Discrepancies in estimates of prevalence and correlates of substance use and disorders between two national surveys.
To assess the degree to which methodological differences might influence estimates of prevalence and correlates of substance use and disorders by comparing results from two recent surveys administered to nationally representative US samples. Post-hoc comparison of data from the 2002 National Survey on Drug Use and Health (NSDUH) with data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) administered in 2001-02. Prevalence estimates for all substance use outcomes were higher in the NSDUH than in the NESARC; ratios of NSDUH to NESARC prevalences ranged from 2.1 to 5.7 for illegal drug use outcomes. In the NSDUH, past-year substance use disorder (SUD) prevalence estimates were higher for cocaine and heroin, but were similar to NESARC estimates for alcohol, marijuana and hallucinogens. However, prevalence estimates for past-year SUD conditional on past-year use were substantially lower in the NSDUH for marijuana, hallucinogens and cocaine. Associations among drug and SUD outcomes were substantially higher in the NESARC. Total SUD prevalence did not differ between surveys, but estimates for blacks and Hispanics were higher in the NSDUH. A number of methodological variables might have contributed to such discrepancies; among plausible candidates are factors related to privacy and anonymity, which may have resulted in higher use estimates in the NSDUH, and differences in SUD diagnostic instrumentation, which may have resulted in higher SUD prevalence among past-year substance users in the NESARC.


In vitro aflatoxin B(1) exposure decreases response to carbamylcholine in the jejunal epithelium of broilers.
The study was conducted to evaluate if aflatoxin B(1) (AFB(1)) has the capacity to affect the electrophysiological variables and active glucose uptake in jejunal epithelium of chicken. For this purpose, intestinal segments from the middle jejunum of broilers (35 to 39 d old) were incubated in Ussing chambers in the presence of 0 (vehicle control), 1.25, 2.50, and 3.75 microg of AFB(1)/mL of buffer. After 40 and 60 min of incubation with AFB(1), d-glucose (20 mmol/L) and carbamylcholine (200 micromol/L; an analog of acetylcholine and inducer of apical Cl(-) secretion) were respectively added to the incubation medium. Addition of 3.75 microg of AFB(1) caused an increase (P < 0.04) in short-circuit current (I(sc)) and transmural potential difference (V(t)) between 12 to 27 min postexposure as compared with the control. Glucose-induced DeltaI(sc) and percentage of DeltaV(t) were reduced (P < 0.04) at 2.5 and 3.75 microg of AFB(1)/mL, respectively, as compared with the control. The carbamylcholine-induced DeltaI(sc) and DeltaV(t) were both lower (P < 0.05) at 3.75 microg of AFB(1)/mL as compared with the control (-0.05 microA/cm(2), 0.1 mV vs. 1.1 microA/cm(2), and 0.6 mV, respectively). These observations indicate that acute exposure to AFB(1) may increase apical anion secretion in the jejunal epithelium of chicken. The negative effect of this increased anion secretion on active glucose uptake was, however, not prominent and may be considered as moderate or progressive in nature.


Retinal pigment epithelial fine structure in the Australian Galah (Eolophus roseicapillus) (Aves).
As part of a comparative morphological study, the fine structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been investigated by light and electron microscopy in the galah (Eolophus roseicapillus), an Australian cockatoo. The RPE consists of a single layer of low cuboidal cells joined basally by a series of zonulae occludentes. Basally (sclerally) the retinal epithelial cells display numerous deep infoldings while apically (vitreally) microvillar processes interdigitate with photoreceptor outer segments. Internally the RPE cells show a large vesicular nucleus, plentiful smooth endoplasmic reticulum (SER) and numerous polysomes but very little rough endoplasmic reticulum (RER). Numerous mitochondria are located basally. In the light-adapted specimens studied, the melanosomes of the RPE are almost exclusively located within the apical processes indicating that retinomotor movement of this pigment probably occurs. Phagosomes and lysosome-like bodies are present as are myeloid bodies which may show ribosomes on their outer surface. The choriocapillaris endothelium is thin but only minimally fenestrated facing Bruch's membrane. Most fenestrations of the choriocapillaris display a single-layered diaphragm while the remainder have a double-layered diaphragm. Bruch's membrane (complexus basalis) is typical of avian species in that it is pentalaminate with the central lamina densa displaced towards the choriocapillaris.


Taurine improves graft survival after experimental liver transplantation.
Relevant mechanisms of reperfusion injury after liver transplantation are most likely mediated by activated Kupffer cells. Recently, it has been demonstrated that taurine prevents Kupffer cell-activation in vitro. Thus, this study was designed to assess the effects of taurine after liver transplantation. Female Sprague-Dawley rats (210-240 g) were infused with taurine dissolved in normal saline, before organ harvest. Controls were infused with the same volume of normal saline without taurine. Following 4 hours of cold ischemia, liver transplantation was performed. Graft and animal survival, serum transaminases, liver histology, perfusion data of intravital microscopy, blood distribution at reperfusion, and both phagocytosis of Kupffer cells and expression of tumor necrosis factor alpha (TNF-alpha) to index cellular activation were investigated. For comparison, both, analysis of variance (ANOVA) and Fisher's exact test were used as appropriate. Results are presented as mean +/- SEM. Controls survived in 60% of cases. Taurine improved survival in a dose-dependent manner to 100% (P < 0.05). In controls, mean aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH) serum levels increased to 3,260 +/- 814; 1,703 +/- 432; and 14,071 +/- 3,177 U/L, respectively, after transplantation. In contrast, these values were between 20 and 45% of control values after taurine (P < 0.05). Histology taken after transplantation confirmed the significant protective effects of taurine, including the reduction of TNF-alpha expression. Time until homogeneous reperfusion of the graft improved to 50% of control values (P < 0.05). Further, taurine significantly decreased both phagocytosis of latex beads by Kupffer cells and leukocyte-endothelial cell interaction. In parallel, flow velocity of red blood cells as well as acinar and sinusoidal perfusion improved (P < 0.05). In conclusion, these data show for the first time in vivo that taurine minimizes reperfusion injury after liver transplantation. Decreased leukocyte-endothelial cell interaction and improved microcirculation are the proposed mechanisms, which are most likely Kupffer cell-dependent.


Distinct Age-Related Epigenetic Signatures in CD4 and CD8 T Cells.
Healthy immune aging is in part determined by how well the sizes of naïve T cell compartments are being maintained with advancing age. Throughout adult life, replenishment largely derives from homeostatic proliferation of existing naïve and memory T cell populations. However, while the subpopulation composition of CD4 T cells is relatively stable, the CD8 T cell compartment undergoes more drastic changes with loss of naïve CD8 T cells and accumulation of effector T cells, suggesting that CD4 T cells are more resilient to resist age-associated changes. To determine the epigenetic basis for these differences in behaviors, we compared chromatin accessibility maps of CD4 and CD8 T cell subsets from young and old individuals and related the results to the expressed transcriptome. The dominant age-associated signatures resembled hallmarks of differentiation, which were more pronounced for CD8 naïve and memory than the corresponding CD4 T cell subsets, indicating that CD8 T cells are less able to keep cellular quiescence upon homeostatic proliferation. In parallel, CD8 T cells from old adults, irrespective of their differentiation state, displayed greater reduced accessibility to genes of basic cell biological function, including genes encoding ribosomal proteins. One possible mechanism is the reduced expression of the transcription factors YY1 and NRF1. Our data suggest that chromatin accessibility signatures can be identified that distinguish CD4 and CD8 T cells from old adults and that may confer the higher resilience of CD4 T cells to aging.


Effects of foot orthoses on the biomechanics of the lower extremities in adults with and without musculoskeletal disorders during functional tasks: A systematic review.
Foot orthoses are among the most commonly used external supports to treat musculoskeletal disorders. It remains unclear how they change the biomechanics of the lower extremities during functional tasks. This systematic review aimed to determine the effects of foot orthoses on primary outcomes (i.e., kinematics, kinetics and electromyography of the lower extremities) in adults with and without musculoskeletal disorders during functional tasks. A literature search was conducted for articles published from inception to June 2021 in Medline, CINAHL, SPORTDiscus, Cochrane libraries and PEDro electronic databases. Two investigators independently assessed the titles and abstracts of retrieved articles based on the inclusion criteria. Of the 5578 citations, 24 studies were included in the qualitative synthesis as they reported the effects of foot orthoses on the primary outcomes. Risk of bias of included studies was determined using the modified Downs and Black Quality Index. During low impact tasks, foot orthoses decrease ankle inversion and increase midfoot plantar forces and pressure. During higher impact tasks, foot orthoses had little effects on electromyography and kinematics of the lower extremities but decreased ankle inversion moments. Even though the effects of foot orthoses on the biomechanics of the lower extremities seem task-dependent, foot orthoses mainly affected the biomechanics of the distal segments during most tasks. However, few studies determined their effects on the biomechanics of the foot. It remains unclear to what extent foot orthoses features induce different biomechanical effects and if foot orthoses effects change for different populations.


Intrathecal interferon in the treatment of multiple sclerosis. Patient follow-up.
Follow-up observations on patients with multiple sclerosis who were treated with human fibroblast interferon (interferon beta) administered intrathecally for six months revealed a persisting beneficial effect in terms of a reduction in exacerbation rates. At the time of our last report in 1982, ten interferon beta recipients had shown a reduction in their mean exacerbation rate from 1.8/yr before the study to 0.2/yr during the study while ten control patients with multiple sclerosis showed no change in their rates during the study (0.69/yr) compared with before it (0.68/yr). That report was based on observations made for means of 1.9 years in the recipients and 1.6 years in the controls. The recipient patients have now been followed up for 4.4 years (mean) and their exacerbation rates have continued to decrease to a current mean level of 0.16/yr. The control patients were "crossed over" and began receiving interferon beta intrathecally after they had been in the study for two years without showing any change in their rate. During the 2.0 years since crossover they also have shown a reduction in exacerbation rate to a mean of 0.30/yr. The toxic side effects of interferon beta administered intrathecally were acceptable in view of the benefit achieved. Interferon was identified in the cerebrospinal fluid (but not the serum) of two patients prior to treatment, which is probably a manifestation of de novo production of interferon by the central nervous system in response to the multiple sclerosis disease process.


