Morphologic texture characterization allied to cigarette smoke increase pigmentation in composite resin restorations.
The staining effect of tobacco smoke on resin color is clinically observed. However, there is no evidence determining whether this staining is increased on texturized surfaces or if the color change is superficial and can be removed by repolishing procedures. To evaluate the effect of tobacco smoke on the color of a composite with smooth or texturized surfaces, before and after repolishing. Forty composite specimens were allocated into four groups (N = 10): Smooth surface not exposed (G1) and exposed to tobacco smoke (G2), texturized surface not exposed (G3), and exposed to tobacco smoke (G4). During 21 days, G2 and G4 were daily exposed to the smoke from 20 cigarettes. Color measurements were carried out at baseline, after 21 days, and after repolishing. Variables L* (luminosity), b* (blue-yellow), and DeltaE (total color change) were statistically analyzed (repeated measures analysis of variance/Tukey). Texturized and smooth specimens presented similar luminosity at baseline. Tobacco smoke significantly reduced L* in G2 and G4, and increased b* in G4. After repolishing, L* increased and b* reduced in stained groups, but values continued to be different from baseline ones. Repolishing significantly reduced DeltaE, but values from stained groups were still greater than that from unstained groups. Tobacco smoke changes the color of composite, and surface texture can increase the staining. Repolishing reduces superficial staining, but this procedure may not return the composite to baseline color. Smokers that will receive anterior composite restorations should be warned about the negative cosmetic effect of the smoking habit on the color of restorations.


[Genetic variations of hepatitis C virus circulating in the Ural region].
A study of distributions of different genetic variations (subtypes) of hepatitis C virus (HCV), circulating in the territories of Yekaterinburg and Chelyabinsk among infected population categories of different social statuses and age, is reported in the paper. The predominance of 1b subtype was shown in the HCV-infected patients at the hemodialysis center (HDC) and at the pediatric oncohematology center (OHC), 83.3% and 84.6% respectively. The summarized results of examinations of patients conducted at HCV-infection departments (97 persons) did not reveal any essential differences between the data, obtained for Moscow and Saint-Petersburg, concerning the distributions of HCV subtypes. However, according to an analysis made in cities of the Urals region, the prevalence of 1b subtype in Chelyabinsk was 2-fold higher than that of 3a subtype, whereas in Yekaterinburg there was an equal ratio (1:1) between the above subtypes. Besides, unequal distributions of HCV subtypes were registered in different age groups. 3a subtype was found to be predominant in patients aged 15 to 27, and prevalence of 1b subtype persisted in persons aged below 15 and above 27. The conclusion is that the redistributed occurrence rates of separate HCV subtypes, with their spectrum in mentioned territories being preserved, is associated with a growing number of young drug-addicts who are more often get infected with 3a subtype.


Molecular Engineering Modulating the Singlet-Triplet Energy Splitting of Indolocarbazole-Based TADF Emitters Exhibiting AIE Properties for Nondoped Blue OLEDs with EQE of Nearly 20.
The development of efficient blue thermally activated delayed fluorescence (TADF) emitters with an aggregation-induced emission (AIE) nature, for the construction of organic light-emitting diodes (OLEDs), is still insufficient. This can be attributed to the challenges encountered in molecular design, including the inherent trade-off between radiative decay and reverse intersystem crossing (RISC), as well as small singlet-triplet energy splitting (ΔEST) and the requirement for high photoluminescence quantum yields (ΦPL). Herein, we present the design of three highly efficient blue TADF molecules with AIE characteristics by combining π-extended donors with different acceptors to modulate the differences in the electron-donating and electron-withdrawing abilities. This approach not only ensures high emission efficiency by suppressing close π-π stacking, weakening nonradiative relaxation, and enhancing radiative transition but also maintains the equilibrium ratio between the triplet and singlet excitons by facilitating the process of RISC. These emitters exhibit AIE and TADF properties, featuring quick radiative rates and low nonradiative rates. The ΦPL of these emitters reached an impressive 88%. Based on their excellent comprehensive performance, nondoped PICzPMO and PICzPMO OLEDs achieved excellent electroluminescence performance, exhibiting maximum external quantum efficiency (EQEmax) of up to 19.5%, while the doped device achieved a higher EQEmax of 20.8%. This work demonstrated that by fusing π-extended large rigid donors with different acceptors, it is possible to regulate the difference in electron-donating and electron-withdrawing abilities, resulting in a small ΔEST, high ΦPL, and fast RISC process, which is a highly feasible strategy for designing efficient TADF molecules.


Fracto-mechanoluminescence induced by impulsive deformation of II-VI semiconductors.
When II-VI semiconductors are fractured, initially the mechanoluminescence (ML) intensity increases with time, attains a maximum value Im at a time tm, at which the fracture is completed. After tm, the ML intensity decreases with time, Im increase linearly with the impact velocity v0 and IT initially increase linearly with v0 and then it attains a saturation value for a higher value of v0. For photoluminescence, the temperature dependence comes mainly from luminescence efficiency, ηo; however, for the ML excitation, there is an additional factor, rt dependent on temperature. During fracture, charged dislocations moving near the tip of moving cracks produce intense electric field, causes band bending. Consequently, tunneling of electrons from filled electron traps to the conduction band takes place, whereby the radiative electron-hole recombination give rise to the luminescence. In the proposed mechanism, expressions are derived for the rise, the time tm corresponding to the ML intensity versus time curve, the ML intensity Im corresponding to the peak of ML intensity versus time curve, the total fracto-mechanoluminescence (FML) intensity IT, and fast and slow decay of FML intensity of II-VI semiconductors. The FML plays a significant role in understanding the processes involved in biological detection, earthquake lights and mine failure.


Quantifying the contribution of foods with unfavourable nutrient profiles to nutritionally adequate diets.
That 'all foods can fit' into a healthy diet is a long-standing principle of dietetic practice. The present study quantified the relative contributions of foods to encourage and foods to limit, using new techniques of individual diet optimisation and nutrient profiling. Individual foods from every food group were assigned to four nutrient profile classes based on the French SAIN,LIM system. Foods with the most favourable nutrient profiles were in class 1, and foods with the least favourable nutrient profiles were in class 4. An optimised diet that met the recommendations for thirty-two nutrients and that respected the existing eating habits was designed for each adult in the nationally representative 'Enquête Individuelle et Nationale sur les Consommations Alimentaires 1' dietary survey (n 1171). The relative proportions of the four nutrient profiling classes were assessed before and after the optimisation process. The contribution of fruits and vegetables, whole grains, milk and fish was significantly increased, whereas the contribution of refined grains, meats, mixed dishes, sugars and fats was decreased. The optimised diets derived more energy (30 v. 21 % in the observed diets) from class 1 foods and less energy (41 v. 56 %) from class 4 foods. They also derived a higher amount of class 1 foods (61 v. 51 %) and a lower amount of class 4 foods (22 v. 32 %). Thus, nutrient adequacy was compatible with the consumption of foods with an unfavourable nutrient profile (one-fifth the basket weight), provided that the diet also contained almost two-thirds of foods with the most favourable profile. Translating these results into concrete and quantified advice may have very tangible public health implications.


Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors.
Octreotide long-acting release (LAR) and lanreotide Autogel (ATG) are the two somatostatin analogs currently approved for treatment of acromegaly and neuroendocrine tumors (NETs). The strength of these drugs has been their specificity for somatostatin receptor subtype 2. However, this peculiarity may become a weakness in some patients with tumors harboring somatostatin receptors different from the subtype 2. Another clinically relevant aspect related to the use of octreotide LAR and lanreotide ATG is the burden of injectable drug regimen that may adversely impact the quality of life of patients with acromegaly and NETs. The authors review the recently published evidence on novel drugs targeting somatostatin receptors developed for treating acromegaly and NETs. Within this article, the authors discuss: i) the pharmacology of somatostatin and traditional somatostatin analogs; ii) the efficacy and safety of multireceptor-targeted somatostatin analogs in acromegaly and NETs; iii) the efficacy of chimeric molecules in acromegaly and NETs; iv) the preliminary data on the use of new injectable, oral and transdermal formulations of octreotide in acromegaly. The development of new somatostatin analogs and new formulations has opened a new scenario for treatment of acromegaly and NETs. That being said, even though there have been big steps taken in the development of new therapies for acromegaly, there are still a number of unresolved issues, while more trials are necessary for the use of somatostatin anaologs in the treatment of NETs.


[The monitoring of application of dabigatran as a remedy of prevention of thromboembolic complications after hip joint arthroplasty].
The analysis was applied to the indicators of hemostasis system under application of new anticoagulant, dabigatran etexilat, after hip joint arthroplasty. It is established that among the coagulation methods analysis the most specific to the effect of dabigatran is the testing of thrombin and echitox time of coagulation. Considering low sensitivity of the echitox to anticoagulation effect of D-dimer the echitox test is optimal for laboratory monitoring of application of dabigatran after orthopedic intervention.


