The role of disorder on the electronic structure of conjugated polymers. The case of poly-2,5-bis(phenylethynyl)-1,3,4-thiadiazole.
Insight into the electronic structure of disordered poly-2,5-bis(phenylethynyl)-1,3,4-thiadiazole in an amorphous region, in comparison to an ideal two-planar cofacial oligomer system, is pursued. The atomic structure of the amorphous polymer was obtained from classical molecular dynamics. It was subsequently used to calculate the electronic states and inter- and intrachain electronic coupling integrals using the density functional theory based charge patching method. The interchain electronic coupling integrals in the amorphous system were found to be an order of magnitude smaller than in the ordered system with similar distances between the chains. The results also suggest that the electronic structure of the whole system cannot be understood as a collection of the electronic structures of individual chains. The band gap of the whole system is significantly smaller than the band gaps of individual chains. This decrease originates from the disordered long range electrostatic potential created by the dipole moments of polymer repeat units, which should be minimized if one seeks good transport properties.


Human-related factors regulate the spatial ecology of domestic cats in sensitive areas for conservation.
Domestic cats ranging freely in natural areas are a conservation concern due to competition, predation, disease transmission or hybridization with wildcats. In order to improve our ability to design effective control policies, we investigate the factors affecting their numbers and space use in natural areas of continental Europe. We describe the patterns of cat presence, abundance and space use and analyse the associated environmental and human constraints in a well-preserved Mediterranean natural area with small scattered local farms. We failed in detecting cats in areas away from human settlements (trapping effort above 4000 trap-nights), while we captured 30 individuals near inhabited farms. We identified 130 cats, all of them in farms still in use by people (30% of 128 farms). All cats were free-ranging and very wary of people. The main factor explaining the presence of cats was the presence of people, while the number of cats per farm was mostly affected by the occasional food provisioning with human refuse and the presence of people. The home ranges of eight radio tagged cats were centred at inhabited farms. Males went furthest away from the farms during the mating season (3.8 km on average, maximum 6.3 km), using inhabited farms as stepping-stones in their mating displacements (2.2 km of maximum inter-farm distance moved). In their daily movements, cats notably avoided entering in areas with high fox density. The presence, abundance and space use of cats were heavily dependent on human settlements. Any strategy aiming at reducing their impact in areas of conservation concern should aim at the presence of settlements and their spatial spread and avoid any access to human refuse. The movements of domestic cats would be limited in areas with large patches of natural vegetation providing good conditions for other carnivore mammals such as red foxes.


Benign lymphangiomatous papules of the skin associated with ovarian fibroma.
Benign lymphangiomatous papules of the skin are considered reactive lymphatic proliferations either caused by disruption of the lymphatic flow or tissue damage produced by operation or radiation therapy. We report a 72-year-old woman with umbilical papules and vesicle-like lesions that led to the diagnosis of a large ovarian fibroma. Histologic study revealed dilated lymphatic spaces manifesting an anastomosing and branched pattern in the papillary and reticular dermis dissecting collagen bundles. The vessels were lined by plump endothelial cells with foci of intravascular papillary endothelial cell hyperplasia. After the ovarian fibroma was removed by laparotomy, umbilical lesions almost disappeared, leaving small flesh-colored papules. A periumbilical dermatosis may herald certain intra-abdominal diseases including those of neoplastic derivation. A heightened awareness of this association may lead to an early diagnosis with a potential for improved patient outcome. Benign lymphangiomatous papules have not been previously described in association with an untreated tumor, without previous operation or radiotherapy. This case advocates for disruption of the lymphatic drainage as the probable pathogenetic mechanism.


Scale of oceanic eddy killing by wind from global satellite observations.
Wind is the primary driver of the oceanic general circulation, yet the length scales at which this energy transfer occurs are unknown. Using satellite data and a recent method to disentangle multiscale processes, we find that wind deposits kinetic energy into the geostrophic ocean flow only at scales larger than 260 km, on a global average. We show that wind removes energy from scales smaller than 260 km at an average rate of -50 GW, a process known as eddy killing. To our knowledge, this is the first objective determination of the global eddy killing scale. We find that eddy killing is taking place at almost all times but with seasonal variability, peaking in winter, and it removes a substantial fraction (up to 90%) of the wind power input in western boundary currents. This process, often overlooked in analyses and models, is a major dissipation pathway for mesoscales, the ocean's most energetic scales.


SPACE SCIENCE: Europe Set to Work on Hubble's Replacement.
NASA scientists and engineers working on the Next Generation Space Telescope (NGST) got a boost from across the Atlantic last week. On 15 September in Paris, the European Space Agency's top science advisory committee recommended that the agency become a major partner in the project. The recommendation puts NGST--along with a handful of other missions the committee also endorsed last week--one short step away from officially becoming part of Europe's space program.


[The pain and behavior of women during labor and the different positions for childbirth].
This study evaluated the pain intensity and behavior during labor and delivery, among women who had natural childbirth, without analgesia, in one of the following positions: semi-sitting, lying on the left side, and lithotomy. This is a descriptive, cross-sectional and correlational study. The instruments used were a validated questionnaire that evaluates pain and behavior during labor and childbirth, from the women's perspective, and two pain scales: one analog and one alphanumerical. It was observed that the pain among women who had childbirth in a lithotomy position was significantly smaller compared to those lying on the left side (p=0.003), though women chose the positions. There was an association between pain and behavior. Pain in labor and childbirth were associated among each other, as was the behavior in these two moments. The results point at an association between the position at childbirth and pain, but it was not possible to identify factors to explain this association; therefore, there is a need for longitudinal studies.


Spontaneous Theory of Mind is reduced for nonhuman-like agents as compared to human-like agents.
Theory of Mind research has shown that we spontaneously take into account other's beliefs. In the current study, we investigate, with a spontaneous Theory of Mind (ToM) task, if this belief representation also applies to nonhuman-like agents. In a series of three experiments, we show here that we do not spontaneously take into account beliefs of nonhuman-like others, or at least we do it to a lesser extent than for human and human-like agents. Further, the experience we have with the other agent, in our case a dog, does not modulate spontaneous ToM: the same pattern of results was obtained when dog owners and no owners were compared. However, when more attention was attracted to the dog behavior, participants' behavior was influenced by the beliefs of the dog. In sum, spontaneous belief representation seems to be primarily restricted to human and human-like agents, but can be facilitated when more attention is drawn to a nonhuman-like agent.


Uncovering implicit theories of HIV prevention providers: it takes a community.
The Implicit Theories Project was a formative research study about what HIV prevention providers believe promotes risk behavior and facilitates behavior change. The study focused on providers who worked directly with clients to uncover providers' implicit theories. We conducted this work across several communities and targeted "risk groups" to uncover any commonalties among these various groupings. We conducted 20 in-depth interviews with HIV prevention providers from five community-based organizations (CBOs) in the San Francisco Bay Area. Although we focused on widely diverse populations, there was a tremendous amount of overlap in what they believed was at the core of behavior change. We also found that their theories of change were based on acknowledging larger structural factors and providing a sense of community. Identifying providers' implicit theories is useful to CBOs and researchers in helping to clarify circumstances that encourage HIV-related risk behaviors among at-risk populations and to inform program development and more formal evaluation efforts.


Using cluster heat maps to investigate relationships between body composition and laboratory measurements in HIV-infected and HIV-uninfected children and young adults.
Cluster heat maps were used to investigate relationships between body composition, lipid levels, and glucose metabolism in HIV-infected and HIV-uninfected children and young adults using data from a cross-sectional study. Three distinct clusters of participants were identified. One group had lower body fat and higher lipid measures and was mostly HIV infected. The other 2 groups were a mix of HIV-infected and HIV-uninfected participants. Of these, 1 cluster had more participants with higher body fat and insulin resistance, which are risk factors for future cardiovascular disease, and the other had relatively normal measurements on all outcomes.


Improving Regulatory Education: Can We Reconcile Employers' Expectations With Academic Offerings?
The growing belief that an effective regulatory function is vital to the successful development of medical products has spurred initiatives in regulatory education. To help prepare highly skilled professionals, some academic institutions have begun to incorporate new competencies into their curricula and to offer innovative programs in the field of regulatory studies. This study is the first national survey aimed at identifying the degree of adoption of an educational model based on well-defined professional competencies for graduate programs in regulatory studies. Respondents disclosed the challenges faced by faculty in implementing such a model. The study revealed the relevancy of this type of model and that a competency-based approach is largely perceived as a prerequisite for aligning a program's mission and vision with the skills that graduates need in the job market. Survey results show a strong general agreement regarding the suitability of a competency-based education model for regulatory studies. The challenges in implementing such a model, as described by survey participants, are significant but can be addressed. The barriers to implementation of regulatory curricula based on a competency-based education model should be better understood so that academic programs can educate highly skilled regulatory professionals. Such a workforce could best contribute to the delivery of high-quality, safe, and effective medical products.


Movable triple points and Dirac points in centrosymmetric AB2 (A = Cr, Mo; B = Si, Ge) compounds.
Topological semimetals with nontrivial band crossing points have attracted widespread interest in recent years. Here, we propose that AB2 (A = Cr, Mo; B = Si, Ge) compounds are topological semimetals that feature a pair of triple points (TPs) on high-symmetry paths in the absence of spin-orbital coupling (SOC). In particular, the existence of this kind of TP is accompanied by a quadratic nodal line (QNL). In addition, we discover that these TPs are movable. Under a triaxial strain, we can change their positions on high-symmetry paths. When considering SOC, TPs transform into two pairs of type-II Dirac points along the high-symmetry path. Akin to TPs without SOC, each pair of Dirac points can also shift their positions on the high-symmetry paths under a triaxial strain. To characterize this property of TPs and Dirac points, we construct an effective model around the TPs and Dirac points, finding that there indeed exists a parameter that could characterize the movable properties for the TPs and Dirac points. According to the bulk-surface correspondence, we also discover that the length of the Fermi arcs that correspond to the nontrivial band crossings are also altered when changing their positions. Meanwhile, the shapes of Fermi arcs are also changed. Therefore, our work provides a platform to study the band crossings that are movable. The controllable fermions are beneficial to utilize the topological materials in nano-devices.