A randomization approach to handling data scaling in nuclear medicine.
In medical imaging, data scaling is sometimes desired to handle the system complexity, such as uniformity calibration. Since the data are usually saved in short integer, conventional data scaling will first scale the data in floating point format and then truncate or round the floating point data to short integer data. For example, when using truncation, scaling of 9 by 1.1 results in 9 and scaling of 10 by 1.1 results in 11. When the count level is low, such scaling may change the local data distribution and affect the intended application of the data. In this work, the authors use an example gated cardiac SPECT study to illustrate the effect of conventional scaling by factors of 1.1 and 1.2. The authors then scaled the data with the same scaling factors using a randomization approach, in which a random number evenly distributed between 0 and 1 is generated to determine how the floating point data will be saved as short integer data. If the random number is between 0 and 0.9, then 9.9 will be saved as 10, otherwise 9. In other words, the floating point value 9.9 will be saved in short integer value as 10 with 90% probability or 9 with 10% probability. For statistical analysis of the performance, the authors applied the conventional approach with rounding and the randomization approach to 50 consecutive gated studies from a clinical site. For the example study, the image reconstructed from the original data showed an apparent perfusion defect at the apex of the myocardium. The defect size was noticeably changed by scaling with 1.1 and 1.2 using the conventional approaches with truncation and rounding. Using the randomization approach, in contrast, the images from the scaled data appeared identical to the original image. Line profile analysis of the scaled data showed that the randomization approach introduced the least change to the data as compared to the conventional approaches. For the 50 gated data sets, significantly more studies showed quantitative differences between the original images and the images from the data scaled by 1.2 using the rounding approach than the randomization approach [46/50 (92%) versus 3/50 (6%), p < 0.05]. Likewise, significantly more studies showed visually noticeable differences between the original images and the images from the data scaled by 1.2 using the rounding approach than randomization [29/50 (58%) versus 1/50 (2%), p < 0.05]. In conclusion, the proposed randomization approach minimizes the scaling-introduced local data change as compared to the conventional approaches. It is preferred for nuclear medicine data scaling.


Metaldehyde poisoning in three horses.
Three horses exhibited nervous and cardiopulmonary signs after ingestins small amounts of metaldehyde, and 2 died in 3 to 5 hours. A colt given 0.1 mg/kg was similarly affected and died.


Adverse early-life environmental exposures and their repercussions on adult respiratory health.
To review in the literature the environmental problems in early life that impact the respiratory health of adults. Non-systematic review including articles in English. Search filters were not used in relation to the publication date, but the authors selected mainly publications from the last five years. In this review, the authors present the exposure pathways and how the damage occurs depending on the child's stage of development; the authors describe the main environmental pollutants - tobacco smoke, particulate matter, air pollution associated with traffic, adverse childhood experiences and socioeconomic status; the authors present studies that evaluated the repercussions on the respiratory system of adults resulting from exposure to adverse environmental factors in childhood, such as increased incidence of Chronic Obstructive Pulmonary Disease (COPD), asthma and allergies; and, a decline in lung function. The authors emphasize that evidence demonstrates that adult respiratory diseases almost always have their origins in early life. Finally, the authors emphasize that health professionals must know, diagnose, monitor, and prevent toxic exposure among children and women. The authors conclude that it is necessary to recognize risk factors and intervene in the period of greatest vulnerability to the occurrence of harmful effects of environmental exposures, to prevent, delay the onset or modify the progression of lung disease throughout life and into adulthood.


Characterization of gastrin-cholecystokinin 2 receptor interaction in relation to c-fos induction.
The interaction of gastrin with the cholecystokinin 2 (CCK2)/gastrin receptor has been studied extensively in relation to gastric acid secretion. However, not much is known about the contribution of individual amino acids of gastrin interacting with the CCK2 receptor, when gastrin is acting as a tumor growth factor. The purpose of the present study was to determine the significance of each individual amino acid residue of human gastrin-17 with respect to CCK2 receptor-mediated cell proliferation. Activation of this receptor was assessed using an in vitro bioassay based on gastrin-induced expression of a c-fos-luciferase reporter, transfected in AR42JB13 and Colo 320 cells, a rat pancreatic and human colorectal cell line respectively. Gastrin-17 dose dependently increased c-fos induction in both cancer cell lines. L365,260, a known CCK2 receptor antagonist, completely blocked the gastrin signal, demonstrating the specificity of this assay. We demonstrated for the first time that four carboxy-terminal amino acids of gastrin-17 are essential for activation of the CCK2 receptor with respect to c-fos induction. Also other residues of gastrin-17, notably glycine-2 for the rat CCK2 receptor and glutamic acid 8-10 and tyrosine-12 for the human receptor, were found to be important, although to a lesser extent. Alanine-substitution variants of each of the four carboxy-terminal amino acids of gastrin-17 showed strongly reduced receptor activation but did not act as competitive inhibitors of gastrin-17. Identification of the essential role of the carboxy-terminal tetrapeptide of gastrin-17 in CCK2 receptor-mediated c-fos induction indicates that gastrin inhibitory therapeutic strategies should mainly be targeted toward this region of gastrin.


Are Proactive and Reactive Aggression Meaningful Distinctions in Adolescents? A Variable- and Person-Based Approach.
This study was designed to examine whether proactive and reactive aggression are meaningful distinctions at the variable- and person-based level, and to determine their associated behavioral profiles. Data from 587 adolescents (mean age 15.6; 71.6 % male) from clinical samples of four different sites with differing levels of aggression problems were analyzed. A multi-level Latent Class Analysis (LCA) was conducted to identify classes of individuals (person-based) with similar aggression profiles based on factor scores (variable-based) of the Reactive Proactive Questionnaire (RPQ) scored by self-report. Associations were examined between aggression factors and classes, and externalizing and internalizing problem behavior scales by parent report (CBCL) and self-report (YSR). Factor-analyses yielded a three factor solution: 1) proactive aggression, 2) reactive aggression due to internal frustration, and 3) reactive aggression due to external provocation. All three factors showed moderate to high correlations. Four classes were detected that mainly differed quantitatively (no 'proactive-only' class present), yet also qualitatively when age was taken into account, with reactive aggression becoming more severe with age in the highest affected class yet diminishing with age in the other classes. Findings were robust across the four samples. Multiple regression analyses showed that 'reactive aggression due to internal frustration' was the strongest predictor of YSR and CBCL internalizing problems. However, results showed moderate to high overlap between all three factors. Aggressive behavior can be distinguished psychometrically into three factors in a clinical sample, with some differential associations. However, the clinical relevance of these findings is challenged by the person-based analysis showing proactive and reactive aggression are mainly driven by aggression severity.


Catalytic Fast Pyrolysis of Biomass Impregnated with Potassium Phosphate in a Hydrogen Atmosphere for the Production of Phenol and Activated Carbon.
A new technique was proposed to co-produce phenol and activated carbon (AC) from catalytic fast pyrolysis of biomass impregnated with K3PO4 in a hydrogen atmosphere, followed by activation of the pyrolytic solid residues. Lab-scale catalytic fast pyrolysis experiments were performed to quantitatively determine the pyrolytic product distribution, as well as to investigate the effects of several factors on the phenol production, including pyrolysis atmosphere, catalyst type, biomass type, catalytic pyrolysis temperature, and catalyst impregnation content. In addition, the pyrolytic solid residues were activated to prepare ACs with high specific surface areas. The results indicated that phenol could be obtained due to the synergistic effects of K3PO4 and hydrogen atmosphere, with the yield and selectivity reaching 5.3 wt% and 17.8% from catalytic fast pyrolysis of poplar wood with 8 wt% K3PO4 at 550°C in a hydrogen atmosphere. This technique was adaptable to different woody materials for phenol production. Moreover, gas product generated from the pyrolysis process was feasible to be recycled to provide the hydrogen atmosphere, instead of extra hydrogen supply. In addition, the pyrolytic solid residue was suitable for AC preparation, using CO2 activation method, the specific surface area was as high as 1,605 m2/g.


Functionally dissociating aspects of event memory: the effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat.
Reciprocal interactions between the hippocampus and the perirhinal and parahippocampal cortices form core components of a proposed temporal lobe memory system. For this reason, the involvement of the hippocampus in event memory is thought to depend on its connections with these cortical areas. Contrary to these predictions, we found that NMDA-induced lesions of the putative rat homologs of these cortical areas (perirhinal plus postrhinal cortices) did not impair performance on two allocentric spatial tasks highly sensitive to hippocampal dysfunction. Remarkably, for one of the tasks there was evidence of a facilitation of performance. The same cortical lesions did, however, disrupt spontaneous object recognition and object discrimination reversal learning but spared initial acquisition of the discrimination. This pattern of results reveals important dissociations between different aspects of memory within the temporal lobe. Furthermore, it shows that the perirhinal-postrhinal cortex is not a necessary route for spatial information reaching the hippocampus and that object familiarity-novelty detection depends on different neural substrates than do other aspects of event memory.


