Bacterial microbiota assemblage in Aedes albopictus mosquitoes and its impacts on larval development.
Interactions between bacterial microbiota and mosquitoes play an important role in mosquitoes' capacity to transmit pathogens. However, microbiota assemblages within mosquitoes and the impact of microbiota in environments on mosquito development and survival remain unclear. This study examined microbiota assemblages and the effects of aquatic environment microbiota on the larval development of the Aedes albopictus mosquito, an important dengue virus vector. Life table studies have found that reducing bacterial load in natural aquatic habitats through water filtering and treatment with antibiotics significantly reduced the larva-to-adult emergence rate. This finding was consistent in two types of larval habitats examined-discarded tires and flowerpots, suggesting that bacteria play a crucial role in larval development. Pyrosequencing of the bacterial 16S rRNA gene was used to determine the diversity of bacterial communities in larval habitats and the resulting numbers of mosquitoes under both laboratory and field conditions. The microbiota profiling identified common shared bacteria among samples from different years; further studies are needed to determine whether these bacteria represent a core microbiota. The highest microbiota diversity was found in aquatic habitats, followed by mosquito larvae, and the lowest in adult mosquitoes. Mosquito larvae ingested their bacterial microbiota and nutrients from aquatic habitats of high microbiota diversity. Taken together, the results support the observation that Ae. albopictus larvae are able to utilize diverse bacteria from aquatic habitats and that live bacteria from aquatic habitats play an important role in larval mosquito development and survival. These findings provide new insights into bacteria's role in mosquito larval ecology.


Timeline of blood pressure changes after intra-arterial therapy for acute ischemic stroke based on recanalization status.
There is sparse literature on the natural history of blood pressure (BP) after intra-arterial therapy (IAT) for acute ischemic stroke (AIS). A retrospective analysis was performed of patients with AIS who underwent IAT without endotracheal intubation for internal carotid artery terminus (ICA-T) or M1 middle cerebral artery occlusion from January 2008 to February 2012. Systolic BP (SBP) values at the beginning (First) and end (End) of IAT and for 36 h after the procedure were collected. Successful recanalization was defined as Thrombolysis In Cerebral Infarction (TICI) 2b-3. Sixty-two patients (14 (22.5%) ICA-T, 46 (74.2%) M1, 2 (3.2%) ICA-T+M1) met the study criteria and 37 (59.7%) achieved successful recanalization. The First and End SBP values were similar in the successful (Group R) and unsuccessful (Group NR) recanalization groups. Taking the whole cohort, End SBP was significantly lower than First SBP, but this decline was significant only in Group R. Subsequently, absolute SBP values in Group R were not significantly different from Group NR. However, when comparing the hourly decline of SBP with First SBP, Group R demonstrated a greater fall than Group NR and the decline was significantly different from hours 8 to 12 post-procedure. The SBP in Group NR then decreased further, and its difference from baseline was similar to Group R from hour 14 onwards. Mean SBP and SBP variability over 36 h were similar between the two groups. SBP falls significantly in patients with AIS with large vessel occlusion who recanalize with IAT. While SBP in non-recanalized patients also drops from baseline, it occurs to a lesser degree and stays higher only for a short period of time before falling to similar levels as in recanalized patients.


[Will health promotion remain a utopia in a fragmented political system? The case of the Wallonia-Brussels Federation].
In the French Community of Belgium (the Wallonia-Brussels Federation), the changing political landscape and the various laws relating to the roles of the federal state, communities and regions introduced since 1980 have had a significant impact on health policy. Since then, there have been significant developments in health education services and activities. In 1997, a government decree was issued to promote the concept of health promotion, to reform the existing system and to define policy priorities as part of a new five-year plan (1998-2003). Significant progress was made during this period as a result of the development of a global approach extending beyond the mere analysis of risk factors. The second five-year plan (2004-2008), aimed at combining preventive medicine and health promotion, resulted in the involvement of a wider range of actors and greater cross-sector collaboration. However, the sheer number of decision-making levels has been a major obstacle to popular participation and consultation. If the question of social and cultural accessibility is not seriously addressed, the focus on preventive medicine programs may prove to be detrimental to the development of an effective health promotion framework. The disconnect between the political vision and the reality of practice has had an adverse impact on health promotion. Health promotion professionals have repeatedly called for a third five-year plan involving all ministers and aimed at developing a cross-sector approach, at addressing the determinants of health, at promoting the active participation of local communities and at reducing social health inequalities. The concerns of health promotion practitioners were further exacerbated by the introduction of an external assessment process initiated by the Ministry of Health in 2010. The current concerns over the future of the Belgian state, the economic crisis and the impact of spending cuts have increased the sense of uncertainty. The upcoming elections provide further incentive for health promotion professionals to continue in their efforts to promote effective policy responses based on the skills and experience of associations and on practice quality.