[Hemopigmented villonodular synovitis of the knee. Apropos of 2 cases].
We report two cases of hemopigmented villonodular synovitis in two girls aged 5 years 9 months and 13 years respectively. This condition is a clinicopathologic entity of unknown pathogenesis and is exceedingly rare in childhood. Patients of both sexes can be affected, with no particular predominance. The clinical picture in our two patients consisted only in chronic hemarthrosis of the knee with occasionally tumor-like features. Arthrographic changes were not specific. Diagnosis was established upon arthrography and results of pathologic studies of biopsy specimens. Therapy of this condition is surgical and recurrences are infrequent.


Ovarian carcinoma identified by psammoma bodies in the cervicovaginal and endometrial smears.
A case of early bilateral serous papillary adenocarcinoma of the ovaries in an asymptomatic 58-year-old woman was diagnosed by the discovery of psammoma bodies in routine cervicovaginal and endometrial smears. Multiple small foci of carcinoma in-situ involving both fallopian tubes were also present. The significance of psammoma bodies in the cervicovaginal smear is discussed and the literature on the subject briefly reviewed.


Donnan potentials from striated muscle liquid crystals. A-band and I-band measurements.
A-band and I-band potentials are measured selectively in crayfish skinned long-tonic muscle fibers. The microelectrode tip diameters used in this study are shown to be sufficiently small to permit the discrete placement of an electrode into either an A-band or I-band. Random and directed impalements into mechanically skinned fibers with microelectrodes yields reproducible trimodal distributions of potentials where the modalities represent the A-band (-1.80 mV), the I-band (-0.76 mV), and the Z-line vicinity (-3.63 mV). In conjunction with Donnan equilibrium theory, fixed charge concentrations are calculated from the measured potentials for the A-band (25.9 mmol e-/l), I-band (10.9 mmol e-/l), and Z-line vicinity (52.3 mmol e-/l). When skinned fibers are treated with Triton X-100, the mean potentials (and charge concentrations) decrease: A-band to -1.71 mV (24.6 mmol e-/l), I-band to -0.71 mV (10.2 mmol e-/l), and the Z-line vicinity to -3.40 mV (49.0 mmol e/l). In the A-band this represents a loss of 1.3 mmol e-/l while in the I-band 0.7 mmol e-/l are lost; both decreases are attributed to the removal of internal membranous structures. In the rigor condition the A-band increases to -2.18 mV (33.1 mmol e-/l) and the I-band increases to -0.88 mV (13.3 mmol e-/l). Relative to the relaxed condition, this represents an increase of 8.5 mmol e-/l and 3.1 mmol e-/l in the A-band and I-band, respectively. The evidence shows that it is practical to measure A-band and I-band potentials selectively. Further, it is demonstrated that similar measurements can be obtained from agar, another polyelectrolyte gel system (see Appendix).


[The research on the edition of Daquanbencao (Complete Collection of Materia Medica)].
Zhengleibencao (Classified Materia Medica) had been formed into several kinds of edition systems during its dissemination, among which there was the edition system of Daquanbencao (Complete Collection of Materia Medica). Daquanbencao was originally carved in the Jin dynasty, thereafter it was re-carved in the Yuan, Ming and Qing dynasties so as to form a series of editions such as the edition of Zhenyou in the second year of the Jin dynasty; the edition of the Zongwenshuyuan college in Dade renyan year of the Yuan dynasty; the WANG Qiu's carved edition of Shangyitang hall in the Ming dynasty; the carved edition of Jishanshuyuan, the Jishang mountain college in the Ming dynasty, the reprinted edition of PENG Duan-wu in the Ming dynasty, the supplementary edition of YANG Bi-da in the Qing dynasty;, and the carved edition of KE Feng-shi in the Qing dynasty. Among all the editions, Chongkanjingshizhengleidaquanbencao (Reprinted Classified Daquan Materia Medica from Historical Classics) was the representative one. As a representative of the above editions, the carved edition of WANG took the edition of the Zongwenshuyuan college of the Yuan dynasty as the original edition, but the images picture of materia medica adopted from the edition of Zhenghebencao (Materia Medica of the Zhenghe era).


What happens when you wait? Effects of Social Security Disability Insurance wait time on health and financial well-being.
While waiting for a decision, individuals who apply for Social Security Disability Insurance face strong incentives to remain out of the labor force and receive no support from the program. An extended period with low income, high uncertainty, and lowered access to health insurance has the potential to harm applicants' well-being along many dimensions. In this study, I estimate the effect of initial wait time on health, healthcare access, and financial well-being, using the prevailing wait at the time an applicant applied as an instrument for their own initial wait. I find that a longer wait decreases the likelihood that an applicant has benefits terminated at the time of survey and increases the likelihood that they are currently receiving benefits, consistent with prior findings that longer waits decrease future work and earnings. Wait time also increases the number of conditions causing activity limitations. This suggests that new or worsening medical conditions contribute to the effect of wait time on employment and earnings, and that wait time has effects that extend beyond labor force outcomes.


[Clinical trial of MCNU for malignant brain tumors].
A total of 71 cases with primary brain tumors (44 cases) and metastatic brain tumors (30 cases) were entered into our clinical studies with MCNU and radiation therapy or MCNU alone. With regard to tumor reduction on CT scan, the response rates obtained for MCNU and radiation were 21.7% for malignant gliomas and 50.0% for metastatic brain tumors. With regard to improvement of neurological signs, the response rates obtained for MCNU and radiation were 62.9% for malignant gliomas and 71.4% for metastatic brain tumors. The response rates for MCNU were 5.8% for malignant gliomas and 46.1% for metastatic brain tumors. In the improvement of performance status, the response rates for MCNU and radiation were 51.8% for malignant gliomas and 64.2% for metastatic brain tumors. The response rates for MCNU were 46.1% for malignant gliomas and 30.7% for metastatic brain tumors. A minimal degree of hematological toxicity occurred but this gradually disappeared. These results suggested that MCNU has relatively effective antitumor activity against metastatic brain tumors and an enhanced effect with radiation against malignant gliomas.


Relative biological effectiveness of alpha particles at radon exposure.
The relative biological effectiveness (RBE) of alpha particles at radon exposure is estimated by comparison of radiation risks at external gamma exposure and radon exposure in different situations. For external gamma exposure, the BEIR VII model of radiation risk assessment was used. For occupational and indoor radon exposure, models such as BEIR VI, WISMUT, Tomasek's and combined miners population were considered. It was demonstrated that RBE values are strongly dependent on models of radiation risk assessment used for RBE calculation, sex of exposed peoples and age at the exposure. The average values of RBE in dependence on model of risk assessment choice are in the range from 1.5 to 12.0 for males and in the range from 0.34 to 2.7 for females.


Occurrence and weight-of-evidence risk assessment of alkyl sulfates, alkyl ethoxysulfates, and linear alkylbenzene sulfonates (LAS) in river water and sediments.
Alkyl sulfates (AS), alkyl ethoxysulfates (AES) and linear alkyl benzene sulfonates (LAS) are all High Production Volume (HPV) and 'down-the-drain' chemicals used globally in detergent and personal care products, resulting in low levels ultimately released to the environment via wastewater effluent. Due to their surfactant properties, they preferentially sorb to sediments. Hence, assessment of their levels and potential perturbations on benthos are of interest. The relative levels of AS/AES decreased with distance from the wastewater treatment plant outfall. However, this was not evident for LAS. Short chained AES and especially AS dominated the homologue distribution for AES. There were no evident patterns in LAS homologue distribution. The overall mean margin of exposure (MoE) for AS/AES and LAS is approximately 40 (range: 3 to 100) suggesting no noteworthy perturbation on biota. The findings in this study are in concordance with previous preliminary hazard screening. Comparative sediment contamination analyses principally based on Chapman and Anderson [Chapman PM, Anderson, J. A decision-making framework for sediment contamination. Integr Environ Assess Mana. 2005; 1: 163-173.] and the U.S. Environmental Protection Agency RAPID assessment methods [USEPA. Rapid bioassessment protocols for use in wadeable streams and rivers: Periphyton, benthic, macroinvertebrates, and fish. 1999. Second Edition. U.S. Environmental Protection Agency Office of Water, Washington, D.C. EPA 841-B-99-002.] did not reveal significant correlations between the surfactant concentrations and ecological status of the sampling locations. Several Lines of Evidence (LoE) of the Weight-of-Evidence (WoE) lead to the conclusion of low aquatic risk associated to the monitored compounds.