Microbial interactions during residual oil and n-fatty acid metabolism by a methanogenic consortium.
Carbon flow in a model methanogenic consortium capable of hydrocarbon degradation was investigated using a combination of stable isotope fractionation, protein-based stable isotope probing, and metaproteomics. Overall δ(13) C enrichment for methane and CO2 in the presence and absence of oil suggests that complex microbial interactions occur during methanogenic hydrocarbon mineralization. Specifically, the Δδ(13) C of CO2 was statistically identical in all incubations irrespective of oil presence, but the Δδ(13) C for methane was greater in the presence of oil compared with fatty acids alone. In addition, carbon from uniformly ((13) C) labelled n-fatty acids was distributed evenly among consortium members in the presence of oil, but used by relatively few community members when provided alone. In all incubations, aceticlastic and hydrogenotrophic methanogens were labelled to an equal extent, suggesting that no pathway is overwhelmingly dominant during methane production by the model consortium. Protein-based stable isotope probing identified key enzymes responsible for methanogenesis from CO2 and acetate labelled with 78.0 ± 4.4% and 73.3 ± 1.0% (13) C respectively. Results suggest that acetate was used directly by methanogens in the presence of n-fatty acids alone, and that methanogenesis from CO2 was a secondary process. Proteins capable of catalysing hydrocarbon activation by addition to fumarate were not found. Collectively, this study demonstrates that significant microbial cooperation is required to recover hydrocarbons as methane.


On the structure of the acyl linkage and the function of fatty acyl chains in the influenza virus haemagglutinin and the glycoproteins of Semliki Forest virus.
The acylation of the haemagglutinin (HA) of different influenza viruses and of the envelope glycoproteins of Semliki Forest virus (SFV) were analysed. The fatty acid linkage in these acylproteins was found to be resistant to a variety of organic solvents and combinations of these, even after pretreatment with various detergents. Fatty acids are released from influenza virus HA at a pH value between 11.8 and 12.1 at room temperature. Although this mild alkaline cleavage occurs rapidly, the release of fatty acids by treatment with hydroxylamine is time-, temperature- and concentration-dependent. By comparison with model esters the linkage in HA is suggested to be of the oxygenester type rather than a thioester linkage. To assay for possible functions of protein-bound fatty acids the biological activities of influenza virus (A/FPV/Rostock/34) and its solubilized spike glycoproteins were measured after deacylation. While viral haemagglutination activity was not hampered at all, its ability to haemolyse erythrocytes and infectivity were drastically reduced. Likewise, viral spike glycoproteins solubilized with detergents failed to induce haemolysis at low pH when fatty acids had been cleaved off. These results indicate the possible involvement of protein-bound fatty acids in fusion induction through the acylated fusogenic spike glycoproteins.


Overexpression of the HDA15 Gene Confers Resistance to Salt Stress by the Induction of NCED3, an ABA Biosynthesis Enzyme.
Salt stress constitutes a major form of abiotic stress in plants. Histone modification plays an important role in stress tolerance, with particular reference to salt stress resistance. In the current study, we found that HDA15 overexpression confers salt stress resistance to young seedling stages of transgenic plants. Furthermore, salt stress induces HDA15 overexpression. Transcription levels of stress-responsive genes were increased in transgenic plants overexpressing HDA15 (HDA15 OE). NCED3, an abscisic acid (ABA) biosynthetic gene, which is highly upregulated in HDA15 transgenic plants, enhanced the accumulation of ABA, which promotes adaptation to salt stress. ABA homeostasis in HDA15 OE plants is maintained by the induction of CYP707As, which optimize endogenous ABA levels. Lastly, we found that the double-mutant HDA15 OE/hy5 ko plants are sensitive to salt stress, indicating that interaction between HDA15 and ELONGATED HYPOCOTYL 5 (HY5) is crucial to salt stress tolerance shown by HDA15 OE plants. Thus, our findings indicate that HDA15 is crucial to salt stress tolerance in Arabidopsis.


On estimating the number of species from the discovery record.
A common approach to estimating the number of species in a taxonomic or other group is to extrapolate the temporal pattern of historical species discoveries or descriptions. A formal statistical approach to this problem is described. This approach involves fitting an explicit model of the discovery record by maximum likelihood and using the fitted model to estimate the number of undiscovered species. The approach is applied to a description record of large marine animals covering the period 1828-1996. The estimated number of undiscovered species in this group is around 10 with an upper 0.95 confidence bound of around 16.


A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease.
Charcot-Marie-Tooth disease (CMT) is a heterogeneous disorder of the peripheral nervous system. So far, mutations in hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit (HADHB) gene exhibit three distinctive phenotypes: severe neonatal presentation with cardiomyopathy, hepatic form with recurrent hypoketotic hypoglycemia, and later-onset axonal sensory neuropathy with episodic myoglobinuria. To identify the causative and characterize clinical features of a Korean family with motor and sensory neuropathies, whole exome study (WES), histopathologic study of distal sural nerve, and lower limb MRIs were performed. WES revealed that a compound heterozygous mutation in HADHB is the causative of the present patients. The patients exhibited an early-onset axonal sensorimotor neuropathy without episodic myoglobinuria, and showed typical clinical and electrophysiological features of CMT including predominant distal muscle weakness and atrophy. Histopathologic findings of sural nerve were compatible with an axonal CMT neuropathy. Furthermore, they didn't exhibit any other symptoms of the previously reported HADHB patients. These data implicate that mutation in HADHB gene can also cause early-onset axonal CMT instead of typical manifestations in mitochondrial trifunctional protein (MTP) deficiency. Therefore, this study is the first report of a new subtype of autosomal recessive axonal CMT by a compound heterozygous mutation in HADHB, and will expand the clinical and genetic spectrum of HADHB.


Measurement of the muonic branching fractions of the narrow upsilon resonances.
The decay branching fractions of the three narrow Upsilon resonances to mu(+)mu(-) have been measured by analyzing about 4.3 fb(-1) e(+)e(-) data collected with the CLEO III detector. The branching fraction B(Upsilon(1S)-->mu(+)mu(-))=(2.49+/-0.02+/-0.07)% is consistent with the current world average, but B(Upsilon(2S)-->mu(+)mu(-))=(2.03+/-0.03+/-0.08)% and B(Upsilon(3S)-->mu(+)mu(-))=(2.39+/-0.07+/-0.10)% are significantly larger than prior results. These new muonic branching fractions imply a narrower total decay width for the Upsilon(2S) and Upsilon(3S) resonances and lower other branching fractions that rely on these decays in their determination.


Advanced therapies for end-stage heart failure.
Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantation and mechanical circulatory support, as well inotropic agents for the short-term. Despite a growing armamentarium of resources, the clinician must carefully weigh the risks and benefits of each therapy to develop an optimal treatment strategy. While cardiac transplantation remains the only true "cure" for end-stage disease, this resource is limited and the demand continues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior to transplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularly for the non-operative patient, intravenous inotropes can be utilized for symptom control. Regardless of the treatments considered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualized care. While survival is important, most patients covet quality of life above all outcomes. An often overlooked component is the patient's control over the dying process. It is vital that clinicians make goals-of-care discussions a priority when seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitates these difficult conversations to ensure that all patient needs are ultimately met.


Prediction and identification of transcriptional regulatory elements at the lung cancer-specific DKK1 locus.
The glycoprotein dickkopf 1 (DKK1) is highly expressed in lung cancer cell lines and tissues. Our previous study demonstrated that DKK1 promoter activity is low in lung cancer cell lines. This may be because it lacks the necessary transcriptional regulatory elements (TREs) required for higher activity levels. However, it is difficult to computationally predict functionally significant TREs, as TREs from different locations can affect large segments of distant DNA. The Encyclopedia of DNA Elements project features multiple integrated technologies and approaches for the discovery and definition of functional elements, including enhancer elements and enhancer-blocking insulators. In the present study, DNase I hypersensitive sites and histone modifications of DKK1 were investigated in the A549 lung cancer cell line using the UCSC Genome Browser. A set of cis-acting enhancer elements were identified by a dual-luciferase reporter gene assay system to increase activity of the DKK1 promoter with lung cancer specificity. To the best of our knowledge, these data provide the first insight into the role of the DKK1 locus in lung cancer, and confirm the contribution of intronic cis-acting elements to the regulation of DKK1 expression, providing a new insight into gene regulation in lung cancer, which could inform the development of targeted therapy.


[Expectoration of cerebrospinal fluid: an unusual complication of ventriculoperitoneal shunt].
A child, who had undergone ventriculoperitoneal shunting, presented with repeated episodes of pneumonia and expectoration of CSF. Chest x-ray demonstrated the presence of the shunt catheter in the base of the left lung. In the present case the distal end of the catheter perforated the diaphragm, entering the thoracic cavity through the pleura and penetrating the pulmonary parenchyma. CSF then flowed freely into the alveoli and bronchi and became expectorated during repeated bouts of coughing associated with pneumonia. This respiratory complication disappeared after the removal of the catheter. We theorize that the penetration of the catheter into the thoracic cavity was secondary to its displacement from the iliac fossa to the left infradiaphragmatic space between the spleen and the diaphragm where the intra-abdominal pressure is lowest. The respiratory movements and the hypertension inside the abdomen created a constant friction of the catheter against the diaphragm which was finally perforated, permitting the passage of the peritoneal end of the shunting device into the thoracic cavity and secondary penetration of the lung.


Front-line hospital staff from six hospitals rate benefits of hospital information systems.
The purpose of these descriptive, correlational studies was to identify benefits realized from computerized hospital information systems (HIS) and the value of those benefits as perceived by front-line system users. A total of 695 respondents from six hospitals described benefits related to the quality of care, interdisciplinary communication, and collaboration; these were realized to a greater extent and were more important than benefits related to cost-savings. Perceptions of nurses regarding the extent to which benefits were realized were not significantly different than those of non-nurse staff; however nurses rated potential benefits much higher in importance than did non-nurses. Perceptions were not consistently linked to demographic variables; the factor most influencing perceptions was the extent of computerization in the department. Findings appear useful to researchers studying HIS benefits and to system designers and vendors endeavoring to make HIS more user-friendly, functional, and marketable.


