Current remote sensing approaches to monitoring forest degradation in support of countries measurement, reporting and verification (MRV) systems for REDD.
Forest degradation is a global phenomenon and while being an important indicator and precursor to further forest loss, carbon emissions due to degradation should also be accounted for in national reporting within the frame of UN REDD+. At regional to country scales, methods have been progressively developed to detect and map forest degradation, with these based on multi-resolution optical, synthetic aperture radar (SAR) and/or LiDAR data. However, there is no one single method that can be applied to monitor forest degradation, largely due to the specific nature of the degradation type or process and the timeframe over which it is observed. The review assesses two main approaches to monitoring forest degradation: first, where detection is indicated by a change in canopy cover or proxies, and second, the quantification of loss (or gain) in above ground biomass (AGB). The discussion only considers degradation that has a visible impact on the forest canopy and is thus detectable by remote sensing. The first approach encompasses methods that characterise the type of degradation and track disturbance, detect gaps in, and fragmentation of, the forest canopy, and proxies that provide evidence of forestry activity. Progress in these topics has seen the extension of methods to higher resolution (both spatial and temporal) data to better capture the disturbance signal, distinguish degraded and intact forest, and monitor regrowth. Improvements in the reliability of mapping methods are anticipated by SAR-optical data fusion and use of very high resolution data. The second approach exploits EO sensors with known sensitivity to forest structure and biomass and discusses monitoring efforts using repeat LiDAR and SAR data. There has been progress in the capacity to discriminate forest age and growth stage using data fusion methods and LiDAR height metrics. Interferometric SAR and LiDAR have found new application in linking forest structure change to degradation in tropical forests. Estimates of AGB change have been demonstrated at national level using SAR and LiDAR-assisted approaches. Future improvements are anticipated with the availability of next generation LiDAR sensors. Improved access to relevant satellite data and best available methods are key to operational forest degradation monitoring. Countries will need to prioritise their monitoring efforts depending on the significance of the degradation, balanced against available resources. A better understanding of the drivers and impacts of degradation will help guide monitoring and restoration efforts. Ultimately we want to restore ecosystem service and function in degraded forests before the change is irreversible.


[Klippel-Feil syndrome and associated malformations. Comments on an unusual case].
An unusual association of Klippel-Feil syndrome and other abnormalities (Sprengel's deformity, 1st cervical and 1st dorsal spina bifida, homovertebral bone, scoliosis, plagiocephaly, basilar impression, pterygium colli, nanism, hypogenitalism, etc.) together with neurological signs of amyotrophic lateral sclerosis, in a 36-yr-old woman is reported. The clinical and radiological pictures are examined and the exterior morphology is examined. The three types of Klippel-Feil syndrome are discussed, together with the particular alterations observed in the present case: Sprengel's deformity, spina bifida, craniostenosis, basilar impression, etc.


RNase J depletion leads to massive changes in mRNA abundance in Helicobacter pylori.
Degradation of RNA as an intermediate message between genes and corresponding proteins is important for rapid attenuation of gene expression and maintenance of cellular homeostasis. This process is controlled by ribonucleases that have different target specificities. In the bacterial pathogen Helicobacter pylori, an exo- and endoribonuclease RNase J is essential for growth. To explore the role of RNase J in H. pylori, we identified its putative targets at a global scale using next generation RNA sequencing. We found that strong depletion for RNase J led to a massive increase in the steady-state levels of non-rRNAs. mRNAs and RNAs antisense to open reading frames were most affected with over 80% increased more than 2-fold. Non-coding RNAs expressed in the intergenic regions were much less affected by RNase J depletion. Northern blotting of selected messenger and non-coding RNAs validated these results. Globally, our data suggest that RNase J of H. pylori is a major RNase involved in degradation of most cellular RNAs.


Barriers to the implementation of practice guidelines in managing patients with nonvariceal upper gastrointestinal bleeding: A qualitative approach.
Guidelines for the management of patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) are inconsistently applied by health care providers, potentially resulting in suboptimal care and patient outcomes. A needs assessment was performed to assess health care providers' barriers to the implementation of these guidelines in Canada. Semistructured telephone interviews were conducted by trained research personnel with 22 selectively sampled health care professionals actively treating and managing NVUGIB patients, including emergency room physicians (ER), intensivists (ICU), gastroenterologists (GI), gastroenterology nurses and hospital administrators. Participants were chosen from a representative sample of six Canadian community- and academic-based hospitals that participated in a national Canadian audit on the management of NVUGIB. Participants reported substantive gaps in the implementation of NVUGIB guidelines that included the following: lack of knowledge of the specifics of the NVUGIB guidelines (ER, ICU, nurses); limited belief in the value of guidelines, especially in areas where evidence is lacking (ER, ICU); limited belief in the value of available tools to support implementation of guidelines (GI); lack of knowledge of the roles and responsibilities of health care professions and disciplines, and lack of effective collaboration skills (ER, ICU and GI); variability of knowledge and skills of health care professionals within professions (eg, variability of nurses' knowledge and skills in endoscopic procedures); and perceived overuse of intravenous proton pump inhibitor treatment, with limited concern regarding cost or side effect implications (all participants). In the present study population, ER, ICU and nurses did not adhere to NVUGIB guidelines because they were neither aware of nor familiar with them, whereas the GI lack of adherence to NVUGIB guidelines was influenced more by attitudinal and contextual barriers. These findings can guide the design of multifaceted educational and behavioural interventions when attempting to effectively disseminate existing guidelines, and for guideline implementation into practice.


Direct spectroscopic evidence for the presence of a 6Fe cluster in an iron-sulfur protein isolated from Desulfovibrio desulfuricans (ATCC 27774)
A novel iron-sulfur protein was purified from the extract of Desulfovibrio desulfuricans (ATCC 27774) to homogeneity as judged by polyacrylamide gel electrophoresis. The purified protein is a monomer of 57 kDa molecular mass. It contains comparable amounts of iron and inorganic labile sulfur atoms and exhibits an optical spectrum typical of iron-sulfur proteins with maxima at 400, 305, and 280 nm. Mössbauer data of the as-isolated protein show two spectral components, a paramagnetic and a diamagnetic, of equal intensity. Detailed analysis of the paramagnetic component reveals six distinct antiferromagnetically coupled iron sites, providing direct spectroscopic evidence for the presence of a 6Fe cluster in this newly purified protein. One of the iron sites exhibits parameters (delta EQ = 2.67 +/- 0.03 mm/s and delta = 1.09 +/- 0.02 mm/s at 140 K) typical for high spin ferrous ion; the observed large isomer shift indicates an iron environment that is distinct from the tetrahedral sulfur coordination commonly observed for the iron atoms in iron-sulfur clusters and is consistent with a penta- or hexacoordination containing N and/or O ligands. The other five iron sites are most probably high spin ferric. Three of them show parameters characteristic for tetrahedral sulfur coordination. In correlation with the EPR spectrum of the as-purified protein which shows a resonance signal at g = 15.3 and a group of signals between g = 9.8 and 5.4, this 6Fe cluster is assigned to an unusual spin state of 9/2 with zero field splitting parameters D = -1.3 cm-1 and E/D = 0.062. Other EPR signals attributable to minor impurities are also observed at the g = 4.3 and 2.0 regions. The diamagnetic Mössbauer component represents a second iron cluster, which, upon reduction with dithionite, displays an intense S = 1/2 EPR signal with g values at 2.00, 1.83, and 1.31. In addition, an EPR signal of the S = 3/2 type is also observed for the dithionite-reduced protein.


Interventions for helping patients to follow prescriptions for medications.
Efforts to assist patients with adherence to prescribed, self-administered medications might improve the benefits and efficiency of health care. To update an ongoing review summarising the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications, focusing on trials that measured both adherence and clinical outcomes. Computerised searches to July 1998 in MEDLINE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsychInfo, Sociofile, and HSTAR; bibliographies in articles on patient adherence; articles in the reviewers' personal collections; and contact with authors. Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. Information on study design features, interventions and controls, and findings were extracted by one reviewer (PM) and a research assistant and confirmed by two of the other reviewers. The studies were too disparate to warrant meta-analysis. For short-term treatments, one study, of counselling and written information, showed an effect on adherence and clinical outcome. Ten of 19 interventions for long-term treatments reported in 17 RCTs were associated with improvements in adherence, but only nine interventions led to improvements in treatment outcomes. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, counselling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Two studies showed that telling patients about adverse effects of treatment did not affect their adherence. The full benefits of medications cannot be realised at currently achievable levels of adherence. Current methods of improving adherence for chronic health problems are mostly complex and not very effective. More studies of innovative approaches to assist patients to follow medication prescriptions are needed.


Smooth pursuit-related information processing in frontal eye field neurons that project to the NRTP.
The cortical pursuit system begins the process of transforming visual signals into commands for smooth pursuit (SP) eye movements. The frontal eye field (FEF), located in the fundus of arcuate sulcus, is known to play a role in SP and gaze pursuit movements. This role is supported, at least in part, by FEF projections to the rostral nucleus reticularis tegmenti pontis (rNRTP), which in turn projects heavily to the cerebellar vermis. However, the functional characteristics of SP-related FEF neurons that project to rNRTP have never been described. Therefore, we used microelectrical stimulation (ES) to deliver single pulses (50-200 microA, 200-micros duration) in rNRTP to antidromically activate FEF neurons. We estimated the eye or retinal error motion sensitivity (position, velocity, and acceleration) of FEF neurons during SP using multiple linear regression modeling. FEF neurons that projected to rNRTP were most sensitive to eye acceleration. In contrast, FEF neurons not activated following ES of rNRTP were often most sensitive to eye velocity. In similar modeling studies, we found that rNRTP neurons were also biased toward eye acceleration. Therefore, our results suggest that neurons in the FEF-rNRTP pathway carry signals that could play a primary role in initiation of SP.