Calixarene-mediated assembly of water-soluble C60-attached ultrathin graphite hybrids for efficient activation of reactive oxygen species to treat neuroblastoma cells.
Unprecedented nano-carbon hybrids consisting of exfoliated ultrathin graphite (or single-walled carbon nanotubes) with pristine C60 molecules attached on the surfaces have been produced in water in the presence of p-phosphonic acid calix[8]arene. The amphiphilic calixarene plays multiple roles in these processes to provide water dispersibility and π-π interactions with flexible conformations complementing curvatures of the carbon surfaces. The significantly increased water solubility and area of exposure of C60 enable efficient activation of reactive oxygen species for enhanced phototoxicity to SH-SY5Y human neuroblastoma cell line under laser irradiation.


Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.
Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r2ncv and q2loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r2Pred) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.


COVID-19 and Iranian Medical Students; A Survey on Their Related-Knowledge, Preventive Behaviors and Risk Perception.
Since December 2019, a novel coronavirus disease (COVID-19) began its journey around the world. Medical students, as frontline healthcare workers, are more susceptible to be infected by the virus. The aim of this study was to assess COVID-19 related knowledge, self-reported preventive behaviors and risk perception among Iranian medical students within the first week after the onset of the outbreak in Iran. This cross-sectional study was conducted from 26th to 28th of February, 2020. Participants were Iranian medical students (5th-7th year) whose knowledge, preventive behaviors and risk perceptions of COVID-19 were assessed using an online questionnaire. The questionnaire consisted of 26 questions including 15 items about COVID-19 related knowledge, 9 items regarding preventive measures and 2 items about COVID-19 risk perception. The validity and reliability of the questionnaire were shown to be satisfactory. A total of 240 medical students completed the questionnaire. The mean age of participants was 23.67 years. The average of correct answers of knowledge was 86.96%; and 79.60% had high level of related knowledge. The average rate of practicing preventive behaviors was 94.47%; and 94.2% had high level of performance in preventive behaviors. The cumulative score of risk perception was 4.08 out of 8 which was in moderate range. Risk perception was significantly different between stagers and interns and between those being trained in emergency room (ER) and non-ER wards. There was a significant negative correlation between preventive behaviors and risk perception. We found a high level of COVID-19 related knowledge and self-reported preventive behaviors and moderate risk perception among Iranian medical students.


The epidemiological and economic impact of a quadrivalent human papillomavirus (hpv) vaccine in Estonia.
This analysis assessed the epidemiological and economic impact of quadrivalent human papillomavirus (HPV4: 6/11/16/18) vaccination in Estonia. A dynamic transmission model was used to assess the epidemiological and economic impact of the routine vaccination of 12-year-old girls with a HPV4 vaccine in preventing cervical cancer, cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 and genital warts. The model projected that at year 100, HPV4 vaccination would lead to a reduction of HPV 16/18 related cervical cancer incidence and deaths by over 97% and the incidence of HPV 6/11 related genital warts among Estonian women and men by over 94% and 81%, respectively. The incremental cost-effectiveness ratio of the HPV4 vaccination strategy was € 4,889 per QALY gained over a time horizon of 100 years. Routine vaccination of 12-year-old girls with HPV4 vaccine appears to be cost-effective in Estonia, in addition to providing both short term and long term health gains.


Blocking PERK resuces vascular smooth muscle cells from homocysteine-induced ER stress and apoptosis.
Hyperhomocysteinemia induces stress response in endoplasmic reticulum (ERS). Here, we tested whether blockage of homocysteine (Hcy) induced ERS and subsequent apoptosis in vascular smooth muscle cells can be inhibited by blockage of PERK/eIF2α/ATF4/CHOP signaling. Short-term exposure of vascular smooth muscle cells to Hcy led to the phosphorylation of PERK (pPERK), which in turn, phosphorylated eIF2 alpha (peIF2a) and inhibited the unfolded protein response. Long-term Hcy exposure, however, increased the expression of ATF-4 and CHOP and led to apoptosis. Treatment of cells with salubrinal, a specific inhibitor for eIF2a decreased the expression of ATF-4 and CHOP, and prevented apoptosis. Together, the results show that PERK pathway is involved in Hcy-induced vascular smooth muscle cell apoptosis and that blocking the PERK pathway protects against this injury.


Seedling emergence, growth and trace elements tolerance and accumulation by Lamiaceae species in a mine soil.
The potential use of three Laminaceae species (Lavandula dentata, Rosmarinus officinalis and Thymus vulgaris) for the phytostabilisation of a trace elements contaminated (acid) soil has been evaluated. These species were grown in mine tailing soil unamended (TS) and amended with calcium carbonate and pig manure (ATS), and unpolluted substrate for control (CT); plant growth, root characterisation, soil trace elements contents and their accumulation in plants were measured. Results indicated that seed emergence was independent from substrate characteristics, but seedlings died in TS with 40% survival in ATS. The biomass of L. dentata and T. vulgaris and root development in R. officinalis were negatively affected when grown in TS but without differences between ATS and CT. Applicating amendments reduced soil exchangeable and extractable fractions concentrations of trace elements in ATS compared with TS. The establishment of L. dentata and R. officinalis were related to trace elements immobilisation. Trace element concentrations in plants grown in tailing soils were similar to those reported for control, although applicating amendments reduced Zn accumulation in all species, and favoured increased absorption and aerial translocation of As and Pb by L. dentata and T. vulgaris; nonetheless, levels were below toxicity thresholds. Thus, these species fulfill the criteria for phytostabilisation purposes, aided by employing amendments.


Planar second-harmonic generation with noncollinear pumps in disordered media.
We study experimentally the process of the second harmonic generation by two noncollinear beams in quadratic nonlinear crystals with a disordered structure of ferroelectric domains. We show that the second-harmonic radiation is emitted in the form of two cones as well as in a plane representing the cross-correlation of the two fundamental pulses. We demonstrate the implementation of this parametric process for characterisation of femtosecond pulses, enabling the estimation of pulse width, chirp, and front tilt. This is achieved through monitoring the evolution of the autocorrelation trace inside the nonlinear crystal.


I find you more attractive … after (prefrontal cortex) stimulation.
Facial attractiveness seems to be perceived immediately. Neuroimaging evidence suggests that the appraisal of facial attractiveness is mediated by a network of cortical and subcortical regions, mainly encompassing the reward circuit, but also including prefrontal cortices. The prefrontal cortex is involved in high-level processes, so how does its activity relate to beauty appreciation? To shed light on this, we asked male and female participants to evaluate the attractiveness of faces of the same and other sex prior and after transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC). We found that increasing excitability via anodal tDCS in the right but not in the left DLPFC increased perceived attractiveness of the faces, irrespective of the sex of the faces or the sex of the viewers. Identical stimulation over the same site did not affect estimation of other facial characteristics, such as age, thereby suggesting that the effects of anodal tDCS over the right DLPFC might be selective for facial attractiveness, and might not generalize to decisions concerning other facial attributes. Overall, our data suggest that the right DLPFC plays a causal role in explicit judgment of facial attractiveness. The mechanisms mediating such effect are discussed.


Mechanism of peroxidase actions for salicylic acid-induced generation of active oxygen species and an increase in cytosolic calcium in tobacco cell suspension culture.
Extracellularly secreted peroxidases in cell suspension culture of tobacco (Nicotiana tabacum L. cv. Bright Yellow-2, cell line BY-2) catalyse the salicylic acid (SA)-dependent formation of active oxygen species (AOS) which, in turn, triggers an increase in cytosolic Ca2+ concentration. Addition of horseradish peroxidase (HRP) to tobacco cell suspension culture enhanced the SA-induced increase in cytosolic Ca2+ concentration, suggesting that HRP enhanced the production of AOS. The mechanism of peroxidase-catalysed generation of AOS in SA signalling was investigated with chemiluminescence sensitive to AOS and electron spin resonance (ESR) spectroscopy, using the cell suspension culture of tobacco, and HRP as a model system of peroxidase reaction. The results showed that SA induced the peroxidase inhibitor-sensitive production of superoxide and H2O2 in tobacco suspension culture, but no production of hydroxy radicals was detected. Similar results were obtained using HRP. It was also observed that SA suppressed the H2O2-dependent formation of hydroxy radicals in vitro. The results suggest that SA protect the cells from highly reactive hydroxy radicals, while producing the less reactive superoxide and H2O2 through peroxidase-catalysed reaction, as the intermediate signals. The formation of superoxide was followed by that of H2O2, suggesting that superoxide was converted to H2O2. In addition, it was observed that superoxide dismutase-insensitive ESR signal of monodehydroascorbate radical was induced by SA both in the tobacco suspension culture and HRP reaction mixture, suggesting that SA free radicals, highly reactive against ascorbate, were formed by peroxidase-catalysed reactions. The formation of SA free radicals may lead to subsequent monovalent reduction of O2 to superoxide.