Fulminating arterial hypertension with pulmonary edema from release of adrenomedullary catecholamines after lesions of the anterior hypothalamus in the rat.
Bilateral electrolytic lesions of the anterior hypothalamus in unrestrained rats resulted in the development, within 2 hours, of arterial hypertension, tachycardia, hyperthermia, and increased locomotor activity, often leading to pulmonary edema and death. Similar lesions in paralyzed, artificially ventilated rats produced comparable changes in arterial blood pressure and body temperature with a similar time course. The arterial hypertension was a consequence of an increase in total peripheral resistance to 15% of control with a reduction in cardiac output to 49% of control. Arterial hypertension, elevated peripheral resistance, and diminished cardiac output were reversed toward normal by alpha-receptor blockade with phentolamine (1 mg/kg, iv). Bilateral adrenalectomy, adrenal demedullation, or adrenal denervation performed prior to lesion placement prevented the development of arterial hypertension and pulmonary edema as well as the changes in peripheral resistance, cardiac output, and body temperature. We conclude that arterial hypertension following lesions of the anterior hypothalamus is due to a neurally mediated increase in peripheral resistance initiated by the release of adrenal medullary catecholamines and that pulmonary edema is due to myocardial failure secondary to the ensuing ventricular overload. Structures originating in or passing through the anterior hypothalamus may exert selective control over the adrenal medulla independent of vasomotor neurons.


Normocephalic Pancraniosynostosis: A Report of a Surgical Technique.
Normocephalic pancraniosynostosis is defined as the premature fusion of 3 or, more major sutures in the absence of another primary etiology, including primary, microcephaly, ventriculoperitoneal shunting, hypothyroidism, rickets, mucopolysaccharidoses, or other lysosomal storage diseases. It is very rare, thus far only 6 patients have been reported in the literature. Patients tend to present much later than those with single sutural, synostoses, and up to half have evidence of elevated intracranial pressure. The authors wish to present another patient, with emphasis on a unique treatment approach.


Next-Generation Novel Noninvasive Cancer Molecular Diagnostics Platforms Beyond Tissues.
In recent years, there has been a revolutionary expansion in technologic advances and therapeutic innovations in cancer medicine. Cancer diagnostics has begun to move away from a sole dependence on direct tumor tissue biopsy for cancer detection, diagnosis, and treatment monitoring. The need for improvement in molecular cancer diagnostics has never been more important, with not only the advent of cancer genomics and genomics-guided precision medicine but also the recent arrival of cancer immunotherapies. Owing to the practical limitations and risks associated with tissue-based biopsy diagnostics, novel noninvasive cancer diagnostics platforms have continued to evolve and expand in recent years. Examples of these platforms include the liquid biopsy, which is used to interrogate ctDNA or circulating tumor cells, proteomics, metabolomics, and exosomes; the urine biopsy, which is used to assay ctDNAs; saliva and stool biopsies, which are used for molecular genomics assays; and the breath biopsy, which measures volatile organic compounds. These next-generation noninvasive molecular diagnostics assays beyond tissues fundamentally transform the potential utilities of cancer diagnostics to enable repeat, prospective, and serial longitudinal "biopsies" to monitor disease response resistance and progression on therapies. Moreover, they allow continual interrogation and molecular in-depth analysis of the evolving tumor's pan-canceromics under therapeutic stress. These technological and diagnostic advances have already brought about paradigm-changing next-generation cancer therapeutic strategies to enhance overall treatment efficacies. This article reviews the key noninvasive next-generation molecular diagnostics platforms beyond tissues, with emphasis on clinical utilities and applications.


Fatal wrong-way collisions on New Mexico's interstate highways, 1990-2004.
Medical examiner files from 1990 through 2004 were reviewed to identify fatalities caused by drivers traveling the wrong direction on interstate highways and identify risk factors and prevention strategies. Other fatal nonpedestrian interstate motor vehicle crashes served as a comparison group. Data abstracted included decedent demographics, driver/passenger status, seatbelt use, blood alcohol concentration, weather and light at time of occurrence and types of vehicles involved. Of 1171, 79 (6.7%) interstate motor vehicle fatalities were because of drivers traveling against the posted direction in 49 crashes, with one to five fatalities per crash. Wrong-way collisions were significantly more likely to occur during darkness (p < 0.0001) and involve legally intoxicated drivers (p < 0.0001). In 29/49 (60%) wrong-way crashes, alcohol was a factor. Prevention strategies aimed at reducing the incidence of driving while intoxicated, as well as improved lighting and signage at ramps, could help reduce the occurrence of fatal wrong-way collisions on interstates.


A practice-based trial of blood pressure control in African Americans (TLC-Clinic): study protocol for a randomized controlled trial.
Poorly controlled hypertension (HTN) remains one of the most significant public health problems in the United States, in terms of morbidity, mortality, and economic burden. Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes (TLC) for blood pressure (BP) reduction, the effectiveness of these approaches in primary care practices remains untested, especially among African Americans, who share a disproportionately greater burden of HTN-related outcomes. This randomized controlled trial tests the effectiveness of a practice-based comprehensive therapeutic lifestyle intervention, delivered through group-based counseling and motivational interviewing (MINT-TLC) versus Usual Care (UC) in 200 low-income, African Americans with uncontrolled hypertension. MINT-TLC is designed to help patients make appropriate lifestyle changes and develop skills to maintain these changes long-term. Patients in the MINT-TLC group attend 10 weekly group classes focused on healthy lifestyle changes (intensive phase); followed by 3 monthly individual motivational interviewing (MINT) sessions (maintenance phase). The intervention is delivered by trained research personnel with appropriate treatment fidelity procedures. Patients in the UC condition receive a single individual counseling session on healthy lifestyle changes and print versions of the intervention materials. The primary outcome is within-patient change in both systolic and diastolic BP from baseline to 6 months. In addition to BP control at 6 months, other secondary outcomes include changes in the following lifestyle behaviors from baseline to 6 months: a) physical activity, b) weight loss, c) number of daily servings of fruits and vegetables and d) 24-hour urinary sodium excretion. This vanguard trial will provide information on how to refine MINT-TLC and integrate it into a standard treatment protocol for hypertensive African Americans as a result of the data obtained; thus maximizing the likelihood of its translation into clinical practice. Clinicaltrials.gov NCT01070056.


Experimental determination of Escherichia coli biomass composition for constraint-based metabolic modeling.
Genome-scale metabolic models (GEMs) are mathematical representations of metabolism that allow for in silico simulation of metabolic phenotypes and capabilities. A prerequisite for these predictions is an accurate representation of the biomolecular composition of the cell necessary for replication and growth, implemented in GEMs as the so-called biomass objective function (BOF). The BOF contains the metabolic precursors required for synthesis of the cellular macro- and micromolecular constituents (e.g. protein, RNA, DNA), and its composition is highly dependent on the particular organism, strain, and growth condition. Despite its critical role, the BOF is rarely constructed using specific measurements of the modeled organism, drawing the validity of this approach into question. Thus, there is a need to establish robust and reliable protocols for experimental condition-specific biomass determination. Here, we address this challenge by presenting a general pipeline for biomass quantification, evaluating its performance on Escherichia coli K-12 MG1655 sampled during balanced exponential growth under controlled conditions in a batch-fermentor set-up. We significantly improve both the coverage and molecular resolution compared to previously published workflows, quantifying 91.6% of the biomass. Our measurements display great correspondence with previously reported measurements, and we were also able to detect subtle characteristics specific to the particular E. coli strain. Using the modified E. coli GEM iML1515a, we compare the feasible flux ranges of our experimentally determined BOF with the original BOF, finding that the changes in BOF coefficients considerably affect the attainable fluxes at the genome-scale.


Expression, purification and crystallization of a functional core of the voltage-dependent calcium channel beta subunit.
Two versions of the functional core of the rabbit voltage-dependent calcium channel beta2a subunit were expressed in Escherichia coli. These proteins were purified to homogeneity and screened for crystallization. Crystallization conditions were refined using the hanging-drop vapour-diffusion method and two crystal forms were pursued. Crystal form I is represented by thick rods with tetragonal symmetry, unit-cell parameters a = b = 75, c = 165 A and a diffraction limit of 3.4 A which were obtained using ammonium sulfate as a precipitant. Crystal form II gives rise to plates with orthorhombic symmetry, unit-cell parameters a = 35, b = 75, c = 165 A and a diffraction limit of 2.3 A which were grown using polyethylene glycol 20K as a precipitant.


Words matter: Recommendations for clarifying coral disease nomenclature and terminology.
Coral diseases have caused significant losses on Caribbean reefs and are becoming a greater concern in the Pacific. Progress in coral disease research requires collaboration and communication among experts from many different disciplines. The lack of consistency in the use of terms and names in the recent scientific literature reflects the absence of an authority for naming coral diseases, a lack of consensus on the meaning of even some of the most basic terms as they apply to corals, and imprecision in the use of descriptive words. The lack of consensus partly reflects the complexity of this newly emerging field of research. Establishment of a nomenclature committee under the Coral Disease and Health Consortium (CDHC) could lead to more standardized definitions and could promote use of appropriate medical terminology for describing and communicating disease conditions in corals. This committee could also help to define disease terminology unique to corals where existing medical terminology is not applicable. These efforts will help scientists communicate with one another and with the general public more effectively. Scientists can immediately begin to reduce some of the confusion simply by explicitly defining the words they are using. In addition, digital photographs can be posted on the CDHC website and included in publications to document the macroscopic (gross) signs of the conditions observed on coral colonies along with precisely written characterizations and descriptions.