Expression and role of adrenomedullin and its receptor in patients with chronic obstructive pulmonary disease.
To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD). Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n = 12) and those with PH were placed in Group B (n = 10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted. The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD (P < 0.01). In situ hybridization showed that ADM mRNA and ADMR mRNA were expressed in the pulmonary artery walls of control subjects. The expression levels were significantly higher in those of COPD sufferers (P < 0.01). Statistically positive relationships were visible between ADM and ADMR, and the plasma ADM level of Group B was significantly higher than that of Group A (P < 0.05). The plasma ADM level had a significantly positive correlation to mPAP and pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO(2). ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.


Incidence of perioperative stroke after neck dissection for head and neck cancer: a regional outcome analysis.
To determine the incidence of perioperative stroke in patients undergoing a neck dissection. The incidence of perioperative stroke in non-head and neck surgery is between 0.08 and 0.2%. In contrast, a critical review of the literature identified 2 studies stating the incidence of perioperative stroke in head and neck surgery to be 3.2% and 4.8%. The implications of these results are significant because they suggest a potential need for preoperative screening and/or intervention for carotid artery pathology. This historical cohort study was conducted using discharge data for all neck dissections performed in a geographically-defined health region in Alberta, Canada, from 1994 to 2002. Subjects were selected for study if they had an assigned ICD-9CM procedure code for a neck dissection at one of the region's 3 adult-care hospitals. Our main outcome measure was perioperative stroke. Patients (n = 499) were identified as having had a neck dissection (mean age 56.5 +/- 15.3 SD, 65.3% male). Seven patients had ICD-9CM codes for postoperative central nervous system complications (incidence of 1.4%). However, on chart review, only one had had a true perioperative stroke corresponding to an incidence of 0.2% (95% confidence interval 0.01, 1.12). No missed strokes were found in a confirmatory random review of 10% of charts. The incidence of perioperative stroke in this study is significantly lower than that previously stated in the literature. This suggests that preoperative screening and/or intervention for carotid artery disease may not be necessary in this patient population.


Diabetic nephropathy and end-stage renal disease in Mexican Americans.
Hispanics are the second largest minority group in the United States. Mexican Americans (MAs) are the largest subgroup at 14 million in 1990. MAs have a two- to threefold increased prevalence of non-insulin-dependent diabetes mellitus. Population-based studies of MAs with non-insulin-dependent diabetes have shown that these patients may be more likely than non-Hispanic whites to develop proteinuria and are more likely to develop end-stage renal disease. The reasons for this excess risk are yet to be completely elucidated, but may be due to worse glycemic control, worse blood pressure control when hypertension does occur, worse access to medical care, and/or genetics. When MAs are treated for diabetic end-stage renal disease, they have better survival. Much less data are available for other Hispanic subgroups. From a public health perspective, higher incidence and longer survival as well as relatively young and rapidly growing population predict an increasing burden for MAs if prevention measures are not instituted soon.


Male Body Image Portrayals on Instagram.
Men are faced with trends that give rise to the desire for a muscular and lean body; this may result in body dissatisfaction. Body dissatisfaction is associated with a plethora of health consequences. Social media has been named as one contributing factor for male body dissatisfaction. Up till now, women have been the focus of body image-related social media studies. Therefore, we conducted a quantitative content analysis of 1,000 relevant Instagram posts that were posted by men (and/or depicted men) to understand how the male body is depicted on Instagram and how user respond to those images. The majority of sampled posts showed high levels of muscularity and leanness. In addition, posts depicting men adhering to this specific body type received significantly more responses (likes and comments). Norms and outcomes related to health (i.e., training to be healthy) were more commonly shown than appearance-related constructs (i.e., training to become attractive), and promotion of physical activity was more common than dietary behavior. However, findings are potential harmful to men's body image, even if one considers that health-related messaging and physical active promotion was prominent. It remains debatable if men need to view very lean and very muscular men to encourage health-related behaviors.


