings may be harmonized by accounting for the phenomenon of reverse sap flow in roots. We suggest that only methods capable of measuring slow and reverse rates of flow and that do not require assumptions of zero flow during the night are applicable to studies with roots. The heat ratio method and the constant power heat balance method fit these criteria, whereas the constant temperature heat balance, compensation heat pulse and thermal dissipation methods do not.


High-Performance Inverted Organic Solar Cells via the Incorporation of Thickness-Insensitive and Low-Temperature-Annealed Nonconjugated Polymers as Electron Transport Materials.
Developing new electron transport layers has been an effective way to fabricate high-performance bulk-heterojunction organic solar cells (OSCs). Resolving the longstanding problems associated with commonly used zinc oxide (ZnO), such as electron traps and light-induced device deterioration, however, is still a great challenge. In this study, glycerol diglycidyl ether (GDE) and 1,4-butanesultone (BS) are blended with polyethyleneimine (PEI) to produce cross-linkable PEI-based materials, PEI-GDE and PEI-GDE-BS, which can function as alternative electron transport layers to replace conventional ZnO cathode-modifying layers in inverted OSCs. PEI-GDE and PEI-GDE-BS are amendable to low-temperature annealing processes to produce cross-linked films. The inverted device structure of ITO/ETL/PM6:BTP-BO-4F:PC71BM/MoO3/Ag was used to evaluate the effects of incorporating PEI-GDE and PEI-GDE-BS as electron transport materials. Compared with ZnO-based devices, the PEI-GDE- and PEI-GDE-BS-based devices exhibit significant improvements in photovoltaic performances due to smoother surface roughness, higher charge collection and exciton dissociation efficiencies, higher electron mobilities, and stronger π-π interactions. In particular, a PEI-GDE-BS-based device shows an outstanding power conversion efficiency (PCE) of 17.55% with a VOC of 0.83 V, a JSC of 27.88 mA/cm2, and an FF of 75.96%, which offers great possibilities in the applications of flexible solar cells.


Phorbol ester-mediated inhibition of IFN-alpha/beta gene transcription in blood mononuclear leukocytes.
The phorbol ester PMA efficiently inhibits the in vitro IFN-alpha and -beta responses in human blood monocytes induced by Sendai virus and in natural IFN-producing cells induced by glutaraldehyde-fixed herpes simplex virus-infected human amnion (WISH) cells. This PMA-mediated inhibition of IFN-alpha/beta secretion is correlated with considerably reduced levels of IFN-alpha/beta mRNA, as determined by Northern blot analysis. Nuclear run-on assays further show that, at least in monocytes, PMA inhibits transcription of the IFN-alpha and -beta genes. The synthetic diacylglycerol 1-oleoyl-2-acetylglycerol has the same effects as PMA, and the protein kinase inhibitor staurosporine prevents the PMA-mediated inhibition of IFN-alpha/beta expression. These results suggest a role for protein kinase C in the inhibition of IFN-alpha/beta responses. The PMA does not inhibit the accumulation of IFN-beta mRNA in monocytes stimulated by Sendai virus in the presence of cycloheximide, indicating that the inhibitory action of the phorbol ester requires de novo protein synthesis.