Treatment of intrasubstance meniscal lesions: a randomized prospective study of four different methods.
This study examined the effect of four different methods for treating intrasubstance meniscal lesions. Forty patients (21 men, 19 women; age 30.4 years, range 16-50) with an isolated and symptomatic painful horizontal grade 2 meniscal lesion on the medial side (documented with MRI) were included. Patients were randomly assigned by the birth date to one of four treatment groups: group A, conservative therapy (n = 12); group B, arthroscopic suture repair with access channels (n = 10); group C, arthroscopic minimal central resection, intrameniscal fibrin clot and suture repair (n = 7); and group D, arthroscopic partial meniscectomy (n = 11). The average length of follow-up was 26.5 months (range 12-38 months). Follow-up evaluation consisted of clinical examination with the findings recorded according to the IKDC protocol, radiographs, and control MRI. Group A had 75% normal or nearly normal final evaluation at follow-up, group B 90%, group C 43%, and group D 100% normal or nearly normal at follow-up. These short-term results indicate that intrasubstance meniscal lesions can be treated best by performing partial meniscectomy. To preserve the important function of the meniscus, arthroscopic suture repair with access channels might give even better medium- to long-term results. Conservative treatment is often not satisfactory. Additionally, our findings show that MRI examinations are not superior to accurate clinical examinations.


How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression.
Intestinal-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas is clinicopathologically distinctive. Our research aimed to elucidate the molecular mechanism of the development and progression of the intestinal-type IPMN. In 60 intestinal-type IPMN specimens, histological transitions from gastric-type epithelia to intestinal-type epithelia were observed in 48 cases (80%). CDX2/MUC2/alcian blue triple staining indicated that CDX2 appeared to precede MUC2 expression and subsequent alcian blue-positive mucin production. Expression of p21 and Ki-67 seemed to be accelerated by CDX2 expression (p = 6.02e-13 and p = 3.1e-09, respectively). p21/Ki-67 double staining revealed that p21 was mostly expressed in differentiated cells in the apex of papillae, while Ki-67 was expressed in proliferative cells in the base of papillae. This clear cellular arrangement seemed to break down with the progression of atypical grade and development of invasion (p = 0.00197). Intestinal-type IPMNs harbored frequent GNAS mutations (100%, 25/25) and RNF43 mutations (57%, 8/14) and shared identical GNAS and KRAS mutations with concurrent gastric-type IPMNs or incipient gastric-type neoplasia (100%, 25/25). RNF43 mutations showed emerging or being selected in intestinal-type neoplasms along with ß-catenin aberration. Activation of protein kinase A and extracellular-regulated kinase was observed in CDX2-positive intestinal-type neoplasm. These results suggest that gastric-type epithelia that acquire GNAS mutations together with induction of intrinsic CDX2 expression may evolve with clonal selection and additional molecular aberrations including RNF43 and ß-catenin into intestinal-type IPMNs, which may further progress with complex villous growth due to disoriented cell cycle regulation, acceleration of atypical grade, and advance to show an invasive phenotype.


Observation of the Larmor and Gouy rotations with electron vortex beams.
Electron vortex beams carrying intrinsic orbital angular momentum (OAM) are produced in electron microscopes where they are controlled and focused by using magnetic lenses. We observe various rotational phenomena arising from the interaction between the OAM and magnetic lenses. First, the Zeeman coupling, proportional to the OAM and magnetic field strength, produces an OAM-independent Larmor rotation of a mode superposition inside the lens. Second, when passing through the focal plane, the electron beam acquires an additional Gouy phase dependent on the absolute value of the OAM. This brings about the Gouy rotation of the superposition image proportional to the sign of the OAM. A combination of the Larmor and Gouy effects can result in the addition (or subtraction) of rotations, depending on the OAM sign. This behavior is unique to electron vortex beams and has no optical counterpart, as Larmor rotation occurs only for charged particles. Our experimental results are in agreement with recent theoretical predictions.


Atomistic modeling of metallic nanowires in silicon.
Scanning tunneling microscope (STM) lithography has recently demonstrated the ultimate in device scaling with buried, conducting nanowires just a few atoms wide and the realization of single atom transistors, where a single P atom has been placed inside a transistor architecture with atomic precision accuracy. Despite the dimensions of the critical parts of these devices being defined by a small number of P atoms, the device electronic properties are influenced by the surrounding 10(4) to 10(6) Si atoms. Such effects are hard to capture with most modeling approaches, and prior to this work no theory existed that could explore the realistic size of the complete device in which both dopant disorder and placement are important. This work presents a comprehensive study of the electronic and transport properties of ultra-thin (<10 nm wide) monolayer highly P δ-doped Si (Si:P) nanowires in a fully atomistic self-consistent tight-binding approach. This atomistic approach covering large device volumes allows for a systematic study of disorder on the physical properties of the nanowires. Excellent quantitative agreement is observed with recent resistance measurements of STM-patterned nanowires [Weber et al., Science, 2012, 335, 64], confirming the presence of metallic behavior at the scaling limit. At high doping densities the channel resistance is shown to be insensitive to the exact channel dopant placement highlighting their future use as metallic interconnects. This work presents the first theoretical study of Si:P nanowires that are realistically extended and disordered, providing a strong theoretical foundation for the design and understanding of atomic-scale electronics.


A Linear Piezoelectric Actuator Using "A-Shaped" Structure.
A new design of linear piezoelectric actuator using "A-shaped" structure was proposed, designed, fabricated, and tested. By fusion design of the piezoelectric transducer and the mechanical structure, the proposed actuator only uses the first bending vibration of the center piezoelectric transducer to work. Frequency degeneration is no longer needed, which enables the actuator to adjust its structural parameters according to the application conditions. When applying an alternating voltage at resonance frequency, the center piezoelectric transducer will be stimulated in the first bending vibration. The vibration energy transmitted to the two driving arms generates alternating tilting movements with a phase difference of 180° between the two driving feet, which enables the actuator to push the linear guide when a vertical preload is applied. Under the preload of 120 N, the actuator gained a maximum thrust force of 9.8 N and a maximum output power of 0.62 W with a self-weight of 0.061 kg. The maximum output thrust density and the maximum output power density were 160.6 N/kg and 10.2 W/kg, respectively.


Antibacterial and cytocompatible nanotextured Ti surface incorporating silver via single step hydrothermal processing.
Nanosurface modification of Titanium (Ti) implants and prosthesis is proved to enhance osseointegration at the tissue-implant interface. However, many of these products lack adequate antibacterial capability, which leads to implant loosening. As a curative strategy, in this study, nanotextured Ti substrates embedded with silver nanoparticles were developed through a single step hydrothermal processing in an alkaline medium containing silver nitrate at different concentrations (15, 30 and 75μM). Scanning electron micrographs revealed a non-periodically oriented nanoleafy structure on Ti (TNL) decorated with Ag nanoparticles (nanoAg), which was verified by XPS, XRD and EDS analysis. This TNLAg substrate proved to be mechanically stable upon nanoindentation and nanoscratch tests. Silver ions at detectable levels were released for a period of ~28days only from substrates incorporating higher nanoAg content. The samples demonstrated antibacterial activity towards both Escherichia coli and Staphylococcus aureus, with a more favorable response to the former. Simultaneously, Ti substrates incorporating nanoAg at all concentrations supported the viability, proliferation and osteogenic differentiation of mesenchymal stem cells. Overall, nanoAg incorporation into surface modified Ti via a simple one-step thermochemical method is a favorable strategy for producing implants with dual characteristics of antibacterial activity and cell compatibility.


Most common 'sporadic' cancers have a significant germline genetic component.
Common cancers have been demarcated into 'hereditary' or 'sporadic' ('non-hereditary') types historically. Such distinctions initially arose from work identifying rare, highly penetrant germline mutations causing 'hereditary' cancer. While rare mutations are important in particular families, most cases in the general population are 'sporadic'. Twin studies have suggested that many 'sporadic' cancers show little or no heritability. To quantify the role of germline mutations in cancer susceptibility, we applied a method for estimating the importance of common genetic variants (array heritability, h(2)g) to twelve cancer types. The following cancers showed a significant (P < 0.05) array heritability: melanoma USA set h(2)g = 0.19 (95% CI = 0.01-0.37) and Australian set h(2)g = 0.30 (0.10-0.50); pancreatic h(2)g = 0.18 (0.06-0.30); prostate h(2)g = 0.81 (0.32-1); kidney h(2)g = 0.18 (0.04-0.32); ovarian h(2)g = 0.30 (0.18-0.42); esophageal adenocarcinoma h(2)g = 0.24 (0.14-0.34); esophageal squamous cell carcinoma h(2)g = 0.19 (0.07-0.31); endometrial UK set h(2)g = 0.23 (0.01-0.45) and Australian set h(2)g = 0.39 (0.02-0.76). Three cancers showed a positive but non-significant effect: breast h(2) g = 0.13 (0-0.56); gastric h(2)g = 0.11 (0-0.27); lung h(2)g = 0.10 (0-0.24). One cancer showed a small effect: bladder h(2)g = 0.01 (0-0.11). Among these cancers, previous twin studies were only able to show heritability for prostate and breast cancer, but we can now make much stronger statements for several common cancers which emphasize the important role of genetic variants in cancer susceptibility. We have demonstrated that several 'sporadic' cancers have a significant inherited component. Larger genome-wide association studies in these cancers will continue to find more loci, which explain part of the remaining polygenic component.