Penetration of penicillin into human phagocytes containing Neisseria gonorrhoeae: intracellular survival and growth at optimum concentrations of antibiotic.
Phagocytes obtained from fresh human buffy coat (predominantly polymorphonuclear phagocytes) or from human buffy coat which had been incubated on a glass surface for 1 to 3 days (predominantly mononuclear phagocytes) were allowed to ingest gonococci, and then incubated with penicillin. More intracellular gonococci were killed at high than at low penicillin concentrations, indicating that penicillin penetrated the phagocytes. This was supported by autoradiography experiments with radiolabelled penicillin. A pilated, small-colony-forming gonococcal strain survived and multiplied for at least 15 h in polymorphonuclear phagocytes which were incubated with penicillin at the optimum concentration for killing the extracellular bacteria but not the intracellular ones; whereas a non-pilated, large-colony-forming strain survived for only 10 h. The former strain survived for at least 6 h in similar experiments with mononuclear phagocytes. Intracellular survival and in growth may be an important facet of the pathogenicity of gonococci.


Distinct initiating events underpin the immune and metabolic heterogeneity of KRAS-mutant lung adenocarcinoma.
The KRAS oncoprotein, a critical driver in 33% of lung adenocarcinoma (LUAD), has remained an elusive clinical target due to its perceived undruggable nature. The identification of dependencies borne through common co-occurring mutations are sought to more effectively target KRAS-mutant lung cancer. Approximately 20% of KRAS-mutant LUAD carry loss-of-function mutations in KEAP1, a negative regulator of the antioxidant response transcription factor NFE2L2/NRF2. We demonstrate that Keap1-deficient KrasG12D lung tumors arise from a bronchiolar cell-of-origin, lacking pro-tumorigenic macrophages observed in tumors originating from alveolar cells. Keap1 loss activates the pentose phosphate pathway, inhibition of which, using 6-AN, abrogated tumor growth. These studies highlight alternative therapeutic approaches to specifically target this unique subset of KRAS-mutant LUAD cancers.


Atomic clouds as distributed sources for the io plasma torus.
Several recent developments have implications for the neutral particle environment of Jupiter. Very hot sulfur ions have been detected in the Io torus with gyrospeeds comparable to the corotation speed, a phenomenon that would result from a neutral sulfur cloud. Current evidence supports the hypothesis that extensive neutral clouds of oxygen and sulfur exist in the Jupiter magnetosphere and that they are important sources of ions and energy for the Io torus.


Proteomic Profiling of Stem Cell Tissues during Regeneration of Deer Antler: A Model of Mammalian Organ Regeneration.
As the only known mammalian organ that can fully and annually regenerate, deer antler has significant advantages over lower-order animal models when investigating the control of stem-cell-based organ regeneration. Antler regeneration is known to be initiated and maintained by neural-crest-derived stem cells in different states of activation. Antler stem cells can therefore be used as a model to study proteins and pathways involved in the maintenance of a stem cell niche and their activation and differentiation during organ formation. In this study, the MSC markers CD73, CD90, and CD105 were examined within the antler tip. Label-free quantification was performed to investigate the protein profiles of antler stem cells under different stages of activation and included dormant pedicle periosteum (DPP), antler growth center (GC), post-active stem cells from mid-beam antler periosteum (MAP), and deer facial periosteum (FP) as a control (n = 3 per group). PEAKS and IPA software were used to analyze the proteomic data. Our research confirmed the central role of stem cell activation in the development of this mammalian organ by localizing the MSC markers within the antler growth center. Label-free quantification revealed that the greatest number of unique proteins (87) was found in the growth center. There were only 12 proteins found with expression levels that significantly differed between DPP and FP. Protein profiles of these two groups indicated that antler stem cells may use similar mechanisms to maintain dormancy within a stem cell niche. The number of significantly regulated proteins among DPP, MAP, and GC was 153. Among them, the majority were upregulated in the growth center. Activation of antler stem cells was associated with many biological processes and signaling pathways, such as Hippo and canonical Wnt signaling. This work identifies the key pathways, molecular/cellular functions, and upstream regulators involved in mammal organ regeneration. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD016824.


Models for the estimation of the probability of dying between birth and exact ages of early childhood.
Abstract This paper develops two models, each of which is designed to estimate the probability of surviving from birth to selected exact ages of early childhood: namely ages two, three and five. The models are designed for use in areas with deficient registration systems. They require, as input, statistics which can be derived from retrospective data supplied by census or survey respondents. The first model, the age model, converts statistics on the proportion dead of children ever born to women in age groups 20-24, 25-29 and 30-34 into estimates of q2, q3 and q5. The second model, the marriage model, converts statistics on the proportion dead of children ever born to women of five-year marriage duration intervals into these estimates. The models can be used independently or simultaneously. These models were developed from data generated by a large number of empirical fertility and mortality schedules. Regression analysis was used to determine the parameter values of the relationships specified, and several sets of equations for estimating values of qa, for a = 2, 3 and 5 comprise the final product of the paper. It should be noted that the conceptual basis for the models was first derived by William Brass. The data generated for the regression analysis provided an opportunity to test the original Brass estimated model. We are able to report that the model performed well over the wide range of fertility and mortality conditions included in the test.


Histoplasmosis mimicking malignant adenopathy during diagnostic thyroid lobectomy.
Benign granulomatous disease may mimic malignant disease in the evaluation of mediastinal or pulmonary lesions. However, histoplasmosis as a cause of cervical lymphadenopathy is relatively rare. We report the first case of Histoplasma infection mimicking malignant adenopathy discovered during diagnostic thyroid lobectomy. A 2.5-cm, calcified, right paratracheal lymph node intimately involving the recurrent laryngeal nerve was discovered during lobectomy for a follicular lesion of undetermined significance with a positive NRAS mutation. Although metastatic thyroid cancer was the most probable diagnosis, results of gross inspection of the bisected thyroid nodule suggested a benign process. Partial removal of the node, sparing the nerve, established the diagnosis of Histoplasma capsulatum infection. Histoplasmosis is a rare cause of cervical adenopathy that should be considered in cases in which a discordance arises between the malignant gross appearance of the adenopathy and the benign gross appearance of an associated thyroid nodule.


Outbreak of a novel disease caused by Staphylococcus pseudintermedius in raccoon dogs (Nyctereutes procyonoides).
This study reports outbreak of a new disease caused by Staphylococcus pseudintermedius (S. pseudintermedius) in raccoon dogs. The disease occurred in a breeding farm of raccoon dogs in Guan County of Shandong Province in China in August of 2019. 47% (425/896) of the raccoon dogs showed some abnormal symptoms; 17.6% (75/425) of which had severe skin and soft tissue infections (SSTIs), dyspnoea and severe pathological lesions in lungs, livers, etc; and 4.2% (18/425) of which died within 4 weeks. The pathogen of the disease was identified as S. pseudintermedius by mass spectrometer detection, animal pathogenicity tests, microscopic examination and biochemical reaction tests. Its nucleotide homology of 16S rRNA gene was 100% with that of other published strains, and its genotype was between the American and Brazilian strains from other animals. The isolated S. pseudintermedius strain from the diseased raccoon dogs could cause ulceration and suppuration in the skins and severe pathological lesions not only in raccoon dogs, but also in mice; and it is confirmed as a methicillin-resistant S. pseudintermedius (MRSP) strain by the amplification of mecA gene; and 12 sensitive drugs were screened by drug sensitivity tests. Full attention should be paid to the great economic loss and the potential zoonotic risk caused by the S. pseudintermedius in raccoon dogs, and this study can provide a reference for the clinical diagnosis and treatment of this new disease.


Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy.
Tafazzin (TAZ) is a phospholipid transacylase that catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mutations of TAZ cause Barth syndrome, which is characterized by mitochondrial dysfunction and dilated cardiomyopathy, leading to premature death. However, the molecular mechanisms underlying the cause of mitochondrial dysfunction in Barth syndrome remain poorly understood. Here we investigated the role of TAZ in regulating mitochondrial function and mitophagy. Using primary mouse embryonic fibroblasts (MEFs) with doxycycline-inducible knockdown of Taz, we showed that TAZ deficiency in MEFs caused defective mitophagosome biogenesis, but not other autophagic processes. Consistent with a key role of mitophagy in mitochondria quality control, TAZ deficiency in MEFs also led to impaired oxidative phosphorylation and severe oxidative stress. Together, these findings provide key insights on mitochondrial dysfunction in Barth syndrome, suggesting that pharmacological restoration of mitophagy may provide a novel treatment for this lethal condition.


[Trichorhinophalangeal syndrome--clinical presentation and genetics].
The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed. The paper is based on four case reports and provides a short review of the condition. Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many. In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.