Cytosolic Internalization of Anti-DNA Antibodies by Human Monocytes Induces Production of Pro-inflammatory Cytokines Independently of the Tripartite Motif-Containing 21 (TRIM21)-Mediated Pathway.
Anti-DNA autoantibodies are a hallmark of systemic lupus erythematosus (SLE). A subset of anti-DNA IgG autoantibodies is cell-internalizable; thus they can enter living cells in the form of free IgG. However, the contribution made by the Fc region of internalized free-form IgG to the cytokine response has not been studied, despite the recent discovery of tripartite motif-containing 21 (TRIM21), a cytosolic Fc receptor involved in immune signaling. This study used an internalizable IgG anti-DNA antibody (3D8) to examine the cytokine responses of human monocytes to the Fc region of cytosolic free IgG. Internalization of 3D8 IgG and a 3D8 single-chain variable fragment-Fc (scFv-Fc) induced production of IL-8 and TNF-α via activation of NF-κB. By contrast, a 3D8 scFv (comprising variable domains alone) did not. This suggests Fc-dependent cytokine signaling. A 3D8 IgG-N434D mutant that is not recognized by TRIM21 induced greater production of cytokines than 3D8 IgG. Moreover the amounts of cytokines induced by 3D8 IgG in TRIM21-knockdown THP-1 cells were higher than those in control cells, indicating that cytokine signaling is not mediated by TRIM21. The results suggest the existence of a novel Fc-dependent signaling pathway that is activated upon internalization of IgG antibodies by human monocytes.


The relationship of stuttering severity and treatment length to temporal measures of stutterers' perceptually fluent speech.
The purpose of this study was to investigate the relationship between stuttering severity and treatment length to temporal measures of stutterers' perceptually fluent speech. Seventeen adult stutterers (4 mild, 8 moderate, and 5 severe) were divided into two treatment categories. One group with limited exposure to treatment (n = 7) consisted of stutterers who had completed 0-10 hr of treatment. Another group with an extensive period of treatment (n = 10) consisted of stutterers who had completed 47-212 hr of treatment. All subjects were asked to repeat a simple phrase and read a prose passage. Spectrographic measures of the stutterers' voice onset times, vowel, consonant, and phrase durations were obtained from perceptibly fluent productions of the isolated phrase and from a phrase extracted from the oral reading. Results showed that there were no significant differences among stuttering severity groups or the two groups with different lengths of treatment. These results suggest that changes in temporal measures of stutterers' fluency might occur through the process of treatment, but those changes are not related to stuttering severity or length of treatment.


Fullerene-porphyrin hybrid nanoparticles that generate activated oxygen by photoirradiation.
The preparation of water-dispersible hybrid nanoparticles comprising fullerene and porphyrin from cyclodextrin complexes is described. In the presence of polyethylene glycol, C60 fullerene and porphyrin were expelled from the cyclodextrin cavity to form fullerene-porphyrin hybrid nanoparticles in water. The fullerene-porphyrin hybrid nanoparticles exhibit improved singlet oxygen generation ability under photoirradiation compared with that of C60 nanoparticles.


Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure.
Losartan is a specific angiotensin II receptor antagonist with no agonist properties. This agent permits evaluation of the response to selective angiotensin II antagonism in patients with congestive heart failure. A study was designed to assess the acute hemodynamic and neurohumoral response to losartan in a controlled, blinded fashion. Sixty-six patients in New York Heart Association functional class II, III or IV with a radionuclide ejection fraction of < 40% were randomly allocated to treatment with placebo and then sequentially to 5, 10, 25, 75 and 150 mg losartan. Hemodynamic and neurohumoral measurements were obtained at selected times for 24 h following ingestion of a single dose of losartan. Treatment with losartan led to dose-dependent vasodilation. Mean arterial pressure and systemic vascular resistance decreased progressively up to a dose of 25 mg. The higher doses of 75 and 150 mg did not produce additional vasodilation. Similarly, the decrease in pulmonary capillary wedge pressure was not greater with doses exceeding 25 mg. The increase in the cardiac index was modest and similar for all doses. No variation in the heart rate was observed at any dose. The hemodynamic changes were accompanied by marked neurohumoral changes. Large dose-related increases in plasma renin activity and angiotensin II levels were observed, especially following the 150-mg dose. Moderate reductions occurred in serum aldosterone and plasma noradrenaline. The peak effect for these parameters occurred 4-6 h after the dose, with persistent changes still evident 24 h after the dose. These data demonstrate that selective blockade of the angiotensin II receptor with losartan causes a favorable vasodilatory and neurohumoral response in patients with heart failure. Further studies are needed to determine the most effective dose in these patients. Nevertheless, losartan should be of substantial clinical use in the management of this large population.


Differential effects and rates of normal aging in cerebellum and hippocampus.
Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4, 8, 12, 18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18- and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4- to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.


Effect of Catalyst Crystallinity on V-Based Selective Catalytic Reduction with Ammonia.
In this study, we synthesized V2O5-WO3/TiO2 catalysts with different crystallinities via one-sided and isotropic heating methods. We then investigated the effects of the catalysts' crystallinity on their acidity, surface species, and catalytic performance through various analysis techniques and a fixed-bed reactor experiment. The isotropic heating method produced crystalline V2O5 and WO3, increasing the availability of both Brønsted and Lewis acid sites, while the one-sided method produced amorphous V2O5 and WO3. The crystalline structure of the two species significantly enhanced NO2 formation, causing more rapid selective catalytic reduction (SCR) reactions and greater catalyst reducibility for NOX decomposition. This improved NOX removal efficiency and N2 selectivity for a wider temperature range of 200 °C-450 °C. Additionally, the synthesized, crystalline catalysts exhibited good resistance to SO2, which is common in industrial flue gases. Through the results reported herein, this study may contribute to future studies on SCR catalysts and other catalyst systems.


Posterior brain ERP patterns related to the go/no-go task in children.
Event-related potentials (ERPs) and performance correlates of inhibition of responses to no-go stimuli were investigated in 6-12-year-old children and young adults. The percent of correct responses to go stimuli was high and similar in both groups; the percent of false alarm errors to no-go was significantly higher in children. Effective inhibition of responses to no-go stimuli was elucidated by a negative component of ERPs, the frontal-central N2, with peak latency 230-430 ms after stimulus onset. In adults, N2 was larger to no-go than to go stimuli, regardless of stimulus frequency. This effect was more prominent in tasks with high (25% no-gos and 75% gos), than with low (75% no-gos and 25% gos) inhibitory demand. In children, the parietal N2 was generally larger to rare than to frequent stimuli, and it was more specifically related to inhibition. The analysis of the relationship of no-go N2 to the inhibitory content of stimuli, probability of stimuli, and the contextual task difficulty suggests that child/adult differences in behavioral responses and ERPs may be related to both the immaturity of the fronto-parietal cortical-cortical network and to different task strategies.


Inferential dependencies in causal inference: a comparison of belief-distribution and associative approaches.
Causal evidence is often ambiguous, and ambiguous evidence often gives rise to inferential dependencies, where learning whether one cue causes an effect leads the reasoner to make inferences about whether other cues cause the effect. There are 2 main approaches to explaining inferential dependencies. One approach, adopted by Bayesian and propositional models, distributes belief across multiple explanations, thereby representing ambiguity explicitly. The other approach, adopted by many associative models, posits within-compound associations--associations that form between potential causes--that, together with associations between causes and effects, support inferences about related cues. Although these fundamentally different approaches explain many of the same results in the causal literature, they can be distinguished, theoretically and experimentally. We present an analysis of the differences between these approaches and, through a series of experiments, demonstrate that models that distribute belief across multiple explanations provide a better characterization of human causal reasoning than models that adopt the associative approach.


Adenosine receptors expression in cardiac fibroblasts of patients with left ventricular dysfunction due to valvular disease.
Adenosine restores tissue homeostasis through the interaction with its membrane receptors (AR) expressed on fibroblasts, endothelial cells, smooth muscle cells and leukocytes, but their modulation is still not fully understood. To evaluate whether changes in the transcriptomic profiling of adenosine receptors (AR) occur in cardiac fibroblasts (CF) of patients (pts) with LV dysfunction due to valvular disease (V). The secondary aim was to compare in the same pts the results obtained at cardiac level with those found in circulating leukocytes. Auricle fragments were excised from 13 pts during prosthetic implantation while blood samples were collected from pts (n = 9) and from healthy subjects (C, n = 7). In 7 pts cardiac biopsy and blood samples were taken simultaneously. A human CF atrial cell line (cc) was used as control. AR higher levels of mRNA expression were observed with real-time PCR in Vpts compared to C, both at cardiac (overexpression A1R:98%, A2AR:63%, A2BR:87%, A3R:85%, CD39:92%, CD73:93%) and at peripheral level (A1R vs C: p = .0056; A2AR vs C: p = .0173; A2BR vs C: p = .0272; A3R vs C: p = .855; CD39 vs C: p = .0001; CD73 vs C: p = .0091). All AR subtypes were overexpressed in CF of Vpts. The same trends in AR expression at cardiac level was assessed on circulating leukocytes, thus opening a new road to minimally invasive studies of the adenosinergic system in cardiac patients.


Typhoid fever in children: a forgotten disease?
All indexed cases of typhoid fever occurring in children over a ten-year period in Jacksonville, Fla, were studied retrospectively. This review revealed that anorexia was the most common gastrointestinal complaint and that neurologic symptoms and signs were nearly as common as gastrointestinal signs. There was a significant delay in diagnosis in most cases because typhoid fever was not included in the differential diagnosis upon admission. This is probably due to the decline in the incidence of typhoid fever in the United States and the resultant lowering of the index of suspicion for the disease on the part of physicians in general. Representative cases are presented in detail.