Menorrhagia Management in Iranian Traditional Medicine.
Menorrhagia is a common problem. Medical management for menorrhagia includes hormonal and nonhormonal treatments. These treatments have different side effects, which reduce quality of life. Complementary and traditional medicines have been used to handle menorrhagia for centuries in many cultures. There is a lot of information and data in Iranian traditional documents or books about medicinal herbs that are used by Iranian traditional medicine scientists for the treatment of menorrhagia. The aim of this study was to review the approaches to menorrhagia in Iranian traditional medicine texts. In this study, some main Iranian traditional medicine manuscripts including Canon of Medicine and Al-Havi of Rhazes were studied to extract important information about menorrhagia management. Iranian traditional medicine physicians have relied on an organized system of etiological theories and treatments for menorrhagia. Their methods for menorrhagia management may be able to convince the desire of many women to preserve their uterus and avoid hormonal therapy.


Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: targeting with a single chain antibody variable domain isolated by phage display.
EGFRvIII is a mutant epidermal growth factor receptor found in glioblastoma, and in carcinoma of the breast, ovary, and lung. The mutant receptor has a deletion in its extracellular domain that results in the formation of a new, tumor-specific extracellular sequence. Mice were immunized with a synthetic peptide corresponding to this sequence and purified EGFRvIII. A single chain antibody variable domain (scFv) phage display library of 8 x 10(6) members was made from the spleen of one immunized mouse. A scFv specific for EGFRvIII was isolated from this library by panning with successively decreasing amounts of synthetic peptide. This was used to make an immunotoxin by fusing the scFv DNA sequence to sequences coding for domains II and III of Pseudomonas exotoxin A. Purified immunotoxin had a Kd of 22 nM for peptide and a Kd of 11 nM for cell-surface EGFRvIII. The immunotoxin was very cytotoxic to cells expressing EGFRvIII, with an IC50 of 1 ng/ml (16 pM) on mouse fibroblasts transfected with EGFRvIII and an IC50 of 7-10 ng/ml (110-160 pM) on transfected glioblastoma cells. There was no cytotoxic activity at 1000 ng/ml on the untransfected parent glioblastoma cell line. The immunotoxin was completely stable upon incubation at 37 degrees C for 24 h in human serum. The combination of good affinity, cytotoxicity and stability make this immunotoxin a candidate for further preclinical evaluation.


Anti-inflammatory and Antimicrobial Effects of Heat-Clearing Chinese Herbs: A Current Review.
Inflammation is a normal immune response; but if the body's regulation of inflammation is dysfunctional, then it will have an adverse effect on the body. Although use of modern drugs for inflammation has a relieving effect, it is still unsatisfactory. Moreover, the emergence of drug-resistant strains and even new kinds of microorganisms is causing significant morbidity and mortality. Recently, more attention has been focused on herbal medicine to treat various diseases because of the ability of the herbs to affect multiple target signaling pathways and their multiple mechanisms of action. Thus, a large number of studies have reported on the anti-inflammatory and antimicrobial effects of the traditional Chinese herbs. Literature survey was performed by conducting systematic electronic search in PubMed, Science Direct, Google Scholar, and in books. This review has listed 11 heat-clearing Chinese herbs (HCCHs) including Scutellaria baicalensis ( Huáng Qín), Coptis chinensis ( Huáng Lián), Flos Lonicerae ( Jīn Yín Hūa), Forsythia suspensa ( Lián Qiào), Isatidis Folium ( Dà Qīn Yè), Radix Isatidis ( Bǎn Lán Gēn), Viola yedoensis ( Zǐ Huā Dì Dīn), Pulsatilla Radix ( Bái Tóu Wēn), Andrographis paniculata ( Chuān Xīn Lián), Houttuynia cordata ( Yú Xīng Cǎo), and Patrinia Herba ( Bài Jiàn Cǎo), which have anti-inflammatory and antimicrobial effects, and has described their effects through different mechanisms of action and multiple targets. Their ability to affect multiple target signaling pathways and their potential mechanisms of action contributing to their anti-inflammatory and antimicrobial activity may be related to their action of removing heat and counteracting toxicity. Further studies are needed on the collection of HCCHs to know the detailed mechanism of action of herbs in this group for the assessment of effective drug.


Quantifying Crustal Thickness in Continental Collisional Belts: Global Perspective and a Geologic Application.
We present compiled geochemical data of young (mostly Pliocene-present) intermediate magmatic rocks from continental collisional belts and correlations between their whole-rock Sr/Y and La/Yb ratios and modern crustal thickness. These correlations, which are similar to those obtained from subduction-related magmatic arcs, confirm that geochemistry can be used to track changes of crustal thickness changes in ancient collisional belts. Using these results, we investigate temporal variations of crustal thickness in the Qinling Orogenic Belt in mainland China. Our results suggest that crustal thickness remained constant in the North Qinling Belt (~45-55 km) during the Triassic to Jurassic but fluctuates in the South Qinling Belt, corresponding to independently determined tectonic changes. In the South Qinling Belt, crustal thickening began at ~240 Ma and culminated with 60-70-km-thick crust at ~215 Ma. Then crustal thickness decreased to ~45 km at ~200 Ma and remained the same to the present. We propose that coupled use of Sr/Y and La/Yb is a feasible method for reconstructing crustal thickness through time in continental collisional belts. The combination of the empirical relationship in this study with that from subduction-related arcs can provide the crustal thickness evolution of an orogen from oceanic subduction to continental collision.


The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters.
Ibogaine, a hallucinogenic alkaloid proposed as a treatment for opiate withdrawal, has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate. Ibogaine binding to SERT increases accessibility in the permeation pathway connecting the substrate-binding site with the cytoplasm. Because of the structural similarity between ibogaine and serotonin, it had been suggested that ibogaine binds to the substrate site of SERT. The results presented here show that ibogaine binds to a distinct site, accessible from the cell exterior, to inhibit both serotonin transport and serotonin-induced ionic currents. Ibogaine noncompetitively inhibited transport by both SERT and the homologous dopamine transporter (DAT). Ibogaine blocked substrate-induced currents also in DAT and increased accessibility of the DAT cytoplasmic permeation pathway. When present on the cell exterior, ibogaine inhibited SERT substrate-induced currents, but not when it was introduced into the cytoplasm through the patch electrode. Similar to noncompetitive transport inhibition, the current block was not reversed by increasing substrate concentration. The kinetics of inhibitor binding and dissociation, as determined by their effect on SERT currents, indicated that ibogaine does not inhibit by forming a long-lived complex with SERT, but rather binds directly to the transporter in an inward-open conformation. A kinetic model for transport describing the noncompetitive action of ibogaine and the competitive action of cocaine accounts well for the results of the present study.


Person-Environment Fit Approach to Trajectories of Cognitive Function Among Older Adults Who Live Alone: Intersection of Life-Course SES Disadvantage and Senior Housing.
Drawing from life course and environmental perspectives, we examined the trajectory of cognitive function and how senior housing moderates the effects of life-course socioeconomic status (SES) disadvantage among older people living alone over time. Six waves of the Health and Retirement Study (HRS) were used with multilevel growth modeling to analyze developmental patterns of cognitive function over time and how various forms of life-course SES disadvantage affect cognitive function depending on senior housing residency status. At baseline, we found a positive role of senior housing in four subgroups: SES disadvantage in childhood only, unstable mobility pattern (disadvantage in childhood and old age only), downward mobility (no disadvantage in childhood, but in later two life stages), and cumulative disadvantage (all three life stages). Over time, the positive role of senior housing for the unstable and the most vulnerable group persisted. Our findings provide a much-needed practical and theoretical underpinning for environmental policy-making efforts regarding vulnerable elders who live alone.


Configuration space as a means for augmenting human performance in teleoperation tasks.
This paper considers an approach to operator-guided real time motion control of robot arm manipulators that's based on the use of configuration space (C-space). The goal is to improve operator performance in a complex environment with obstacles, In such tasks, traditional teleoperation techniques, which are all based on control in work space (W-space), suffer from human errors tied to deficiencies in human spatial reasoning. The C-space approach transforms the problem into one humans are much better equipped to handle-moving a point in a maze-and results in a significant improvement in performance: shorter path, less time to complete the task, and virtually no arm-obstacle collisions. Versions of the approach are described for two-dimensional (2-D) and three-dimensional (3-D) tasks, and tools are developed to efficiently interface the human and machine intelligence. Effectiveness of the C-space approach is demonstrated by a series of experiments, showing an improvement in performance on the order of magnitude in the 2-D case and a factor of two to four in the 3-D case, compared to usual work space control.


Electrical cardioversion-effectiveness of quinidine prophylaxis following countershock.
Direct current countershock was given to 46 patients with chronic atrial fibrillation of diverse causes, with successful conversion in 87 per cent of them. Patients were observed while receiving quinidine prophylaxis, with serial determination of serum quinidine levels, for up to 22 months. Two quinidine preparations were employed, one a long-acting form, in various dosage regimens and both preparations were found to be effective prophylactic agents for maintaining reliable serum quinidine levels. Fifty per cent of patients remained in normal sinus rhythm at three months, 28 per cent at six months and 13 per cent at twelve months.


Renaturation of skeletal muscle tropomyosin: implications for in vivo assembly.
The observation that the alpha beta heterodimer is the predominant species of tropomyosin in rabbit skeletal muscles has led to the suggestion that this species assembles preferentially. To understand the molecular basis of this assembly process, we have studied renaturation under conditions that favor heterodimer formation. When skeletal muscle tropomyosin composed of equal amounts of alpha and beta subunits is renatured either by cooling or by dialysis a distribution that favors homodimers is generated. In contrast, rapid renaturation by dilution from urea favors the heterodimer. Further analysis of this latter renaturation procedure with cysteine-cleavage fragments of tropomyosin using circular dichroic measurements shows that as few as 30 residues in the NH2-terminal third of each tropomyosin subunit are involved in the initial interaction that results in heterodimer formation. Based on the density of sequence substitutions between the alpha and beta subunits, that region probably includes residues 36-64.


