[Neurological aspect of clinical symptoms, pathophysiology and correction in attention deficit hyperactivity disorder].
We studied prevalence of attention deficit hyperactivity disorder (ADHD) in senior schoolchildren of Nefteyugansk (Khanty-Mansysky autonomic region) it was 8% (13% among boys and 3% among girls). Clinical examination of 122 children, aged 6-11 years, revealed that risk factors for ADHD were perinatal CNS injures, familial predisposition, unfavorable social and psychological influences. Neuropsychological, neurophysiologic (electroencephalography) and biochemical study showed mild neurological disturbances, some peculiarities of motor and emotional spheres and higher mental functions. Moreover, there were such biochemical alterations as a decrease of magnesium level in the plasma and erythrocytes and a reduction of Mg(2+)-ATPase activity. The use of MAGNE-B6 allowed us to correct many of the disturbances.


IL-11 is required for A1 adenosine receptor-mediated protection against ischemic AKI.
A1 adenosine receptor activation ameliorates ischemic AKI through the induction of renal proximal tubular sphingosine kinase-1. However, systemic adverse effects may limit A1 adenosine receptor-based therapy for ischemic AKI, indicating a need to identify alternative therapeutic targets within this pathway. Here, we evaluated the function of renal proximal tubular IL-11, a clinically approved hematopoietic cytokine, in A1 adenosine receptor-mediated induction of sphingosine kinase-1 and renal protection. Treatment of human proximal tubule epithelial (HK-2) cells with a selective A1 adenosine receptor agonist, chloro-N(6)-cyclopentyladenosine (CCPA), induced the expression of IL-11 mRNA and protein in an extracellular signal-regulated kinase-dependent manner, and administration of CCPA in mice induced renal synthesis of IL-11. Pretreatment with CCPA protected against renal ischemia-reperfusion injury in wild-type mice, but not in IL-11 receptor-deficient mice. Administration of an IL-11-neutralizing antibody abolished the renal protection provided by CCPA. Similarly, CCPA did not induce renal IL-11 expression or protect against renal ischemia-reperfusion injury in mice lacking the renal proximal tubular A1 adenosine receptor. Finally, treatment with CCPA induced sphingosine kinase-1 in HK-2 cells and wild-type mice, but not in IL-11 receptor-deficient or renal proximal tubule A1 adenosine receptor-deficient mice. Taken together, these results suggest that induction of renal proximal tubule IL-11 is a critical intermediary in A1 adenosine receptor-mediated renal protection that warrants investigation as a novel therapeutic target for the treatment of ischemic AKI.


[Roentgenologic assessment of articular lesions in rheumatoid arthritis].
The article presents a comparative analysis of methods for quantitative assessment of roengenologic changes in the joints in rheumatoid arthritis that have come to be widely used in USA and Europe. It is noted that the Steinbroker's method widely employed by clinicians fails to give an integral assessment of the articular affection. Expediency is documented of employment of the Sharp's method in roentgenologic monitoring in clinical trials of new antirheumatic drug preparations. In a routine clinical setting the Larsen's method or its modifications are to be preferred since in spite of its low sensitivity investigation time is cut down 2.3-fold by comparison with the Sharp's method.


Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric patients treated with high-dose methotrexate and cytarabine plus anti-CD20.
Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B-cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients achieved a continuous complete remission with front-line therapy. The overall 5-year survival was 91.7%, and event-free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti-CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.


Knowledge and acceptability of the human papillomavirus vaccine among health professionals in Acre state, western Amazon.
To evaluate the knowledge and acceptability of the human papillomavirus (HPV) vaccine among health professionals from western Amazonia. A cross-sectional study was conducted in the Sistema Assistencial è Saúde da Mulher e da Criança (Health Care System for Women and Children; SASMC) in Acre, Brazil, in 2017. The participants comprised 196 health professionals. The data collection instrument contained 31 questions about HPV, its clinical repercussions for women, and the HPV vaccine. Quantitative variables were presented as medians and 95% confidence intervals (CIs), and p<0.05 was considered statistically significant. For the analyses, chi-square tests and Mann-Whitney tests were used. The collected data were analyzed using Stata®11.0. Of the 196 health professionals, 39.8% (n=76) were physicians and 61.2% (n=120) were other health professionals. The interviewees were mostly female (n=143, 73%, 95% CI 66.1 to 78.9%) who worked in the medical field (n=81, 41.3%, 95% CI 34.4 to 48.6%), and the median age was 38 years (95% CI 36.0 to 39.7). Physicians had increased knowledge regarding only the statement "cervical cancer is one of the main causes of cancer in women", with a proportion ratio of 0.88 (0.80; 0.97) and p<0.001. Regarding clinical knowledge of the HPV vaccine, a low proportion of correct answers was obtained for all the questions, and no significant differences were found between the groups. Acceptability and knowledge of HPV and its vaccine were similar among health professionals, with knowledge gaps in questions about the relation between smoking and cervical cancer and specific clinical knowledge.


Bifunctional up-converting lanthanide nanoparticles for selective in vitro imaging and inhibition of cyclin D as anti-cancer agents.
Inhibition of the CDK4/cyclin D complex through the substrate recruitment site on the cyclin positive regulatory subunit is recognised as being a promising anti-cancer target. Specific peptide sequences can be used to selectively disrupt this target, but the development of peptides as anti-tumor agents in vitro/in vivo presents several obstacles. Poor cell internalization, low sensitivity towards enzymatic degradation in vivo, and ineffectiveness in monitoring via indirect screening are all issues which must be overcome. Herein, we describe the surface functionalization of lanthanide nanoparticles with cyclin D-specific peptides to prepare novel nanomaterials (UCNPs-P1) which can target the CDK4/cyclin D complex. The nanomaterials prepared (UCNPs-P1) are cell permeable and they display parallel emission spectra in vitro and in an aqueous biological environment. They can also be used in low dose concentrations under harmless NIR excitation and emission via upconversion. Uniquely, in addition to acting as a bioimaging probe, UCNPs-P1 also exhibits promising cytotoxicity towards cancer cells. In light of the aforementioned properties, the prepared functionalized nanomaterials (UCNPs-P1) offer the first real dual acting system for cyclin D imaging and simultaneous inhibition of cancer cell division.


Effects of Helicobacter pylori and Nitrate-Reducing Bacteria Coculture on Cells.
Helicobacter pylori infection is an important risk factor for developing gastric cancer. However, only a few H. pylori-infected people develop gastric cancer. Thus, other risk factors aside from H. pylori infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by H. pylori infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by H. pylori infection. Among the isolated bacteria, Actinomyces oris, Actinomyces odontolyticus, Rothia dentocariosa, and Rothia mucilaginosa were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the Actinomyces and Rothia species were enhanced when cocultured with H. pylori. Th1/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, H. pylori and Actinomyces activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with H. pylori may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development.


[Correlations between mental maturity and higher mental function in preschool children].
This communication presents the results of comparative study of 23 quantitative characteristics of the mental development of a child (the data of neuropsychological diagnosis of higher cortical functions by the procedure developed by I. F. Markovskaya, 1993) and 112 parameters of higher mental functions (perception, memory, assimilation and reproduction of rhythmic stimuli, behavioral strategy in the determined environment) recorded by a complex of microprocessor psychophysiological apparatuses, such as "Rhythmotest", "Mnemotest", and "Binatest".


Organizational Directors' Perceptions About Awareness of Services Among Their Employees and the Older Adults They Serve.
Objectives: This study explores the extent to which directors of organizations perceive that (a) older adults are aware of and interested in using services, and (b) their employees are aware of complementary services in the community and are willing to coordinate care or refer older adults to these services. Method: We conducted 41 qualitative semistructured interviews with organizational directors who provide services to older adults. Results: Directors perceived that not only older adults but also some providers were unaware of services in the community. Directors reported that some older adults felt stigmatized and were unwilling to use services, but services providers implemented strategies to overcome these barriers. Discussion: Understanding the perceptions of organizational directors may help identify opportunities for older adults to learn about community services and for providers to better coordinate care.


Phospholipase Dα1 mediates the high-Mg2+ stress response partially through regulation of K+ homeostasis.
Intracellular levels of Mg2+ are tightly regulated, as Mg2+ deficiency or excess affects normal plant growth and development. In Arabidopsis, we determined that phospholipase Dα1 (PLDα1) is involved in the stress response to high-magnesium conditions. The T-DNA insertion mutant pldα1 is hypersensitive to increased concentrations of magnesium, exhibiting reduced primary root length and fresh weight. PLDα1 activity increases rapidly after high-Mg2+ treatment, and this increase was found to be dose dependent. Two lines harbouring mutations in the HKD motif, which is essential for PLDα1 activity, displayed the same high-Mg2+ hypersensitivity of pldα1 plants. Moreover, we show that high concentrations of Mg2+ disrupt K+ homeostasis, and that transcription of K+ homeostasis-related genes CIPK9 and HAK5 is impaired in pldα1. Additionally, we found that the akt1, hak5 double mutant is hypersensitive to high-Mg2+ . We conclude that in Arabidopsis, the enzyme activity of PLDα1 is vital in the response to high-Mg2+ conditions, and that PLDα1 mediates this response partially through regulation of K+ homeostasis.