Input-Output Characteristics of Late Corticospinal Silent Period Induced by Transcranial Magnetic Stimulation.
Corticospinal silent period (SP) may be interrupted by a burst of muscle activity followed by a second (late) SP, generally assumed to be a continuation from the primary SP. Our objective was to characterize the input-output behavior of the late SP. Transcranial magnetic stimulation was applied on the cortical representation area of the right-hand muscles of 12 healthy subjects. Single-pulse transcranial magnetic stimulation was given with varying stimulation intensities normalized to the individual resting motor threshold (60% to 130% of the resting motor threshold) during voluntary muscle contraction. Electromyogram was recorded from first dorsal interosseous and abductor pollicis brevis muscles. Primary and late SPs were analyzed as absolute SPs, and input-output characteristics were assessed. The late SP exhibited fundamentally different input-output characteristics from that of the primary SP. The late SP most likely presented itself at stimulation intensities of 90% to 100% of the resting motor threshold. Different input-output characteristics of the late SP compared with the primary SP indicate that the late SP possess mechanisms different from the primary SP. The exact origin of the late SP remains unclear. Understanding the origins of the late SP could provide valuable insight on corticospinal inhibitory processes.


Saccadic suppression precedes visual motion analysis.
There is now good evidence that perception of motion is strongly suppressed during saccades (rapid shifts of gaze), presumably to blunt the disturbing sense of motion that saccades would otherwise elicit. Other aspects of vision, such as contrast detection of high-frequency or equiluminant gratings, are virtually unaffected by saccades [1] [2] [3] [4] [5]. This has led to the suggestion that saccades may suppress selectively the magnocellular pathway (which is strongly implicated in motion perception), leaving the parvocellular pathway unaffected [5] [6]. Here, we investigate the neural level at which perception of motion is suppressed. We used a simple technique in which an impression of motion is generated from only two frames, allowing precise control over the stimulus [7] [8]. One frame has a certain fixed contrast, whereas the contrast of the other (the test frame) is varied to determine the threshold for motion discrimination (that is, the lowest test-frame contrast level at which the direction of motion can be correctly guessed). Contrast thresholds of the test depended strongly and non-monotonically on the contrast of the fixed-contrast frame, with a minimum at medium contrast. To study the effect of saccadic suppression, we triggered the two-frame sequence by a voluntary saccade. Thresholds during saccades increased in a way that suggested that saccadic suppression precedes motion analysis: when the test frame was first in the motion sequence there was a general depression of sensitivity, whereas when it was second, the contrast response curve was shifted to a higher contrast range, sometimes even resulting in higher sensitivity than without a saccade. The dependence on presentation order suggests that saccadic suppression occurs at an early stage of visual processing, on the single frames themselves rather than on the combined motion signal. As motion detection itself is thought to occur at an early stage, saccadic suppression must take place at a very early phenomenon.


Changing trends in mastitis.
The global dairy industry, the predominant pathogens causing mastitis, our understanding of mastitis pathogens and the host response to intramammary infection are changing rapidly. This paper aims to discuss changes in each of these aspects. Globalisation, energy demands, human population growth and climate change all affect the dairy industry. In many western countries, control programs for contagious mastitis have been in place for decades, resulting in a decrease in occurrence of Streptococcus agalactiae and Staphylococcus aureus mastitis and an increase in the relative impact of Streptococcus uberis and Escherichia coli mastitis. In some countries, Klebsiella spp. or Streptococcus dysgalactiae are appearing as important causes of mastitis. Differences between countries in legislation, veterinary and laboratory services and farmers' management practices affect the distribution and impact of mastitis pathogens. For pathogens that have traditionally been categorised as contagious, strain adaptation to human and bovine hosts has been recognised. For pathogens that are often categorised as environmental, strains causing transient and chronic infections are distinguished. The genetic basis underlying host adaptation and mechanisms of infection is being unravelled. Genomic information on pathogens and their hosts and improved knowledge of the host's innate and acquired immune responses to intramammary infections provide opportunities to expand our understanding of bovine mastitis. These developments will undoubtedly contribute to novel approaches to mastitis diagnostics and control.


Amino acid networks in a (β/α)₈ barrel enzyme change during catalytic turnover.
Proteins can be viewed as small-world networks of amino acid residues connected through noncovalent interactions. Nuclear magnetic resonance chemical shift covariance analyses were used to identify long-range amino acid networks in the α subunit of tryptophan synthase both for the resting state (in the absence of substrate and product) and for the working state (during catalytic turnover). The amino acid networks observed stretch from the surface of the protein into the active site and are different between the resting and working states. Modification of surface residues on the network alters the structural dynamics of active-site residues over 25 Å away and leads to changes in catalytic rates. These findings demonstrate that amino acid networks, similar to those studied here, are likely important for coordinating structural changes necessary for enzyme function and regulation.