Expression and Clinicopathological Significance of SOX11 in Small-Cell Lung Cancer.
This study aims to investigate the expression of neuronal transcription factor SOX11 in small-cell lung cancer (SCLC) and compare it with the expression of CD56 (nerve cell adhesion molecule), synaptophysin (Syn), chromogranin A (CgA), and thyroid transcription factor-1 (TTF-1) to explore the application value of SOX11 in the pathological diagnosis of SCLC. Immunohistochemical methods were used to detect the expression of SOX11, TTF-1, CD56, Syn, and CgA in 120 lung tumor tissues, and experimental results were analyzed using SPSS23.0 statistical software. Immunohistochemical results showed that in the 120 lung tumor samples, SOX11 was highly expressed in SCLC and localized to the nucleus, with low or no expression in control carcinoid/lung neuroendocrine tumors, lung adenocarcinomas, and lung squamous cell carcinomas. Statistical analysis results revealed the following points. First, the expression of SOX11 was closely related to the tumor histological type. The expression of SOX11 in SCLC (positive rate of 63.33%) was significantly higher than that in carcinoid/neuroendocrine tumors (positive rate of 12.50%), lung adenocarcinoma (positive rate of 0%), and lung squamous cell carcinoma (positive rate of 0%). Second, immunohistochemical investigation of 60 SCLC cases revealed that the highest positive rates of CD56, TTF-1, and Syn, respectively, were 93.33 percent, 95 percent, and 86.67 percent. SOX11 also exhibited high sensitivity (0.633) and specificity (0.875) in SCLC. The positive rates of SOX11 and CgA were 63.33% and 50.00%, respectively. Statistical results revealed that the positive rate of CgA had no significant difference (P > 0.05). Lastly, the combined use of antibodies SOX11, CgA, CD56, Syn, and TTF-1 was more beneficial to improving the diagnosis rate of SCLC than the single use of one or two antibodies. The expression of SOX11 in different histological types of lung tumors differs considerably. SOX11 is highly expressed in SCLC. SOX11 can be used as a beneficial supplement to the combination of classical neuroendocrine markers and in combination with CgA, CD56, Syn, and TTF-1 to assist in the diagnosis of SCLC.


Attenuated signature-tagged mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice.
For this study, we screened 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M in a mouse model of infection and found 36 of them to be attenuated in vivo. Molecular characterization of transposon insertion sites showed that for four mutants, the affected genes were only present in Rhizobiaceae. Another mutant contained a disruption in a gene homologous to mosA, which is involved in rhizopine biosynthesis in some strains of Rhizobium, suggesting that this sugar may be involved in Brucella pathogenicity. A mutant was disrupted in a gene homologous to fliF, a gene potentially coding for the MS ring, a basal component of the flagellar system. Surprisingly, a mutant was affected in the rpoA gene, coding for the essential alpha-subunit of the RNA polymerase. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. The results presented here highlight the fact that the ability of Brucella to induce pathogenesis shares similarities with the molecular mechanisms used by both Rhizobium and Agrobacterium to colonize their hosts.


Prognostic value of body composition on survival outcomes in melanoma patients receiving immunotherapy.
The influence of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with melanoma is still uncertain in clinical practice. Therefore, the objective of this study was to examine the potential association between body composition and clinical outcomes in patients with melanoma undergoing ICIs treatment. A systematic literature search was performed across several databases, including PubMed, Embase, Cochrane Library and Google Scholar, to gather relevant studies. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), assessed by hazard ratios (HR). Secondary outcomes, such as adverse events (AE), were evaluated using odds ratios (OR). This meta-analysis comprised ten articles involving a total of 1,283 patients. Systemic analysis of all collected evidence revealed that body composition, including low skeletal muscle index (SMI) (OS: HR = 1.66, 95% CI = 1.13-2.43, p = 0.010; PFS: HR = 1.28, 95% CI = 1.06-1.55, p = 0.009), high subcutaneous adipose tissue density (SMD) (OS: HR = 1.93, 95% CI = 1.09-3.44, p = 0.025; PFS: HR = 1.31, 95% CI = 1.06-1.63, p = 0.012), and sarcopenia (OS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022; PFS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022), were significantly associated with OS and PFS in melanoma patients treated with ICIs. However, these markers did not show a significant association with treatment-related adverse events. Interestingly, no significant correlation was found between visceral fat index (VFI) (OS: HR = 0.71, 95% CI = 0.29-1.76, p = 0.462; PFS: HR = 0.98, 95% CI = 0.93-1.02, p = 0.274) and OS or PFS in melanoma patients under ICIs treatment. Body composition was found to be associated with decreased treatment response and lower long-term efficacy in patients with melanoma undergoing immune checkpoint inhibitor (ICI) therapy. However, it is important to note that body composition did not appear to contribute to increased incidence of adverse events in these patients.


Genomic analysis of carboxyl/cholinesterase genes in the silkworm Bombyx mori.
Carboxyl/cholinesterases (CCEs) have pivotal roles in dietary detoxification, pheromone or hormone degradation and neurodevelopment. The recent completion of genome projects in various insect species has led to the identification of multiple CCEs with unknown functions. Here, we analyzed the phylogeny, expression and genomic distribution of 69 putative CCEs in the silkworm, Bombyx mori (Lepidoptera: Bombycidae). A phylogenetic tree of CCEs in B. mori and other lepidopteran species was constructed. The expression pattern of each B. mori CCE was also investigated by a search of an expressed sequence tag (EST) database, and the relationship between phylogeny and expression was analyzed. A large number of B. mori CCEs were identified from a midgut EST library. CCEs expressed in the midgut formed a cluster in the phylogenetic tree that included not only B. mori genes but also those of other lepidopteran species. The silkworm, and possibly also other lepidopteran species, has a large number of CCEs, and this might be a consequence of the large cluster of midgut CCEs. Investigation of intron-exon organization in B. mori CCEs revealed that their positions and splicing site phases were strongly conserved. Several B. mori CCEs, including juvenile hormone esterase, not only showed clustering in the phylogenetic tree but were also closely located on silkworm chromosomes. We investigated the phylogeny and microsynteny of neuroligins in detail, among many CCEs. Interestingly, we found the evolution of this gene appeared not to be conserved between B. mori and other insect orders. We analyzed 69 putative CCEs from B. mori. Comparison of these CCEs with other lepidopteran CCEs indicated that they had conserved expression and function in this insect order. The analyses showed that CCEs were unevenly distributed across the genome of B. mori and suggested that neuroligins may have a distinct evolutionary history from other insect order. It is possible that such an uneven genomic distribution and a unique neuroligin evolution are shared with other lepidopteran insects. Our genomic analysis has provided novel information on the CCEs of the silkworm, which will be of value to understanding the biology, physiology and evolution of insect CCEs.


Children With Inflammatory Bowel Disease in the COVID-19 Main Endemic Focus: The Lombardy Experience.
Objectives: In the era of Coronavirus 2019 (COVID-19), concern has been raised for immunosuppressed patients, including children with inflammatory bowel diseases (IBD). We aimed to collect data from IBD tertiary centers of Lombardy during pandemic. Methods: A cross-sectional survey enrolling IBD children has been completed by seven major IBD centers in Lombardy during lockdown. The clinical form included questions on any symptom consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the IBD adherence treatment. Furthermore, we have reviewed all IBD medical records including new IBD diagnoses and flares in known IBD patients after the lockdown. Results: Questionnaires of 290 IBD children were returned during lockdown. Out of them, 24 children (8%) complained of mild symptoms suspicious of SARS-CoV-2 infection without needing hospitalization or changing IBD treatment. During the lockdown, one patient presented with IBD flare and one had infectious colitis, with no new IBD cases. Conversely, after lockdown, 12/290 (4%) children relapsed and 15 children were newly diagnosed with IBD. Last year, in the same timeframe, 20/300 (7%) children presented with IBD flare, while 17 children had IBD onset with no statistical difference. Conclusions: Our data on children with IBD in a high COVID-19 prevalence region are reassuring. Only a minority of IBD children had mild symptoms, and no hospitalization or treatment modification was needed. Standard IBD treatments including biologics were safely continued. New IBD diagnoses and flares in known IBD children occurred after the lockdown phase, although no significant difference was found compared with the previous year.


Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats.
In exercising skeletal muscle, vasoconstrictor responses to alpha-adrenoceptor activation are attenuated in part by nitric oxide (NO) produced by the neuronal isoform of NO synthase (nNOS), which is expressed constitutively in skeletal muscle cells. In skeletal muscle of pregnant animals, nNOS mRNA is upregulated, suggesting that muscle nNOS expression is modulated by the steroid hormone oestrogen. Whether oestrogen-induced changes in nNOS expression have measurable effects on vasoregulation in skeletal muscle is unknown. In this study, we hypothesized that oestrogen deficiency would reduce muscle nNOS expression, resulting in impaired modulation of sympathetic vasoconstriction in exercising skeletal muscle. Compared to gonadally intact rats, we found that ovariectomized (OVX) rats were characterized by greater sympathetic vasoconstriction in contracting hindlimb and reduced nNOS, but not eNOS, in skeletal muscle. In addition, NOS inhibition resulted in a greater enhancement of sympathetic vasoconstriction in contracting hindlimbs of intact compared to OVX rats. These effects of oestrogen deficiency were prevented by chronic treatment of OVX rats with 17beta-oestradiol, but not with chronic progesterone or acute oestradiol. Further analysis revealed that skeletal muscle nNOS correlated directly with plasma 17beta-oestradiol and inversely with the magnitude of sympathetic vasoconstrictor responses in contracting hindlimbs. These data indicate that NO-dependent attenuation of sympathetic vasoconstriction in contracting skeletal muscle is impaired in oestrogen-deficient female rats, and suggest that this impairment may be mediated by reduced skeletal muscle nNOS expression.