The effect of ascorbic acid on the activity of lipoprotein lipase in the baboon (Papio ursinus).
The intravenous administration of heparin-released lipoprotein lipase (LPL) into the circulatory system of the baboon (Papio ursinus) is described. After a single heparin injection, a peak value of LPL activity appeared in the circulation with 5 minutes. At low doses of heparin (less than 100 units heparin/kg body mass), LPL disappeared from the circulation in an exponential fashion with a half-life of about 20 minutes. An increase in the heparin dose increased the amount of LPL released into the circulation. In baboons which were deficient in ascorbic acid, less LPL was released into the circulation after specific doses of heparin than in animals that were amply supplied with this vitamin (ascorbic acid 16 mg/kg body mass/day). The separation of plasma LOL, released by heparin, on Sephadex G-150, revealed several distinct molecular species of LPL in the eluant from the columns. In vitro studies indicated that ascorbic acid inhibited cardiac LPL strongly, whereas it had little effect on "post-heparin plasma" LPL. 2somolar concentrations of another reducing agent, mercapto-ethanol, slightly stimulated cardiac LPL in baboons.


Micro-CT scan with virtual dissection of left ventricle is a non-destructive, reproducible alternative to dissection and weighing for left ventricular size.
Micro-CT scan images enhanced by iodine staining provide high-resolution visualisation of soft tissues in laboratory mice. We have compared Micro-CT scan-derived left ventricular (LV) mass with dissection and weighing. Ex-vivo micro-CT scan images of the mouse hearts were obtained following staining by iodine. The LV was segmented and its volume was assessed using a semi-automated method by Drishti software. The left ventricle was then dissected in the laboratory and its actual weight was measured and compared against the estimated results. LV mass was calculated multiplying its estimated volume and myocardial specific gravity. Thirty-five iodine-stained post-natal mouse hearts were studied. Mice were of either sex and 68 to 352 days old (median age 202 days with interquartile range 103 to 245 days) at the time of sacrifice. Samples were from 20 genetically diverse strains. Median mouse body weight was 29 g with interquartile range 24 to 34 g. Left Ventricular weights ranged from 40.0 to 116.7 mg. The segmented LV mass estimated from micro-CT scan and directly measured dissected LV mass were strongly correlated (R2 = 0. 97). Segmented LV mass derived from Micro-CT images was very similar to the physically dissected LV mass (mean difference = 0.09 mg; 95% confidence interval - 3.29 mg to 3.1 mg). Micro-CT scanning provides a non-destructive, efficient and accurate visualisation tool for anatomical analysis of animal heart models of human cardiovascular conditions. Iodine-stained soft tissue imaging empowers researchers to perform qualitative and quantitative assessment of the cardiac structures with preservation of the samples for future histological analysis.


Fast improvements in functional status after osteopathic manipulative treatment based on myofascial release in patients with moderate or severe fibromyalgia: a retrospective study.
Fibromyalgia (FM) is a chronic pain syndrome characterized by a large variety of symptoms. Evidence suggests that an alteration of central nervous system processing of pain could be involved. The purpose of this study is to analyze clinical records of patients affected by FM who underwent osteopathic manipulative treatment (OMT), predominantly based on a myofascial release approach (MFR). This retrospective study considered records of 21 FM patients with moderate or severe functional impact, who consented to OMT in addition to their usual care. The assessment considered the following measures: FIQ (functional status), SF36 (quality of life), VAS (pain), TSK (kinesiophobia) and PSQI (quality of sleeping). Patients were preliminarily assessed over a 1 month run-in phase, then after 1, 2 and 4 months; a 1 month follow-up was also considered. After one month, 71% of patients reported a decrease in functional impact and scores remained stable until follow-up (from 69.8 to 52.37, p≤0.001). Overall, after four months, patients improved their quality of life, with a score ranging from 33.47 to 42.6 (p≤0.05). We also observed a reduction of pain (p≤0.05). A series of OMT sessions based on MFR could play a therapeutic role in improving functional status, pain and quality of life over a period of 4 months.


[Design and validation of a self-reported dietary polyphenol intake frequency questionnaire.]
Introduction: although there is evidence linking polyphenol consumption with better health outcomes, information on consumption patterns, particularly in Latin American countries, is scarce. Objective: to design and evaluate the validity of an online self-reported food frequency questionnaire to measure dietary total polyphenol intake in the Chilean adult population. Methods: the designed questionnaire (FFQ-P) was submitted to expert opinion for content validity coefficient estimation; then a pilot study was conducted in 47 adults who completed FFQ-P, in addition to a six-day food record as a reference method. Wilcoxon was applied in related samples, Spearman's correlation to determine the strength of association and Bland-Altman diagrams to examine the difference between methods. Results: content validity reflected concordant values for adequacy (0.94 ± 0.04) and relevance (0.93 ± 0.05). The percentage difference between both methods was 1.2 %, with greater variability observed in fruits (9 %) and alcoholic beverages (4 %). The Wilcoxon test showed no significant differences between food groups. Medium reliability was observed for vegetables, fruits, tea, and coffee (0.26 to 0.5) and moderate reliability for alcoholic beverages (0.5 to 0.75). The mean value of the difference was 9.8, being within a short distance of zero. Conclusion: FFQ-P is reliable for estimating polyphenol intake from fruits, vegetables, alcoholic beverages, tea, and coffee; however, the intake of non-alcoholic beverages, nuts and olives should be interpreted with reservation.


Schistosoma haematobium infection in Abeokuta.
Ten years after the initial report of the outbreak of schistosomiasis in the vicinity of Sokori stream (a tributary of Ogun River) in Abeokuta, Nigeria, investigation was carried out to determine the present status of the disease, given the increased socioeconomic activities in the city. A total of 1670 school pupils in three schools within one kilometer radius of the stream, and 234 adults found using the stream for some water related activities were examined for eggs in their urine. One hundred and ninety-eight (11.9%) of the pupils and 98 (7.7%) of the adult group were infected. Compared to results of earlier surveys 1985 (55%) and 1987 (60.9%), there was a considerable reduction in the prevalence of infection. Also, 20.1% of pupils examined in the 1987 survey excreted between 200 and 1000 eggs/10 ml urine while the highest egg count in this survey was 189 eggs/10 ml urine. In addition to the improved water supply observed in the city, there has also been increased alternative recreational sites which may have reduced the propensity of the children to swim in the stream. Three snail species were seen (Bulinus forskalii, Physa waterlotti, and Melanoides voltae), none of which was naturally infected with cercariae.


Informatic parcellation of the network involved in the computation of subjective value.
Understanding how the brain computes value is a basic question in neuroscience. Although individual studies have driven this progress, meta-analyses provide an opportunity to test hypotheses that require large collections of data. We carry out a meta-analysis of a large set of functional magnetic resonance imaging studies of value computation to address several key questions. First, what is the full set of brain areas that reliably correlate with stimulus values when they need to be computed? Second, is this set of areas organized into dissociable functional networks? Third, is a distinct network of regions involved in the computation of stimulus values at decision and outcome? Finally, are different brain areas involved in the computation of stimulus values for different reward modalities? Our results demonstrate the centrality of ventromedial prefrontal cortex (VMPFC), ventral striatum and posterior cingulate cortex (PCC) in the computation of value across tasks, reward modalities and stages of the decision-making process. We also find evidence of distinct subnetworks of co-activation within VMPFC, one involving central VMPFC and dorsal PCC and another involving more anterior VMPFC, left angular gyrus and ventral PCC. Finally, we identify a posterior-to-anterior gradient of value representations corresponding to concrete-to-abstract rewards.


Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty.
Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty (PTCA)-with an autoperfusion balloon or active system-facilitates prolonged balloon inflation. Prolonged inflations may tack up intimal dissections and improve the primary angioplasty result in complex lesions. Additionally, distal perfusion may reduce the likelihood of cardiogenic shock during high-risk PTCA. Autoperfusion balloons are most frequently used to treat acute or threatened closure. There currently is no prospective clinical study showing that stent implantation for this complication is more successful and more cost-effective. The blood flow rates through autoperfusion balloons may not abolish myocardial ischemia, and higher flow rates can often be achieved with pumps. Therefore, during high-risk PTCA, pumps may be preferred to prevent hemodynamic collapse. Clinical application of perfusion pumps is hampered by the risk for mechanical hemolysis during prolonged perfusion and the high velocity of the bloodstream that exits the PTCA catheter, causing distal vessel wall trauma.


The efficient magneto-mechanical actuation of cancer cells using a very low concentration of non-interacting ferrimagnetic hexaferrite nanoplatelets.
Magneto-mechanical actuation (MMA) using the low-frequency alternating magnetic fields (AMFs) of magnetic nanoparticles internalized into cancer cells can be used to irreparably damage these cells. However, nanoparticles in cells usually agglomerate, thus greatly augmenting the delivered force compared to single nanoparticles. Here, we demonstrate that MMA also decreases the cell viability, with the MMA mediated by individual, non-interacting nanoparticles. The effect was demonstrated with ferrimagnetic (i.e., permanently magnetic) barium-hexaferrite nanoplatelets (NPLs, ∼50 nm wide and 3 nm thick) with a unique, perpendicular orientation of the magnetization. Two cancer-cell lines (MDA-MB-231 and HeLa) are exposed to the NPLs in-vitro under different cell-culture conditions and actuated with a uniaxial AMF. TEM analyses show that only a small number of NPLs internalize in the cells, always situated in membrane-enclosed compartments of the endosomal-lysosomal system. Most compartments contain 1-2 NPLs and only seldom are the NPLs found in small groups, but never in close contact or mutually oriented. Even at low concentrations, the single NPLs reduce the cell viability when actuated with AMFs, which is further increased when the cells are in starvation conditions. These results pave the way for more efficient in-vivo MMA at very low particle concentrations.