Anterior-inferior plate fixation of middle-third fractures and nonunions of the clavicle.
Results of surgical treatment for clavicle injuries using standard approaches have shown relatively high complication rates including loss of fixation, persistent nonunion, implant related problems, and the need for subsequent surgeries are common. The purpose of this study is to evaluate the clinical results of patients treated for clavicle fractures and painful clavicular nonunions with anterior-inferior plating using a 3.5 mm plate. Consecutive clinical series. 3 tertiary care academic trauma centers (Level 1 and 2). Eighty consecutive patients with a middle-third fracture or painful nonunion of the clavicle. Open reduction and internal fixation using an anterior-inferior plating technique with a precontoured 3.5 mm plate and lag screw(s). Nonunions received autologous bone grafts. Patients were evaluated using physical and radiographic examination, the American Shoulder and Elbow Surgeons Shoulder Assessment (ASES), and the Short Form-36 (SF-36) outcomes questionnaire. Fifty-eight patients had sufficient records and follow-up of at least 24 months (mean 49 months). Clinical and radiographic union was present at a mean of 9.5 weeks for patients treated for acute fracture and 10.5 weeks those treated for nonunion. Complications included 1 failure of fixation, 1 nonunion, and 3 infections. Two patients underwent implant removal for bothersome hardware. Shoulder motion was good or excellent in all patients except those with neurologic injury. Functional results (ASES and SF-36) were good or excellent for the vast majority of patients, except those with neurologic injury. Anterior-inferior plating of acute middle-third fractures of the clavicle and clavicular nonunions using a plate and lag screws typically results in early healing, few complications and an excellent return of function. Advantages of this technique include stable bony fixation with instrumentation directed away from potentially dangerous infraclavicular structures and a minimal incidence of implant prominence problems.


Chediak-Higashi syndrome: neurocognitive and behavioral data from infancy to adulthood after bone marrow transplantation.
Chediak-Higashi syndrome (CHS) is a rare autosomal disorder characterized by immunodeficiency, albinism, and progressive neurologic abnormalities. While survivors of the childhood-onset disease are known to exhibit learning disabilities and neuropsychiatric disorders followed by middle-age dementia, we lack detailed data on the progression. We present the case of a young adult with records from infancy to the first signs of deterioration. An early neuropsychological and neuropsychiatric profiling is crucial to intervention selection as children with CHS may not benefit from regular special education. Our patient never showed neuropsychiatric symptoms but high levels of socioemotional adaptability.


Causes of secondary deformity after surgery to correct Wassel type IV-D thumb duplication.
This study was undertaken to document the causes of secondary deformities after surgery for correction of Wassel type IV-D thumb duplication. We carefully dissected and observed the flexor pollicis longus, and bone and joint anatomy in eight patients with secondary deformities after surgical correction. We transferred the flexor pollicis longus and thenar muscle attachments, reconstructed the A2 pulley, released and tightened the joint capsule, and performed osteotomies to correct skeletal malalignment. Kirschner wire fixation was used for 4-5 weeks, followed by brace fixation for 3 months. Patients were followed up for 13-34 months (mean 20 months). According to the Tada scores, the outcomes were good in six patients, and fair and poor in one patient each. The main causes of the secondary deformities were failure to reconstruct the A2 pulley, to transfer the flexor pollicis longus and thenar muscles, and incomplete resection of the radial metacarpal head. Brace fixation after Kirschner wire removal is crucial in preventing secondary deformities. IV.


Spongiform leucoencephalomyelopathy in border terriers: clinical, electrophysiological and imaging features.
A novel spongiform leucoencephalomyelopathy was reported in border terrier puppies in 2012 causing a shaking puppy phenotype, but no information regarding clinical progression, imaging or electrophysiological findings were available. The aim of the present study was to describe the clinical, electrophysiological and MRI features of this disease in seven dogs and compare them with human white matter disorders. All cases presented with cerebellar ataxia and severe generalised coarse body tremors, which started at three weeks of age. The three cases that were not euthanased showed slow but progressive improvement over several months. Brainstem auditory evoked response demonstrated a normal wave I, reduced amplitude of wave II and an absence of waves III-VII. MRI revealed bilateral and symmetrical T2-weighted hyperintensities affecting the brainstem and cerebellar white matter. Histological examination of the brain and spinal cord showed spongiform change affecting the white matter of the cerebellum, brainstem and spinal cord with decreased myelin content. In summary, this leucoencephalomyelopathy has a pathognomonic clinical presentation with defining MRI and electrophysiological characteristics, and it is the first report to describe a long-term improvement of this condition.


Association of an Mr 50,000 cap binding protein with the cytoskeleton in BHK cells.
A monoclonal antibody (anti-CBP antibody) is shown to be directed against cap binding protein(s) (CBP) by virtue of its ability to inhibit the translation of capped reovirus mRNA in a cell-free system derived from L-cells and inhibit the specific (cap analogue-inhibited) cross-linking of proteins to the oxidized 5' terminal cap structure of reovirus mRNA. Anti-CBP antibody reacts with an Mr 50,000 polypeptide in rabbit reticulocyte polysomes and this polypeptide appears to be associated with the 5' cap structure of mRNA. In BHK-21 cells immunofluorescence microscopy reveals that the antibody reacts with a fibrous network extending through the cytoplasm in a radial arrangement. The network behaves like intermediate filaments in colchicine-treated cells suggesting a direct or indirect linkage of CBP with intermediate filaments. The association of CBP with a cytoskeletal element is further confirmed by isolation of proteins from Triton X-100-extracted cells and identification of CBP in the cytoskeletal fraction with anti-CBP antibody. The major polypeptide reacting with anti-CBP antibody is an Mr 50,000 component. Tryptic peptide mapping shows that this polypeptide is related to an Mr 24,000 polypeptide identified as cap binding protein in earlier experiments [Sonenberg, Morgan, Merrick & Shatkin (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4843-4847].


Regulation of Lipid Membrane Partitioning of Tamoxifen by Ionic Strength and Cholesterol.
The purpose of this study was to inspect the interactions between an anti-breast cancer, TAM, with model of lipid membranes composed of either zwitterionic DPPC LUVs or anionic DPPG LUVs and how they depend on ionic strength and cholesterol. The Kp of TAM into DPPC and DPPG LUVs were determined at three different NaCl concentrations by second derivative UV-Vis spectrophotometry. The effect of cholesterol incorporated into these LUVs on TAM's Kp was also assessed. The ATR-FTIR measurements were carried out to verify structural changes within the acyl chain and head group regions of the liposomes upon TAM partitioning. Increasing salt concentration produced negligible impact on the partitioning of TAM into DPPC bilayer as its Kp remained unaffected whilst induced outstanding reduction of TAM's Kp into DPPG liposomes. Furthermore, TAM was found to disorder the lipids' acyl chains, which could result in an increase in the membrane fluidity, a necessary piece of information to refer to when prescribing TAM dosage for administration. Additionally, cholesterol showed astoundingly opposite contribution to the partitioning of TAM into the LUVs, as its Kp value reduced in DPPC/Chol bilayer yet increased in DPPG/Chol liposomes. Ionic strength and cholesterol play a noteworthy role in regulation of TAM partitioning into lipid membranes as they could obstruct or promote such action.


[Challenge in modern intensive care: chronic critical illness - pathophysiology and therapeutic options].
The recent developments in intensive care have resulted in improved survival rates of patients treated with acute organ deficiency. As a consequence, the rate of those who survive the acute phase and subsequently require protracted organ support due to persisting organ dysfunction has been growing. Several survivors display chronic health status deterioration leading to prolonged rehabilitation or nursing, and repeated hospitalizations. The condition developed following the survival of the acute phase and requiring long-lasting intensive care is frequently termed as chronic critical illness (CCI). Several definitions exist, most of these are based on the number of ventilator days, or days of stay at the intensive care unit. Nevertheless, in spite of the initially heterogenous etiology of the acute illness, the complications associated with CCI, as well as the pathophysiological processes underlying these, are relatively uniform. This causes CCI to be a unique clinical syndrome characterized by the development of secondary infections, myopathy, central and peripheral neuropathy, and typical alterations of the hormonal and immune system functions. The outcome is heavily influenced by the frailty and comorbidities of the patient, in addition to the severity of the acute illness. The treatment of CCI patients presents a complicated task requiring multidisciplinary view and individualized therapeutic measures. Since the aging of the population and the continuously improving success rates in overcoming acute conditions also facilitate the development of CCI, the systematic overview of the underlying pathophysiological processes is pivotal for the optimization of the medical, nursing, social and economical burden presented by this syndrome. Orv Hetil. 2023; 164(18): 702-712.


Chronic Chagas Cardiomyopathy Patients and Resynchronization Therapy: a Survival Analysis.
Chagas disease represents an important health problem with socioeconomic impacts in many Latin-American countries. It is estimated that 20% to 30% of the people infected by Trypanosoma cruzi will develop chronic Chagas cardiomyopathy (CCC), which is generally accompanied by heart failure (HF). Cardiac resynchronization therapy (CRT) may be indicated for patients with HF and electromechanical dysfunctions. The primary endpoint of this study was to analyze the response to CRT in patients with CCC, while the secondary endpoint was to estimate the survival rates of CRT responder patients. This is an observational, cross-sectional and retrospective study. The records of 50 patients with CRT pacing devices implanted between June 2009 and March 2017 were analyzed. For statistical analyses, Pearson's correlation was used along with Student's t-test, and survival was analyzed using the Kaplan-Meier method. A P value of <0.05 was considered significant. Out of 50 patients, 56% were male, with a mean age of 63.4±13.3 years and an average CRT duration of 61.2±21.7 months. The mean QRS duration was 150.12±12.4 ms before and 116.04±2.2 ms after the therapy (P<0.001). The mean left ventricular ejection fractions (LVEF) were 29±7% and 39.1±12.2% before and after CRT, respectively (P<0.001). A total of 35 (70%) patients had a reduction of at least one New York Heart Association (NYHA) functional class after six months of therapy (P=0.014). The survival rate after 72 months was 45%. This study showed clinical improvement and a nonsignificant survival rate in patients with CCC after the use of CRT.