Using commercial application' software. Integrating clinic office practices.
Automation of clinic business office practices has often been accomplished by the use of the procedures obtained from the provider of automated services. With the availability of the microcomputer and the commercially available business application software, the desired automated procedures may be obtained by discretionary use of the products. By describing the integration and the operational use of business application software within a multiphysician specialty clinic, the author highlights both the problems encountered and the benefits achieved.


Socio-cultural modalities in population control.
Overpopulation with its identifiable and noxious results, is probably the most ominous and potentially destructive condition existing in current world society. The etiology of this problem includes the failure of mankind to develop compatible interrelationships between members of his own family, clan, society, and world population. The author predicts that all efforts to achieve world population control will be essentially ineffective unless the insights of the holistically oriented science of social psychiatry are refined into principles and rules which direct population control endeavors. This paper reviews the extent and severity of the problem and stresses the need for the operational implementation of the value systems and methodologies of social psychiatry. The author believes that effective population control is possible if the actions of world leaders are directed toward efforts to achieve satisfaction of the basic (Ur) needs of all individuals and groups for physical survival, socialization, and transcendence.


Pathologic markers of allograft arteriopathy: insight into the pathophysiology of cardiac allograft chronic rejection.
Transplant-associated coronary artery disease (CAD) is the principal limiting factor for the long-term survival of heart transplant patients. This review discusses early risk factors for the subsequent development of transplant-associated CAD. Early risk factors associated with a prothrombogenic microvasculature, such as deposition of microvascular fibrin, depletion of vascular tissue plasminogen activator, presence of endothelial activation of the allograft arterial tree, and loss of vascular antithrombin, as well as changes in circulation (ie, detectable serum cardiac troponin I and elevated serum soluble intercellular adhesion molecule-1 levels) are presented and discussed. New therapies that could improve the status of the allograft microvasculature and may prevent or mitigate the development of transplant-associated CAD are considered.


Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status.
Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4 T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status.


[Protective effect rendered by human ceruloplasmin on erythrocytes in hepatocerebral dystrophy].
In order to elucidate the protective effect of human ceruloplasmin (CP) on erythrocytes in patients with hepatocerebral dystrophy (HCD), the parameters reflecting the interaction of CP from the blood of healthy donors (n-CP) and of HCD patients (h-CP) with erythrocytes from healthy donors (n-ER) and from HCD patients (h-ER) were estimated. The protective effects of n-CP and h-CP on n-ER and h-ER during the Cu2+-induced lysis were compared. It was shown that the ability of h-CP to prevent the human ER breakdown upon Cu2+-induced lysis is much lower (approximately 3-fold) than that of n-CP. The differences in the protective effect of n-CP and h-CP are manifested in a greater degree during the n-ER lysis than during the h-ER lysis.


An Automated Algorithm for the Identification of Somatosensory Cortex Using Magnetoencephalography.
The localization of eloquent cortex is crucial for many neurosurgical applications, such as epilepsy and tumor resection. Non-invasive localization of these cortical areas using magnetoencephalography (MEG) is generally performed using equivalent current dipoles. While this method is clinically validated, source localization depends on several subjective parameters. This paper aimed to develop an automated algorithm for identifying the cortical area activated during a somatosensory task from MEG recordings. Our algorithm uses singular value decomposition to outline the cortical area involved in this task. For proof of concept, we evaluate our algorithm using data from 10 subjects with epilepsy. Our algorithm has a statistically significant overlap with the somatosensory cortex (the expected active area in healthy subjects) in 6 of 10 subjects. Having thus demonstrated proof of concept, we conclude that our algorithm is ready for further testing in a larger cohort of subjects.Clinical relevance- Our algorithm identifies the dominant cortical area and boundary of the cortical tissue involved in a task-related response.


Deep Learning of Electrocardiograms in Sinus Rhythm From US Veterans to Predict Atrial Fibrillation.
Early detection of atrial fibrillation (AF) may help prevent adverse cardiovascular events such as stroke. Deep learning applied to electrocardiograms (ECGs) has been successfully used for early identification of several cardiovascular diseases. To determine whether deep learning models applied to outpatient ECGs in sinus rhythm can predict AF in a large and diverse patient population. This prognostic study was performed on ECGs acquired from January 1, 1987, to December 31, 2022, at 6 US Veterans Affairs (VA) hospital networks and 1 large non-VA academic medical center. Participants included all outpatients with 12-lead ECGs in sinus rhythm. A convolutional neural network using 12-lead ECGs from 2 US VA hospital networks was trained to predict the presence of AF within 31 days of sinus rhythm ECGs. The model was tested on ECGs held out from training at the 2 VA networks as well as 4 additional VA networks and 1 large non-VA academic medical center. A total of 907 858 ECGs from patients across 6 VA sites were included in the analysis. These patients had a mean (SD) age of 62.4 (13.5) years, 6.4% were female, and 93.6% were male, with a mean (SD) CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age, sex category) score of 1.9 (1.6). A total of 0.2% were American Indian or Alaska Native, 2.7% were Asian, 10.7% were Black, 4.6% were Latinx, 0.7% were Native Hawaiian or Other Pacific Islander, 62.4% were White, 0.4% were of other race or ethnicity (which is not broken down into subcategories in the VA data set), and 18.4% were of unknown race or ethnicity. At the non-VA academic medical center (72 483 ECGs), the mean (SD) age was 59.5 (15.4) years and 52.5% were female, with a mean (SD) CHA2DS2-VASc score of 1.6 (1.4). A total of 0.1% were American Indian or Alaska Native, 7.9% were Asian, 9.4% were Black, 2.9% were Latinx, 0.03% were Native Hawaiian or Other Pacific Islander, 74.8% were White, 0.1% were of other race or ethnicity, and 4.7% were of unknown race or ethnicity. A deep learning model predicted the presence of AF within 31 days of a sinus rhythm ECG on held-out test ECGs at VA sites with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI, 0.85-0.86), accuracy of 0.78 (95% CI, 0.77-0.78), and F1 score of 0.30 (95% CI, 0.30-0.31). At the non-VA site, AUROC was 0.93 (95% CI, 0.93-0.94); accuracy, 0.87 (95% CI, 0.86-0.88); and F1 score, 0.46 (95% CI, 0.44-0.48). The model was well calibrated, with a Brier score of 0.02 across all sites. Among individuals deemed high risk by deep learning, the number needed to screen to detect a positive case of AF was 2.47 individuals for a testing sensitivity of 25% and 11.48 for 75%. Model performance was similar in patients who were Black, female, or younger than 65 years or who had CHA2DS2-VASc scores of 2 or greater. Deep learning of outpatient sinus rhythm ECGs predicted AF within 31 days in populations with diverse demographics and comorbidities. Similar models could be used in future AF screening efforts to reduce adverse complications associated with this disease.


Phase III randomized study of carboplatin pemetrexed with or without bevacizumab with initial versus "at progression" cerebral radiotherapy in advanced non squamous non-small cell lung cancer with asymptomatic brain metastasis.
The role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM. This open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin-pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537]. The trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4-7.5 versus 4.8, 95% CI: 2.4-6.5 months, for median OS: 8.5, 95% CI:.6-11.1 versus 8.3, 95% CI:4.5-11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable. The significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.


Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD.
Fibroblast growth factor-23 (FGF23) levels are elevated in ESRD and have been associated with adverse outcomes. The effects of various treatments for secondary hyperparathyroidism on FGF23 levels in ESRD have not been examined in a clinical trial. We assessed intact FGF23 levels in 91 subjects over the course of the ACHIEVE trial, which was designed to compare escalating doses of Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) with titration of calcitriol analogs alone (Flex-D) to suppress parathyroid hormone. Between-group and within-group changes in log-transformed FGF23 levels were analyzed. Factors associated with change in FGF23 were assessed using a multiple regression model. Intact FGF23 levels were markedly elevated in subjects at baseline. A statistically significant difference in percent change in log FGF23 levels was observed between treatment groups (P < 0.002). The Cinacalcet-D group had a significant decrease in percent change in log FGF23 levels (corrected P = 0.021), whereas FGF23 levels trended toward an increase in the Flex-D group. Change in FGF23 level was significantly associated with changes in levels of phosphate (P < 0.0001) and calcium (P = 0.0002) but not parathyroid hormone. Treatment with Cinacalcet plus low-dose calcitriol analogs results in lower FGF23 levels compared with a treatment regimen using calcitriol analogs alone in ESRD. The mechanisms underlying the differential effects of these treatment regimens on FGF23 levels and the clinical impact of these changes on FGF23 remain to be defined.


[A study of the polyploid nuclei of the giant trophoblast cells of several species of rodents using phase contrast microscopy].
Patterns of chromosome morphology in high polyploid trophoblast nuclei of placenta were compared in the rat, rabbit and Microtus arvalis. In the rat and rabbit placenta two types of nuclei were recognized. Some nuclei have ribbon-like chromosomes, while others display thin oligotene fibrils with paired chromomers evenly distributed throughout all karyoplasm. In the latter case, the polytenic structure of chromosomes is seen preserved only near the nucleoli. In the rat and rabbit trophoblast nuclei, the ribbon-like polytene chromosomes could be distinguished only with phase contrast microscopy. In the trophoblast nuclei of Microtus arvalis polytene chromosomes were found only at early stages of embryonic development (9 day old embryo). On later stages of cell differentiation, the chromosomes or chromosome rosetts are seen. Similarities in mechanisms of polyploidization in the high polyploid nuclei of Diptera and in trophoblast nuclei of rodents are discussed.