Post-treatment work patterns amongst survivors of lymphoma treated with high-dose chemotherapy with autologous stem-cell transplantation.
This study describes post-treatment work patterns in lymphoma survivors treated with high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). It aims to identify determinants for labour force participation and exclusion after HDT-ASCT. All survivors treated with HDT-ASCT for lymphoma in Norway between 1995 and 2008, aged ≥18 years at HDT-ASCT and alive at survey in 2012-2013 were eligible. We divide survivors by current employment status (full-time, part-time and unemployed). Main outcomes are current employment status, work hours and work ability. Withdrawals are patients employed when diagnosed but not before HDT-ASCT. Of the 274 who completed the survey, 82% (N = 225) were included in the final analyses. Mean age at survey was 52 years, 39% were female, 85% were employed when diagnosed, 77% before HDT-ASCT and 69% at survey. Employment before HDT-ASCT corresponds with a higher probability of employment at survey for a given symptom burden. In the most extensive statistical model, it increases with 37.3 percentage points. Work hours amongst withdrawals plummet after HDT-ASCT while work ability shows a rebound effect. The potential economic gain from their re-enter into the work force equals 70% of the average annual wage in Norway in 2012. For a given symptom burden, staying employed throughout diagnosis and treatment is associated with a higher probability of future employment. These results favour policies for labour force inclusion past diagnosis and treatment increasing cancer survivors' probability of future employment. However, we need more research on withdrawal mechanisms, and on policy measures that promote inclusion.


Effect of depth information on multiple-object tracking in three dimensions: A probabilistic perspective.
Many daily situations require us to track multiple objects and people. This ability has traditionally been investigated in observers tracking objects in a plane. This simplification of reality does not address how observers track objects when targets move in three dimensions. Here, we study how observers track multiple objects in 2D and 3D while manipulating the average speed of the objects and the average distance between them. We show that performance declines as speed increases and distance decreases and that overall tracking accuracy is always higher in 3D than in 2D. The effects of distance and dimensionality interact to produce a more than additive improvement in performance during tracking in 3D compared to 2D. We propose an ideal observer model that uses the object dynamics and noisy observations to track the objects. This model provides a good fit to the data and explains the key findings of our experiment as originating from improved inference of object identity by adding the depth dimension.


A model of global citizenship: antecedents and outcomes.
As the world becomes increasingly interconnected, exposure to global cultures affords individuals opportunities to develop global identities. In two studies, we examine the antecedents and outcomes of identifying with a superordinate identity--global citizen. Global citizenship is defined as awareness, caring, and embracing cultural diversity while promoting social justice and sustainability, coupled with a sense of responsibility to act. Prior theory and research suggest that being aware of one's connection with others in the world (global awareness) and embedded in settings that value global citizenship (normative environment) lead to greater identification with global citizens. Furthermore, theory and research suggest that when global citizen identity is salient, greater identification is related to adherence to the group's content (i.e., prosocial values and behaviors). Results of the present set of studies showed that global awareness (knowledge and interconnectedness with others) and one's normative environment (friends and family support global citizenship) predicted identification with global citizens, and global citizenship predicted prosocial values of intergroup empathy, valuing diversity, social justice, environmental sustainability, intergroup helping, and a felt responsibility to act for the betterment of the world. The relationship between antecedents (normative environment and global awareness) and outcomes (prosocial values) was mediated by identification with global citizens. We discuss the relationship between the present results and other research findings in psychology, the implications of global citizenship for other academic domains, and future avenues of research. Global citizenship highlights the unique effect of taking a global perspective on a multitude of topics relevant to the psychology of everyday actions, environments, and identity.


Methods for determining favorable conditions for freeze-drying biological reference materials.
By predetermining favorable conditions for freeze-drying samples through pilot runs, one can gain more assurance that relatively large batches of lyophilized biological reference materials produced have the desired characteristics. Included in the pilot studies are the determination of the characteristics of the lyophilizer with a specific freeze-drying cycle, simulation of the water load expected for the production run, residual moisture analyses of the lyophilized samples, and biological activity of the samples before lyophilization and after exposure to elevated temperatures. Various reference materials have been lyophilized by these procedures. Among them are clinical chemistry reference samples, bacterial suspensions, and candidate serum-protein reference immunological standards. A batch of 6,300 vials of the latter was successfully freeze-dried and showed less than 0.1% residual moisture; different proteins (including complement) were both functionally (enzymatically) and antigenically active.


pH of mucus in rat trachea.
The pH of the mucous coat of the trachea was measured in vivo through a tracheal window in anesthetized rats. Readings ranged from 7.42 to 7.57 and averaged 7.52 +/- 0.05 (SD) pH units. Injections of pilocarpine (cholinomimetic) were followed by a statistically significant decrease in pH to 7.46 +/- 0.05 (SD) and a subsequent return to initial values. These readings are in the region of what is accepted as the gel point of mucus. This closeness to the inflection point between sol and gel was not reported before and may explain some of the in situ flow properties of mucus.


Behavioral treatment of panic-related disorders: a review.
Behavioral theories and therapy techniques for panic-related disorders are reviewed. A variety of research studies and measurement techniques are discussed, and methodological issues are highlighted, particularly with respect to outcome measures and controversies in the literature regarding treatment assessments. The preponderance of treatments and research to date have examined the effects of various combinations of treatments on panic disorder. More recently, the use of behavioral therapy for panic disorders has received increasing empirical support. This paper describes treatments for panic-related disorders, especially phobic avoidance behavior, from a behavioral therapy context.


Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study.
Both alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are closely related to glucose homeostasis in the body, and the main objective of this study was to investigate the association between ALT to HDL-C ratio (ALT/HDL-C ratio) and the risk of diabetes in a Chinese population. The current study included 116,251 participants who underwent a healthy physical examination, and the study endpoint was defined as a diagnosis of new-onset diabetes. Multivariate Cox regression models and receiver operator characteristic curves were used to assess the association of the ALT/HDL-C ratio with diabetes onset. During the average observation period of 3.10 years, a total of 2,674 (2.3%) participants were diagnosed with new-onset diabetes, including 1,883 (1.62%) males and 791 (0.68%) females. After fully adjusting for confounding factors, we found a significant positive association between the ALT/HDL-C ratio and the risk of diabetes [Hazard ratios 1.06, 95% confidence intervals: 1.05, 1.06], and this association was significantly higher in males, obese individuals [body mass index ≥ 28 kg/m2] and individuals aged < 60 years (All P interaction < 0.05). In addition, the ALT/HDL-C ratio was significantly better than its components ALT and HDL-C in predicting diabetes in the Chinese population. There was a positive relationship between ALT/HDL-C ratio and diabetes risk in the Chinese population, and this relationship was significantly stronger in males, obese individuals, and individuals younger than 60 years old.


Accurate measurement of refraction and dispersion of a solid by a double-layer interferometer.
A silica plate of plane-parallel faces is inserted into one gap of a double-layer interferometer that transmits white light to a prism spectrograph in order to produce elliptic rings of equal chromatic order (RECO's). The silica plate is rotated and the expanding RECO's are counted at their center while this center is coincident with a standard wavelength. An analytic formula that relates the fringe count to the rotated angle enables the refractive index of the rotated plate to be accurately determined for different wavelengths. The results are fitted to a single-term Sellmeier dispersion function to find the peak wavelength of the ultraviolet absorption band and the atomic number density for such a transition. The variation of either the dispersion coefficient or the group-velocity factor with wavelength is determined from either the displacement of the RECO center across the visible spectrum if one of the double-layer interferometer's mirrors is displaced parallel to itself or from measurements on the RECO diameters.


Thermosensitivity patterns of Old vs. New World cutaneous strains of Leishmania growing within mouse peritoneal macrophages in vitro.
Infection of mouse peritoneal macrophages in vitro was used to examine the effect of elevated temperature on the intracellular replication of various strains of Leishmania. Of eight cutaneous strains examined, all grew optimally at 35 degrees C. At 37 degrees C the reduction in growth was most pronounced for the New World cutaneous strains, and at 39 degrees C three of four New World cutaneous strains were completely destroyed whereas all of the L. tropica strains survived and exhibited at least 100% growth after 3 days. The results of these in vitro studies correlate closely with the outcome of heat therapy on two patients with cutaneous disease, suggesting that, in general, cutaneous lesions due to L. tropica strains might be less responsive to heat therapy than lesions due to L. mexicana and related strains.


Considering iatrogenic psychosis after malignant glioma resection.
It is generally well known that medial temporal lobe resections have been associated with a variety of postoperative neuropsychiatric disturbances. Most of the neurosurgical literature on psychiatric disturbances after a temporal lobectomy concern patients with a strong history of epilepsy; however, relatively few articles have been reported due to a mesial temporal lobectomy following tumour removal. We report the case of a patient who underwent a gross total resection of a malignant astrocytoma in the temporal lobe who developed transient psychosis. Difficulties in diagnosing and predicting this condition are discussed as along with management considerations.