Feasibility of a Novel Fluoroscopic Trainer for the Orthopaedic Trainee.
We sought to create a novel method of teaching orthopedic trainees to efficiently obtain intraoperative radiographs using nonfluoroscopic digital cameras. Specifically, teaching them to make minor, uniplanar, adjustments while limiting the number of fluoroscopy images obtained during placement of a guidewire "start-point," for intramedullary nailing. Prospective cohort study including medical students from 2 academic centers. Two nonfluoroscopic digital cameras simulating orthogonal fluoroscopic images were utilized. A sponge was used to simulate soft tissue resistance while navigating a guidewire to the desired starting point. Three cannulated parallel cylinders in a triangular configuration are used to simulate our "start point." Students completed 4 phases; trial and error, teaching, testing and retention. The protocol was completed at a single academic teaching hospital at the primary authors institution. We utilized medical students from 2 GME accredited medical schools to complete the protocol. Students were selected from orthopedic surgery interest groups at their respective institutions and participation was voluntary. Twenty-one medical students completed the protocol. The number of seconds to achieve each target along with the number of pictures to achieve each target were recorded and averaged. The paired t-test was used to compare the difference between phases. There is a statistically significant difference in the mean number of seconds to achieve each target between phase 1 (baseline) and phase 3 (testing) (p < 0.0001). This statistically significant difference was retained in phase 4 (retention) (p < 0.0001). We were able to demonstrate a statistically significant decrease in the number of images and time to obtain the correct "start point." This could theoretically decrease operative time and morbidity while teaching students in a low-stress training environment without exposure to radiation.


Bouncing jet: a Newtonian liquid rebounding off a free surface.
We find that a liquid jet can bounce off a bath of the same liquid if the bath is moving horizontally with respect to the jet. Previous observations of jets rebounding off a bath (e.g., the Kaye effect) have been reported only for non-Newtonian fluids, while we observe bouncing jets in a variety of Newtonian fluids, including mineral oil poured by hand. A thin layer of air separates the bouncing jet from the bath, and the relative motion replenishes the film of air. Jets with one or two bounces are stable for a range of viscosity, jet flow rate and velocity, and bath velocity. The bouncing phenomenon exhibits hysteresis and multiple steady states.


HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc.
c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc-mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis.


Association between age and severity to leptospirosis in children.
In endemic areas, leptospirosis is more common and more severe in adults compared with children. Reasons to explain this discrepancy remain unclear and limited data focusing on adolescents are available. The objective of the study was to describe disease spectrum and outcome differences in children and adolescents admitted for leptospirosis in a large at-risk population. Clinical and laboratory data were obtained on hospitalized cases in New Caledonia from 2006 to 2012. Data of 60 patients <18 years of age (25 children under 14 and 35 adolescents aged 14 to 17) with confirmed leptospirosis were analyzed. Compared with children, adolescents presented more often with classic features of Weil disease (p = 0.02), combining hepatic and renal involvement with or without pulmonary participation. Jarisch-Herxheimer reactions were observed more often among adolescents (p<0.01). The overall case fatality rate was low (1 adolescent versus 0 children). Severe leptospirosis in adolescents may be more likely to show adults' characteristics compared with children. Further studies are required to explore age-dependant host factors, including puberty-related physiological changes.


Antihypertensive peptides from curd.
Curd (Dadhi) peptides reduce hypertension by inhibiting angiotensin converting enzyme (ACE) and serum cholesterol. Peptides vary with bacterial species and milk type used during fermentation. To isolate and assay the antihypertensive peptides, before and after digestion, in two commercially available curd brands in Sri Lanka. Whey (Dadhi Mastu) separated by high-speed centrifugation was isolated using reverse-phase-high- performance liquid chromatography (HPLC). Eluted fractions were analyzed for ACE inhibitory activity using modified Cushman and Cheung method. Curd samples were subjected to enzymatic digestion with pepsin, trypsin, and carboxypeptidase-A at their optimum pH and temperature. Peptides isolated using reverse-phase-HPLC was assayed for ACE inhibitory activity. Whey peptides of both brands gave similar patterns (seven major and five minor peaks) in HPLC elution profile. Smaller peptides concentration was higher in brand 1 and penta-octapeptides in brand 2. Pentapeptide had the highest ACE inhibitory activity (brand 2-90% and brand 1-73%). After digestion, di and tri peptides with similar inhibitory patterns were obtained in both which were higher than before digestion. Thirteen fractions were obtained, where nine fractions showed more than 70% inhibition in both brands with 96% ACE inhibition for a di-peptide. Curd has ACE inhibitory peptides and activity increases after digestion.


Role of contact tracing in containing the 2014 Ebola outbreak: a review.
The 2014 outbreak of Ebola virus disease which emerged in the month of March in the year 2014 in Guinea has been declared as a public health emergency of international concern. The objectives of the review article are to assess the role of contact tracing in the Ebola outbreak and to identify the challenges faced by the health workers while performing contact tracing. An extensive search of all materials related to the Ebola outbreak and contact tracing was carried out in PubMed, Medline, World Health Organization website and Google Scholar search engines. Keywords used in the search included Ebola virus disease, West-Africa, contact tracing, World Health Organization. Overall 60 articles were selected and included in the discussion. Contact tracing is an important strategy in epidemiology and refers to the identification and diagnosis of those individuals who have come in contact with an infected person. It ultimately aims to reduce the time span required to detect and treat a case of an infectious disease and hence significantly minimize the risk of transmission to the subsequent susceptible individuals. In-fact, contact tracing continues to remain an important measure, as it aids the epidemiologist in containing the infection. The strategy of contact tracing has a great potential to significantly reduce the incidence of cases of Ebola virus disease. However, its success is eventually determined by the level of trust between the community and the public health system and the quality of the diagnostic & treatment services.


The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3.
The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.


Adiposity in dialysis: good or bad?
There exists in the general population a complex and mostly positive relationship between adiposity and mortality risk. Because the dialysis population has a high prevalence of excess adiposity, in addition to a strikingly elevated mortality rate, the effects of obesity are of potential clinical importance. In contrast to the general population, the preponderance of data in dialysis, particularly hemodialysis patients, suggest that adiposity has a neutral or even protective association with mortality. Although methodological concerns exist with regards to confounding and survival bias, among others, the major limitation of this body of literature is its inability to establish causality. Thus, although obese dialysis patients, with certain exceptions, appear to live longer, there is no evidence to suggest that intentional weight loss adversely affects patient outcomes. In light of these limitations and the substantial body of literature implicating obesity as a pathophysiological state, it is currently premature to advocate for excess adiposity as being beneficial or intentional weight loss as dangerous. Decisions regarding optimal weight should be made by clinicians on an individual basis and with close supervision and follow-up. Efforts should be made to preserve lean mass during weight loss regimens by encouraging exercise and recommending sufficient protein consumption. Future research efforts in this area should focus on interventional trials designed to manipulate weight and measure outcomes, identifying potentially beneficial secretory products of adipose tissue, and documenting obesity's effects on quality of life and resource utilization in the dialysis setting.


Brain State Differentiation and Behavioral Inflexibility in Autism.
Autism spectrum disorders (ASDs) are characterized by social impairments alongside cognitive and behavioral inflexibility. While social deficits in ASDs have extensively been characterized, the neurobiological basis of inflexibility and its relation to core clinical symptoms of the disorder are unknown. We acquired functional neuroimaging data from 2 cohorts, each consisting of 17 children with ASDs and 17 age- and IQ-matched typically developing (TD) children, during stimulus-evoked brain states involving performance of social attention and numerical problem solving tasks, as well as during intrinsic, resting brain states. Effective connectivity between key nodes of the salience network, default mode network, and central executive network was used to obtain indices of functional organization across evoked and intrinsic brain states. In both cohorts examined, a machine learning algorithm was able to discriminate intrinsic (resting) and evoked (task) functional brain network configurations more accurately in TD children than in children with ASD. Brain state discriminability was related to severity of restricted and repetitive behaviors, indicating that weak modulation of brain states may contribute to behavioral inflexibility in ASD. These findings provide novel evidence for a potential link between neurophysiological inflexibility and core symptoms of this complex neurodevelopmental disorder.


Evolution of Influenza A(H3N2) Viruses in 2 Consecutive Seasons of Genomic Surveillance, 2021-2023.
The circulation and the genomic evolution of influenza A(H3N2) viruses during the 2021/2022 and 2022/2023 seasons were studied and associated with infection outcomes. Remnant influenza A-positive samples following standard-of-care testing from patients across the Johns Hopkins Health System (JHHS) were used for the study. Samples were randomly selected for whole viral genome sequencing. The sequence-based pEpitope model was used to estimate the predicted vaccine efficacy (pVE) for circulating H3N2 viruses. Clinical data were collected and associated with viral genomic data. A total of 121 683 respiratory specimens were tested for influenza at JHHS between 1 September 2021 and 31 December 2022. Among them, 6071 (4.99%) tested positive for influenza A. Of these, 805 samples were randomly selected for sequencing, with hemagglutinin (HA) segments characterized for 610 samples. Among the characterized samples, 581 were H3N2 (95.2%). Phylogenetic analysis of HA segments revealed the exclusive circulation of H3N2 viruses with HA segments of the 3C.2a1b.2a.2 clade. Analysis of a total of 445 complete H3N2 genomes revealed reassortments; 200 of 227 of the 2022/2023 season genomes (88.1%) were found to have reassorted with clade 3C.2a1b.1a. The pVE was estimated to be -42.53% for the 2021/2022 season and 30.27% for the 2022/2023 season. No differences in clinical presentations or admissions were observed between the 2 seasons. The increased numbers of cases and genomic diversity of influenza A(H3N2) during the 2022/2023 season were not associated with a change in disease severity compared to the previous influenza season.