Who wants to be a citizen scientist? Identifying the potential of citizen science and target segments in Switzerland.
Driven by the proliferation of digital media, citizen science - the involvement of non-scientists in scientific research - represents one of the most important recent developments in science communication as it brings science and the public closer together. So far, however, citizen science projects have mostly attracted people that are highly educated, mostly male and already have very positive attitudes towards science. Based on nationally representative survey data (N = 1051), our study explores the potential of citizen science in Switzerland. Using regression analysis, we show that attitudes towards science are significant antecedents of respondents' interest in participating in citizen science - but that gender and education are not. In addition, latent class analysis identifies five segments, representing over one-third of the Swiss population, who are interested in citizen science and could potentially be engaged: 'Free-Timers', 'Senior Sciencephiles', 'Young Sciencephiles', 'Intrigued Adolescents' and 'Fully Employed Parents'. Additional description suggests that previously overlooked segments are best addressed online via YouTube or offline in zoos or botanical gardens. Overall, our analysis suggests that citizen science's potential is far higher than previous projects were able to realize.


Neural network potential energy surface and dynamical isotope effects for the N+(3P) + H2→ NH+ + H reaction.
The N+(3P) + H2(X1Σ) → NH+(X2Π) + H(2S) reaction is important for initiating the chain reaction of ammonia synthesis in the universe. To study the dynamics of this reaction, a global accurate potential energy surface (PES) of the ground state NH was constructed by combining numerous high-level ab initio energy points with the permutation invariant polynomial neural network method. Utilizing this newly constructed PES, time-dependent wave packet calculations were performed on the state-to-state reactions of N+(3P0) + H2 (v = 0, j = 0) and N+(3P0) + D2 (v = 0, j = 0) in order to study the microscopic reaction mechanisms and dynamical isotope effects. Isotope effects have a significant influence on the rovibrational state distributions and state resolved angle distributions of the product. The total differential cross sections (DCSs) present in the aforementioned reactions are dominated by both forward and backward scattering, as expected from the observable deep well along the reaction path. Meanwhile, the rovibrational state-resolved DCSs show that both reactions are not entirely statistical at the state-to-state level.


Development and Function of the Drosophila Tracheal System.
The tracheal system of insects is a network of epithelial tubules that functions as a respiratory organ to supply oxygen to various target organs. Target-derived signaling inputs regulate stereotyped modes of cell specification, branching morphogenesis, and collective cell migration in the embryonic stage. In the postembryonic stages, the same set of signaling pathways controls highly plastic regulation of size increase and pattern elaboration during larval stages, and cell proliferation and reprograming during metamorphosis. Tracheal tube morphogenesis is also regulated by physicochemical interaction of the cell and apical extracellular matrix to regulate optimal geometry suitable for air flow. The trachea system senses both the external oxygen level and the metabolic activity of internal organs, and helps organismal adaptation to changes in environmental oxygen level. Cellular and molecular mechanisms underlying the high plasticity of tracheal development and physiology uncovered through research on Drosophila are discussed.


Emergency nursing: historical, current, and future roles.
Building upon a historical context, the current and future roles of the clinical emergency nurse are reviewed. For several reasons, emergency nurse availability is expected to be insufficient to meet staffing demands in the near future. Emergency physicians can partner with emergency nurses and hospital administrators to pursue the following strategies for addressing the nursing shortage: (1) improve the workplace environment by improving nurse-to-patient ratios and avoiding the boarding of admitted patients in the emergency department (ED); (2) refocus the emergency nurse job description to patients and their families; (3) promote mutually supportive relationships and comradeship between emergency nurses and physicians; (4) create an environment that allows unique solutions to staff scheduling and accommodates shiftwork; (5) increase nursing wages, and recognize special contributions of emergency nurses with financial reward; (6) identify and promote the personnel of the hospital ED as members of an elite unit; (7) develop preceptorships and internships for nurses new to emergency nursing and invest in clinical specialists or nurse-mentors to assist in "on-the-job" instruction of nurses with previous experience; and (8) invest in nursing education. Taking these steps today will strengthen the ED health care safety net for decades to come.


Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis.
LINCL (late-infantile neuronal ceroid lipofuscinosis) is a fatal neurodegenerative disease resulting from mutations in the gene encoding the lysosomal protease TPPI (tripeptidyl-peptidase I). TPPI is expressed ubiquitously throughout the body but disease appears restricted to the brain. One explanation for the absence of peripheral pathology is that in tissues other than brain, other proteases may compensate for the loss of TPPI. One such candidate is another lysosomal aminopeptidase, DPPI (dipeptidyl-peptidase I), which appears to have overlapping substrate specificity with TPPI and is expressed at relatively low levels in brain. Compensation for the loss of TPPI by DPPI may have therapeutic implications for LINCL and, in the present study, we have investigated this possibility using mouse genetic models. Our rationale was that if DPPI could compensate for the loss of TPPI in peripheral tissues, then its absence should exacerbate disease in an LINCL mouse model but, conversely, increased CNS (central nervous system) expression of DPPI should ameliorate disease. By comparing TPPI and DPPI single mutants with a double mutant lacking both proteases, we found that the loss of DPPI had no effect on accumulation of storage material, disease severity or lifespan of the LINCL mouse. Transgenic expression of DPPI resulted in a approximately 2-fold increase in DPPI activity in the brain, but this had no significant effect on survival of the LINCL mouse. These results together indicate that DPPI cannot functionally compensate for the loss of TPPI. Therapeutic approaches to increase neuronal expression of DPPI are therefore unlikely to be effective for treatment of LINCL.


Elective central compartment neck dissection in patients with papillary thyroid carcinoma recurrence.
To investigate the role of elective central compartment neck dissection (CND) in patients with recurrent papillary thyroid carcinoma in the jugular chain lymph nodes. Retrospective medical record review and analysis of survival outcomes. The study was conducted at Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University. Fifty-one patients who had prior thyroidectomy underwent therapeutic lateral neck dissection (LND) without radiological evidence of central neck metastases. Therapeutic LND without elective CND was performed in 17 patients, and 34 patients had elective CND. The clinical variables were similar in both groups. The median follow-up was 44 months. Disease-free survival and overall survival were the main outcome measures. The recurrence rate in the central neck was 9% (n = 3/34) in patients undergoing CND and 12% (n = 2/17) in patients without CND. The overall recurrence rate was 18% (6/34) in patients with CND and 36% (6/17) in patients without CND (P = 0.16). The 5-year disease-free survival rate was 82% and 65% in patients with or without CND, respectively (P = 0.69). Long-term thyroglobulin levels and complication rates were similar in both groups. The lack of significant disease-free survival advantage demonstrates the need for a prospective evaluation of the common practice of this disease.


Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis.
Alcohol is the leading cause of cirrhosis, but most patients go undetected until decompensation occurs despite frequent contacts with the healthcare system. We aimed to evaluate the diagnostic accuracy of routine liver function tests compared with indirect and direct fibrosis markers and to assess doctors' abilities to diagnose significant and advanced alcohol-related liver fibrosis. This study was a retrospective evaluation of liver function tests for diagnosing alcohol-related liver disease compared to indirect fibrosis tests, the ELF test, and transient elastography. We also surveyed nine doctors who were presented with 225 patient cases from a cross-sectional, biopsy-controlled, single-centre study that evaluated diagnostic tools for alcohol-related liver fibrosis. The doctors assessed each case for significant (≥F2) or advanced (≥F3) fibrosis. We assessed inter-rater variability with Fleiss' kappa. Routine liver function tests had poor diagnostic accuracy (highest area under the ROC curve for platelet count = 0.752) and poor sensitivities (10%-67%) when using the upper or lower normal limits as cut-offs. Indirect fibrosis indices performed significantly better but were still inferior to the ELF test and transient elastography. The nine doctors disagreed substantially in their predictions, with Fleiss' kappa of 0.24 (95% CI0.22-0.26) and 0.51 (0.44-0.55) for significant and advanced fibrosis. All nine doctors exhibited poor case-finding abilities with sensitivities of 22-93%. When using routine liver function tests, doctors may fail to diagnose more than half of all alcohol-overusing patients with advanced fibrosis, probably because they rely on upper and lower normal limits of routine liver function tests.


Surgical options for obstructive sleep apnea.
The pathology associated with obstructive sleep apnea is cumulative and progressive. When patients fail to improve with continuous nasal airway pressure or other, less-invasive treatments, surgery should be considered. The initial approach to the surgical patient is identification of all areas of potential obstruction. There are often several sites of obstruction, which can occur anywhere in the upper respiratory tract. One or more procedures may be needed to address these areas. The objective of surgery is to relieve these obstructing sites without interfering with the normal functionality of the upper airway.


An interview with Bernie Auchter. Interview by Walter S DeKeseredy.
Since the creation of the 1994 Violence Against Women Act (VAWA), Bernie Auchter and his colleagues affiliated with the National Institute of Justice's (NIJ) Violence Against Women Research and Evaluation Program have done much to assist the efforts of progressive researchers, practitioners, activists, and policy makers. Their work also helped enhance the health and well-being of countless women victimized by violence. This article is based on an interview with Bernie and chronicles some of his key contributions to the field.


Conductivity mapping of graphene on polymeric films by terahertz time-domain spectroscopy.
Fast inline characterization of the electrical properties of graphene on polymeric substrates is an essential requirement for quality control in industrial graphene production. Here we show that it is possible to measure the sheet conductivity of graphene on polymer films by terahertz time-domain spectroscopy (THz-TDS) when all internally reflected echoes in the substrate are taken into consideration. The conductivity measured by THz-TDS is comparable to values obtained from four point probe measurements. THz-TDS maps of 25x30 cm2 area graphene films were recorded and the DC conductivity and carrier scattering time were extracted from the measurements. Additionally, the THz-TDS conductivity maps highlight tears and holes in the graphene film, which are not easily visible by optical inspection.