[Experimental evaluation of the occupational exposure to static magnetic fields on a 3 T magnetic resonance scanner].
The recent postponement until 31 October 2013 of the deadline for transposition of the EU Directive 2004/40/EC, concerning the minimum health requirementsfor the exposure of workers to the risks arising from electromagnetic fields between 0 and 300 GHz, keeps on suspending the Italian law which was aimed to implement the EU regulations on the occupational exposure to electromagnetic fields, including those generated by Magnetic Resonance Imaging (MRI) units. Waiting for the revision of the exposure limits proposed by the EU Directive taking into account results from new studies and evolution of knowledge, the time-weighted values of static magnetic field proposed by the Italian Ministry of Health (D.M 02/08/91) still survive as limits for worker's exposure. The comparison between the proposed thresholds and the time required to position patients allows to calculate how long the MRI staff can stay at different values of static magnetic field, i.e. the maximum workload of each worker. In order to evaluate more accurately how many time the members of MRI staff are near the magnet bore and the real value of worker's exposure to the static magnetic field during the handling of patients, a teslameter Metrolab THM1176-PDA was used. Personal exposure measurements on the radiologists and the radiographers who worked on a 3 T GE Healthcare Discovery 750 MR were carried out during the positioning of self-sufficient and collaborative patients. The sensor was worn at the chest level on the side that was nearest to the magnet bore. Results show wide variations occurring between individual working procedures concerning the handling of patients, especially during the initial position phase. The mean values of the time spent by radiographers inside the magnet room (B > 0.5 mT) to place the patient and to take him outside at the end of the exam were respectively 220 and 127 seconds. The mean value of the time spent by radiologists was 162 seconds when they had to insert a peripheral vein access (arm) and inject contrast medium. The time fraction spent in magnetic flux density above 200 mT was near 31% for radiographers and about 7% for radiologists. The maximum of the static magnetic field recorded was 1550 mT for radiographers and 409 mT for radiologists. The measuring system has proven to be useful in evaluating the compliance with time weighted exposure limit stated by Italian law and also to find the maximum magnetic flux density to which the staff is actually exposed. This is the quantity of significance in evaluating workers' exposure following international guidelines.


Randomized comparison of nasojejunal and nasogastric feeding in critically ill patients.
Critically ill patients often develop large gastric residual volumes during nasogastric feeding as a result of poor gastroduodenal motility. Nasojejunal feeding may decrease the severity of this complication. The aim of this study was to determine whether nasojejunal feeding improved tolerance of enteral nutrition by reducing gastric residual volumes. Randomized, prospective, clinical study. Intensive care unit of a university-affiliated hospital. Seventy-three intensive care unit patients expected to require nutritional support for at least 3 days. Patients were randomized to receive enteral nutrition via a nasojejunal tube (placed endoscopically) (34 patients) or a nasogastric tube (39 patients). A strict protocol was followed, which included regular gastric residual volume measurement (in both groups), the use of predetermined criteria for intolerance, and an attempt at nasojejunal feeding for those nasogastrically fed patients who were intolerant of enteral nutrition. Endoscopic placement of nasojejunal tubes was successful in 98% with no complications of insertion. Patients fed via a nasojejunal tube had 1) a reduced total gastric residual volume in both the first 24 (197 vs. 491 mL, p = .02) and 48 hrs (517 vs. 975 mL, p = .02); 2) a reduced incidence of a single gastric residual volume >150 mL (32% vs. 74%, p = .001); and 3) a trend toward a reduced incidence of intolerance of enteral nutrition (13% vs. 31%, p = .09). Only 13% of those nasogastrically fed patients who were initially intolerant of enteral nutrition remained intolerant once fed via a nasojejunal tube, and only 1.4% of all patients met criteria for commencement of parenteral nutrition. Enteral nutrition delivered via a nasojejunal tube is associated with a significant reduction in gastric residual volume, a strong trend toward improved tolerance of enteral nutrition, and an extremely low requirement for parenteral nutrition.


Global Ethical Considerations Regarding Mandatory Vaccination in Children.
Whether children should be vaccinated against coronavirus disease-2019 (COVID-19) (or other infectious diseases such as influenza) and whether some degree of coercion should be exercised by the state to ensure high uptake depends, among other things, on the safety and efficacy of the vaccine. For COVID-19, these factors are currently unknown for children, with unanswered questions also on children's role in the transmission of the virus, the extent to which the vaccine will decrease transmission, and the expected benefit (if any) to the child. Ultimately, deciding whether to recommend that children receive a novel vaccine for a disease that is not a major threat to them, or to mandate the vaccine, requires precise information on the risks, including disease severity and vaccine safety and effectiveness, a comparative evaluation of the alternatives, and the levels of coercion associated with each. However, the decision also requires balancing self-interest with duty to others, and liberty with usefulness. Separate to ensuring vaccine supply and access, we outline 3 requirements for mandatory vaccination from an ethical perspective: (1) whether the disease is a grave threat to the health of children and to public health, (2) positive comparative expected usefulness of mandatory vaccination, and (3) proportionate coercion. We also suggest that the case for mandatory vaccine in children may be strong in the case of influenza vaccination during the COVID-19 pandemic.


Canine parainfluenza-Bordetella bronchiseptica vaccine immunogenicity.
The immunogenicity and safety of 3 serials of a canine parainfluenza (CPI) virus-Bordetella bronchiseptica vaccine was evaluated. Each serial was used to vaccinate 10 dogs with single doses given intranasally. The 30 vaccinated and 10 nonvaccinated controls dogs were challenge exposed with aerosols of virulent CPI virus and B bronchiseptica at 18 days and at 21 days, respectively, after vaccination. After challenge exposure, none of the 30 vaccinated dogs had clinical signs of disease; however, 9 of the 10 nonvaccinated dogs developed coughing problems. The CPI virus was isolated from nasal swab specimens obtained from nonvaccinated dogs on an average of 5.1 days after challenge exposure, but was not isolated from any of the specimens obtained from the vaccinated dogs. Bordetella bronchiseptica was isolated from nasal swab specimens obtained from both vaccinated and nonvaccinated dogs up to 18 days after challenge exposure. The erythrocyte sedimentation rates and total leukocyte counts for control dogs were generally increased, in contrast to those for the vaccinated groups. Dogs showed a primary serologic response to CPI virus and B bronchiseptica after vaccination and an anamnestic response to the bacterium after challenge exposure. Adverse local or systemic reactions attributable to the bivalent vaccine were not observed in the vaccinated dogs.


Assessment and hormonal management of osteoporosis.
Postmenopausal osteoporosis is a frequent health issue in women. Because osteoporosis-related fractures cause a significant increase in mortality and morbidity, it is clinically important to identify as soon as possible women at increased risk for future fracture so that preventive measures can be instituted. At the beginning of menopause, evaluation of the subsequent risk of fracture is not so easy. Most screening tools fail to accurately identify those women who will fracture within the next 10 years. A history of a prior fracture and low bone mineral density are the only major consistently found predictors for the risk of fracture. On the other hand, it is no longer a question whether menopause hormone therapy is efficient not only to prevent postmenopausal bone loss but also the incidence of fragility fracture. Over the last years, utility of menopause hormone therapy for the prevention of osteoporosis has been questioned due to safety concerns. In light of the most recent reports on a more favorable benefit/risk balance than was initially claimed in early postmenopausal women, this needs to be reconsidered. Prevention of bone loss in those women with a moderate or slightly high risk of fracture is likely a strategy to reduce fracture risk in older women. Menopause hormone therapy must be considered as a true primary preventive therapy more than an anti-fracture therapy at an age when the risk of fracture is likely much lower than later in life. Only thereafter should other anti-osteoporotic medications be discussed in women still at high risk for fracture.


tert-Butyl phenyl sulfoxide: a traceless sulfenate anion precatalyst.
tert-Butyl phenyl sulfoxide is employed as a traceless precatalyst for the generation of sulfenate anions under basic conditions and has been used to catalyze the coupling of benzyl halides to trans-stilbenes. The advantage of this precatalyst over previous precatalysts is that the byproduct generated on catalyst formation is a gas, facilitating product isolation in high purity. Using this second generation catalyst, a variety of trans-stilbenes were generated in 39-98% isolated yield.


Suppression of an acoustic mode by an elastic mode of a liquid-filled spherical shell resonator.
The purpose of this paper is to report on the suppression of an approximately radial (radially symmetric) acoustic mode by an elastic mode of a water-filled, spherical shell resonator. The resonator, which has a 1-in. wall thickness and a 9.5-in. outer diameter, was externally driven by a small transducer bolted to the external wall. Experiments showed that for the range of drive frequencies (19.7-20.6 kHz) and sound speeds in water (1520-1570 m/s) considered in this paper, a nonradial (radially nonsymmetric) mode was also excited, in addition to the radial mode. Furthermore, as the sound speed in the liquid was changed, the resonance frequency of the nonradial mode crossed with that of the radial one and the amplitude of the latter was greatly reduced near the crossing point. The crossing of the eigenfrequency curves of these two modes was also predicted theoretically. Further calculations demonstrated that while the radial mode is an acoustic one associated with the interior fluid, the nonradial mode is an elastic one associated with the shell. Thus, the suppression of the radial acoustic mode is apparently caused by the overlapping with the nonradial elastic mode near the crossing point.