Corn Yield Prediction With Ensemble CNN-DNN.
We investigate the predictive performance of two novel CNN-DNN machine learning ensemble models in predicting county-level corn yields across the US Corn Belt (12 states). The developed data set is a combination of management, environment, and historical corn yields from 1980 to 2019. Two scenarios for ensemble creation are considered: homogenous and heterogenous ensembles. In homogenous ensembles, the base CNN-DNN models are all the same, but they are generated with a bagging procedure to ensure they exhibit a certain level of diversity. Heterogenous ensembles are created from different base CNN-DNN models which share the same architecture but have different hyperparameters. Three types of ensemble creation methods were used to create several ensembles for either of the scenarios: Basic Ensemble Method (BEM), Generalized Ensemble Method (GEM), and stacked generalized ensembles. Results indicated that both designed ensemble types (heterogenous and homogenous) outperform the ensembles created from five individual ML models (linear regression, LASSO, random forest, XGBoost, and LightGBM). Furthermore, by introducing improvements over the heterogenous ensembles, the homogenous ensembles provide the most accurate yield predictions across US Corn Belt states. This model could make 2019 yield predictions with a root mean square error of 866 kg/ha, equivalent to 8.5% relative root mean square and could successfully explain about 77% of the spatio-temporal variation in the corn grain yields. The significant predictive power of this model can be leveraged for designing a reliable tool for corn yield prediction which will in turn assist agronomic decision makers.


Social evaluation-induced amylase elevation and economic decision-making in the dictator game in humans.
Little is known regarding the relationship between social evaluation-induced neuroendocrine responses and generosity in game-theoretic situations. Previous studies demonstrated that reputation formation plays a pivotal role in prosocial behavior. This study aimed to examine the relationships between a social evaluation-induced salivary alpha-amylase (sAA) response and generosity in the dictator game. The relationship is potentially important in neuroeconomics of altruism and game theory. We assessed sAA and allocated money in the dictator game in male students with and without social evaluation. RESULTS Social evaluation-responders allocated significantly more money than controls; while there was no significant correlation between social evaluation-induced sAA elevation and the allocated money. Social evaluation significantly increases generosity in the dictator game, and individual differences in trait characteristics such as altruism and reward sensitivity may be important determinants of generosity in the dictator game task.


From Multiple Organ Support Therapy to Extracorporeal Organ Support in Critically Ill Patients.
Critically ill patients developing severe forms multiple organ dysfunction syndrome (MODS) may not be adequately supported by pharmacologic management. In these complex cases, a single form of extracorporeal organ support (ECOS) may be required, but multiple organ support therapy (MOST) is currently seen as a feasible approach. Severe renal dysfunction is a typical syndrome requiring renal replacement therapy (RRT) in the context of MODS. After more than a decade of RRT application in various intensive care settings, ECOS are not anymore seen as extraordinary or particularly aggressive techniques in MODS patients. Nowadays, a significant increase in the use of extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal is occurring. When renal and cardio-pulmonary ECOS are used together, a multidisciplinary approach is necessary to minimize negative interactions and unwanted adverse effects. In this editorial, we focus on the organ crosstalk between the native and artificial organs, including the advantages and disadvantages of organ support on multiorgan function. Much of current experience on MOST has been gained upon RRT connected to other organ support therapies. Overall, available literature has not definitely established the ideal timing of these interventions, and whether early implementation impacts organ recovery and optimizes resource utilization is still a matter of open debate: it is possible that future research will be devoted to identify patient groups that may benefit from short- and long-term multiple organ support. Video Journal Club "Cappuccino with Claudio Ronco" at https://www.karger.com/Journal/ArticleNews/490694?sponsor=52.


Disentangling in vivo the effects of iron content and atrophy on the ageing human brain.
Evidence from magnetic resonance imaging (MRI) studies shows that healthy aging is associated with profound changes in cortical and subcortical brain structures. The reliable delineation of cortex and basal ganglia using automated computational anatomy methods based on T1-weighted images remains challenging, which results in controversies in the literature. In this study we use quantitative MRI (qMRI) to gain an insight into the microstructural mechanisms underlying tissue ageing and look for potential interactions between ageing and brain tissue properties to assess their impact on automated tissue classification. To this end we acquired maps of longitudinal relaxation rate R1, effective transverse relaxation rate R2* and magnetization transfer - MT, from healthy subjects (n=96, aged 21-88 years) using a well-established multi-parameter mapping qMRI protocol. Within the framework of voxel-based quantification we find higher grey matter volume in basal ganglia, cerebellar dentate and prefrontal cortex when tissue classification is based on MT maps compared with T1 maps. These discrepancies between grey matter volume estimates can be attributed to R2* - a surrogate marker of iron concentration, and further modulation by an interaction between R2* and age, both in cortical and subcortical areas. We interpret our findings as direct evidence for the impact of ageing-related brain tissue property changes on automated tissue classification of brain structures using SPM12. Computational anatomy studies of ageing and neurodegeneration should acknowledge these effects, particularly when inferring about underlying pathophysiology from regional cortex and basal ganglia volume changes.


Nature of the facilitated messenger ribonucleic acid transport from isolated nuclei.
Cytoplasmic macromolecules were previously identified which regulate both qualitatively and quantitatively the release of messenger-like RNA from isolated nuclei. These macromolecules are now shown to be denatured at 45-50 degrees C and their synthesis is sensitive to pactamycin or cycloheximide. The putative regulatory proteins are essentially quantitatively precipitated with high specificity from the cytosol by streptomycin at a concentration 10-fold higher than that used to precipitate RNA. The nuclear concentration-dependence of RNA transport from successive samples of nuclei strongly suggests that the regulatory factors are recycled. Quantitative changes in the sequences transported at various dilutions of the cytosol suggest that not all the different classes of the putative regulatory macromolecules are present in an effective concentration at any one dilution.


A controlled study of psychiatric manifestations and electroencephalography findings in chronic kidney disease patients with Sagliker syndrome.
Sagliker syndrome (SS) is a novel syndrome that was described in 2004 in patients with chronic kidney disease (CKD). The aim of this study was to assess psychiatric evaluations and electroencephalography (EEG) findings of patients with CKD and SS to compare them with patients with CKD having characteristics similar to that of the study group, in terms of age and gender. The study group comprised 13 patients with CKD and SS. The control group included 13 patients with CKD. Psychiatric diseases were diagnosed using the Structure Clinical Interview. Beck Depression Inventory, Beck Anxiety Inventory, Social Comparison Scale, Hopelessness Scale, and Mini Mental State Examination (MMSE) were administered to the groups. Moreover, EEG recording for all the patients was performed. According to the results obtained from the Structure Clinical Interview, 69.2% of patients with CKD and SS were diagnosed with a mental disease, as compared with only 3 (23.1%) patients with CKD. There was a significant difference between the study and the control group (P < .001). As compared with the control group, patients with CKD and SS had significantly higher scores on the Beck Depression Inventory, the Beck Anxiety Inventory, and the Hopelessness Scale. However, patients with CKD and SS had significantly lower scores on the Social Comparison Scale. The MMSE scores were not significantly different between the 2 groups. When the 2 groups were evaluated separately, no significant differences were found between the EEG abnormalities and psychiatric diagnosis of both the groups. However, an evaluation of EEG abnormalities in all cases with CKD suggested a statistically significant difference between them. In the EEG recordings, electrical seizures activity was not enrolled in any of the cases. In the present study, psychiatric morbidity for patients with CKD and SS was worse than for patients with only CKD. These results indicate a need to develop an effective psychologic strategy for dealing with psychiatric disorders among patients with CKD and SS.


Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.
Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.


Mutagenesis of echinocandin B overproducing Aspergillus nidulans capable of using starch as main carbon source.
Echinocandin B, a kind of antimycotic with cyclic lipo-hexapeptides, was produced by fermentation with Aspergillus nidulans using fructose as main carbon source. The objective of this study was to screen a high-yield mutant capable of using cheap starch as main carbon source by atmospheric and room temperature plasma (ARTP) treatment in order to decrease the production cost of echinocandin B. A stable mutant A. nidulans ZJB19033, which can use starch as optimal carbon source instead of expensive fructose, was selected from two thousands isolates after several cycles of ARTP mutagenesis. To further increase the production of echinocandin B, the optimization of fermentation medium was performed by response surface methodology (RSM), employing Plackett-Burman design (PBD) followed by Box-Behnken design (BBD). The optimized fermentation medium provided the optimal yield of echinocandin B, 2425.9 ± 43.8 mg/L, 1.3-fold compared to unoptimized medium. The results indicated that the mutant could achieve high echinocandin B production using cheap starch as main carbon source, and the cost of carbon sources in fermentation medium reduced dramatically by about 45%.


Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders.
Growing consensus suggests that autism spectrum disorders (ASD) are associated with atypical brain networks, thus shifting the focus to the study of connectivity. Many functional connectivity studies have reported underconnectivity in ASD, but results in others have been divergent. We conducted a survey of 32 functional connectivity magnetic resonance imaging studies of ASD for numerous methodological variables to distinguish studies supporting general underconnectivity (GU) from those not consistent with this hypothesis (NGU). Distinguishing patterns were apparent for several data analysis choices. The study types differed significantly with respect to low-pass filtering, task regression, and whole-brain field of view. GU studies were more likely to examine task-driven time series in regions of interest, without the use of low-pass filtering. Conversely, NGU studies mostly applied task regression (for removal of activation effects) and low-pass filtering, testing for correlations across the whole brain. Results thus suggest that underconnectivity findings may be contingent on specific methodological choices. Whereas underconnectivity reflects reduced efficiency of within-network communication in ASD, diffusely increased functional connectivity can be attributed to impaired experience-driven mechanisms (e.g., synaptic pruning). Both GU and NGU findings reflect important aspects of network dysfunction associated with sociocommunicative, cognitive, and sensorimotor impairments in ASD.


Evaluation of a rehabilitative pedorthic: plantar pressure alterations with scaphoid pad application.
Scaphoid or longitudinal arch pads are frequently prescribed pedorthics for foot and ankle rehabilitation. These pedorthics are reported to be effective in mechanically supporting the medial longitudinal arch while reducing plantar and medial soft tissue strain. The objective of this study was to measure alterations in ambulatory plantar pressure metrics in a group of adults secondary to scaphoid pad application. The biomechanical rationale of this study was that the geometry of foot contact would be altered secondary to foot inversion. Ten adult male subjects with biomechanically normal feet were evaluated during multiple trials. A Holter type microprocessor-based portable in-shoe plantar pressure data acquisition system was used to record the dynamic data. Pressures were recorded from eight discrete plantar locations at the hindfoot, midfoot, and forefoot regions of the insole. Statistically significant (p < or = 0.05) increases in peak pressures were seen laterally with scaphoid pad application, while significant decreases in peak pressures with pad usage occurred at the hallux and the calcaneal region of the foot. At the medial longitudinal arch, peak pressures increased from near 0 to 115.3 kPa, contact durations increased from near 0 to 438 ms, and pressure-time integrals increased from near 0 to 33.4 kPa.s.


Natural killer cell activity in Sjögren's syndrome and systemic lupus erythematosus: stimulation with interferons and interleukin-2 and correlation with immune complexes.
Natural killer (NK) cell activity and its stimulation by interferons (IFNs) and interleukin-2 (IL-2) are diminished in Sjögren's syndrome and systemic lupus erythematosus (SLE). Serum samples of these patients often contain circulating immune complexes, which may influence NK cell activity. Sixteen patients with Sjögren's syndrome (14/16 immune complex positive), 14 with SLE (9/14 immune complex positive), and 11 controls (immune complex negative) were studied. Mononuclear cells collected from a Percoll gradient were preincubated with recombinant IFN-alpha (rIFN-alpha) (100 U/ml), rIFN-gamma (1000 U/ml), rIL-2 (100 U/ml), or without cytokine. Natural killer cell activity was determined by incubating the mononuclear cells with carboxyfluorescein labelled K562 cells, and the percentage decrease of fluorescence was measured on an FACS Analyzer. In patients with Sjögren's syndrome and SLE NK cell activity and the numbers of cells expressing the NK cell associated antigens CD16 and Leu7 were diminished compared with the controls. Interleukin-2 stimulated NK cell activity significantly in comparison with the non-stimulated value in all studied groups, whereas IFN-gamma only stimulated NK cell activity in both patient groups and IFN-alpha only in patients with Sjögren's syndrome. There was no correlation between NK cell activity, with or without stimulation, and the immune complex concentrations. It is concluded that NK cell activity is decreased in Sjögren's syndrome and SLE and that it may be partially restored by IL-2 and IFN-gamma in both diseases, and by IFN-alpha in Sjögren's syndrome. The decrease of NK cell activity did not correlate with immune complex concentrations; on the other hand, decreased numbers of NK cells (CD16+ or Leu7+) and of cytokine concentrations might be important in the impaired NK cell activity in both diseases.


Modified procedure of a direct in vitro exposure system for mammalian cells to whole cigarette smoke.
In vitro biological studies on cigarette smoke have usually been made using either cigarette smoke condensate--obtained by trapping the particulate phase of smoke on a filter, or soluble smoke components--obtained by trapping cigarette smoke in buffer solution. However, these approaches may not truly reflect the physical and chemical condition of freshly generated smoke. Clearly it is important to be able to evaluate the biological effects of fresh smoke on mammalian cells for a better understanding of the potential effects of smoking. The CULTEX technology is a new experimental system for cultivation and exposure techniques enhanced the efficiency of in vitro studies, and allows direct exposure of cells intermittently at the air/liquid interface with ultrafine particles, gases, or mixtures of both which fixedly flows. The CULTEX technology has therefore been modified to evaluate the biological effects of whole cigarette smoke in an in vitro system. The exposure system design was based on a combination of the sedimentation procedure and the CULTEX cultivation technique. After freshly generated smoke was delivered onto cells, the flow was shut off and the medium was slowly removed. In this manner, cells were exposed to both the vapor and particulate phase of smoke efficiently. Cells were maintained in the liquid medium except during the exposure period to maintain the culture conditions and to protect the cells from both the influence of puff pressure and the airflow, which served to remove residual cigarette smoke. The medium was changed at every puff of smoke and so effectively eliminating the possibility of any effects caused by accumulation of soluble cigarette smoke components into the medium. This cycle was repeated and cells were exposed to freshly generated cigarette smoke intermittently.


Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations.
This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). LVM regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index [LVMi] ≥ 149 g/m(2) men, ≥ 122 g/m(2) women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. Compared with patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p = 0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression. In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression.


Data quality in hospital strategic information systems: a summary of survey findings.
Fundamental changes in health care financing and delivery have resulted in an unprecedented need for data and information. The application of computer technology to daily hospital operations has gone far toward aiding various kinds of organizational decision making. The quality of those decisions, however, is dependent upon the quality of the data delivered by the various information systems used in the course of health care delivery and management. What remains unknown is the extent to which poor data quality occurs and what actions are taken to measure and control data quality in information systems used for strategic decision making. This article summarizes the results of a survey that was conducted for the purpose of explaining what information systems are important to hospital administrators in their strategic decision making, the frequency with which strategic decision makers encounter data quality problems, and what, if any, actions are taken to prevent, control, or correct apparent data quality problems.


Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.
Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. Previously, we determined that decreased expression of the cytosolic pentose phosphate pathway (PPP) enzyme transaldolase activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan. Here we report that transaldolase (tald-1) deficiency impairs mitochondrial function in vivo, as evidenced by altered mitochondrial morphology, decreased respiration, and increased cellular H2O2 levels. Lifespan extension from knockdown of tald-1 is associated with an oxidative stress response involving p38 and c-Jun N-terminal kinase (JNK) MAPKs and a starvation-like response regulated by the transcription factor EB (TFEB) homolog HLH-30. The latter response promotes autophagy and increases expression of the flavin-containing monooxygenase 2 (fmo-2). We conclude that cytosolic redox established through the PPP is a key regulator of mitochondrial function and defines a new mechanism for mitochondrial regulation of longevity.


Intact alveolar epithelial permeability and transalveolar fluid absorption after thoracic irradiation in rats.
We have addressed the question of how the alveolar space stays relatively free of fluid when thoracic irradiation injures the pulmonary capillary endothelium and plasma fluid leaks into the interstitium. A single dose of 15 Gy to the thorax of rats significantly increased the pulmonary capillary filtration coefficient and the lung wet/dry weight ratio 2 h after irradiation. However, there was no significant increase in the release of lactose dehydrogenase or leaking of Evans blue dye into the alveolar space, indicating that alveolar epithelial permeability remained intact. We found no significant difference in the basal alveolar fluid clearance between control and irradiated animals. There was also no significant difference in blockage of alveolar fluid clearance by amiloride. This indicates that the function of the alveolar epithelial Na(+) channels is not impaired and that alveolar epithelium absorbs fluid normally. Examination of lung tissue by light microscopy demonstrated accumulation of fluid in the perivascular region but not in the alveolar space. Our data appear to indicate that the alveolar epithelial barrier function is more resistant to radiation than that of the pulmonary capillary endothelium. We conclude that intact alveolar epithelial permeability and normal transalveolar epithelial fluid absorption ability are of critical importance in keeping the alveolar space relatively free of fluid during acute radiation lung injury.