Radiological evaluation of primary breast sarcoidosis presenting as bilateral breast lesions.
Sarcoidosis is an idiopathic multisystemic inflammatory disease that may exceptionally involve the breast and can have imaging features suspicious for benign or malignant lesions. Biopsy should be required to distinguish between breast sarcoidosis and malignancy, because clinical, mammographic and sonographic findings can be ambiguous or inconclusive. This case discusses the radiological manifestations and the value of different diagnostic features, and names the most relevant differential diagnosis.


Isoflavones are safe compounds for therapeutical applications - evaluation of in vitro data.
Isoflavone-rich food and food supplements have gained increasing popularity also in the Western world. Their weak estrogenic effect has been considered as a potential risk, although all epidemiological studies and clinical trials show a significant cancer protection and decreased risk of cardiovascular diseases. In vitro data suggest that the concerted action of the isoflavones and their metabolites show antiproliferative behaviour, reduce angiogenesis, reduce tumor progression and exert antiinflammatory effects. For the evaluation of the biological effects, special emphasis has to be put on the concerted action between the isoflavones and their metabolites. For instance, while isolated genistein shows some growth promoting effect at low concentrations, the metabolite equol or soy extract show growth retardation as well as higher concentrations of genistein do. The isoflavones have multiple affinities to other members of the steroid hormone receptor superfamily. The beneficial effect on metabolic diseases and weight reduction by isoflavone consumption can be partly explained by its affinity for the PPAR family. In light of the in vitro experiments, together with the epidemiological observations and the clinical experience, isoflavones can be considered as safe compounds and their consumption as food and food supplements has to be promoted.


Caudate volume as an outcome measure in clinical trials for Huntington's disease: a pilot study.
Previous research has demonstrated that longitudinal change in caudate volume could be observed over a period of 3 years in subjects with Huntington's disease (HD). The current pilot study was designed to determine whether measurement of caudate change on magnetic resonance imaging (MRI) is a feasible and valid outcome measure in an actual clinical trial situation. We measured caudate volumes on pre- and post-treatment MRI scans from 19 patients at two sites who were participating in CARE-HD (Co-enzyme Q10 and Remacemide: Evaluation in Huntington's Disease), a 30-month clinical trial of remacemide and co-enzyme Q(10) in symptomatic patients with HD. Results from this pilot study indicated that decrease in caudate volume was significant over time. Power analysis indicated that relatively small numbers of subjects would be needed in clinical trials using caudate volume as an outcome measure. Advantages and disadvantages of using MRI caudate volume as an outcome measure are presented. We recommend the adoption of quantitative neuroimaging of caudate volume as an outcome measure in future clinical trials for treatments of HD.


Tracing the Transformation and Allocation of the Newly Applied-P in Calcareous Soil Using an Enriched Oxygen Isotope Labeling Technique.
Different phosphorus (P) fertilizations significantly impact the transformation of the applied-P in soils. However, knowledge about how different P fertilization regimes influence the allocation of the amended-P in soil remains incomplete. Herein, we carried out a pot experiment to explore the fate of applied-P in calcareous soil using an oxygen isotope labeling technique (18O-P18O43-). Treatments included check (CK), single, and repeated applications. The phosphorus mass balance result showed that more than 48.5% of the applied-P was held in labile and moderately labile fractions with the repeated treatment, while approximately 27.4% of the added-P was recovered in nonlabile forms in the single application treatment. The isotopic tracer (18O-P18O43-) result demonstrated that the δ18OP values of NaHCO3-P and NaOH-P in the repeated P application were significantly higher than those in the single P application. Ultimately, better agronomic performances of the crops and higher PUE were achieved in the repeated treatment. Our findings highlighted that repeated P fertilization can improve P availability by reducing P fixation. These results pronounced that the enriched oxygen isotope technique can be considered an effective approach for tracing applied-P in soils.


The time to remember: Temporal compression and duration judgements in memory for real-life events.
Recent studies suggest that the continuous flow of information that constitutes daily life events is temporally compressed in episodic memory, yet the characteristics and determinants of this compression mechanism remain unclear. This study examined this question using an experimental paradigm incorporating wearable camera technology. Participants experienced a series of real-life events and were later asked to mentally replay various event sequences that were cued by pictures taken during the original events. Estimates of temporal compression (the ratio of the time needed to mentally re-experience an event to the actual event duration) showed that events were replayed, on average, about eight times faster than the original experiences. This compression mechanism seemed to operate by representing events as a succession of moments or slices of prior experience separated by temporal discontinuities. Importantly, however, rates of temporal compression were not constant and were lower for events involving goal-directed actions. The results also showed that the perceived duration of events increased with the density of recalled moments of prior experience. Taken together, these data extend our understanding of the mechanisms underlying the temporal compression and perceived duration of real-life events in episodic memory.


Post-Progression Survival Is Strongly Associated with Overall Survival in Patients Exhibiting Postoperative Relapse of Non-Small-Cell Lung Cancer Harboring Sensitizing EGFR Mutations.
Background and Objective: Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations show a good response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). The subsequent treatments influence the evaluability of the efficacy of front-line therapy on overall survival (OS). Consequently, we evaluated the associations of relapse-free survival (RFS) and post-progression survival (PPS) with OS in patients who exhibited postoperative relapse of EGFR-mutated NSCLC. Materials and Methods: We analyzed the data of 35 patients with EGFR-mutated NSCLC who underwent complete resection between January 2007 and June 2019. The correlations of RFS and PPS with OS were evaluated at the individual patient level. Results: Linear regression and Spearman's rank correlation analyses demonstrated that the PPS highly correlated with OS (r = 0.91, p < 0.05, R2 = 0.85), whereas the RFS weakly associated with OS (r = 0.36, p < 0.05, R2 = 0.25). Age and performance status at relapse were significantly associated with PPS. Conclusion: Overall, PPS was more strongly and significantly associated with OS than RFS. These results suggest that the OS of our cohort may be affected by treatments, besides postoperative relapse. However, larger-scale prospective studies are needed to confirm these results.


Current Understanding of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Signaling in T-Cell Biology and Disease Therapy.
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.


Anaesthetic suppression of transmitter actions in neocortex.
1. The effects of general anaesthetics were investigated on neuronal sensitivities to transmitter substances, which were determined by iontophoretic applications of acetylcholine, glutamate, N-methyl-D-aspartate (NMDA) and gamma-aminobutyrate (GABA) during intracellular recording in in vitro slice preparations of neocortex (guinea-pig). 2. In most of the 65 neurones studied, perfusion of isoflurane (0.5-2.5 minimum alveolar concentration (MAC)) or Althesin (25-200 microM) and, in some cases, halothane (0.5-2 MAC), markedly reduced the depolarizing responses and associated membrane conductance changes evoked by dendritic applications of acetylcholine, glutamate, NMDA and GABA. 3. The order of depression was acetylcholine greater than glutamate or NMDA much greater than GABA. This selectivity could also be assessed from the EC50 for the isoflurane-induced depression of the just-maximal responses to acetylcholine, which was 0.9 MAC compared with an EC50 = 1.9 MAC for the suppression of glutamate responses. The selectivity was less pronounced in the case of the actions of Althesin, where the EC50s were 75 microM for the depression of acetylcholine responses and 90 microM for the depression of glutamate responses. 4. The hyperpolarizing responses observed when GABA was applied near the perikaryon in 7 neurones, were slightly reduced (approximately 15%) in 4, and unchanged in 3 neurones during anaesthetic application. 5. The pronounced depression of the responsiveness to the putative arousal transmitters and an observed blockade of acetylcholine-induced potentiation of glutamate actions suggest that anaesthetics produce unconsciousness, at least in part, by interfering with subsynaptic mechanisms of neocortical activation.


TNFalpha-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?
Injury and disease in the CNS increases the amount of tumor necrosis factor alpha (TNFalpha) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFalpha might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFalpha on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFalpha causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFalpha-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFalpha-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response. Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFalpha can be central in causing neuronal disorders. We have further investigated the effects of TNFalpha on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFalpha-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFalpha might present a novel target to aid the development of new neuroprotective drugs.


Charge transport in carbon nanotubes: quantum effects of electron-phonon coupling.
This review deals with the role of electron-phonon (e-ph) coupling in quantum transport of carbon nanotubes. First, the case of low-energy phonons and weak localization phenomena is addressed, followed by a summary of inelastic scattering lengths within the Fermi golden rule. A second part outlines the contribution of high-energy optic phonon modes, and discusses the applicability limits of semi-classical transport theory. The computational methodologies used to deepen the phonon-induced dephasing or inelastic transmission range from the time-dependent Schrödinger equation and Kubo framework to a novel many-body treatment of e-ph interaction.


Epigenetic changes and assisted reproductive technologies.
Children conceived by Assisted Reproductive Technologies (ART) are at moderately increased risk for a number of undesirable outcomes, including low birth weight. Whether the additional risk is associated with specific procedures used in ART or biological factors that are intrinsic to infertility has been the subject of much debate, as has the mechanism by which ART or infertility might influence this risk. The potential effect of ART clinical and laboratory procedures on the gamete and embryo epigenomes heads the list of mechanistic candidates that might explain the association between ART and undesirable clinical outcomes. The reason for this focus is that the developmental time points at which ART clinical and laboratory procedures are implemented are precisely the time points at which large-scale reorganization of the epigenome takes place during normal development. In this manuscript, we review the many human studies comparing the epigenomes of ART children with children conceived in vivo, as well as assess the potential of individual ART clinical and laboratory procedures to alter the epigenome.