Prevalence of sleep disorders in early-treated phenylketonuric children and adolescents. Correlation with dopamine and serotonin status.
Phenylketonuric (PKU) patients are a population at risk for sleep disorders due to deficits in neurotransmitter synthesis. We aimed to study the prevalence of sleep disorders in early-treated PKU children and adolescents and assessed correlations with dopamine and serotonin status. We compared 32 PKU patients (16 females, 16 males; mean age 12 years), with a healthy control group of 32 subjects (16 females, 16 males; mean age 11.9 years). 19 PKU patients were under dietary treatment and 13 on tetrahydrobiopterin therapy. Concurrent phenylalanine (Phe), index of dietary control and variability in Phe in the last year, tyrosine, tryptophan, prolactin, and ferritin in plasma, platelet serotonin concentration, and melatonin, homovanillic and 5-hydroxyindoleacetic acid excretion in urine were analyzed. Sleep was assessed using Bruni's Sleep Disturbance Scale for Children. Sleep disorders were similar in both groups, 15.6% in control group and 12.5% in PKU group. In PKU patients, no correlations were found with peripheral biomarkers of neurotransmitter synthesis nor different Phe parameters, 43.3% had low melatonin excretion and 43.8% low platelet serotonin concentrations. Despite melatonin and serotonin deficits in early-treated PKU patients, the prevalence of sleep disorders is similar to that of the general population.


[Changes in buoyant density of planarian mitochondria under starvation and nutrition].
The changes in buoyant density of mitochondria during starvation and nutrition of planaria have been revealed. The buoyant density of mitochondria decreases during starvation and reversibly increases under nutrition. The decrease of the buoyant density of planarian mitochondria under starvation is probably due to a decrease in the level of synthesis of mitochondrial protein.


Polaribacter huanghezhanensis sp. nov., isolated from Arctic fjord sediment, and emended description of the genus Polaribacter.
A Gram-negative, orange-colony-forming, aerobic and non-flagellated bacterium, designated strain SM1202(T), was isolated from marine sediment of Kongsfjorden, Svalbard. Analysis of 16S rRNA gene sequences revealed that strain SM1202(T) was phylogenetically closely related to the genus Polaribacter. It shared the highest 16S rRNA gene sequence similarity with the type strain of Polaribacter dokdonensis (94.2 %) and 92.7-93.9 % sequence similarity with type strains of other known species of the genus Polaribacter. The strain grew at 4-35 °C and with 1.0-5.0 % (w/v) NaCl. It contained iso-C15 : 0, iso-C15 : 0 3-OH, iso-C13 : 0, C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH and C15 : 1ω6c as predominant cellular fatty acids and menaquinone-6 (MK-6) as the major respiratory quinone. The polar lipids of strain SM1202(T) were phosphatidylethanolamine, one unidentified lipid, two unidentified aminophospholipids and one unidentified aminolipid. The genomic DNA G+C content of strain SM1202(T) was 36.4 mol%. On the basis of the data from this polyphasic taxonomic study, strain SM1202(T) represents a novel species in the genus Polaribacter of the family Flavobacteriaceae, for which the name Polaribacter huanghezhanensis sp. nov. is proposed. The type strain of Polaribacter huanghezhanensis is SM1202(T) ( = CCTCC AB 2013148(T) = KCTC 32516(T)). An emended description of the genus Polaribacter is also presented.


The effect of tobacco smoke on oxytocin concentrations and selected oxidative stress parameters in plasma during pregnancy and post-partum - an experimental model.
Tobacco smoking is a serious threat to life and health of society. Among the most vulnerable to the toxic effects of tobacco smoke are foetuses and newborns. The objective of the research was to assess the impact of tobacco smoke exposure on oxytocin levels and biochemical oxidative stress parameters during pregnancy and after birth in an experimental model. In the experiment, exposure to tobacco smoke of gravid and non-gravid rats was monitored. A reliable biomarker of exposure - cotinine - was used in the process and it was determined by means of high-performance liquid chromatography with diode array detection, which ensured high analytical accuracy and precision. Determination of oxytocin was performed by means of enzyme-linked immunosorbent assay. The levels of selected oxidative stress parameters: total protein concentration, uric acid, trolox equivalent antioxidant capacity, protein S-nitrosylation and lipid peroxidation (thiobarbituric acid reactive substances) were measured by spectrophotometric methods. The effect of prenatal and postnatal exposure to tobacco smoke was a lower medium body mass of rat foetuses and pups. Oxidative stress during pregnancy, additionally intensified by tobacco smoke exposure, led to adaptive changes in properties of plasmatic antioxidant barriers. Moreover, the disturbance of oxidoreductive balance by tobacco smoke affects oxytocin fluctuations, what was observed in this study during lactation period. Therefore, women who smoke may breastfeed their children less frequently and for a shorter period.


Extrahepatic cell membrane lipid abnormalities and cellular dysfunction in liver disease.
Liver disease is associated with characteristic changes in the lipid composition of the surface coat of plasma lipoprotein particles. Cholesterol and lecithin molecules accumulate as hepatic secretion of lecithin-cholesterol acyltransferase decreases, and the arachidonate content, the precursor for eicosanoid production, is also reduced. By exchange and equilibration processes, such abnormal circulating lipoproteins should tend to induce corresponding changes in cell membrane lipid composition; studies in both human and experimental liver disease confirm that this does occur and that it is wide-spread. The correct functioning of membrane proteins, which serve as receptors or are responsible for enzymatic and transport processes, is most commonly dependent on the fluidity of their lipid bilayer matrix. Because cholesterol enrichment of biomembranes reduces bulk lipid fluidity, it can be predicted that extrahepatic membrane dysfunction might be a general feature of severe liver disease. This concept is supported by increasing experimental evidence and, as a consequence, it is proposed that many of the cellular disturbances and metabolic abnormalities accompanying hepatic disease result from, or are exacerbated by, lipoprotein-induced changes in membrane lipid composition and function. Importantly, this mechanism also suggests that drugs which can fluidise membranes, such as S-adenosyl-L-methionine (SAMe), might help ameliorate cellular dysfunction.


Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.
Leber congenital amaurosis (LCA) is a group of autosomal recessive blinding retinal diseases that are incurable. One molecular form is caused by mutations in the RPE65 (retinal pigment epithelium-specific 65-kDa) gene. A recombinant adeno-associated virus serotype 2 (rAAV2) vector, altered to carry the human RPE65 gene (rAAV2-CBSB-hRPE65), restored vision in animal models with RPE65 deficiency. A clinical trial was designed to assess the safety of rAAV2-CBSB-hRPE65 in subjects with RPE65-LCA. Three young adults (ages 21-24 years) with RPE65-LCA received a uniocular subretinal injection of 5.96 x 10(10) vector genomes in 150 microl and were studied with follow-up examinations for 90 days. Ocular safety, the primary outcome, was assessed by clinical eye examination. Visual function was measured by visual acuity and dark-adapted full-field sensitivity testing (FST); central retinal structure was monitored by optical coherence tomography (OCT). Neither vector-related serious adverse events nor systemic toxicities were detected. Visual acuity was not significantly different from baseline; one patient showed retinal thinning at the fovea by OCT. All patients self-reported increased visual sensitivity in the study eye compared with their control eye, especially noticeable under reduced ambient light conditions. The dark-adapted FST results were compared between baseline and 30-90 days after treatment. For study eyes, sensitivity increases from mean baseline were highly significant (p < 0.001); whereas, for control eyes, sensitivity changes were not significant (p = 0.99). Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE65-LCA that were carried out contemporaneously and reported.


Blood-brain barrier and traumatic brain injury.
The blood-brain barrier (BBB) is an anatomical microstructural unit, with several different components playing key roles in normal brain physiological regulation. Formed by tightly connected cerebrovascular endothelial cells, its normal function depends on paracrine interactions between endothelium and closely related glia, with several recent reports stressing the need to consider the entire gliovascular unit in order to explain the underlying cellular and molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI) and significant events in incidence and potential clinical consequences in pediatric and adult ages, little is known about the actual role of BBB disruption in its diverse pathological pathways. This Mini-Review addresses the current literature on possible factors affecting gliovascular units and contributing to posttraumatic BBB dysfunction, including neuroinflammation and disturbed transport mechanisms along with altered permeability and consequent posttraumatic edema. Key mechanisms and its components are described, and promising lines of basic and clinical research are identified, because further knowledge on BBB pathological interference should play a key role in understanding TBI and provide a basis for possible therapeutic targets in the near future, whether through restoration of normal BBB function after injury or delivering drugs in an increased permeability context, preventing secondary damage and improving functional outcome.


Auditory perceptual objects as generative models: Setting the stage for communication by sound.
Communication by sounds requires that the communication channels (i.e. speech/speakers and other sound sources) had been established. This allows to separate concurrently active sound sources, to track their identity, to assess the type of message arriving from them, and to decide whether and when to react (e.g., reply to the message). We propose that these functions rely on a common generative model of the auditory environment. This model predicts upcoming sounds on the basis of representations describing temporal/sequential regularities. Predictions help to identify the continuation of the previously discovered sound sources to detect the emergence of new sources as well as changes in the behavior of the known ones. It produces auditory event representations which provide a full sensory description of the sounds, including their relation to the auditory context and the current goals of the organism. Event representations can be consciously perceived and serve as objects in various cognitive operations.


Molecular cloning and functional characterization of pigeon IKKε.
Inhibitor of nuclear factor kappa-B kinase ε (IKKε), a member of the non-canonical IκB kinase family, plays a critical role in connecting various signaling pathways associated with the initiation of type I interferon (IFN) production. Although the importance of IKKε in innate immunity has been well established in mammals and fish, its characterization and function in pigeons have remained largely unexplored. In this study, we successfully cloned pigeon IKKε (piIKKε) from pigeon embryo fibroblasts (PEFs) for the first time. This gene encodes 722 amino acids and shares high amino acid similarity with its duck and goose counterparts. piIKKε showed a diffuse cytoplasmic distribution and broad expression in all tissues examined. Overexpression of piIKKε in PEFs significantly activated the IFN-β promoter, with both the kinase and CC domains of piIKKε playing key roles in initiating IFN-β expression. Knockdown of piIKKε using small interfering RNA significantly reduced the levels of IFN-β induced by NDV, AIV, poly (I:C), or SeV. Furthermore, the presence of piIKKε resulted in a remarkable reduction in the replication of both avian influenza virus (AIV) H9N2 and Newcastle disease virus (NDV) in PEFs. Our results demonstrate that piIKKε plays a critical role in mediating antiviral innate immunity in pigeons.