Long-term survival of a urodele amphibian despite depleted major histocompatibility complex variation.
Depletion of polymorphism at major histocompatibility complex (MHC) genes has been hypothesized to limit the ability of populations to respond to emerging pathogens, thus putting their survival at risk. As pathogens contribute substantially to the global amphibian decline, assessing patterns of MHC variation is important in devising conservation strategies. Here, we directly compare levels of MHC class II and neutral variation between multiple populations of the great crested newt (Triturus cristatus) from refugial (REF: Romania) and postglacial expansion (PGE: Germany, Poland and UK) areas. REF populations harboured high levels of adaptive variation (24 expressed alleles), exhibiting clear signatures of historical positive selection, which points to the overall importance of MHC class II variation in this species. On the other hand, PGE populations were extremely depauperate (two alleles) but nevertheless have survived for c. 10,000 years, since the postglacial expansion. Variation in putative MHC class II pseudogenes, microsatellites and allozymes also showed a significant southern richness-northern purity pattern. The populations in the postglacial expansion area thus provide the clearest example to date of the long-term survival of populations in which MHC variation, historically under positive selection, has been depleted.


4-hydroxynonenal induces mitochondrial oxidative stress, apoptosis and expression of glutathione S-transferase A4-4 and cytochrome P450 2E1 in PC12 cells.
An excessive and sustained increase in reactive oxygen species (ROS) production and oxidative stress have been implicated in the pathogenesis of many diseases. In the present study, we have demonstrated that 4-hydroxynonenal (4-HNE), a product of lipid peroxidation, alters glutathione (GSH) pools and induces oxidative stress in PC12 cells in culture. This increase was accompanied by alterations in subcellular ROS and glutathione (GSH) metabolisms. The GSH homeostasis was affected as both mitochondrial and extramitochondrial GSH levels, GSH peroxidase and glutathione reductase activities were inhibited and glutathione S-transferase (GST) activity was increased after 4-HNE treatment. A concentration- and time-dependent increase in cytochrome P450 2E1 (CYP 2E1) activity in the mitochondria and postmitochondrial supernatant was also observed. 4-HNE-induced oxidative stress also caused an increase in the expression of GSTA4-4, CYP2E1 and Hsp70 proteins in the mitochondria. Increased oxidative stress in PC12 cells initiated apoptosis as indicated by the release of mitochondrial cytochrome c, activation of poly-(ADP-ribose) polymerase (PARP), DNA fragmentation and decreased expression of antiapoptotic Bcl-2 proteins. Mitochondrial respiratory and redox functions also appeared to be affected markedly by 4-HNE treatment. These results suggest that HNE-induced oxidative stress and apoptosis might be associated with altered mitochondrial functions and a compromised GSH metabolism and ROS clearance.


Surgical correction of high postkeratoplasty astigmatism. Relaxing incisions vs wedge resection.
Improved techniques and procedures have resulted in a higher rate of clear grafts after penetrating keratoplasty. A clear graft, however, does not give a good visual result if high corneal astigmatism prevents the successful wearing of spectacles or contact lenses. This article describes the methods and results of two microsurgical techniques--the corneal wedge resection to steepen the flat meridian and relaxing incisions to flatten the steep meridian. Average reduction in corneal astigmatism was greater for the wedge resection (ten cases) (6.50 diopters as compared with 4.25 D [16 cases] for the relaxing incisions). The relaxing incisions operation was successful in 75% of cases with stabilization of corneal curvature readings in an average of three weeks and is an outpatient procedure. After a wedge resection, corneal stabilization usually takes months. We believe that wedge resection should be reserved for cases in which relaxing incisions are unsuccessful.


Puzzle Pieces: Neural Structure and Function in Prader-Willi Syndrome.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, with the exception of eating behaviour, the neural physiology is currently less well understood. A systematic review was undertaken to explore findings relating to neural structure and function in PWS, using search terms designed to encompass all published articles concerning both in vivo and post-mortem studies of neural structure and function in PWS. This supported the general paucity of research in this area, with many articles reporting case studies and qualitative descriptions or focusing solely on the overeating behaviour, although a number of systematic investigations were also identified. Research to date implicates a combination of subcortical and higher order structures in PWS, including those involved in processing reward, motivation, affect and higher order cognitive functions, with both anatomical and functional investigations indicating abnormalities. It appears likely that PWS involves aberrant activity across distributed neural networks. The characterisation of neural structure and function warrants both replication and further systematic study.


Associations of sexually transmitted infections with condom problems among young men who have sex with men.
Young men who have sex with men (YMSM) are disproportionately infected with sexually transmitted infections (STIs). Condom use is the most widely available means of preventing the transmission of STIs, but effectiveness depends on correct use. Condom errors such as using an oil-based lubricant have been associated with condom failures such as breakage. Little research has been done on the impact of condom problems on the likelihood of contracting an STI. Data came from Crew 450, a longitudinal study of HIV risk among YMSM (N = 450). All self-report data were collected using computer-assisted self-interview technology, and clinical testing was done for gonorrhea, chlamydia, and HIV. Nearly all participants made at least 1 error, with high rates of using oil-based lubricant and incomplete use. No differences were found in rates of condom problems during anal sex with a man versus vaginal sex with a woman. Black YMSM reported significantly higher use of oil-based lubricants than white and Hispanic YMSM, an error significantly associated with HIV status (adjusted odds ratio, 2.60; 95% confidence interval, 1.04-6.51). Participants who reported a condom failure were significantly more likely to have an STI (adjusted odds ratio, 3.27; 95% confidence interval, 1.31-8.12). Young men who have sex with men report high rates of condom problems, and condom failures were significantly associated with STIs after controlling for unprotected sex. Educational programs are needed to enhance correct condom use among YMSM. Further research is needed on the role of oil-based lubricants in explaining racial disparities in STIs and HIV.


Clinical manifestations and predictors of severe malaria in Indian children.
Although the greatest morbidity and mortality attributable to malaria occurs among children in Africa, up to one third of the world's malaria burden is borne by non-African countries, where levels of endemicity are lower. Because there are few published criteria for managing life-threatening malaria in children in these countries, we conducted a study of major syndromes and predictors of death among critically ill Indian children to identify factors that could be used to improve the approach to their treatment. A prospective study was conducted at the pediatric ward of SCB Medical College in eastern India (Orissa). Baseline demographic data were collected on all of the patients with confirmed slide-positive falciparum malaria. Patients satisfying any 1 of the 2000 World Health Organization criteria for severe malaria were included in the analysis. Prevalence of and mortality as a result of major symptoms were calculated followed by multiple regression modeling to identify major predictors of death. Of 1682 confirmed cases of malaria during a 32-month period, 374 subjects met the World Health Organization criteria for severe malaria. The case fatality rate was 12% in this series. Multiple regression analysis identified respiratory distress, coma, multiple organ dysfunctions, and hyperparasitemia as major predictors of death. Anemia and jaundice did not emerge as important markers of mortality. Many patients presented with multiple major complications, and the mortality rate was consistently high when >1 major predictor was present in a patient. Clinical features in Indian children differed from those reported in most studies that involved an African population. Multiple organ dysfunctions emerged as an important presenting feature and a new predictor of death in childhood malaria.


Omega-3 Fatty acids and neural development to 2 years of age: do we know enough for dietary recommendations?
The omega (omega)-3 fatty acids are essential nutrients, explained by the absence of a Delta-15 desaturase in mammalian cells. The omega-3 fatty acids are found in the diet as alpha-linolenic acid (18:3omega-3) and eicosapentaenoic acid (20:5omega-3), as well as docosahexaenoic acid (DHA), with different functions of each of the omega-3 fatty acids in different cells. One essential role of the omega-3 fatty acids is fulfilled by the 22 carbon DHA (22:6omega-3). Depletion of DHA from brain and retina interferes with normal neurogenesis and neurological function, and visual signaling pathways. Observation and intervention studies with pregnant and lactating women, and with infants fed some formulas show that dietary DHA is associated with higher scores on tests of visual and neural development in infants and children. The estimated average requirement and variability in requirement among individuals both of which are needed to set dietary recommended intakes (DRIs) for the different omega-3 fatty acids are unknown. However, because omega-3 fatty acids are essential, adequate intakes to minimize risk of poor neural development and function can be justified, but dose-response data to provide a safe upper limit with different omega-6 fatty acid intakes are needed. Dietary recommendations do affect the food supply and supplements and are used in labeling, all impacting population health. When scientific information is incomplete, consideration must be given to the implications of recommendations that focus on individual nutrients, rather than dietary patterns such as breast-feeding and consuming fish that promote health and minimize disease risk.