Screening of Natural Bioactive Metabolites and Investigation of Antioxidant, Antimicrobial, Antihyperglycemic, Neuropharmacological, and Cytotoxicity Potentials of Litsea polyantha Juss. Ethanolic Root Extract.
This study was designed to identify some bioactive phytochemicals from ethanolic extract of roots of Litsea polyantha and to evaluate some of its pharmacological activities. Phytochemical tests indicated the presence of reducing sugar, combined reducing sugar, tannins, flavonoids, alkaloids, terpenoids, and phenol. In the antioxidant assay using 2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging method, the IC50 value was found to be 82.31 μg/mL. Total content of phenolic compounds, flavonoid, and tannin was found to be 152.69 mg GAE/gm, 85.60 mg QE/gm, and 77.22 mg GAE/gm of dry extract, respectively. In disc diffusion antibacterial assay, the extract exhibited highest zone of inhibition up to 12.25 mm against Escherichia coli at the concentration of 500 μg/disc. For brine shrimp lethality bioassay, the extract exhibited LC50 56.082 μg/mL. In in vivo antihyperglycemic activity test by oral glucose tolerance test using Swiss Albino mice at the oral dose of 250 and 500 mg/kg, the extract showed statistically significant antihyperglycemic effect. Finally, in vivo, the extract exhibited the dose dependent CNS depressant effects by reducing the locomotors of Swiss Albino mice which was confirmed through three different neuropharmacological activity tests such as open field, hole cross, and hole board test.


Evaluation of temporary portal vein arterialization: the minimum arterialized blood flow for maintaining liver viability.
The effect of temporary portal vein arterialization (PVA) on hepatic energy metabolism was investigated by changes in the arterial blood ketone body ratio (KBR) and hepatic energy charge (EC) level in 17 dogs. The KBR decreased markedly after clamping the hepatic hilar vessels combining mesocaval shunt and remained at a low level throughout hepatic ischemia. After PVA, the KBR was rapidly restored and maintained at sufficient levels. EC at 60 min after arterialization also recovered to the preclamping level. By reducing the arterial shunt flow, the critical point of arterialized blood flow for maintaining the KBR at high levels was assessed to be about 10% of the total hepatic blood flow (THBF). These findings demonstrate that temporary PVA is an effective method for maintaining the functional capacity of the liver, and that the minimum arterialized blood flow needed to preserve liver viability is only about 10% of the total hepatic blood flow.


The mitochondrial genome of Smerinthus planus (Lepidoptera: Sphingidae) and its comparative analysis with other Lepidoptera species.
In the present study, the complete mitochondrial genome of Smerinthus planus Walker (Lepidoptera: Sphingidae) was sequenced and analyzed to add additional traits for expanding our knowledge on systematics and phylogenetics of world-wide studied Sphingidae moths. The mitochondrial genome is a circular double-stranded DNA molecule, 15368 bp in size. It includes 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, twenty-two transfer RNA (tRNA) genes, and an adenine (A) + thymine (T) rich region. All the PCGs start with the typical ATN start codons, except for the nad5 gene, which initiates with TTA. The codon usage analysis revealed that Phe, Ile, Lys, Leu, Asn, and Tys were the most common amino acids, while Cys and Trp were least common. Among the 13 PCGs, nine genes harbor the complete termination codon TAA, whereas the remaining four genes (nad1, cob, nad4, and nad3) terminate with TAG. The A+T rich region of S. planus is 318 bp. This region displays the highest A+T rich content, accounting for 91.50%, with both AT skew (-0.09) and GC skew (-0.26) are negative. Like other Lepidopterans, the A+T-rich region of the S. planus also contains some conserved regions, including the motif 'ATAGA' followed by an 18 bp poly-T stretch, a microsatellite-like (AT)8 and a poly-A element. Phylogenetic relationships, based on nucleotide sequences from the genomes of 31 species, confirmed that S. planus belong to the Sphingidae family. This study is aimed to improve the mitochondrial genome database of moths and provide valuable information for studying the genetic evolution and phylogeny of Lepidopteran species.


COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors.
To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib). The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID dispensing and > or =1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for > or =60 days during the first year (n = 58 770); others were acute users (n = 538 420). Multivariate analysis was performed by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents, anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease. The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/- 17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138 +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were 0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events. Coxib users had significantly lower rates of GI events. Further research should elucidate the possible impact of selection bias.


Increased Expression of Glutaminase in Osteoblasts Promotes Macrophage Recruitment in Periapical Lesions.
Recently, we have shown that tissue hypoxia stimulates the progression of periapical lesions by up-regulating glycolysis-dependent apoptosis of osteoblasts. Other facets of hypoxia-induced metabolic reprogramming in disease pathogenesis require further investigation. In this study, we examined the connection between hypoxia-augmented glutamine catabolism in osteoblasts and the development of periapical lesions. Primary human osteoblasts were cultured under hypoxia. The expression of glutaminase 1 (GLS1) was examined using Western blot analysis. The production of glutamate was measured by colorimetric assay. Knockdown of GLS1 was performed with small interfering RNA technology. C-C motif chemokine ligand 2 (CCL2) secretion and chemotaxis of J774 macrophages were examined by enzyme-linked immunosorbent assay and transwell migration assay, respectively. In a rat model of induced periapical lesions, the relations between disease progression and osteoblastic expression of GLS1 or macrophage recruitment were studied. Hypoxia enhanced GLS1 expression and subsequent glutamate production in osteoblasts. Glutamate induced chemoattraction of macrophages by osteoblasts through up-regulation of CCL2 synthesis. Hypoxia promoted CCL2 secretion and macrophage recruitment through augmentation of glutaminolysis. Knockdown of GLS1 abolished hypoxia-induced effects. In rat periapical lesions, progressive bone resorption was significantly related to elevated GLS1 expression in osteoblasts and increased macrophage recruitment. In addition to the rise in glycolytic activity, the progression of periapical lesions is also associated with enhanced glutamine catabolism in osteoblasts. GLS1 may be a potential therapeutic target in the management of periapical lesions.


Modelling the force of infection for hepatitis B and hepatitis C in injecting drug users in England and Wales.
Injecting drug use is a key risk factor, for several infections of public health importance, especially hepatitis B (HBV) and hepatitis C (HCV). In England and Wales, where less than 1% of the population are likely to be injecting drug users (IDUs), approximately 38% of laboratory reports of HBV, and 95% of HCV reports are attributed to injecting drug use. Voluntary unlinked anonymous surveys have been performed on IDUs in contact with specialist agencies throughout England and Wales. Since 1990 more than 20,000 saliva samples from current IDUs have been tested for markers of infection for HBV, HCV testing has been included since 1998. The analysis here considers those IDUs tested for HBV and HCV (n = 5,682) from 1998-2003. This study derives maximum likelihood estimates of the force of infection (the rate at which susceptible IDUs acquire infection) for HBV and HCV in the IDU population and their trends over time and injecting career length. The presence of individual heterogeneity of risk behaviour and background HBV prevalence due to routes of transmission other than injecting are also considered. For both HBV and HCV, IDUs are at greatest risk from infection in their first year of injecting (Forces of infection in new initiates 1999-2003: HBV = 0.1076 95% C.I: 0.0840-0.1327 HCV = 0.1608 95% C.I: 0.1314-0.1942) compared to experienced IDUs (Force of infection in experienced IDUs 1999-2003: HBV = 0.0353 95% C.I: 0.0198-0.0596, HCV = 0.0526 95% C.I: 0.0310-0.0863) although independently of this there is evidence of heterogeneity of risk behaviour with a small number of IDUs at increased risk of infection. No trends in the FOI over time were detected. There was only limited evidence of background HBV infection due to factors other than injecting. The models highlight the need to increase interventions that target new initiates to injecting to reduce the transmission of blood-borne viruses. Although from the evidence here, identification of those individuals that engage in heightened at-risk behaviour may also help in planning effective interventions. The data and methods described here may provide a baseline for monitoring the success of public health interventions.


Prediction of infectious events by high-sensitivity C-reactive protein level before undergoing chemotherapy for acute myeloid leukaemia.
We retrospectively evaluated the serum high-sensitivity C-reactive protein (CRP) level before chemotherapy for the prediction of infectious events during neutropenia in patients with acute myeloid leukaemia. Thirty-eight patients who underwent first induction chemotherapy and 37 patients who underwent first consolidation chemotherapy were analyzed separately. A receiver-operating characteristic (ROC) curve revealed that the serum CRP level just before the first consolidation chemotherapy, but not just before the induction chemotherapy, had a significant predictive value for febrile neutropenia (FN) at a cut-off value of 0.19 mg/dl and documented infection (DI) at a cut-off value of 0.26 mg/dl. The high-sensitivity CRP measurement enabled the detection of slight increases in the serum CRP level, which might reflect a minute inflammation by occult infection, and discriminated high-risk patients for infectious events.


Are asthma and allergy associated with increased root resorption following orthodontic treatment? A meta-analysis.
The aim of this study is to systematically investigate the available evidence from human studies regarding the association of asthma and/or allergy with EARR. Unrestricted searches in 6 databases and manual searching were performed up to May 2022. We looked for data on EARR after orthodontic treatment in patients with/without asthma or allergy. Relevant data were extracted, and the risk of bias was assessed. An exploratory synthesis was carried out using the random effects model, and the overall quality of the evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation. From the initially retrieved records, nine studies met the inclusion criteria (three cohort and six case-control). Overall, increased EARR was observed in the individuals with allergies in their medical history (Standardised Mean Difference [SMD]: 0.42, 95% Confidence Interval [CI]: 0.19 to 0.64). No difference in EARR development was observed among individuals with or without a medical history of asthma (SMD: 0.20, 95% CI: -0.06 to 0.46). The quality of available evidence, excluding studies at high risk, was rated as moderate for the exposure to allergy, and low for the exposure to asthma. Increased EARR was noted in individuals with allergies compared to the control group, while no difference was observed for individuals with asthma. Until more data become available, good practice would suggest that it is important to identify patients with asthma or allergy and consider the possible implications.