Aerosol and snow transfer processes: An investigation on the behavior of water-soluble organic compounds and ionic species.
The concentrations of water-soluble compounds (ions, carboxylic acids, amino acids, sugars, phenolic compounds) in aerosol and snow have been determined at the coastal Italian base "Mario Zucchelli" (Antarctica) during the 2014-2015 austral summer. The main aim of this research was to investigate the air-snow transfer processes of a number of classes of chemical compounds and investigate their potential as tracers for specific sources. The composition and particle size distribution of Antarctic aerosol was measured, and water-soluble compounds accounted for 66% of the PM10 total mass concentration. The major ions Na+, Mg2+, Cl- and SO42- made up 99% of the total water soluble compound concentration indicating that sea spray input was the main source of aerosol. These ionic species were found mainly in the coarse fraction of the aerosol resulting in enhanced deposition, as reflected by the snow composition. Biogenic sources were identified using chemical markers such as carboxylic acids, amino acids, sugars and phenolic compounds. This study describes the first characterization of amino acids and sugar concentrations in surface snow. High concentrations of amino acids were found after a snowfall event, their presence is probably due to the degradation of biological material scavenged during the snow event. Alcohol sugars increased in concentration after the snow event, suggesting a deposition of primary biological particles, such as airborne fungal spores.


Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis.
Fijiolide A, a potent inhibitor of TNF-alpha-induced NFkappaB activation, along with fijiolide B, were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NFkappaB activation by 70.3%, with an IC(50) value of 0.57 micro-M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 microg/mL (28.4 microM). The concentration required to double the activity was 1.8 microM. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.


Evaluation of associations between common variation in mitotic regulatory pathways and risk of overall and high grade breast cancer.
Mitotic regulatory pathways insure proper timing of mitotic entry, sister chromatid cohesion and separation, and cytokinesis. Disruption of this process results in inappropriate chromosome segregation and aneuploidy, and appears to contribute to cancer. Specifically, disregulation and somatic mutation of mitotic regulators has been observed in human cancers, and overexpression of mitotic regulators is common in aggressive and late stage tumors. However, the role of germline variation in mitotic pathways and risk of cancer is not well understood. We tested 1,084 haplotype-tagging and functional variants from 164 genes in mitotic regulatory pathways in 791 Caucasian women with breast cancer and 843 healthy controls for association with risk of overall and high grade breast cancer. Sixty-one single nucleotide polymorphisms (SNPs) from 40 genes were associated (P < 0.05) with risk of breast cancer in a log-additive model. In addition, 60 SNPs were associated (P < 0.05) with risk of high grade breast cancer. However, none of these associations were significant after Bonferroni correction for multiple testing. In gene-level analyses, CDC25C, SCC1/RAD21, TLK2, and SMC6L1 were associated (P < 0.05) with overall breast cancer risk, CDC6, CDC27, SUMO3, RASSF1, KIF2, and CDC14A were associated with high grade breast cancer risk, and EIF3S10 and CDC25A were associated with both. Further investigation in breast and other cancers are needed to understand the influence of inherited variation in mitotic genes on tumor grade and cancer risk.


Retrievable closed cell intracranial stent for foreign body and clot removal.
To assess the technical feasibility of using a retrievable, closed cell intracranial stent delivered through a microcatheter for safe removal of foreign bodies or clot. In vitro and in vivo testing were performed to demonstrate the feasibility of using retrievable intracranial stents for foreign body or clot removal. In vitro testing was performed in an anatomically correct silicone vascular replica by partially deploying the stent around a coil, then retracting the stent into the microcatheter to trap the coil. Withdrawal of the stent delivery system into the guide catheter resulted in coil removal. Subsequently, the technique was evaluated in a porcine model of intracranial aneurysms, wherein both fresh clot and herniated coils were extracted from the carotid arteries. In these experimental procedures, both herniated coils and fresh clot were safely and easily removed from the in vitro and in vivo models. No periprocedural adverse events were observed. These in vitro and in vivo studies suggest the potential use of retrievable stents for the removal of foreign bodies or clot from the intracranial circulation.


Sleep-related disorders in patients with type 1 diabetes mellitus: current insights.
Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results from destruction of beta cells in the pancreas. Several reviews have concluded that sleep contributes to poor glycemic control, diabetes management, and diabetes-related complications in individuals with T1DM and represents an untapped opportunity for intervention. However, at the current juncture, the American Diabetes Association's Standards of Medical Care are devoid of recommendations about how to address sleep in the management of T1DM. This article summarizes reviews of sleep in youth and adults with T1DM and empirical studies that have examined various sleep parameters ranging from sleep disturbances (general, perceived sleep quality, sleepiness, awakenings, and sleep efficiency), sleep duration, sleep consistency, sleep-disordered breathing (SDB), and sleep architecture. The data show that many individuals with T1DM sleep less than recommendations; individuals with the poorest sleep have difficulties with diabetes management; and sleep deficiency including SDB often corresponds to several disease morbidities (neuropathy, nephropathy, etc). Mixed findings exist regarding direct associations of various sleep parameters and glycemic control. SDB appears to be just as prevalent, if not more, than other conditions that have been recommended for universal screening in individuals with T1DM. The article concludes with recommendations for collaborative research efforts to further elucidate the role of sleep in diabetes-related outcomes; investigations to test behavioral strategies to increase sleep quantity and consistency; and considerations for clinical care to address sleep.


Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?
Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases.


Patient Reported Pain and Disability Following a Distal Radius Fracture: A Prospective Study.
Fractures of the distal radius are common. Few studies investigating the extended long term outcomes of participants following a distal radius fracture (especially beyond 2 years) and they have relied on subjective measures or single objective tests to measure participant's final outcome. The objective of this study was to describe the pain and disability in long-term follow-up of participants after a distal radius fracture. Participants who had previously participated in a prospective study, where baseline and standardized one-year follow-up were performed, were contacted to volunteer to participate in this follow-up (FU) study. Sixty-five participants (17 males, 48 females) with an average age of 57 (SD 13) years at the time of injury and 67 (SD 13 years) at follow-up were evaluated at an average of 11(SD 6) years (range 2-20 years). The majority of patients (85%) participants reported no change or had less pain and disability (PRWE) (<5 point difference) at their long-term follow-up compared to their one year PRWE scores. One year PRWE scores were found to be predictive (19.1%) of the variability in long term PRWE score (p=0.02). Age, gender, and mechanism of fall were not significant predictors of worsened outcome. The majority of people that are experiencing no or low patient reported pain and disability one year following a DRF can expect to retain their positive outcome 10-20 years later. This study did not identify how to predict worsened outcome.


Brain mechanisms supporting violated expectations of pain.
The subjective experience of pain is influenced by interactions between experiences, future predictions, and incoming afferent information. Expectations of high pain can exacerbate pain, whereas expectations of low pain during a consistently noxious stimulus can produce significant reductions in pain. However, the brain mechanisms associated with processing mismatches between expected and experienced pain are poorly understood, but are important for imparting salience to a sensory event to override erroneous top-down expectancy-mediated information. This investigation examined pain-related brain activation when expectations of pain were abruptly violated. After conditioning participants to cues predicting low or high pain, 10 incorrectly cued stimuli were administered across 56 stimulus trials to determine whether expectations would be less influential on pain when there is a high discordance between prestimulus cues and corresponding thermal stimulation. Incorrectly cued stimuli produced pain ratings and pain-related brain activation consistent with placebo analgesia, nocebo hyperalgesia, and violated expectations. Violated expectations of pain were associated with activation in distinct regions of the inferior parietal lobe, including the supramarginal and angular gyrus, and intraparietal sulcus, the superior parietal lobe, cerebellum, and occipital lobe. Thus, violated expectations of pain engage mechanisms supporting salience-driven sensory discrimination, working memory, and associative learning processes. By overriding the influence of expectations on pain, these brain mechanisms are likely engaged in clinical situations in which patients' unrealistic expectations of pain relief diminish the efficacy of pain treatments. Accordingly, these findings underscore the importance of maintaining realistic expectations to augment the effectiveness of pain management.


Comparative Genomics of X-linked Muscular Dystrophies: The Golden Retriever Model.
Duchenne muscular dystrophy (DMD) is a devastating disease that dramatically decreases the lifespan and abilities of affected young people. The primary molecular cause of the disease is the absence of functional dystrophin protein, which is critical to proper muscle function. Those with DMD vary in disease presentation and dystrophin mutation; the same causal mutation may be associated with drastically different levels of disease severity. Also contributing to this variation are the influences of additional modifying genes and/or changes in functional elements governing such modifiers. This genetic heterogeneity complicates the efficacy of treatment methods and to date medical interventions are limited to treating symptoms. Animal models of DMD have been instrumental in teasing out the intricacies of DMD disease and hold great promise for advancing knowledge of its variable presentation and treatment. This review addresses the utility of comparative genomics in elucidating the complex background behind phenotypic variation in a canine model of DMD, Golden Retriever muscular dystrophy (GRMD). This knowledge can be exploited in the development of improved, more personalized treatments for DMD patients, such as therapies that can be tailor-matched to the disease course and genomic background of individual patients.