Viability of Bacillus popilliae after lyophilization of liquid nitrogen frozen cells.
The per cent viability of Bacillus popilliae after lyophilization of liquid nitrogen frozen cells was determined. Lyophilization of 9- to 12-hr cells which had been suspended in 5% sodium glutamate plus 0.5% gum tragacanth, frozen in liquid nitrogen vapor, and dried 4 to 5 hr with the ampoules exposed to room temperature resulted in survival of 64.6% of the original cells. After storage of these lyophilized preparations for 6 months at room temperature, 10.5% of the original cells were still viable.


Cisapride versus ranitidine in the treatment of reflux esophagitis.
The healing effect of the prokinetic drug cisapride (10 mg q.i.d.) on esophageal lesions, and its therapeutic control of gastroesophageal reflux symptoms were compared with the effects of the H2-antagonist ranitidine (150 mg b.i.d. + placebo b.i.d.) in a double-blind trial. In each group, 28 patients with Savary-Miller Grade I or II esophagitis were treated for 6 or 12 weeks. At the end of treatment, follow-up endoscopy showed that mucosal lesions were absent in 89% of the cisapride patients and in 79% of the ranitidine patients. In addition, 86% and 82% of the patients in the cisapride and the ranitidine group, respectively, had no, or only mild, reflux symptoms. Minor side effects were experienced in both groups. From these data, cisapride appears to be as effective as ranitidine in controlling reflux symptoms and in promoting the healing of mucosal lesions in milder forms of reflux esophagitis.


[Teaching of gerontogeriatric nursing and complexity].
The present study had the objectives of identifying the characteristics of gerontogeriatric nursing and of reflecting on this teaching, based on identified characteristics, in the light of Complexity. A qualitative research, its data sources were nine proceedings volumes of Brazilian Nursing congresses and seven Brazilian nursing publications of the 1991-2000 period. The main body of this article was comprised of 16 scientific articles; QRSNUD* IST4 was used for analysis. Results showed that this teaching does take place, and it is carried out through: mandatory disciplines in the curriculum; practical activities; activities during curricular training; extra-curricular activities; participation on specific or general Nursing events in which studies are presented; other activities. To use the principles of Complexity is tantamount to perceiving educative teaching as trying to convey a culture that will enable future workers to understand the human condition and to think in a contextualized, open, globalized, ethical way.


Desegregating health statistics and health research in South Africa.
This article aims: (i) to re-examine the use and usefulness of categorisation based on 'race', ethnicity and 'population group' membership in public health research; and (ii) to assess the consequences of using these categories for describing, analysing and redressing disparities in health within South Africa. The utility of categorisation based on 'race', ethnicity and 'population group'. Categorising populations and comparing patterns of disease between different groups of people can be a useful technique for identifying potential causes of disease. In this context, ethnicity is a valid social concept that could be used to investigate the consequences of self-ascribed identity on health. Likewise, 'population group', as defined during apartheid in South Africa, represents a valid political concept that could be used for assessing the impact of social discrimination on health. However, both these concepts are often seen, and used, as euphemisms for 'race', even though there are no genetically distinct human subspecies that can be identified and categorised as discrete 'races'. Indeed, 'race' as a biological concept has no validity in human biology. Nevertheless, categories based on 'race', ethnicity and 'population group; continue to be used in health research, and reinforce the perception that differences in disease between different 'racial', ethnic and 'population' groups are the result of heritable biological characteristics. In so doing, they undermine support for health interventions that would otherwise address the social and political origins of 'racial' and ethnic disparities in health. The utility of 'population group' for redressing the consequences of apartheid. Despite these problems, 'population group' classification provides important information for assessing the impact of apartheid on disparities in health within South Africa. Yet, the abolition of apartheid legislation is likely to result in extensive socio-economic and geographical migration that will weaken the sensitivity and specificity of 'population group' as an indicator for identifying inequalities in health. For this reason, targeting corrective action at specific population groups in order to tackle disparities in health, runs the risk of ignoring alternative social causes of inequalities in health, and ignoring disadvantaged individuals from elsewhere in the population. The continued use of 'population group' classification might also perpetuate the root cause of disparities in health, by maintaining the process used to formalise discrimination. If the purpose of health research is to monitor inequalities in health and to help target resources aimed at reducing these inequalities, then it should seek, in its language, concepts and methods to undermine the root cause of disadvantage. Health research aimed at monitoring and redressing the consequences of social disadvantage on health should therefore focus on non-biological determinants of social disparities in health. As a general rule, health researchers should avoid using categories based on 'race', ethnicity and 'population group' when collecting and analysing health data; journal editors should not accept articles that use these categories without justification; and health authorities should not collect data routinely segregated by 'race', ethnicity or 'population group'.


Interaction of truncated human interferon gamma variants with the interferon gamma receptor: crucial importance of Arg-129.
Recombinant human interferon gamma (IFN-gamma), produced in Escherichia coli, was selectively truncated at its C-terminus with chymotrypsin, clostripain or plasmin. The C-terminal amino acid residues of the three truncated IFN-gamma variants were identified as Phe136, Arg129 and Lys128, indicating the removal of 7, 14 and 15 amino acid residues from the full-length molecule. The absence of seven C-terminal residues did not influence the binding of IFN-gamma to its receptor. In contrast, the truncation of 14 residues resulted in a decrease in the Ka value to 1/24, as determined by surface plasmon resonance analysis. The removal of one additional amino acid residue from the C-terminal region of IFN-gamma led to a marked loss of receptor-binding capacity and biological activity. These observations demonstrate that Arg129 is an essential part of a functionally important C-terminal IFN-gamma sequence that is involved in receptor interaction.


Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1⁻4 μM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 μM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-β, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.


Host quality and spatial patterning in infections of the Eastern mudsnail (Ilyanassa obsoleta) by two trematodes (Himasthla quissetensis and Zoogonus rubellus).
Several studies have suggested that the fitness of a parasite can be directly impacted by the quality of its host. In such cases, selective pressures could act to funnel parasites towards the highest-quality hosts in a population. The results of this study demonstrate that snail host quality is strongly correlated with spatial patterning in trematode infections and that habitat type is the underlying driver for both of these variables. Two trematodes (Himasthla quissetensis and Zoogonus rubellus) with very different life cycles assume the same spatial infection pattern in populations of the first intermediate host (Ilyanassa obsoleta) in coastal marsh habitats. Infected snails are disproportionately recovered from intertidal panne habitats, which offer more hospitable environs for snails than do adjacent habitats (intertidal creeks, coastal flats, and subtidal creeks), in terms of protection from turbulence and wave action, as well as the availability of food stuffs. Snails in intertidal panne habitats are of higher quality when assessed in terms of average size-specific mass, growth rate, and fecundity. In mark-recapture experiments, snails frequently dispersed into intertidal pannes but were never observed leaving them. In addition, field experiments demonstrate that snails confined to intertidal panne habitats are disproportionately infected by both trematode species, relative to conspecifics confined to adjacent habitats. Laboratory experiments show that infected snails suffer significant energetic losses and consume more than uninfected conspecifics, suggesting that infected snails in intertidal pannes may survive better than in adjacent habitats. We speculate that 1 possible mechanism for the observed patterns is that the life cycles of both trematode species allows them to contact the highest-quality snails in this marsh ecosystem.


ClpP is required for proteolytic regulation of type II toxin-antitoxin systems and persister cell formation in Streptococcus mutans.
The type II toxin-antitoxin (TA) modules, mazEF and relBE, in Streptococcus mutans have been implicated in stress response, antibiotic tolerance and persister cell formation. However, how S. mutans regulates these systems to prevent unwanted toxin activation and persister cell formation is unclear. In this study, we provide evidence that ClpP is required for the proteolytic regulation of these TA systems and persister cell formation in S. mutans following antibiotic challenge. A persister viability assay showed that S. mutans UA159 (WT) formed a larger quantity of persister cells than its isogenic mutant ΔclpP following antibiotic challenge. However, the lux reporter assay revealed that clpP deletion did not affect the transcriptional levels of mazEF and relBE, since no significant differences (P>0.05) in the reporter activities were detected between the wild-type and ΔclpP background. Instead, all antibiotics tested at a sub-minimum inhibitory concentration (sub-MIC) induced transcriptional levels of mazEF and relBE operons. We then examined the protein profiles of His-tagged MazE and RelB proteins in the UA159 and ΔclpP backgrounds by Western blotting analysis. The results showed that S. mutans strains grown under non-stress conditions expressed very low but detectable levels of MazE and RelB antitoxin proteins. Antibiotics at sub-MICs induced the levels of the MazE and RelB proteins, but the protein levels decreased rapidly in the wild-type background. In contrast, a stable level of MazE and RelB proteins could be detected in the ΔclpP mutant background, suggesting that both proteins accumulated in the ΔclpP mutant. We conclude that ClpP is required for the proteolytic regulation of cellular levels of the MazE and RelB antitoxins in S. mutans , which may play a critical role in modulating the TA activities and persister cell formation of this organism following antibiotic challenge.