An active interface between medical science and aeronautical technology: the physiological investigations for the XC-35.
Although the advantages of flight at high altitude were early recognized, so also were the physiological problems standing in the way of its realization. The idea of surmounting such problems by means of a pressurized cabin was advocated as early as 1909, while the first attempt to translate the concept into actuality occurred in 1921. Neither it nor several successive attempts enjoyed any real success until a project launched by the U. S. Air Corps in 1935 produced a breakthrough aircraft designated the XC-35. The major reason for the favorable termination of that venture was the thoroughness of the engineering involved. But it is equally notable that this was the first instance in the age of powered flight where there was an active collaboration between the scientists and engineers, a rather curious circumstance in view of the fact that the achievement of altitude record-setting balloon flights in the nineteenth century had owed a great deal to an interconnection of aeronauts and scientists' laboratories. This paper focuses on the physiological investigations which informed the XC-35 engineers while at the same time bringing into being a new aeromedical laboratory taking the first small step toward turning aeromedicine into space medicine.


Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil.
In the context of universal access to antiretroviral therapy, the surveillance of human immunodeficiency virus type 1 (HIV-1) genetic diversity and resistance becomes pivotal. In this work our purpose was to describe the genetic variability; prevalence of drug-resistance mutations; and genotypic resistance profiles in HIV-1 infected individuals under antiretroviral treatment, from the Federal District, Brasilia, Central Brazil. The entire viral protease and codons 19 to 234 of the reverse transcriptase gene from 45 HIV-1 isolates were amplified and sequenced for subtyping and genotyping. By phylogenetic analysis, 96% of the samples clustered with subtype B and the remaining 4% with HIV-1 subtype F sequences. One major protease inhibitor resistance-associated mutation, I50V, was detected in 38% of the samples. Minor mutations were also found at the protease gene: L10I/V (7%), K20M (2%), M36I (11%), L63P (20%), A71T (2%), and V77I (7%). Many mutations associated with reduced susceptibility to nucleoside or non-nucleoside reverse transcriptase inhibitors were detected: M41L (11%), E44D (4%), D67N (11%), T69D (2%), K70R (11%), L74V (2%), L100I (4%), K103N (18%), V118I (9%), Y181C (11%), M184V (18%), G190A (4%), T215Y (4%), and K219E (4%). This study has shown that 84% of the studied population from the Federal District, showing evidences of therapy failure, presented viral genomic mutations associated with drug resistance. The main antiretrovirals to which this population showed resistance were the PI amprenavir (38%), the NNRTIs delavirdine, nevirapine (31%), and efavirenz (24%), and the NRTIs lamivudine (18%), abacavir, and zidovudine (13%).


Segmented chirped-pulse Fourier transform submillimeter spectroscopy for broadband gas analysis.
Chirped-pulse Fourier transform spectroscopy has recently been extended to millimeter wave spectroscopy as a technique for the characterization of room-temperature gas samples. Here we present a variation of this technique that significantly reduces the technical requirements on high-speed digital electronics and the data throughput, with no reduction in the broadband spectral coverage and no increase in the time required to reach a given sensitivity level. This method takes advantage of the frequency agility of arbitrary waveform generators by utilizing a series of low-bandwidth chirped excitation pulses paired in time with a series of offset single frequency local oscillators, which are used to detect the molecular free induction decay signals in a heterodyne receiver. A demonstration of this technique is presented in which a 67 GHz bandwidth spectrum of methanol (spanning from 792 to 859 GHz) is acquired in 58 μs.


A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes.
Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.


Smartphone and Tablet Software Apps to Collect Data in Sport and Exercise Settings: Cross-sectional International Survey.
Advances in smartphone technology have facilitated an increase in the number of commercially available smartphone and tablet apps that enable the collection of physiological and biomechanical variables typically monitored in sport and exercise settings. Currently, it is not fully understood whether individuals collect data using mobile devices and tablets, independent of additional hardware, in their practice. This study aims to explore the use of smartphone and tablet software apps to collect data by individuals working in various sport and exercise settings, such as sports coaching, strength and conditioning, and personal training. A total of 335 practitioners completed an electronic questionnaire that surveyed their current training practices, with a focus on 2 areas: type of data collection and perceptions of reliability and validity regarding app use. An 18-item questionnaire, using a 5-point Likert scale, evaluated the perception of app use. A total of 204 respondents reported using apps to directly collect data, with most of them (196/335, 58.5%) collecting biomechanical data, and 41.2% (138/335) respondents reported using at least one evidence-based app. A binomial general linear model determined that evidence accessibility (β=.35, 95% CI 0.04-0.67; P=.03) was significantly related to evidence-based app use. Age (β=-.03, 95% CI -0.06 to 0.00; P=.03) had a significant negative effect on evidence-based app use. This study demonstrates that practitioners show a greater preference for using smartphones and tablet devices to collect biomechanical data such as sprint velocity and jump performance variables. When it is easier to access information on the quality of apps, practitioners are more likely to use evidence-based apps. App developers should seek independent research to validate their apps. In addition, app developers should seek to provide clear signposting to the scientific support of their software in alternative ways.


Trabecular bone structure correlates with hand posture and use in hominoids.
Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan), suspensory (Pongo, Hylobates and Symphalangus) and manipulative (Homo) taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus) correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link between inferred behaviour and trabecular structure in extant hominoids that can be informative for reconstructing behaviour in fossil primates.


Aggressive temperament predicts ethanol self-administration in late adolescent male and female rhesus macaques.
Anxiety and aggression are associated with ethanol self-administration, but these behaviors can serve as either risk factors for or consequences of heavy drinking in rodents and humans. Baseline levels of aggressive-like and anxious-like behavior in non-human primates have not yet been characterized in relation to future or prior ethanol intake. The objective of the study was to test the association between temperament at baseline with future ethanol self-administration in late adolescent male (n = 21) and female (n = 11) rhesus monkeys. Shortly after entering the laboratory and before exposure to ethanol, the Human Intruder Test (HIT) and the Novel Object Test (NOT) were used to determine baseline anxious-like and aggressive-like behavior in age-matched male and female rhesus monkeys (Macaca mulatta). The monkeys were induced to drink ethanol 4 % (w/v) using a schedule-induced polydipsia procedure, followed by "open-access" ethanol self-administration in which the monkeys were allowed a choice of water or 4 % ethanol (w/v) for 22 h/day for 52 weeks. Aggressive monkeys self-administered more ethanol and attained higher blood ethanol concentrations (BECs). No significant differences in ethanol intakes or BECs were found between anxious and non-anxious monkeys or between behaviorally inhibited and non-inhibited monkeys. Baseline aggressive behavior positively correlated with ethanol intake and intoxication. Baseline reactive aggression was associated with higher future ethanol intake and intoxication. While significant sex differences in HIT reactivity were observed, the relationship between aggression and ethanol drinking was observed across sex and is not sex-specific.


Role of the pathotype-specific ACRTS1 gene encoding a hydroxylase involved in the biosynthesis of host-selective ACR-toxin in the rough lemon pathotype of Alternaria alternata.
The rough lemon pathotype of Alternaria alternata produces host-selective ACR-toxin and causes Alternaria leaf spot disease of the rootstock species rough lemon (Citrus jambhiri) and Rangpur lime (C. limonia). Genes controlling toxin production were localized to a 1.5-Mb chromosome carrying the ACR-toxin biosynthesis gene cluster (ACRT) in the genome of the rough lemon pathotype. A genomic BAC clone containing a portion of the ACRT cluster was sequenced which allowed identification of three open reading frames present only in the genomes of ACR-toxin producing isolates. We studied the functional role of one of these open reading frames, ACRTS1 encoding a putative hydroxylase, in ACR-toxin production by homologous recombination-mediated gene disruption. There are at least three copies of ACRTS1 gene in the genome and disruption of two copies of this gene significantly reduced ACR-toxin production as well as pathogenicity; however, transcription of ACRTS1 and production of ACR-toxin were not completely eliminated due to remaining functional copies of the gene. RNA-silencing was used to knock down the remaining ACRTS1 transcripts to levels undetectable by reverse transcription-polymerase chain reaction. The silenced transformants did not produce detectable ACR-toxin and were not pathogenic. These results indicate that ACRTS1 is an essential gene in ACR-toxin biosynthesis in the rough lemon pathotype of A. alternata and is required for full virulence of this fungus.


First Documented Cases of Canine Neuroangiostrongyliasis Due to Angiostrongylus cantonensis in Hawaii.
Two young dogs domiciled in Honolulu, Hawaii, were presented in November and December 2018 (respectively) for spinal hyperesthesia, hindlimb weakness, and proprioceptive ataxia. Both dogs had neurologic findings referable to spinal cord disease. Both dogs had a combination of lower motor neuron signs (reduced muscle mass, decreased withdrawal reflexes, low tail carriage) and long tract signs (conscious proprioceptive deficits, crossed extensor response, increased myotatic reflexes). Peripheral eosinophilia was present in the second case, but hematology and serum biochemistries were otherwise unremarkable. Plain radiographs and computed tomography scans ± contrast were unremarkable. Cerebrospinal fluid (CSF) from both patients demonstrated eosinophilic pleocytosis, and real-time polymerase chain reaction testing demonstrated Angiostrongylus cantonensis deoxyribonucleic acid in CSF, confirming a diagnosis of neuroangiostrongyliasis. Treatment included glucocorticoid therapy, ± anthelmintic (fenbendazole). Both dogs made a complete recovery. These are the first confirmed cases of autochthonous neuroangiostrongyliasis in canine patients in the United States and the first dogs anywhere to be diagnosed definitively with A cantonensis infection based on real-time polymerase chain reaction testing of CSF. A clinician examining a patient with severe spinal hyperesthesia and a combination of upper and lower motor signs should consider A cantonensis as a differential, especially in endemic areas.