Amygdala functional connectivity predicts pharmacotherapy outcome in pediatric bipolar disorder.
The aim of this study was to determine functional connectivity among patients with pediatric bipolar disorder (PBD) who are responders to pharmacotherapy and those who are nonresponders, and learn how they differ from healthy controls (HC) while performing a task that engages affective and cognitive neural systems. PBD participants (n = 34; 13.4 ± 2.3 years) were defined as responders if there was ≥ 50% improvement in Young Mania Rating Scale (YMRS) scores (n = 22) versus nonresponders with < 50% improvement (n = 12) with one of three mood stabilizing medications (divalproex, risperidone, or lamotrigine). HC (n = 14; 14.2 ± 3.1 years) participants also were scanned at baseline and follow-up. During functional magnetic resonance imaging, participants performed a color-matching task in which they had to match the color of positive, negative, or neutral words with colored dots. Independent component analysis was used to identify functionally connected networks across the whole brain, which were subsequently interrogated using region-of-interest analyses to test for group differences. A frontolimbic network was identified that showed impaired functional integration in PBD relative to HC when participants viewed negatively valenced words. PBD medication responders showed greater connectivity of the amygdala into the network before and after treatment compared with nonresponders, with responders showing a pattern more similar to HC than to nonresponders. Regardless of medication type, the degree of amygdala functional connectivity predicted medication response as well as the improvement in YMRS scores across responders and nonresponders. These findings suggest that increased functional integration of the amygdala within the frontolimbic network might be a biomarker of general mood stabilizer medication responsivity in bipolar disorder.


Gynecologic and reproductive outcomes in fibrous dysplasia/McCune-Albright syndrome.
Autonomous ovarian activation with recurrent estrogen-producing cysts is a hallmark feature of the rare bone and endocrine disorder fibrous dysplasia/McCune-Albright syndrome. Precocious puberty in girls with McCune-Albright syndrome has been well-described, however long-term effects on gynecologic and reproductive function are unknown. Concerningly, case reports have described poor skeletal outcomes associated with pregnancy in women with fibrous dysplasia. Thirty-nine women with fibrous dysplasia/McCune-Albright syndrome were evaluated as part of a natural history study. Clinical, radiographic, and biochemical data were reviewed. Women were contacted to obtain detailed menstrual and reproductive histories. Abnormal uterine bleeding affected 77% of women (30/39), and was associated with severe anemia requiring blood transfusion in 3 cases. Nine women underwent hysterectomy for management of bleeding, including 67% (6/9) at the unusually young age of less than age 35 years. Infertility affected 43% of women (9/21), including 2 women who developed primary ovarian insufficiency after undergoing surgical treatment of ovarian cysts. Of 25 spontaneous pregnancies in 14 women, 35% (8) were unplanned. Among the 14 pregnancies, pregnancy was associated with no change in bone pain in 7 subjects (53%), increased bone pain in 4 subjects (31%), and decreased bone pain in 2 subjects (15%). No additional skeletal complications were reported during pregnancies. Women with fibrous dysplasia/McCune-Albright syndrome report a high prevalence of gynecologic morbidity and reduced fertility. There is no clear association between pregnancy and poor skeletal outcomes in this population.


Arginine stimulates cdx2-transformed intestinal epithelial cell migration via a mechanism requiring both nitric oxide and phosphorylation of p70 S6 kinase.
In intestinal cells, arginine (Arg) is 1 of the 2 most potent amino acid activators of p70(s6k), a key regulator of 5'- terminal oligopyrimidine mRNA translation, a necessary condition for increased cell migration. To investigate the mechanism of response to Arg, we used the rat crypt cell line cdx2-transformed IEC-6 cells (cdx2-IEC) and measured cell migration, immunocytochemical analysis of p70(s6k) activation in response to Arg, and production of nitric oxide (NO). When treated with Arg, cdx2-IEC increased in phosphorylation on Thr-389 of p70(s6k) (pp70(s6k)) compared with control (P < 0.01). Phospho-Thr-421/Ser-424-p70(s6k) was located in the nucleus shortly after Arg treatment. Arg enhanced pp70(s6k), cell migration (55% wound coverage), and NO production. In comparison, the branched-chain amino acid leucine (Leu) activated pp70(s6k), was a weaker stimulator of migration (23% coverage), and did not increase NO. A total of 25 micromol/L DETA-NONOate (DETA/NO) did not significantly enhance phosphorylation of p70(s6k) but enhanced the rate of cell migration by approximately 25%. Wound coverage with Leu plus DETA/NO (25 micromol/L) was greater than coverage with DETA/NO alone (P < 0.01). These and our previous studies lead to a model in which Arg must stimulate both pp70(s6k) (in the nucleus) and NO release to enhance intestinal epithelial cell migration, which may be relevant to diseases that involve intestinal villous injury.


Cloninger's TCI associations with adaptive and maladaptive emotion regulation strategies.
Cognitive emotion regulation plays a crucial role in psychopathology, resilience and well-being by regulating response to stress situations. However, the relationship between personality and adaptive and maladaptive regulation has not been sufficiently examined. Adaptive and maladaptive cognitive emotion regulation strategies of 247 university students were measured using the Cognitive Emotion Regulation Questionnaire (CERQ) and their temperament and character characteristics were analyzed with the Temperament and Character Inventory-Revised Short (TCI-RS). Two-step hierarchical multiple regression analyses were used to analyze whether TCI-RS explains the use of adaptive and maladaptive cognitive emotion regulation strategies. The latent classes of cognitive emotion regulation strategies were extracted with Latent Class Analysis (LCA) and significant differences in the subscales of CERQ and TCI-RS were examined with Analysis of Covariance (ANCOVA) and Profile Analysis after controlling for sex and age. The two-step hierarchical multiple regression model using the seven TCI-RS subscales explained 32.30% of the adaptive and 41.70% of the maladaptive CERQ subscale scores when sex and age were introduced in the first step as covariates. As for temperament, Novelty Seeking (NS) and Persistence (PS) were pivotal for adaptive and Harm Avoidance (HA) and PS for maladaptive CERQ total scores. In addition, the character traits Self-Directedness (SD) and Cooperativeness (CO) were critical for high adaptive and low maladaptive CERQ scores. Four latent emotion regulation classes were confirmed through LCA, and distinct TCI-RS profiles were found. The temperament trait HA and character trait SD were significantly different among the four latent emotion regulation classes. This study demonstrated that SD and CO are related to cognitive emotion regulation strategies along with psychological health and well-being, and that PS exhibits dualistic effects when combined with NS or HA on response to stressful situations. The importance of developing mature character represented by higher SD and CO in regard to mental health and its clinical implementation was discussed.


Cranial neural crest cell migration in the Australian lungfish, Neoceratodus forsteri.
A crucial role for the cranial neural crest in head development has been established for both actinopterygian fishes and tetrapods. It has been claimed, however, that the neural crest is unimportant for head development in the Australian lungfish (Neoceratodus forsteri), a member of the group (Dipnoi) which is commonly considered to be the living sister group of the tetrapods. In the present study, we used scanning electron microscopy to study cranial neural crest development in the Australian lungfish. Our results, contrary to those of Kemp, show that cranial neural crest cells do emerge and migrate in the Australian lungfish in the same way as in other vertebrates, forming mandibular, hyoid, and branchial streams. The major difference is in the timing of the onset of cranial neural crest migration. It is delayed in the Australian lungfish in comparison with their living sister group the Lissamphibia. Furthermore, the delay in timing between the emergence of the hyoid and branchial crest streams is very long, indicating a steeper anterior-posterior gradient than in amphibians. We are now extending our work on lungfish head development to include experimental studies (ablation of selected streams of neural crest cells) and fate mapping (using fluoresent tracer dyes such as Dil) to document the normal fate as well as the role in head patterning of the cranial neural crest in the Australian lungfish.


Prevalence of genetic mutations that predispose to thrombophilia in a Greek Cypriot population.
Several hereditary disorders, particularly those affecting the physiological anticoagulation systems, have been well established as risk factors for venous thromboembolism. In the present study, we investigated the prevalence of the following thrombogenic mutations in a Greek-Cypriot population: the G1691 factor V Leiden mutation, the G20210A mutation in the prothrombin gene, and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR). All three variants have been documented to be significant risk factors for various cardiovascular conditions. Ninety unrelated subjects were screened. For the Leiden mutation, 11 subjects (12.2%) were heterozygous and one (1.1%) was homozygous. Seven subjects (7.8%) were heterozygous for the G20210A variant in prothrombin; no homozygotes were identified. The C677T mutation in MTHFR was found in 40 individuals in the heterozygous state (44.4%), and in 16 individuals in the homozygous state (17.8%). These data demonstrate that Greek-Cypriots have an increased frequency of thrombogenic mutations, and suggest that screening for these mutations should be seriously considered, especially when surgery or pregnancy is planned. This is the first study for the frequency of mutations in risk factors that predispose to thrombophilia on the island of Cyprus.


Long-term follow-up of aviators after functional endoscopic sinus surgery for sinus barotrauma.
Prior to endonasal endoscopic advances for the treatment of sinus disease, surgical results for aviators with recurrent sinus barotrauma (RSB) were inconsistent. Between 1988 and 1992, 54 aviators, who were permanently or temporarily grounded, underwent functional endoscopic sinus (FES) surgery in an attempt to return them to active flying status. Follow-up in the immediate postoperative period revealed that 98% of these aviators returned to active flight duty. A questionnaire was mailed to each of these aviators to compare their preoperative and long-term postoperative symptoms and determine their current flying status. Long-term follow-up time ranged from 20 to 72 mo with average of 48 mo. Of the aviators who responded to the survey, 92% have continued their flying duties and do not report difficulties with RSB. We conclude that FES surgery is effective in the short- and long-term management RSB in aviators.