Multiorgan microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases.
Metabolic and inflammatory disorders such as autoimmune and neurodegenerative diseases are increasing at alarming rates. Many of these are not tissue-specific occurrences but complex, systemic pathologies of unknown origin for which no cure exists. Such complexity obscures causal relationships among factors regulating disease progression. Emerging technologies mimicking human physiology, such as microphysiological systems (MPSs), offer new possibilities to provide clarity in systemic metabolic and inflammatory diseases. Controlled interaction of multiple MPSs and the scalability of biological complexity in MPSs, supported by continuous multiomic monitoring, might hold the key to identifying novel relationships between interorgan crosstalk, metabolism, and immunity. In this perspective, I aim to discuss the current state of modeling multiorgan physiology and evaluate current opportunities and challenges.


Three-Dimensional Printed Models to Accelerate Resident Surgical Learning Curve for Standard Endoscopic Sinus Surgery Techniques.
Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees. Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog scale before and after tasks. Two- tailed paired T-tests were used to analyze the data. Results: All residents rated their post-intervention "overall sinus surgery skills" higher than pre-intervention. They rated simulations to provide more significant utility as an adjunct to surgical education after the intervention. All but one participant reported improved spatial awareness working with the endoscopes and surgical instruments. There was subjectively improved proficiency in using 0-degree and angled endoscopes as well as cutting, grasping, and curved instruments after the intervention. The simulations led to subjective improvements in spatial awareness, bimanual dexterity, and increased confidence in selecting correct surgical instruments. Conclusion: Our set of novel 3D printed models to improve sinus surgery skillset was well accepted by the resident cohort. The 3D models can serve as an adjunct tool to traditional residency education.


Genetic population structure of the blister beetle, Gnathium minimum: core and peripheral populations.
Populations on the periphery of a species' range tend to contain lower genetic variation and increased genetic differentiation compared to populations at the core of a species range, although some exceptions to this generalization occur. The blister beetle Gnathium minimum (Say) exhibits a wide-ranging distribution in the western United States but has peripheral or disjunct populations in Mexico, Florida, and Wisconsin. We used amplified fragment length polymorphism (AFLP) to compare the genetic variation and magnitude of genetic differentiation of the Wisconsin peripheral population to western core populations (Colorado, Kansas, New Mexico, and Texas). The proportion of polymorphic loci was 53.6 and 54.3, and expected heterozygosity 0.1864 and 0.1933 for the Kansas/Colorado (n = 87) and New Mexico/Texas (n = 35) regions, respectively. Specimens from Wisconsin (n = 121) had a lower proportion of polymorphic loci (38.4) and expected heterozygosity (0.1475). Genetic cluster estimation with GENELAND and F ST values showed greater genetic differentiation among the sampling locations within Wisconsin compared to core regions. Significant isolation-by-distance (IBD) was also observed in Wisconsin but not within the core regions. Lower genetic variation and increased isolation may reduce the Wisconsin population's ability to respond to change, thereby increasing their susceptibility to extinction.


Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum.
The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.


Racial and ethnic disparities in the primary care experiences of children: a review of the literature.
Substantial racial and ethnic disparities persist in children's health and use of health services in the United States. Although equitable access to primary care services is widely promoted as one of the most feasible remedies to reduce health disparities, there has only recently been an effort to assess its quality, particularly for children. Racial and socioeconomic differences in access to care have been previously well documented, but recent research has begun to elucidate differences in more qualitative experiences in the receipt of primary care. This article presents a synthesis and critique of the existing research according to the core attributes of primary care: first-contact care, longitudinality, comprehensiveness, and coordination. Finally, the article proposes an agenda for further research into the pathways by which racial and ethnic disparities in primary care exist.


Ontogenic changes rather than difference in temperature cause understory trees to leaf out earlier.
In a temperate climate, understory trees leaf out earlier than canopy trees, but the cause of this discrepancy remains unclear. This study aims to investigate whether this discrepancy results from ontogenic changes or from microclimatic differences. Seedlings of five deciduous tree species were grown in spring 2012 in the understory and at canopy height using a 45-m-high construction crane built into a mature mixed forest in the foothills of the Swiss Jura Mountains. The leaf development of these seedlings, as well as conspecific adults, was compared, taking into account the corresponding microclimate. The date of leaf unfolding occurred 10-40 d earlier in seedlings grown at canopy level than in conspecific adults. Seedlings grown in the understory flushed c. 6 d later than those grown at canopy height, which can be attributed to the warmer temperatures recorded at canopy height (c. 1°C warmer). This study demonstrates that later leaf emergence of canopy trees compared with understory trees results from ontogenic changes and not from the vertical thermal profile that exists within forests. This study warns against the assumption that phenological data obtained in warming and photoperiod experiments on juvenile trees can be used for the prediction of forest response to climate warming.