[Relapsing polychondritis. A case report of a patient treated with methotrexate and celecoxib].
Relapsing polychondritis is a rare illness in which the cartilaginous tissues such as auricles, nose, laryngotracheal structures, joints and others, are affected. Customary treatment is based on corticosteroids and traditional antiinflammatory agents including aspirin and indomethacin. We describe a case of relapsing polychondritis in an 82-year-old man with associated diabetes mellitus and special features treated successfully with alternative therapy based on methotrexate and celecoxib.


Proteolytic system of plant mitochondria.
The existence of a proteolytic system which can specifically recognize and cleave proteins in mitochondria is now well established. The components of this system comprise processing peptidases, ATP-dependent peptidases and oligopeptidases. A short overview of experimentally confirmed proteases mainly from Arabidopsis thaliana is provided. The role of the mitochondrial peptidases in plant growth and development is emphasized. We also discuss the possibility of existence of as yet unidentified plant homologs of yeast mitochondrial ATP-independent proteases.


The effect of folic acid on the development of stomach and other gastrointestinal cancers.
To evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers. In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: (1) folate (FA, 20 mg per day plus vitamin B(12) 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); (2) natural beta-carotene (N-betaC, 30 mg per day for first year, then 30 mg two times a week for the next); (3) synthetic beta-carotene (S-betaC, administered as in N-betaC); and (4) placebo. Follow-ups continued from 1994 to 2001. A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-betaC and S-betaC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P = 0.04). A similar trend was observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03 - 0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P = 0.04), reversed intestinal metaplasia (P = 0.06) at the end of follow-up, and reversed displasia (P = 0.017) at 12 months. Two cases of false jaundice were found in beta-carotene groups with no influence on administration, and no side-effects were reported in FA group. This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of beta-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.


A comprehensive evaluation of the toxicology of cigarette ingredients: aromatic carbonyl compounds.
Aromatic carbonyls are typically used in the processing or flavoring of tobacco used in the manufacture of cigarettes. A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing different added levels of aromatic carbonyl compounds. Ten aromatic carbonyl compounds, nine of which have been reported in tobacco or in tobacco smoke, were added individually to experimental cigarettes at three different levels. The tenth compound, not found naturally in tobacco, was 2-phenoxyethyl isobutyrate. The lowest target inclusion level was 100 ppm and the highest was 10,000 ppm. Smoke from each of the 10 experimental cigarette types was evaluated using analytical chemistry, in vitro cytotoxicity, and mutagenicity testing. For one of the compounds, ethyl vanillin, a 90-day smoke inhalation study using rats was also performed. Smoke chemistry was effectively unchanged by the addition of any of the compounds. Cytotoxicity, assessed by the neutral red uptake assay and using both gas-vapor and particulate phases of smoke, was unaffected by the addition of any of the test compounds. Mutagenicity, assessed by five strains of Salmonella typhimurium treated with smoke condensate, also was unaffected by any of the test compounds. In the rat inhalation study, there were effectively no differences between cigarettes without added ethyl vanillin and cigarettes containing ~8000 ppm of ethyl vanillin. Even at the exaggerated inclusion levels in cigarette tobacco used in these tests, no adverse toxicological responses occurred for any of aromatic carbonyl compounds tested.


Patient autonomy versus parentalism.
Several decision-making models have been advanced to characterize the patient-physician relationship. These include the parental model, the informed decision-making model, the interpretive model, and the deliberative model. Although these models are useful to consider in reflecting on the care we give to critically ill patients at the end of life, they require adaptation to the intensive care unit (ICU). Many clinicians adapt their approach to each individual patient and change their approach to the same patient over time. Moreover, instead of the dyadic model of one patient and one physician, multiple voices often speak for the patient and a team of clinicians care for the ICU patient. Analysis of human relationships and communication with critically ill patients and their families require transdisciplinary, multicultural, and multidisciplinary interpretation.


The Canadian Pain Society: A historical perspective.
This article reviews the major features and events that have characterized the 40-year history of the Canadian Pain Society/Société canadienne de la douleur, which is a chapter of the International Association for the Study of Pain (IASP). The review first describes its early formative years in the 1970s as eastern and western chapters of IASP and then its evolution as a Canada-wide chapter and society. Also highlighted is the formulation in this period of its purpose to foster pain research, education, and management and the many activities in which the Society has been engaged to reinforce this purpose over the ensuing decades. These include its annual scientific meetings and the establishment of publications, guidelines, and other educational material as well as awards to support research and trainees. Many of these activities have included engagement with key partners who have also collaborated with the Society in national and international advocacy for pain. The review also outlines some of the features and factors underpinning the Society's national and international reputation and impact resulting from the many contributions that its members have made to the advances in pain research, education, and management over the past 40 years. The review concludes by noting that by way of its rich history and its past and present experiences, the Society is well positioned to continue its many activities and contributions to address the many challenges still facing the pain field in Canada and around the world.


Granulocyte colony stimulating factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.
Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined. We aimed to explore the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults. A search was performed using the Cochrane Central Register of Controlled Trials (issue 1, 2003); MEDLINE (January 1966 to April 2003); EMBASE (1988 to 2003); online databases of clinical trials; contact with corresponding authors; and contact with the manufacturers and distributors of G-CSF and reviews of citations in publications identified by the above strategies. We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia. Studies identified were reviewed independently by two reviewers with data abstracted onto standardized data collection forms. The primary outcome measure was 28 day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled OR 0.91, 95% CI: 0.73, 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.99, 95% CI 0.77, 1.29). There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.


Metabolic response to severe surgical illness: overview.
Severe surgical illness results in metabolic responses that mobilize substrate (amino acids and fatty acids) from body stores to support vital organs, enhance resistance to infection, and ensure wound healing. Central to this process is the redistribution of body protein, which moves from skeletal muscle to support the central viscera. If unsupported, this protein-wasting state could result in prolonged convalescence, diminished immunity, and poor wound healing. Present evidence suggests that the central nervous system plays a major role in regulating this protein catabolic response. Infusing exceedingly small quantities of the proinflammatory cytokines into the brain can mimic injury responses, and central cytokine blockade may be one therapeutic approach to attenuating these responses safely in the future. Additional evidence also demonstrates that the function of the hypothalamus and anterior pituitary is dampened during the later stages of severe surgical illness, and the possibility of hormonal replacement therapy needs to be explored.


Complementary UV-absorption of mycosporine-like amino acids and scytonemin is responsible for the UV-insensitivity of photosynthesis in Nostoc flagelliforme.
Mycosporine-like amino acids (MAAs) and scytonemin are UV-screening compounds that have presumably appeared early in the history of life and are widespread in cyanobacteria. Natural colonies of the UV-insensitive Nostoc flagelliforme were found to be especially rich in MAAs (32.1 mg g DW(-1)), concentrated in the glycan sheath together with scytonemin. MAAs are present in the form of oligosaccharide-linked molecules. Photosystem II activity, measured using PAM fluorescence and oxygen evolution, was used as a most sensitive physiological parameter to analyse the effectiveness of UV-protection. Laboratory experiments were performed under controlled conditions with a simulated solar radiation specifically deprived of UV-wavebands with cut-off filters (295, 305, 320, 345 and 395 nm). The UV-insensitivity of N. flagelliforme was found to cover the whole UV-A (315-400 nm) and UV-B (280-320 nm) range and is almost certainly due to the complementary UV-absorption of MAAs and scytonemin. The experimental approach used is proposed to be suitable for the comparison of the UV-protection ability in organisms that differ in their complement of UV-sunscreen compounds. Furthermore, this study performed with a genuinely terrestrial organism points to the relevance of marine photoprotective compounds for life on Earth, especially for the colonization of terrestrial environments.


12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center.
Background and purpose - Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods - From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results - 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69-82) and the 10-year survival rate was 68% (60-77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72-0.98) and preoperative talus angle at 0.95 (0.90-1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation - Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.


An insidious preauricular sinus presenting as an infected postauricular cyst.
Preauricular sinuses are common congenital malformations that usually occur at the anterior margin of the ascending limb of the helix. We present three paediatric patients with postauricular infected cysts and coincidentally discovered auricular pits. Single-stage operations were performed to remove the cysts, pits and involved cartilage. Histopathology revealed a preauricular sinus with inflammation. Although uncommon, a postauricular infected cyst may indicate the presence of a preauricular sinus. Detailed physical examination of preauricular pits should be performed, and the operating microscope may aid during surgery to remove remnants and prevent recurrence. An infected preauricular sinus can be effectively treated with single-stage excision.