Helcococcus kunzii as sole isolate from an infected sebaceous cyst.
Helcococcus kunzii was isolated in pure culture from pus drained from an infected sebaceous cyst associated with marked cellulitis. The cyst was excised one month later after the inflammation had subsided with flucloxacillin treatment. This is the first report of the isolation of H. kunzii as the sole pathogen from an infected site.


Isotonic saline solution as maintenance intravenous fluid therapy to prevent acquired hyponatremia in hospitalized children.
This review aims to evaluate if the use of hypotonic saline solutions as maintenance intravenous fluid therapy in hospitalized children increases the risk of hyponatremia, if the administration of isotonic fluids is able to protect against acquired hyponatremia and if the isotonic solutions increase the risks of deleterious effects such as hypernatremia or fluid overload. We researched the relevant literature on the PubMed (Jan 01 1969 to Jul 13 2011), EMBASE (1989 to 2011) and Cochrane Library (1989 to 2011) databases. Furthermore, references of selected studies were included. Hospitalized children are potentially at risk of developing hyponatremia and the use of hypotonic saline solutions is the main risk factor for this disease. Isotonic saline solutions have shown a protective effect against hyponatremia, and, so far, there have been no significant deleterious effects such as fluid overload, hypernatremia or phlebitis. The evidence found indicates that the traditional recommendation of Holliday and Segar to use maintenance fluid therapy for sick and hospitalized children deserves to be reconsidered due to the adverse effects found to arise from it, apart from the better results obtained by using isotonic solutions.


Ultrastructural study of rotavirus replication in cultured cells.
A systematic ultrastructural analysis of the replication cycle of the simian rotavirus SA11 in permissive MA104 cells was performed under reproducible conditions. At 8 h p.i., small areas of viroplasm were seen adjacent to swollen vesicles of the rough endoplasmic reticulum (rer) containing a few 80 to 90 nm virus particles. At later times, the size and number of these inclusions increased and the rer contained large numbers of the 80 to 90 nm particles as well as 52 to 65 nm particles. Infected cells eventually lysed, releasing progeny virus. Other cytological alterations included virus particles sequestered in lysosome-like bodies, 15 to 20 nm tubular structures in the nucleus and/or cytoplasm, convoluted membranes within the rer, filament bundles associated with virus particles, and mitochondria containing 1 to 5 virus particles. In addition, SA11 replication was studied in several less permissive cell lines. The results were similar to those with MA104 cells except that a smaller percentage of the cells were productively infected.


Distal-less and dachshund pattern both plesiomorphic and apomorphic structures in chelicerates: RNA interference in the harvestman Phalangium opilio (Opiliones).
The discovery of genetic mechanisms that can transform a morphological structure from a plesiomorphic (=primitive) state to an apomorphic (=derived) one is a cardinal objective of evolutionary developmental biology. However, this objective is often impeded for many lineages of interest by limitations in taxonomic sampling, genomic resources, or functional genetic methods. In order to investigate the evolution of appendage morphology within Chelicerata, the putative sister group of the remaining arthropods, we developed an RNA interference (RNAi) protocol for the harvestman Phalangium opilio. We silenced the leg gap genes Distal-less (Dll) and dachshund (dac) in the harvestman via zygotic injections of double-stranded RNA (dsRNA), and used in situ hybridization to confirm RNAi efficacy. Consistent with the conserved roles of these genes in patterning the proximo-distal axis of arthropod appendages, we observed that embryos injected with Dll dsRNA lacked distal parts of appendages and appendage-like structures, such as the labrum, the chelicerae, the pedipalps, and the walking legs, whereas embryos injected with dac dsRNA lacked the medial podomeres femur and patella in the pedipalps and walking legs. In addition, we detected a role for these genes in patterning structures that do not occur in well-established chelicerate models (spiders and mites). Dll RNAi additionally results in loss of the preoral chamber, which is formed from pedipalpal and leg coxapophyses, and the ocularium, a dorsal outgrowth bearing the eyes. In one case, we observed that an embryo injected with dac dsRNA lacked the proximal segment of the chelicera, a plesiomorphic podomere that expresses dac in wild-type embryos. This may support the hypothesis that loss of the cheliceral dac domain underlies the transition to the two-segmented chelicera of derived arachnids.


A chromosome-scale genome assembly for the holly (Ilex polyneura) provides insights into genomic adaptations to elevation in Southwest China.
Southwest China is a plant diversity hotspot. The near-cosmopolitan genus Ilex (c. 664 spp., Aquifoliaceae) reaches its maximum diversity in this region, with many narrow-range and a few widespread species. Divergent selection on widespread species leads to local adaptation, with consequences for both conservation and utilization, but is counteracted by geneflow. Many Ilex species are utilized as teas, medicines, ornamentals, honey plants, and timber, but variation below the species level is largely uninvestigated. We therefore studied the widespread Ilex polyneura, which occupies most of the elevational range available and is cultivated for its decorative leafless branches with persistent red fruits. We assembled a chromosome-scale genome using approximately 100x whole genome long-read and short-read sequencing combined with Hi-C sequencing. The genome is approximately 727.1 Mb, with a contig N50 size of 5 124 369 bp and a scaffold N50 size of 36 593 620 bp, for which the BUSCO score was 97.6%, and 98.9% of the assembly was anchored to 20 pseudochromosomes. Out of 32 838 genes predicted, 96.9% were assigned functions. Two whole genome duplication events were identified. Using this genome as a reference, we conducted a population genomics study of 112 individuals from 21 populations across the elevation range using restriction site-associated DNA sequencing (RADseq). Most populations clustered into four clades separated by distance and elevation. Selective sweep analyses identified 34 candidate genes potentially under selection at different elevations, with functions related to responses to abiotic and biotic stresses. This first high-quality genome in the Aquifoliales will facilitate the further domestication of the genus.


Novel Antioxidative Activity of Astaxanthin and Its Synergistic Effect with Vitamin E.
Astaxanthin (Asx) is known to be a potent quencher of singlet oxygen and an efficient scavenger of superoxide anion. However, the scavenging activity of Asx toward the hydroxyl radical was currently unclear because the high lipophilicity of Asx prevents analysis of such activity in water. Liposomes containing Asx (Asx-lipo) were previously shown to be dispersed in water. Analysis of the hydroxyl radical scavenging activity of Asx-lipo demonstrated a dose-dependence in water, with the effect of Asx being more potent than the vitamin E α-tocopherol (α-T). Furthermore, liposomes co-encapsulating Asx and vitamin E derivatives, namely tocotrienols (T3), showed a synergistic elimination effect on singlet oxygen and hydroxyl radical, although the antioxidative activity of liposomes co-encapsulating Asx and α-T was lower than the calculated additive value of each independent activity. A calculation of the most stable structure of Asx in the presence of α-T or T3, suggested that only T3 was able to hydrogen bond with Asx, and the Asx polyene chain partially interacting with the α-T3 triene chain, which could explain the synergistic effect between Asx and T3, but not Asx and α-T. This review introduces the hydroxyl radical scavenging activity of Asx, and its synergistic effect with T3.


The SLC14 gene family of urea transporters.
Carrier-mediated urea transport allows rapid urea movement across the cell membrane, which is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. Urea transporters mediate passive urea uptake that is inhibited by phloretin and urea analogues. Facilitated urea transporters are divided into two classes: (1) the renal tubular/testicular type of urea transporter, UT-A1 to -A5, encoded by alternative splicing of the SLC14A2 gene, and (2) the erythrocyte urea transporter UT-B1 encoded by the SLC14A1 gene. The primary structure of urea transporters is unique, consisting of two extended, hydrophobic, membrane-spanning domains and an extracellular glycosylated-connecting loop. UT-A1 is the result of a gene duplication of this two-halves-structure, and the duplicated portions are linked together by a large intracellular hydrophilic loop, carrying several putative protein kinase A (PKA) and -C (PKC) phosphorylation sites. UT-A1 is located in the apical membrane of the kidney inner medullary collecting duct cells, where it is stimulated acutely by cAMP-mediated phosphorylation in response to the antidiuretic hormone vasopressin. Vasopressin also up-regulates UT-A2 mRNA/protein expression in the descending thin limb of the loops of Henle. UT-A1 and UT-A2 are regulated independently and respond differently to changes in dietary protein content. UT-A3 and UT-A4 are located in the rat kidney medulla and UT-A5 in the mouse testis. The widely expressed UT-B participates in urea recycling in the descending vasa recta, as demonstrated by a relatively mild "urea-selective" urinary concentrating defect in transgenic UT-B null mice and individuals with the Jk(null) blood group.


[Surgical treatment of adenosquamous carcinoma of the lung--analysis of 223 cases].
The curative effect of 223 cases of primary pulmonary adenosquamous carcinoma. The adenosquamous carcinoma made up 10.8 percent of the total primary lung cancer in the same therapeutic period. We reexamined the specimen which had been excised in operation about 187 cases under the optic microscope and found out the amount of squamous cell is more than adenocarcinoma. The ratio is about 56.7 and 34.8 percent respectively. But the curative effect of adenosquamous carcinoma not only was worse than that of the squamous carcinoma, but also the adenocarcinoma and small cell lung cancer. So it reminds us the adenosquamous carcinoma has it's specific biologic characteristics. The operation is the most important way in curing adenosquamous carcinoma. The stage I and II should be operated early, and for stage III, we must follow the indication strictly. We select the comprehensive method in stage IIIb, such as radiotherapy or chemical therapy to raise the existent rate.