Precision Measurement of the Beam-Normal Single-Spin Asymmetry in Forward-Angle Elastic Electron-Proton Scattering.
A beam-normal single-spin asymmetry generated in the scattering of transversely polarized electrons from unpolarized nucleons is an observable related to the imaginary part of the two-photon exchange process. We report a 2% precision measurement of the beam-normal single-spin asymmetry in elastic electron-proton scattering with a mean scattering angle of θ_{lab}=7.9° and a mean energy of 1.149 GeV. The asymmetry result is B_{n}=-5.194±0.067(stat)±0.082 (syst) ppm. This is the most precise measurement of this quantity available to date and therefore provides a stringent test of two-photon exchange models at far-forward scattering angles (θ_{lab}→0) where they should be most reliable.


Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression.
Neutrophils can generate extracellular net-like structures by releasing their DNA-histone complexes and antimicrobial peptides, which is called neutrophil extracellular traps (NETs). Various stimuli can induce NET formation. In particular, neutrophils and NET formation are abundant in tumor tissue. This study investigated how cancer cells induce NET formation and whether this NET formation promotes plasma thrombin generation and cancer progression. Induction of NET formation by a pancreatic cancer cell line (AsPC-1) was assessed by measuring the histone-DNA complex level. The endogenous thrombin potential (ETP) was measured by thrombin generation assay. In vitro migration, invasion, and tubule formation assays were performed. The circulating levels of NET markers and hypercoagulability markers were assessed in 62 patients with pancreatobiliary malignancy and 30 healthy controls. AsPC-1 significantly induced NET formation in a dose-dependent manner. Conditioned medium (CM) from AsPC-1 also induced NETs. Interestingly, NET-formation was abolished by heat-inactivated CM, but not by lipid-extracted CM, suggesting an important role of protein components. A reactive oxygen species inhibitor did not inhibit cancer cell-induced NET formation, but prostaglandin E1 (PGE1, cyclic adenosine monophosphate inducer) and antithrombin did. NETs significantly increased ETP of normal plasma. Of note, NETs promoted cancer cell migration and invasion as well as angiogenesis, which were inhibited by histone-binding agents (heparin, polysialic acid), a DNA-degrading enzyme, and Toll-like receptor neutralizing antibodies. In patients with pancreatobiliary malignancy, elevated NET markers correlated well with hypercoagulability makers. Our findings indicate that cancer cell-induced NET formation enhances both hypercoagulability and cancer progression and suggest that inhibitors of NET formation such as PGE1 and antithrombin can be potential therapeutics to reduce both hypercoagulability and cancer progression.


Lyme borreliosis in rhesus macaques: effects of corticosteroids on spirochetal load and isotype switching of anti-borrelia burgdorferi antibody.
Experimental Borrelia burgdorferi infection of rhesus monkeys is an excellent model of Lyme disease and closely parallels the infection in humans. Little is known about the interaction of host immunity with the spirochete in patients with chronic infection. We hypothesized that rapid development of anti-B. burgdorferi antibody in immunocompetent nonhuman primates (NHPs) is the major determinant of the reduction of the spirochetal load in Lyme borreliosis. This hypothesis was tested by measurement of the spirochetal load by PCR in association with characterization of the anti-B. burgdorferi humoral immune response in immunocompetent NHPs versus that in corticosteroid-treated NHPs. Although anti-B. burgdorferi immunoglobulin G (IgG) antibody was effectively inhibited in dexamethasone (Dex)-treated NHPs, anti-B. burgdorferi IgM antibody levels continued to rise after the first month and reached levels in excess of IgM levels in immunocompetent NHPs. This vigorous production of anti-B. burgdorferi IgM antibodies was also studied in vitro by measurement of antibody produced by B. burgdorferi-stimulated peripheral blood mononuclear cells. Despite these high IgM antispirochetal antibodies in Dex-treated NHPs, spirochetal loads were much higher in these animals. These data indicate that Dex treatment results in interference with isotype switching in this model and provide evidence that anti-B. burgdorferi IgG antibody is much more effective than IgM antibody in decreasing the spirochetal load in infected animals.


Dynamic Interplay of Metabolic and Transcriptional Responses in Shrimp during Early and Late Infection Stages of Enterocytozoon hepatopenaei (EHP).
Enterocytozoon hepatopenaei (EHP) is a microsporidian parasite that infects Litopenaeus vannamei, causing severe hepatopancreatic microsporidiosis (HPM) and resulting in significant economic losses. This study utilizes a combined analysis of transcriptomics and metabolomics to unveil the dynamic molecular interactions between EHP and its host, the Pacific white shrimp, during the early and late stages of infection. The results indicate distinct immunological, detoxification, and antioxidant responses in the early and late infection phases. During early EHP infection in shrimp, immune activation coincides with suppression of genes like Ftz-F1 and SEPs, potentially aiding parasitic evasion. In contrast, late infection shows a refined immune response with phagocytosis-enhancing down-regulation of Ftz-F1 and a resurgence in SEP expression. This phase is characterized by an up-regulated detoxification and antioxidant response, likely a defense against the accumulated effects of EHP, facilitating a stable host-pathogen relationship. In the later stages of infection, most immune responses return to baseline levels, while some immune genes remain active. The glutathione antioxidant system is suppressed early on but becomes activated in the later stages. This phenomenon could facilitate the early invasion of EHP while assisting the host in mitigating oxidative damage caused by late-stage infection. Notably, there are distinctive events in polyamine metabolism. Sustained up-regulation of spermidine synthase and concurrent reduction in spermine levels suggest a potential role of polyamines in EHP development. Throughout the infection process, significant differences in genes such as ATP synthase and hexokinase highlight the continuous influence on energy metabolism pathways. Additionally, growth-related pathways involving amino acids such as tryptophan, histidine, and taurine are disrupted early on, potentially contributing to the growth inhibition observed during the initial stages of infection. In summary, these findings elucidate the dynamic interplay between the host, Litopenaeus vannamei, and the parasite, EHP, during infection. Specific phase differences in immune responses, energy metabolism, and antioxidant processes underscore the intricate relationship between the host and the parasite. The disruption of polyamine metabolism offers a novel perspective in understanding the proliferation mechanisms of EHP. These discoveries significantly advance our comprehension of the pathogenic mechanisms of EHP and its interactions with the host.


Infection after shoulder surgery.
Infection after shoulder surgery is rare but potentially devastating. Normal skin flora, including Staphylococcus aureus, Staphylococcus epidermidis, and Propionibacterium acnes, are the most commonly isolated pathogens. Perioperative measures to prevent infection are of paramount importance, and clinical acumen is necessary for diagnosis. Superficial infections may be managed with local wound measures and antibiotics; deep infections require surgical débridement in combination with antibiotic treatment. Treating physicians must make difficult decisions regarding antibiotic duration and the elimination of the offending organisms by resection arthroplasty, direct implant exchange, or staged revision arthroplasty. Eradication of a deep infection is usually successful, but the course of treatment is often protracted, and tissue destruction and scar may adversely affect functional outcome.


[Severe maternal morbidity in an obstetric ICU in Recife, Northeast of Brasil].
To evaluate patients admitted with near miss maternal mortality criteria to an Obstetric ICU. This is a secondary analysis of a study conducted in an Obstetric ICU of IMIP (Recife, Pernambuco), from February 2003 to February 2007, from which 291 patients with near miss criteria or severe maternal morbidity were selected. Data concerning cause of admission, time of admission related to delivery, age, parity, education, prenatal care, associated clinical conditions, gestational age at admission and delivery, diagnosis, complications and procedures as well as length of ICU stay were collected. The most common reasons of admission were hypertensive disorders (78.4%), haemorrhage (25.4%) and infection (16.5%). The great majority of patients was admitted after delivery (80.4%) and transferred from other units. Patient age ranged from 12 to 44 years, median of parity was 1 and prenatal care was absent in 9.9% of cases. Cesarean section was the mode of delivery in 68.4%. Medical conditions were present in 18.7% of the patients, 37% required blood product transfusions, 10.8% vasoactive infusions, 9.1% mechanical ventilation and 13.4% a central line. Eclampsia was present in 38.8 % of the patients, hemorrhagic shock in 27.1%, renal failure in 11.7%, and pulmonary edema in 9.1% and respiratory failure in 6.5%. Patients classified as near miss maternal mortality constitute an important group admitted to an Obstetric ICU. Better information about these patients is fundamental to improve care and prevent maternal mortality.


Hormonal regulation of Drosophila microRNA let-7 and miR-125 that target innate immunity.
The steroid 20-hydroxy-ecdysone (20-HE) and the sesquiterpenoid Juvenile Hormone (JH) coordinate insect life stage transitions. 20-HE exerts these effects by the sequential induction of response genes. In the nematode Caenorhabditis elegans hormones also play a role in such transitions, but notably, microRNA such as let-7 and lin-4 have likewise been found to help order developmental steps. Little is known about the corresponding function of homologous microRNA in Drosophila melanogaster, and the way microRNA might be regulated by 20-HE in the fly is ambiguous. Here we used Drosophila S2 cells to analyze the effects of 20-HE on D. melanogaster microRNA let-7 and miR-125, the homolog of lin-4. The induction by 20-HE of let-7 and miR-125 in S2 cells is inhibited by RNAi knockdown of the ecdysone receptor and, as previously shown, by knockdown of its cofactor broad-complex C. To help resolve the currently ambiguous role of 20-HE in the control of microRNA, we show that nanomolar concentrations of 20-HE primes cells to subsequently express microRNA when exposed to micromolar levels of 20-HE. We then explore the role microRNA plays in the established relationship between 20-HE and the induction of innate immunity. We show that the 3'UTR of the antimicrobial peptide diptericin has a let-7 binding site and that let-7 represses translation from this site. We conclude that 20-HE facilitates the initial expression of innate immunity while it simultaneously induces negative regulation via microRNA control of antimicrobial peptide translation.