Characterization of the dynamic events of GPCRs by automated computational simulations.
The recent advances in membrane protein crystallography have provided extremely valuable structural information of the superfamily of GPCRs (G-protein-coupled receptors). This has been particularly true for a few receptors whose structure was solved several times under different biochemical conditions. It follows that the mechanisms of receptor conformational equilibrium and related dynamic events can be explored by computational simulations. In the present article, we summarize our recent understanding of several dynamic features of GPCRs, accomplished through the use of MD (molecular dynamics) simulations. Our pipeline for the MD simulations of GPCRs, implemented in the web service http://gpcr.usc.es, is updated in the present paper and illustrated by recent applications. Special emphasis is put on the A2A adenosine receptor, one of the selected cases where crystal structures in several conformations and conditions exist, and on the dimerization process of the CXCR4 (CXC chemokine receptor 4).


Total scalp reconstruction with bilateral anterolateral thigh flaps.
Large scalp defects can require complicated options for reconstruction, often only achieved with free flaps. In some cases, even a single free flap may not suffice. We review the literature for options in the coverage of all reported large scalp defects, and report a unique case in which total scalp reconstruction was required. In this case, two anterolateral thigh (ALT) flaps were used to resurface a large scalp and defect, covering a total of 743 cm(2). The defect occurred after resection and radiotherapy for desmoplastic melanoma, with several failed skin grafts and local flaps and osteoradionecrosis involving both inner and outer tables of the skull. The reconstruction was achieved as a single-stage reconstruction and involved wide resection of cranium and overlying soft-tissues and reconstruction with calcium phosphate bone graft substitute, titanium mesh, and two large ALT flaps. The reconstruction was successfully achieved, with minor postoperative complications including tip necrosis of one of the flaps and wound breakdown at one of the donor sites. This is the first reported case of two large ALT flaps for scalp resurfacing and may be the largest reported scalp defect to be completely resurfaced by free flaps. The use of bilateral ALT flaps can be a viable option for the reconstruction of large and/or complicated scalp defects.


Complications During Maxillary Sinus Augmentation Associated with Interfering Septa: A New Classification of Septa.
A new classification of maxillary sinus interfering septa based on its orientation is presented along with its relationship to the prevalence and severity of sinus membrane perforations. Additionally, the impact of membrane perforation on post-operative complications and marginal bone loss during the first year of loading is evaluated. Retrospective chart review of 79 consecutive sinus lift procedures with lateral window technique and 107 implants. Preoperative Cone Beam Computed Tomography (CBCT) images were evaluated for the incidence and the direction of maxillary septa. Chart notes were examined for the incidence of membrane perforation and postoperative complications. Measurements of mesial and distal marginal bone levels and average bone resorption adjacent to each implant were calculated in intraoral radiographs taken at implant placement and during follow up appointments. Interfering septa were identified in 48.1 percent of sinuses. 71.1 percent of them had the septum oriented in a buccal-lingual direction (Class I). The overall incidence of membrane perforation was 22.8 percent, and the presence of an interfering septum on CBCT scan was found to be significantly associated with the occurrence of a sinus membrane perforation (P<0.001). The mean implant marginal bone loss for sinuses, which did not experience a membrane perforation, was 0.6±0.8mm, compared with 0.9 ± 0.9 mm for the sinuses that did experience a perforation (P = 0.325). Septa should be identified, classified and managed with a meticulous attention to technical details. A classification based on the septal orientation is proposed since the orientation of the septa can complicate the surgical procedure and requires modification of the surgical technique.


Cholecystostomy hazard in acute cholangitis.
Four patients with acute cholangitis were seen, all of whom died following cholecystostomy or cholecystoduodenostomy. The diagnosis of cholangitis is frequently missed in elderly patients with jaundice and sepsis. Cholecystostomy, in the face of cholangitis without documentation of patency of the cystic duct, is uniformly fatal. Diagnosis of cholangitis should be confirmed and immediately followed by adequate common duct drainage. Finally, immediate reoperation, rather than antibiotic manipulation, is advised to establish common duct drainage in those patients who do not respond to cholecystostomy within 24 hours.