Structure of motor nerve terminals in chickens with hereditary muscular dystrophy.
The structure and size of 1-week to 1-year-old normal (line 412) and dystrophic (line 413) chicken motor nerve terminals were studied using combined pre- and postsynaptic histologic endplate staining. The main result is that adult dystrophic terminals have abnormal structure and are significantly smaller than normal. These differences occurred progressively during development. At 1 week ex ovo, dystrophic motor nerve terminals were similar to normals in size and appearance. By 8 weeks, differences between normal and dystrophic terminal size and structural organization began to emerge. Qualitatively, beginning at 8 weeks and becoming more frequent by 1 year of age (the endpoint of this study), dystrophic motor endplates differed from normal in having: generally smaller synaptic boutons, often separated by extremely thin branching interconnectives; increasing incidence of multiple innervation; and frequent occurrences of apparent partial or total denervation, terminal sprouting, and reinnervation.


The anti-human CD21 antibody, BU33, identifies equine B cells.
The number of antibodies for identifying equine B cells is small and the number that react with well-defined epitopes even smaller. The monoclonal antibody, BU33, which is directed against human CD21 (Complement Receptor 2; CR2) was shown to identify (1) follicular lymphocytes in the lymph nodes and spleen of three horses, and (2) a mean of 18 +/- 6% (SEM) of peripheral blood lymphocytes from 10 horses. These findings indicate that the antibody identifies equine B cells and possibly equine CR2 or a related molecule. This study adds to the reagents available for equine research and diagnostic pathology.


Multigenerational backcrossing and introgression between two woodrat species at an abrupt ecological transition.
When organisms experience secondary contact after allopatric divergence, genomic regions can introgress differentially depending on their relationships with adaptation, reproductive isolation, recombination, and drift. Analyses of genome-wide patterns of divergence and introgression could provide insight into the outcomes of hybridization and the potential relationship between allopatric divergence and reproductive isolation. Here, we generate population genetic data (26,262 SNPs; 353 individuals) using a reduced-representation sequencing approach to quantify patterns of ancestry, differentiation, and introgression between a pair of ecologically distinct mammals-the desert woodrat (N. lepida) and Bryant's woodrat (N. bryanti)-that hybridize at a sharp ecotone in southern California. Individual ancestry estimates confirmed that hybrids were rare in this bimodal hybrid zone, and entirely consisted of a few F1 individuals and a broad range of multigenerational backcrosses. Genomic cline analyses indicated more than half of loci had elevated introgression from one genomic background into the other. However, introgression was not associated with relative or absolute measures of divergence, and loci with extreme values for both were not typically found near detoxification enzymes previously implicated in dietary specialization for woodrats. The decoupling of differentiation and introgression suggests that processes other than adaptation, such as drift, may underlie the extreme clines at this contact zone.


Trade-off between chemical and biotic antiherbivore defense in the South East Asian plant genus Macaranga.
The plant genus Macaranga is known for its manifold mutualistic associations with ants. The plants provide food for the ants and in turn get protection from herbivores. Depending on the strength of the plant-ant interaction, the plant's investment in ants and the biotic defense derived from them is more or less effective. We conducted a comparative study on tannin content in 12 Macaranga species that were selected based on their associations with ants (three nonmyrmecophytes and nine myrmecophytes, three of which start their ontogeny as nonmyrmecophytes). Different developmental stages were investigated in three Macaranga species. Extracts of every individual plant analyzed for tannins were also tested for their effects on larval growth employing larvae of the common cutworm (Spodoptera littoralis). The studied Macaranga species differed significantly in their tannin contents as well as in the effects of their leaf extracts on the growth of S. littoralis larvae. A correlation analysis shows a connection between tannin contents and larval growth. High tannin contents and, thus more effective chemical defense, were observed in nonmyrmecophytic Macaranga species associated only facultatively with ants as compared to obligate myrmecophytes. Our study supports the hypothesis of a trade-off between chemical and biotic defense in the genus Macaranga.


[Case report: Isolated pituitary sarcoidosis: MRI findings].
Sarcoidosis is a multisystem granulomatous disease with an unknown etiology. Symptomatic central nervous system involvement occurs in 5% of cases. MRI shows a wide range of central nervous abnormalities including hypothalamic-pituitary infiltrating lesions, cerebral parenchymal masses, leptomeningeal lesions, and focal white-matter lesions. The patients with sarcoidosis may rarely present with sellar masses. A case of isolated pituitary sarcoidosis was presented in this report with pre-treatment and post-treatment MRI pictures.


Aesthetic Outcome of a Case of Orbital Floor Fracture Treated Using a Retroseptal Transconjunctival Approach.
The orbital floor is a bone structure frequently involved in orbital fractures. Various methods have been documented to approach the orbital floor and infraorbital rim. Traditionally, transcutaneous approaches like infraorbital, subciliary, and subtarsal have been employed to access the orbital floor and infraorbital rim. A significant amount of complications including a visible, prominent scar, eyelid abnormalities like ectropion, lower lid retraction, and increased scleral show result from these transcutaneous approaches. To overcome these complications, the transconjunctival approach has been preferred recently. However, the transconjunctival approach has been associated with rare complications like entropion, synechia, or trichiasis. In the present article, we report a case of orbital floor fracture treated using a retroseptal transconjunctival approach. We intend to evaluate the aesthetic outcome of a case of orbital floor fracture treated using a retroseptal transconjunctival approach.


PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate.
The abuse potential of methylphenidate has been related to the drug's capacity to produce a rapid onset of blockade of the presynaptic dopamine transporter in the brain. An oral once-a-day osmotic controlled-release formulation of methylphenidate produces a more gradual rise in plasma methylphenidate concentration, compared with immediate-release methylphenidate. The authors hypothesized that osmotic-release methylphenidate would also produce a slower onset of blockade of the presynaptic dopamine transporter and would be associated with a lower risk for detection and likeability, compared to immediate-release methylphenidate. Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Doses predicted to produce equivalent maximum concentration (C(max)) values were selected (40 mg of immediate-release methylphenidate and 90 mg of osmotic-release methylphenidate). Plasma d-methylphenidate levels and responses to detection/likeability questionnaire items were obtained hourly for 10 hours after administration of methylphenidate on two separate occasions for each subject. Dopamine transporter receptor occupancies were measured at hours 1, 3, 5, and 7 by using a carbon-11-labeled imaging agent (Altropane) and positron emission tomography. Despite similar C(max) values for both formulations, osmotic-release methylphenidate was associated with a longer time to maximum concentration, longer time to maximum CNS dopamine transporter occupancy, and no detection/likeability, compared with immediate-release methylphenidate. The findings suggest that the abuse potential of oral methylphenidate is strongly influenced by the rate of delivery and not solely by the magnitude of plasma concentration or brain transporter occupancy. These results advance understanding of the underlying central effects of methylphenidate in humans and identify a potentially less abusable methylphenidate formulation.


[The changes of EEG correlation synchrony at depressive disorder of psychogenic type].
In this work we use the alternative method of assessing the EEG-synchrony which previously has proved its high sensitivity to the differentiation of psychopathological and functional states. The original recording of EEG had been performed in the state of quiet wakefulness with eyes closed for two groups of examinees/patients at the age of 49-82 years: a group of normal subjects (n = 29) and the group of subjects with depressive deviations of F43.21 category according to ICD-10 (n = 51). As a result of research it is received the comprehensive picture of significant topographical, interhemispheric and regional differences between groups of norm and depression. One of basic features of the obtained integrated picture is existence at a depression of the extended zones of reduced EEG-synchrony covering the entire premedial region in the frontal-occiptal direction, including intrahemispheric connections as well as lateral frontal-temporal connections in both hemispheres. It testifies to the deep deprivation with depression frontal-occipital and interhemispheric interaction. As a compensatory reaction during depression the increase of synchrony in axial aimed intrahemispheric pairs of derivations. It is noted the similarity of changes in EEG-synchrony topography of depression to those observed in schizophrenia. The used method has provided close to 100% reliability of the classification of the EEG norms and depressive deviations, which makes possible and promising its use as an auxiliary quantitative differential indicator.


Surface and confinement effects on the dielectric relaxation of a monohydroxy alcohol.
2-ethyl-1-hexanol (2E1H) was confined to the surface of a collagen matrix at various concentration levels c. Dielectric spectroscopy revealed that upon decreasing c, the alcohol's prominent hydrogen-bond mediated Debye-like relaxation broadens and turns nonexponential. This destabilization of the supramolecular association is accompanied by an increasing relative strength of the structural relaxation in 2E1H up to a point beyond which the two processes are merged when the solvent molecules are sufficiently diluted. These results demonstrate that the contribution of the Debye-like relaxation can be completely suppressed and concomitantly the limit of a simple, nonassociating liquid is reached. Confinement of the alcohol in a monolithic glass with nanoscopic pores subjected to different internal surface treatments is also demonstrated to bear a large impact on the relative strengths of the two processes.