Preparation and characterization of 3D bioprinted gelatin methacrylate hydrogel incorporated with curcumin loaded chitosan nanoparticles for in vivo wound healing application.
This study developed a biomimetic composite bioink consisting of gelatin methacrylate (GelMA) /chitosan nanoparticles (CSNPs) for extrusion-based 3D bioprinting. Additionally, curcumin(Cur)-loaded nanoparticles were incorporated which increased the proliferation and antibacterial activity of biomimetic skin constructs. The hydrogel, curcumin-loaded NPs, and the biocomposite was characterized chemically and physically. The results indicated proper modified gelatin with tunable physical characteristics, e.g., swelling ratio and biodegradability up to 1200 % and 25 days, respectively. In addition, the characterized CSNPs showed good distribution with a size of 370 nm and a zeta potential of 41.1 mV. We investigated the mechanical and cytocompatibility properties of chitosan nanoparticles encapsulated in hydrogel for emulating an extracellular matrix suitable for skin tissue engineering. CSNPs entrapped in GelMA (15 % w/v) exhibited controlled drug release during 5 days, which was fitted into various kinetic models to study the mass transfer mechanism behavior. Also, the composite hydrogels were effective as a barrier against both gram-positive and gram-negative bacteria at a concentration of 50 μg/ml nanoparticles in GelMA 15 %. Furthermore, the biocomposite was applied on Wistar rats for wound healing. As a result, this study provides a GelMA-NP50-Cur3 scaffold that promotes cell proliferation and decreases microbial infections in wounds.


[The cloning and expression of the beta-galactosidase gene of Candida pseudotropicalis yeasts in Escherichia coli cells].
The gene encoding the beta-galactosidase of the yeast Candida pseudotropicalis was cloned on YEp13 shuttle vector as the XhoI-fragment of chromosomal DNA of about 9.5 kb. SalGI-fragment of 7.5 kb with the beta-galactosidase gene was subcloned from the pG2 hybrid plasmid obtained into the pBR322 plasmid and then shortened to give 5.2 kb via deletion on XhoI site. This plasmid constructed was designated pBG2-1. In DNA/DNA hybridization studies the appearance of one XhoI-fragment and seven EcoRI-fragments in DNA C. pseudotropicalis hybridized to the DNA cloned fragment and the absence of hybridization to DNA Escherichia coli were shown. The beta-galactosidase activity of cells of transformants of E. coli was lower than the activity of prototrophic strain. The beta-galactosidase biosynthesis in transformants was insignificantly induced by lactose and IPTG and was not repressed by glucose.


Patterns of pregabalin initiation and discontinuation after its subsidy in Australia.
Following the 2013 public subsidy of pregabalin in Australia for neuropathic pain not responding to other medicines, use and misuse increased substantially. We used pharmaceutical dispensing claims for a 10% sample of Australians to quantify initiation, discontinuation and dispensing of other analgesics before and after initiation. We identified 130 770 people initiating pregabalin between 2013/14 and 2017/18 (median age: 61 years; 56.8% female). Discontinuation rates at 1-year increased from 77.0% in 2013/14 to 85.9% in 2017/18; 38% only had 1 dispensing. Approximately 1/3 (37.5%) initiated on the lowest strength capsule (25 mg) with only 31.2% later up-titrating to a higher strength. 47.4% and 53.0% were dispensed opioids within 180 days before and after pregabalin initiation, respectively. Many individuals are using pregabalin for short treatment durations and low dose ranges not consistent with treatment of neuropathic pain, which is generally a chronic condition. This may suggest poorer tolerability than observed in clinical trials, or use for other conditions, some of which may be for indications where the balance of benefits and risk is less clear.


Occurrence of a community with high morbidity associated with Schistosoma mansoni infection regardless of low infection intensity in north-east Brazil.
To establish the relationship between schistosome-associated morbidity and infection intensity in northeast Brazil, a parasitological and ultrasonographical study was carried out on 484 inhabitants of 4 villages (I, II, III and IV) in São Lourenço da Mata, Pernambuco, Brazil, where schistosomiasis is endemic. Quantitative stool examination using Knight's method demonstrated a high prevalence and moderate intensity of Schistosoma mansoni infection, and also that the subjects in village IV had a significantly lower prevalence and intensity of infection than those of the other villages. By ultrasonography, periportal fibrosis (PPF) and splenomegaly were found in 52% of the 299 infected subjects and 66% of the 146 infected subjects aged over 16 years old, respectively; 32% and 31% of the 299 infected subjects had abnormally high values of total bile acid (TBA) and alkaline phosphatase (ALP) activity, respectively. Liver and spleen size, PPF, and serum level of TBA and ALP were not correlated with infection intensity. There was no significant difference in the morbidity assessed by liver and spleen size, PPF, and serum analysis between the subjects in village IV and the other villages. These findings suggest the occurrence of a community with high morbidity associated with schistosomiasis regardless of low infection intensity.


Biomechanical Comparison: Single-Bundle versus Double-Bundle Posterior Cruciate Ligament Reconstruction Techniques.
Controversy exists regarding double-bundle (DB) versus single-bundle (SB) posterior cruciate ligament (PCL) reconstruction, with differences in multiple variables affecting biomechanical and clinical results. Our objective was to compare immediate postimplantation biomechanics of SB versus DB reconstructions to determine the relative importance of restoring both PCL bundles versus total graft volume. Twenty knees were randomly assigned to five techniques (n = 4 knees/technique), performed by three surgeons experienced in their technique(s), three SB techniques (n = 12; all-inside arthroscopic inlay, all-inside suspensory fixation, and arthroscopic-assisted open onlay), and two DB techniques (n = 8; arthroscopic-assisted open inlay and all-inside suspensory fixation). Each knee was tested in three conditions: PCL-intact, PCL-deficient, and post-PCL reconstruction. Testing consisted of a posterior-directed force at four knee flexion angles, 10, 30, 60, and 90 degrees, to measure load to 5 mm of posterior displacement, maximum displacement (at 100 N load), and stiffness. Data for each knee were normalized, combined into two groups (SB and DB), and then compared using one-way analysis of variance. Graft volumes were calculated and analyzed to determine if differences significantly influenced the biomechanical results. Intact knees were stiffer than both groups at most angles (p < 0.02; p < 0.05). DB was stiffer than SB at all angles except 30 degrees (p < 0.05). Intact knees had less laxity than SB (p < 0.03) and DB (p < 0.05) at 60 and 90 degrees. DB had less laxity than SB at all angles except 60 degrees (p < 0.05). Intact knees required more load than SB at 30, 60, and 90 degrees (p < 0.01) and more than DB at 60 and 90 degrees (p < 0.05). DB required more load than SB at 30, 60, and 90 degrees (p < 0.01). Graft volumes did not have strong correlations (r = 0.13-0.37) to any measurements. Neither group of PCL reconstruction techniques was able to replicate native PCL biomechanics. DB reconstructions were biomechanically superior to SB reconstructions; they may be preferred for clinical use when immediate post-reconstruction graft strength and stability are critical. These results were not strongly influenced by graft size differences, further supporting the PCL codominance theory.


Members of the low-density lipoprotein receptor-related proteins provide a differential molecular signature between parental and CD133+ DAOY medulloblastoma cells.
Members of the low-density lipoprotein receptor-related protein (LRP) family are involved in metabolic stress and resistance phenotypes of cancer cells. New breakthroughs in brain cancer therapy have exploited that molecular signature and proved that efficient delivery of therapeutic agents involve LRP-mediated mechanisms. We performed gene expression profiling of CD133, a cell surface cancer stem cell marker, and of LRP in response to in vitro nutrient deprivation. We found that CD133 was selectively induced in serum-starved DAOY medulloblastoma cells but not in U87MG glioblastoma cells. Such CD133 induction was correlated to increases in LRP-1 and LRP-1b gene and protein expression. When a specific CD133(+) DAOY cell population was sorted from parental DAOY, we found increases in LRP-5 and LRP-8. Uptake of alpha(2)-macroglobulin, a specific LRP-1/1b ligand, was increased in serum-starved parental DAOY cells but not in CD133(+) DAOY cells, and receptor-associated protein (RAP), which binds to all cell surface LRPs, was able to compete for that uptake. Conversely, RAP binding was increased in serum-starved parental DAOY but alpha(2)-macroglobulin was unable to compete for such uptake. Strategies aiming at targeting cancer stem cell metabolic adaptative responses, such as that through LRP differential expression within the brain tissue microenvironmental niche, can now be envisioned.


A survey of the computer literacy of undergraduate dental students at a University Dental School in Ireland during the academic year 1997-98.
As dental practice management becomes more computer-based, the efficient functioning of the dentist will become dependent on adequate computer literacy. A survey has been carried out into the computer literacy of a cohort of 140 undergraduate dental students at a University Dental School in Ireland (years 1-5), in the academic year 1997-98. Aspects investigated by anonymous questionnaire were: (1) keyboard skills; (2) computer skills; (3) access to computer facilities; (4) software competencies and (5) use of medical library computer facilities. The students are relatively unfamiliar with basic computer hardware and software: 51.1% considered their expertise with computers as "poor"; 34.3% had taken a formal typewriting or computer keyboarding course; 7.9% had taken a formal computer course at university level and 67.2% were without access to computer facilities at their term-time residences. A majority of students had never used either word-processing, spreadsheet, or graphics programs. Programs relating to "informatics" were more popular, such as literature searching, accessing the Internet and the use of e-mail which represent the major use of the computers in the medical library. The lack of experience with computers may be addressed by including suitable computing courses at the secondary level (age 13-18 years) and/or tertiary level (FE/HE) education programmes. Such training may promote greater use of generic softwares, particularly in the library, with a more electronic-based approach to data handling.