The C Terminus of the RNA Polymerase II Transcription Factor IID (TFIID) Subunit Taf2 Mediates Stable Association of Subunit Taf14 into the Yeast TFIID Complex.
The evolutionarily conserved RNA polymerase II transcription factor D (TFIID) complex is composed of TATA box-binding protein (TBP) and 13 TBP-associated factors (Tafs). The mechanisms by which many Taf subunits contribute to the essential function of TFIID are only poorly understood. To address this gap in knowledge, we present the results of a molecular genetic dissection of the TFIID subunit Taf2. Through systematic site-directed mutagenesis, we have discovered 12 taf2 temperature-sensitive (ts) alleles. Two of these alleles display growth defects that can be strongly suppressed by overexpression of the yeast-specific TFIID subunit TAF14 but not by overexpression of any other TFIID subunit. In Saccharomyces cerevisiae, Taf14 is also a constituent of six other transcription-related complexes, making interpretation of its role in each of these complexes difficult. Although Taf14 is not conserved as a TFIID subunit in metazoans, it is conserved through its chromatin-binding YEATS domain. Based on the Taf2-Taf14 genetic interaction, we demonstrate that Taf2 and Taf14 directly interact and mapped the Taf2-Taf14 interaction domains. We used this information to identify a Taf2 separation-of-function variant (Taf2-ΔC). Although Taf2-ΔC no longer interacts with Taf14 in vivo or in vitro, it stably incorporates into the TFIID complex. In addition, purified Taf2-ΔC mutant TFIID is devoid of Taf14, making this variant a powerful reagent for determining the role of Taf14 in TFIID function. Furthermore, we characterized the mechanism through which Taf14 suppresses taf2ts alleles, shedding light on how Taf2-Taf14 interaction contributes to TFIID complex organization and identifying a potential role for Taf14 in mediating TFIID-chromatin interactions.


Speech-language therapy for adolescents with written-language difficulties: the South African context.
To investigate whether privately practising speech-language therapists in South Africa are fulfilling their role of identification, assessment and intervention for adolescents with written-language and reading difficulties. Further needs concerning training with regard to this population group were also determined. A survey study was conducted, using a self-administered questionnaire. Twenty-two currently practising speech-language therapists who are registered members of the South African Speech-Language-Hearing Association (SASLHA) participated in the study. The respondents indicated that they are aware of their role regarding adolescents with written-language difficulties. However, they feel that South-African speech-language therapists are not fulfilling this role. Existing assessment tools and interventions for written-language difficulties are described as inadequate, and culturally and age inappropriate. Yet, the majority of the respondents feel that they are adequately equipped to work with adolescents with written-language difficulties, based on their own experience, self-study and secondary training. The respondents feel that training regarding effective collaboration with teachers is necessary to establish specific roles, and to promote speech-language therapy for adolescents among teachers. Further research is needed in developing appropriate assessment and intervention tools as well as improvement of training at an undergraduate level.


[Electroreceptor characteristics of elasmobranchs with pint sources of the electric field].
Using mathematical modelling methods and experimental data possible space mechanisms of information conversion processes with Lorenzinian ampullary apparatus during detection of the dipole electric field were studied. The space selectivity of the ampullary groups was shown and its biological significance is discussed.


[Resistance of liposomes with different physico-chemical characteristics to the effect of plasma].
The chemical composition, liquid content sign and value of charge as well as structure and size of lipid vesicles are studied for the effect they exert on the liposome permeability for 22Na+ in the presence of human blood plasma. The rate of the isotope outlet from the electroneutral lecithin liposomes is determined by the size of vesicles and the quantity of phospholipid bilayers in their membrane. The presence either of a negative or a positive charge on the surface of the liposome membrane has no essential effect on the outlet rate of the radioactive marker. Introduction of different amounts of cholesterol or sphingomyelin into the liposome composition decreases considerably the lipid vesicle permeability and an increase in the liquid content of their membranes due to the temperature elevation is accompanied by a sharp rise in the isotope outlet rate. A conclusion is drawn on the possibility to control the outlet rate of the liposome content in the presence of blood plasma.


Investigation of an Elevational Gradient Reveals Strong Differences Between Bacterial and Eukaryotic Communities Coinhabiting Nepenthes Phytotelmata.
Elevation is an important determinant of ecological community composition. It integrates several abiotic features and leads to strong, repeatable patterns of community structure, including changes in the abundance and richness of numerous taxa. However, the influence of elevational gradients on microbes is understudied relative to plants and animals. To compare the influence of elevation on multiple taxa simultaneously, we sampled phytotelm communities within a tropical pitcher plant (Nepenthes mindanaoensis) along a gradient from 400 to 1200 m a.s.l. We use a combination of metabarcoding and physical counts to assess diversity and richness of bacteria, micro-eukaryotes, and arthropods, and compare the effect of elevation on community structure to that of regulation by a number of plant factors. Patterns of community structure differed between bacteria and eukaryotes, despite their living together in the same aquatic microhabitats. Elevation influences community composition of eukaryotes to a significantly greater degree than it does bacteria. When examining pitcher characteristics, pitcher dimorphism has an effect on eukaryotes but not bacteria, while variation in pH levels strongly influences both taxa. Consistent with previous ecological studies, arthropod abundance in phytotelmata decreases with elevation, but some patterns of abundance differ between living inquilines and prey.


Setting priorities for teaching and learning: an innovative needs assessment for a new family medicine program in Lao PDR.
Lao People's Democratic Republic (Lao PDR) is a small, tropical, landlocked country in southeast Asia. It is one of the least developed countries in the region, and its socioeconomic indicators are among the lowest 25% in the world. The World Health Organization has long called for increased equity in primary health care access around the world. To meet this need in Lao PDR, the Family Medicine Specialist Program was developed, a Lao-generated postgraduate training program designed to produce community-oriented primary care practitioners to serve the rural, remote areas of Lao PDR, where 80% of the population lives. An innovative method of needs assessment was required to determine the health care priorities to be met by this new program. Through the use of a modified Delphi technique, local key leaders in medical education, clinical specialists, and teachers were consulted to develop prioritized objectives for the hospital-based curriculum of the program. By setting priorities for teaching and learning in the unique and needy circumstances of Lao PDR, a novel approach to curriculum planning in a low-income country was explored and ultimately formed the foundation of the new curriculum. This process served to direct the allocation of scarce resources during implementation of this groundbreaking program. More importantly, this model of needs assessment could potentially be used to customize medical curricula in other low-income countries facing challenges similar to those in Lao PDR.


Reactive oxygen species and redox compartmentalization.
Reactive oxygen species (ROS) formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatio-temporal manner. This makes ROS signaling similar to that of Ca(2+) or other second messengers. Some subcellular compartments are more oxidizing (such as lysosomes or peroxisomes) whereas others are more reducing (mitochondria, nuclei). Moreover, although more reducing, mitochondria are especially susceptible to oxidation, most likely due to the high number of exposed thiols present in that compartment. Recent advances in the development of redox probes allow specific measurement of defined ROS in different cellular compartments in intact living cells or organisms. The availability of these tools now allows simultaneous spatio-temporal measurements and correlation between ROS generation and organelle and/or cellular function. The study of ROS compartmentalization and microdomains will help elucidate their role in physiology and disease. Here we will examine redox probes currently available and how ROS generation may vary between subcellular compartments. Furthermore, we will discuss ROS compartmentalization in physiological and pathological conditions focusing our attention on mitochondria, since their vulnerability to oxidative stress is likely at the basis of several diseases.


A Method for Producing Highly Pure Magnetosomes in Large Quantity for Medical Applications Using Magnetospirillum gryphiswaldense MSR-1 Magnetotactic Bacteria Amplified in Minimal Growth Media.
We report the synthesis in large quantity of highly pure magnetosomes for medical applications. For that, magnetosomes are produced by MSR-1 Magnetospirillum gryphiswaldense magnetotactic bacteria using minimal growth media devoid of uncharacterized and toxic products prohibited by pharmaceutical regulation, i.e., yeast extract, heavy metals different from iron, and carcinogenic, mutagenic and reprotoxic agents. This method follows two steps, during which bacteria are first pre-amplified without producing magnetosomes and are then fed with an iron source to synthesize magnetosomes, yielding, after 50 h of growth, an equivalent OD565 of ~8 and 10 mg of magnetosomes in iron per liter of growth media. Compared with magnetosomes produced in non-minimal growth media, those particles have lower concentrations in metals other than iron. Very significant reduction or disappearance in magnetosome composition of zinc, manganese, barium, and aluminum are observed. This new synthesis method paves the way towards the production of magnetosomes for medical applications.


Drug use and sexual arrangements among gay couples: frequency, interdependence, and associations with sexual risk.
Rates of drug use among gay men are higher than their heterosexual counterparts and drug use is a prominent risk factor for HIV transmission. Studies using heterosexual samples have found that being partnered reduces the risk of drug use and individuals in a relationship tend to have similar use patterns. Studies among gay men suggest that sexual agreements may be an important predictor of drug use. Data from 322 partnered gay men were collected and the 161 matched couples were categorized as monogamous (52.8 %), monogamish (14.9 %), open (13.0 %), and discrepant (19.3 %). Patterns of significance and significant trends suggested that monogamous men reported lower rates of marijuana and other drug use compared to open and monogamish men. Men in discrepant relationships did not differ from any other group. Partners' marijuana and other drug use was significantly interdependent in the overall sample; however, substantial variation in the magnitude and significance of interdependence was observed across sexual arrangement categories. Sexual arrangement and the use of drugs during sex both contributed to the prediction of UAI with casual partners among non-monogamous men. Implications for substance use treatment and HIV prevention are discussed.