The Preventive Health Education and Medical Home Project: a predictive and contextual model for low-income families.
The Preventive Health Education and Medical Home Project (PHEMHP) is a predictive and contextual model intended to reduce low levels of health services utilization and improve preventive health techniques and disease self-management for low-income families in South Central Los Angeles, with the ultimate goal of attaching each child to a medical home. The model is designed to be implemented through educational and case management strategies. This paper presents the conceptual framework, critical intervention activities, and the different implementation variations the PHEMHP has already assumed. Implications for research, policy, and practice are discussed.


Flexible Transparent Electrodes Based on Gold Nanomeshes.
The transmittance, conductivity, and flexibility are the crucial properties for the development of next-generation flexible electrodes. Achieving a good trade-off between transmittance and conductivity of flexible electrodes has been a challenge because the two properties are inversely proportional. Herein, we reveal a good trade-off between transmittance and conductivity of gold nanomesh (AuNM) can be achieved through appropriately increasing the AuNM thickness no more than 40 nm, the mean free path of electrons in Au metal. The further flexibility investigation indicates that the AuNM electrodes with mesh structure show higher tolerance than the Au bulk film, and the AuNM electrodes with smaller inter-aperture wire width can accommodate more tensile strains than a counterpart with bigger inter-aperture wire width. The simulated results based on finite element analysis (FEA) show good agreement with experimental results, which indicates the fabrication method of versatile nanosphere lithography (NSL) is reliable. These results established a promising approach toward next-generation large-scale flexible transparent AuNM electrodes for flexible electronics.


A rapid and simple capillary electrophoresis method for indirect determination of the biocide 2,2-dibromo-3-nitrilo-propionamide (DBNPA) in cooling waters.
A capillary zone electrophoresis (CE) method was developed for the determination of the biocide 2,2-dibromo-3-nitrilo-propionamide (DBNPA) in water used in cooling systems. The biocide is indirectly determined by CE measurement of the concentration of bromide ions produced by the reaction between the DBNPA and bisulfite. The relationship between the bromide peak areas and the DBNPA concentrations showed a good linearity and a coefficient of determination (R²) of 0.9997 in the evaluated concentration range of 0-75 μmol L⁻¹. The detection and quantification limits for DBNPA were 0.23 and 0.75 μmol L⁻¹, respectively. The proposed CE method was successfully applied for the analysis of samples of tap water and cooling water spiked with DBNPA. The intra-day and inter-day (intermediary) precisions were lower than 2.8 and 6.2%, respectively. The DBNPA concentrations measured by the CE method were compared to the values obtained by a spectrophotometric method and were found to agree well.


Mind the Gap: Genetic Variation and Personalized Therapies for Cardiomyopathies.
Inherited cardiomyopathies are cardiovascular disorders that are one of the leading causes of death and are strongly associated with genetic mutations. These include hypertrophic, dilated, restrictive, as well as arrhythmogenic right ventricular cardiomyopathies. Among the patients presenting with these specific forms of cardiomyopathies, there is significant phenotypic, genotypic, and environmental heterogeneity. Over the years, the identification of the underlying mutations common to specific forms of cardiomyopathies have facilitated clinic diagnosis. However, the variation between patient genetics and phenotypes highlights the need for improved understanding of these diseases and the development of innovative treatments. To better understand the diseases, researchers are capitalizing on two innovative technologies: cardiac reprogramming and gene editing using CRISPR-Cas9. Deriving cardiomyocytes from patient blood samples and gene editing allows for the efficient generation of cellular and animal models that allow researchers to model the disease more accurately. In addition, the recent advances in high throughput drug screening allows for the efficient testing of patient-derived cardiomyocytes for patient-specific susceptibility to various drugs that are currently approved. In addition, this technology can facilitate the development of new pharmacological compounds for the treatment of specific cardiomyopathies. Overall, the recent technological advances in molecular medicine now presents an opportunity to gain unprecedented insight into solving the complex issue of inherited cardiomyopathies. These techniques pave the way for the new generation of personalized medicine in treating cardiovascular diseases.


[Pathogen role of coronavirus in pediatric intensive care: retrospective analysis of 19 positive samples with indirect immunofluorescence].
Coronaviruses (CV) are ARN-containing agents that are responsible for mild upper respiratory tract infections in adults and children. Their pathogenicity in neonates is not wellknown. Eighty five samples of tracheal or nasopharyngeal secretions were obtained from January to October 1991 from 53 children (29 less than 1 month of age; 19 from 1 month to 1 year; five older than 1 year). They were examined for respiratory syncytial virus, adenovirus, myxovirus influenza and parainfluenza and coronavirus by immunofluorescence (IF). Nineteen samples from nine newborns and three infants were positive for coronavirus. The mean birth weight of the nine neonates was 2100 +/- 840 g; their mean gestational age was 34 +/- 5 weeks and their mean age at diagnosis was 21 +/- 9 days. Apnea and bradycardia were the main symptoms in this group. Blood C-reactive protein was not elevated and blood cultures were sterile. One infant was admitted for near-miss; the two others were admitted at birth because they suffered from chronic lung disease (pulmonary hypoplasia and bronchopulmonary dysplasia). An acute episode of pulmonary deterioration occurred at the time of coronavirus infection. Both died one at 4 months and the other at 10 months. Coronaviruses seem to be responsible for respiratory tract infections in hospitalized neonates and chronically ventilated infants.


Drosophila: genetics meets behaviour.
Genes are understandably crucial to physiology, morphology and biochemistry, but the idea of genes contributing to individual differences in behaviour once seemed outrageous. Nevertheless, some scientists have aspired to understand the relationship between genes and behaviour, and their research has become increasingly informative and productive over the past several decades. At the forefront of behavioural genetics research is the fruitfly Drosophila melanogaster, which has provided us with important insights into the molecular, cellular and evolutionary bases of behaviour.


Clinical uses of recombinant human thyrotropin.
Recombinant human thyroid-stimulating hormone (rhTSH), used to enhance diagnostic radioiodine whole body scanning and thyroglobulin testing, has dramatically altered the management of patients with thyroid cancer. Withdrawal from thyroid hormone suppression therapy and subsequent hypothyroidism is no longer the only safe and effective method for thyroid cancer surveillance. Currently, rhTSH is only approved for the monitoring of low-risk patients with well-differentiated thyroid cancer and radioactive iodine administration, in selected cases. Additional applications of rhTSH include enhancing the sensitivity of positron emission tomography in thyroid cancer, the management of multinodular goiter, and dynamic testing of thyroid reserve. The diagnostic and therapeutic role of rhTSH in these areas is discussed in this review.


TGFbeta/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability.
Homeobox (Hox) gene mutations and their altered expressions are frequently linked to human leukemia. Here, we report that transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) inhibits the bone marrow transformation capability of Hoxa9 and Nup98-Hoxa9, the chimeric fusion form of Hoxa9 identified in human acute myeloid leukemia (AML), through Smad4, the common Smad (Co-Smad) in the TGFbeta/BMP signaling pathway. Smad4 interacts directly with the homeodomain of Hoxa9 and blocks the ability of Nup98-Hoxa9 to bind DNA, thereby suppressing its ability to regulate downstream gene transcription. Mapping data revealed that the amino-terminus of Smad4 mediates this interaction and overexpression of the Hoxa9 interaction domain of Smad4 was sufficient to inhibit the enhanced serial replating ability of primary bone marrow cells induced by Nup98-Hoxa9. These studies establish a novel mechanism by which TGFbeta/BMP regulates hematopoiesis and suggest that modification of Hox DNA-binding activity may serve as a novel therapeutic intervention for those leukemias that involve deregulation of Hox.


Parental causes of death in primary intracerebral haemorrhage.
There are many reports of familial aggregation in stroke. Previously, examining parental causes of death, we found no evidence for familial risk in stroke once socioeconomic and socioenvironmental factors were controlled for. However, the number of patients with primary intracerebral haemorrhage (PICH) was small in this sample and we could not exclude a moderate effect of familial factors in this important subgroup. We therefore matched all cases with PICH on the Lothian Stroke Register with 2 controls per case of the same sex, born in the same year, district, and whose fathers had the same occupation. Presence on parental death certificates of cerebrovascular disease, other vascular disease, bronchial carcinoma, hypertension, diabetes mellitus and other causes of death was recorded. No significant difference in risk was found for cases with parental cerebrovascular disease (OR 0.75, 95% CI 0.40-1.40). Other forms of vascular disease in parents were not associated with significant risk either (OR 0.93, 95% CI 0.51-1.68). We conclude that familial factors do not contribute substantially to risk in most cases of PICH.


Pulmonary hemorrhage in experimental cerebral ischemia in mongolian gerbils. Brain metabolism and lung pathology.
Pulmonary changes in acute cerebral ischemia were studied in anesthetized Mongolian gerbils, in which both carotid arteries were occluded simultaneously. Lactate, pyruvate and adenosine triphosphate (ATP) in the brain were measured as indicators of the severity of cerebral ischemia. Microscopic changes in the lung were arbitrarily scored from 0 (normal) to 3 points (severely affected) by the grade and the extent of lesions. Mean arterial pressure (MAP) was also measured through the cannulated femoral artery before and after carotid artery occlusion in a separate group of animals. Cerebral lactate was increased while ATP decreased in ischemic animals in which pulmonary changes such as intra-alveolar hemorrhages were prominent and frequent. The lung pathology score averaged 1.3 in animals with severe ischemia (lactate greater than or equal to 10 mM/Kg), 0.7 in moderate ischemia (5-10 mM/Kg) and 0.3 in mild or no ischemia (less than 5 mM/Kg), respectively, suggesting that severe brain ischemia may cause fulminant pulmonary changes. The mechanism of pulmonary lesions in acute cerebral ischemia is discussed.