Antimicrobial activity of essential oil and methanol extracts of Achillea sintenisii Hub. Mor. (Asteraceae).
The essential oil, obtained by Clevenger distillation, and water-soluble and water-insoluble parts of the methanol extracts of Achillea sintenisii Hub. Mor. were individually assayed for their antimicrobial activities against 12 bacteria and two yeasts, Candida albicans and C. krusei. No activity was exhibited by the water-soluble subfraction, whereas both the water-insoluble subfraction of the methanol extracts and the essential oil were found to be active against some test microorganisms studied. Since the essential oil possessed stronger activity than the other extracts tested, it was further fractionated and the fractions were evaluated for their antimicrobial activity, followed by GC-MS analysis, resulting in the identification of 32 compounds which constituted 90.2% of the total oil. The GC-MS analysis of the oil and its fractions revealed that the main components of the oil, e.g. camphor and eucalyptol, possessed appreciable activity against C. albicans and Clostridium perfringens. The fi ndings presented here also suggest that the other constituents of the oil, e.g. borneol and piperitone can also be taken into account for the activity observed.


Pressure tuning of the optical properties of GaAs nanowires.
The tuning of the optical and electronic properties of semiconductor nanowires can be achieved by crystal phase engineering. Zinc-blende and diamond semiconductors exhibit pressure-induced structural transitions as well as a strong pressure dependence of the band gaps. When reduced to nanoscale dimensions, new phenomena may appear. We demonstrate the tuning of the optical properties of GaAs nanowires and the induction of a phase transition by applying an external pressure. The dependence of the E(0) gap on the applied pressure was measured, and a direct-to-indirect transition was found. Resonant Raman scattering was obtained by pressure tuning of the E(0) and the E(0) + Δ(SO) gaps with respect to the excitation energy. The resonances of the longitudinal optical modes LO and 2LO indicate the presence of electron-phonon Fröhlich interactions. These measurements show for the first time a variation of ionicity in GaAs when in nanowire form. Furthermore, the dependence of the lattice constant on applied pressure was estimated. Finally, we found a clear indication of a structural transition above 16 GPa.


Isolation of a lentivirus from a macaque with lymphoma: comparison with HTLV-III/LAV and other lentiviruses.
A retrovirus has been isolated on the human T-cell line HuT 78 after cocultivation of a lymph node from a pig-tailed macaque (Macaca nemestrina) that had died with malignant lymphoma in 1982 at the University of Washington primate center. This isolate, designated MnIV (WPRC-1) (M. nemestrina immunodeficiency virus, Washington Primate Research Center) shows the characteristic morphology of a lentivirus and replicates to high titers in various lymphocyte lines of human and primate origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified MnIV revealed multiple bands of structural proteins, including a major viral gag protein of 28 kilodaltons, that did not comigrate with the viral proteins of a human immunodeficiency virus (HIV [FRE-1]) that was also isolated on HuT 78 cells. The relatedness of MnIV to other lentiviruses (HTLV-III/LAV, EIAV, and visna) was examined in radioimmunoassays, by immunoblot techniques, and by N-terminal amino acid sequence analysis of the viral p28 gag protein. The immunoassays revealed cross-reactivity only between MnIV p28 and HTLV-III/LAV p24, and sequence analysis showed that 14 of the 24 N-terminal residues of MnIV p28 and HTLV-III/LAV p24 are identical. These results indicate that MnIV belongs to the same lentivirus family as HTLV-III/LAV but is only partially related to these human acquired immune deficiency syndrome retroviruses.


Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes.
Aging is a major determinant of the incidence and severity of ischaemic heart disease. Preclinical information suggests the existence of intrinsic cellular alterations that contribute to ischaemic susceptibility in senescent myocardium, by mechanisms not well established. We investigated the role of altered mitochondrial function in the adverse effect of aging. Isolated perfused hearts from old mice (> 20 months) displayed increased ischaemia-reperfusion injury as compared to hearts from adult mice (6 months) despite delayed onset of ischaemic rigor contracture. In cardiomyocytes from aging hearts there was a more rapid decline of mitochondrial membrane potential (Δψm) as compared to young ones, but ischaemic rigor shortening was also delayed. Transient recovery of Δψm observed during ischaemia, secondary to the reversal of mitochondrial FoF1 ATP synthase to ATPase mode, was markedly reduced in aging cardiomyocytes. Proteomic analysis demonstrated increased oxidation of different subunits of ATP synthase. Altered bionergetics in aging cells was associated with reduced mitochondrial calcium uptake and more severe cytosolic calcium overload during ischaemia-reperfusion. Despite attenuated ROS burst and mitochondrial calcium overload, mitochondrial permeability transition pore (mPTP) opening and cell death was increased in reperfused aged cells. In vitro studies demonstrated a significantly reduced calcium retention capacity in interfibrillar mitochondria from aging hearts. Our results identify altered FoF1 ATP synthase and increased sensitivity of mitochondria to undergo mPTP opening as important determinants of the reduced tolerance to ischaemia-reperfusion in aging hearts. Because ATP synthase has been proposed to conform mPTP, it is tempting to hypothesise that oxidation of ATP synthase underlie both phenomena.


Tropical trials: the problems of research in the tropics.
Eleven scientists who, like Herbert Gilles, have spent many years in the study of tropical disease, responded to an inquiry about the most problematic aspects of conducting intervention trials in the tropics. Areas of challenge or difficulty that figured most frequently in the replies were: (1) the proper interests, involvement and perceptions of the studied community; (2) maintaining a research team's standards and motivation over long periods; (3) good study design; (4) communications; and (5) the provision of adequate remuneration and incentives to local scientists. Other problems mentioned included the need to translate results into policy, the importance of a long-term view, the correct use of controls, the attitudes of donors, and the influences of national and local politics. Careful attention must be given to these aspects in the planning and conduct of international research.


Morphology Optimization via Side Chain Engineering Enables All-Polymer Solar Cells with Excellent Fill Factor and Stability.
All-polymer solar cells (all-PSCs) composed of conjugated polymers as both donor and acceptor components in bulk heterojunction photoactive layers have attracted increasing attention. However, it is a big challenge to achieve optimal morphology in polymer:polymer blends. In response, we report herein a new strategy to adjust the nanoscale organization for all-PSCs. Specifically, side chain engineering of the well-known naphthalene diimide (NDI)-based polymer N2200 is modulated by introducing a fraction of linear oligoethylene oxide (OE) side chains to replace branched alkyl chains on the NDI units and by synthesizing a series of NDI-based polymer acceptors NOE x, where x is the percentage of OE chain substituted NDI units relative to total NDI units. Compared to the reference polymer NOE0, OE-chain-containing polymer NOE10 offers a much higher power conversion efficiency (PCE) of 8.1% with a record high fill factor (FF) of 0.75 in all-PSCs. Moreover, the NOE10-based all-PSC exhibits excellent long-term and thermal stabilities with >97% of the initial PCE being maintained after 300 h of aging at 65 °C. This work demonstrates an effective morphology optimization strategy to achieve highly efficient and stable all-PSCs and shows the excellent potential of NOE10 as an alternative to commercially available acceptor polymers N2200.


Gonadotropin- and lipoprotein-supported progesterone production by primate luteal cell types in culture.
This study examined the ability of gonadotropin and lipoproteins to support progesterone (P) production during long-term culture of luteal cell types obtained from rhesus macaques at midluteal phase of the menstrual cycle. Mixed (unsorted) luteal cells and small and large cells sorted by flow cytometry were cultured with human IDL, acetylated (ac)LDL or high density lipoprotein (HDL) (0-100 μg protein/ml) with or without hCG (100 ng/ml). In mixed cells, daily P levels declined during culture, although treatment with hCG alone increased P levels on all days of culture. Treatment with LDL, acLDL or HDL alone had no effect on P levels. However, hCG + LDL sustained P levels through day 4 at or above day 1 control values. Treatment with hCG + acLDL also increased P production above that of hCG alone, but hCG + HDL only modestly enhanced P production (180%). Although hCG stimulated P production by freshly-harvested large, but not small, cells during acute (3h) incubation, both cell types responded to hCG with up to an eightfold increase in P production on days 1-4 of culture. P levels were essentially nondetectable in both sorted cell groups by day 4. Small cells did not respond to any of the three lipoprotein treatments; large cells responded to LDL or acLDL on day 1, but this response was not apparent later in culture. Treating small or large cells with hCG + lipoprotein was no different from hCG alone. Thus, (1) LDL, and to some extent modified LDL, supports gonadotropinstimulated steroidogenesis by mixed cell populations in the monkey corpus luteum; (2) the lack of LDL response by sorted cell types suggests that the culture conditions or absence of other cell types renders lipoprotein treatment ineffective; and (3) small luteal cells develop the cellular components necessary for gonadotropin-stimulated steroidogenesis within 24 h of culture.