Gene Co-expression Network Reveals Potential New Genes Related to Sugarcane Bagasse Degradation in Trichoderma reesei RUT-30.
The biomass-degrading fungus Trichoderma reesei has been considered a model for cellulose degradation, and it is the primary source of the industrial enzymatic cocktails used in second-generation (2G) ethanol production. However, although various studies and advances have been conducted to understand the cellulolytic system and the transcriptional regulation of T. reesei, the whole set of genes related to lignocellulose degradation has not been completely elucidated. In this study, we inferred a weighted gene co-expression network analysis based on the transcriptome dataset of the T. reesei RUT-C30 strain aiming to identify new target genes involved in sugarcane bagasse breakdown. In total, ~70% of all the differentially expressed genes were found in 28 highly connected gene modules. Several cellulases, sugar transporters, and hypothetical proteins coding genes upregulated in bagasse were grouped into the same modules. Among them, a single module contained the most representative core of cellulolytic enzymes (cellobiohydrolase, endoglucanase, β-glucosidase, and lytic polysaccharide monooxygenase). In addition, functional analysis using Gene Ontology (GO) revealed various classes of hydrolytic activity, cellulase activity, carbohydrate binding and cation:sugar symporter activity enriched in these modules. Several modules also showed GO enrichment for transcription factor activity, indicating the presence of transcriptional regulators along with the genes involved in cellulose breakdown and sugar transport as well as other genes encoding proteins with unknown functions. Highly connected genes (hubs) were also identified within each module, such as predicted transcription factors and genes encoding hypothetical proteins. In addition, various hubs contained at least one DNA binding site for the master activator Xyr1 according to our in silico analysis. The prediction of Xyr1 binding sites and the co-expression with genes encoding carbohydrate active enzymes and sugar transporters suggest a putative role of these hubs in bagasse cell wall deconstruction. Our results demonstrate a vast range of new promising targets that merit additional studies to improve the cellulolytic potential of T. reesei strains and to decrease the production costs of 2G ethanol.


Modifications to husbandry and housing conditions of laboratory rodents for improved well-being.
For a change to be considered enriching, the change must enhance animal welfare and improve biological functioning of the animals. A review of the literature shows that a consensus on the definition of changes constituting "environmental enrichment" has yet to be reached. For this reason, the results of studies on the effects of rodent enrichment are inconsistent. In many cases, changes have not been shown to be real improvements. However, enrichment is increasingly appreciated as a way to improve the well-being of rodents, providing them with opportunities for species-specific behaviors that might be available to them in the wild. Frequently defined as "change to the environment," enrichment can be as complex as devices (frequently termed "toys") or as simple as the provision of tissues from which mice readily construct nests. Nest making is a learned behavior in rats, and laboratory rats do show preferences for chewable objects in their environment. Rather than attempting a comprehensive review of the entire literature on environmental enrichment and its effects on rodent physiology and behavior, this paper focuses on husbandry and housing alterations that may improve the welfare of laboratory rodents. The effects of beneficial changes in housing and husbandry on rodent well-being and on experimental variability--and thus cost--are discussed. Areas that require more research are suggested. Also suggested are possible inexpensive and effective enrichment schemes for laboratory mice that might include reducing the cage floor space per mouse combined with providing nesting material.


A wavelet-based watermarking algorithm for ownership verification of digital images.
Access to multimedia data has become much easier due to the rapid growth of the Internet. While this is usually considered an improvement of everyday life, it also makes unauthorized copying and distributing of multimedia data much easier, therefore presenting a challenge in the field of copyright protection. Digital watermarking, which is inserting copyright information into the data, has been proposed to solve the problem. In this paper, we first discuss the features that a practical digital watermarking system for ownership verification requires. Besides perceptual invisibility and robustness, we claim that the private control of the watermark is also very important. Second, we present a novel wavelet-based watermarking algorithm. Experimental results and analysis are then given to demonstrate that the proposed algorithm is effective and can be used in a practical system.


Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.
Hot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes. This phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. Eligible participants were healthy women aged 40-62 years, having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome, who had not had a menstrual period for at least 12 months, and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks. Participants received 4 weeks of MLE4901 (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. Randomisation was completed by a central computer, and participants were allocated to treatment number in numerical order. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. All analyses were prespecified in the study protocol. The trial is registered at ClinicalTrials.gov, number NCT02668185. 68 women were screened between Feb 3 and Oct 10, 2016, of which 37 were randomly assigned and included in an intention-to-treat analysis. 28 participants completed the trial and were included in a per-protocol analysis. MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22-67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 [95% CI 40·81-58·56] vs MLE4901 19·35 [15·99-23·42]; adjusted estimate of difference 29·66 [17·39-42·87], p<0·0001). Treatment was well tolerated. Three participants developed a transaminase rise (alanine aminotransferase 4·5-5·9 times the upper limit of normal) with a normal bilirubin 28 days after starting MLE4901, which normalised within 90 days. Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure. Larger scale studies of longer duration are now indicated. UK Medical Research Council and National Institute for Health Research.