Occurrence of shigellosis in pediatric diarrheal patients in Chattogram, Bangladesh: A molecular based approach.
Shigellaa Gram-negative, non-motile bacillus, is the primary causative agent of the infectious disease shigellosis, which kills 1.1 million people worldwideevery year. The children under the age of five are primarily the victims of this disease. This study has been conducted to assess the prevalence of shigellosis through selective plating, biochemical test and conventional PCR assays, where the samples were collected from suspected diarrheoal patients. Invasive plasmid antigen H (ipaH) and O-antigenic rfc gene were used to identify Shigella spp. and S. flexneri respectively. For validation of these identification, PCR product of ipaH gene of a sample (Shigella flexneri MZS 191) has been sequenced and submitted to NCBI database (GenBank accession no- MW774908.1). Further this strain has been used as positive control. Out of 204, around 14.2% (n = 29)(P> 0.01) pediatric diarrheoal cases were screened as shigellosis. Another interesting finding was that most of shigellosis affected children were 7 months to 1 year (P> 0.01).The significance of this study lies in the analyses of the occurrenceand the molecular identification of Shigellaspp. and S. flexneri that can be utilized in improving the accurate identification and the treatment of the most severe and alarming shigellosis.


Viability of Streptococcus mutans on transparent and opaque toothbrushes.
The objective of this study was to evaluate the viability of the microorganism Streptococcus mutans on toothbrushes made of opaque and transparent materials. Twenty-eight toothbrushes (14 opaque and 14 transparent) were inoculated in tubes with brain heart infusion (BHI) broth of a standard strain of S. mutans and incubated in candle jars at 37 degrees C for 24 hours. Both the opaque and transparent toothbrushes were removed at T = 0 h (control); T = 0.5 h; T = 1 h; T = 2 h; T = 4 h; T = 8 h; and T = 24 h. Individual toothbrushes were subjected to agitation in a saline solution and samples of the solution were diluted and inoculated in Bacitracin Sucrose Agar--SB-20. After half an hour (T2) there was a significant decrease in the number of microorganisms on the transparent and opaque toothbrushes, respectively 6.0 x 10(5) and 9.4 x 10(5), when compared to the control. After the T3 = 1 hour, T4 = 2 hours, T5 = 4 h, the number of microorganisms decreased from 4.1 x 10(5); 2.1 x 10(5); 1.4 x 10(5); and 9.2 x 10(5); 5.7 x 10(5); 1.2 x 10(5) to zero (0.0) in T6 = 8 h, respectively on the transparent and opaque toothbrushes. The reduction in viable microorganisms was more obvious with the transparent toothbrushes, although the number of viable microorganisms was not significantly different for the two types of toothbrushes at the end of the experiment, T5 = 1.4 x 10(5) (transparent) and T5 = 1.2 x 10(5) (opaque). With both opaque and transparent toothbrushes, the number of microorganisms decreased with time. A reduction in the number of microorganisms on the transparent toothbrushes was observed following inoculation and incubation. This suggests the transparent toothbrushes inhibit the viability of the S. mutans.


Muscle spasms after spinal cord injury stem from changes in motoneuron excitability and synaptic inhibition, not synaptic excitation.
Muscle spasms are common in chronic spinal cord injury (SCI), posing challenges to rehabilitation and daily activities. Pharmacological management of spasms mostly targets suppression of excitatory inputs, an approach known to hinder motor recovery. To identify better targets, we investigated changes in inhibitory and excitatory synaptic inputs to motoneurons as well as motoneuron excitability in chronic SCI. We induced either a complete or incomplete SCI in adult mice of either sex and divided those with incomplete injury into low or high functional recovery groups. Their sacrocaudal spinal cords were then extracted and used to study plasticity below injury, with tissue from naïve animals as a control. Electrical stimulation of the dorsal roots elicited spasm-like activity in preparations of chronic severe SCI but not in the control. To evaluate overall synaptic inhibition activated by sensory stimulation, we measured the rate-dependent depression of spinal root reflexes. We found inhibitory inputs to be impaired in chronic injury models. When synaptic inhibition was blocked pharmacologically, all preparations became clearly spastic, even the control. However, preparations with chronic injuries generated longer spasms than control. We then measured excitatory postsynaptic currents (EPSCs) in motoneurons during sensory-evoked spasms. The data showed no difference in the amplitude of EPSCs or their conductance among animal groups. Nonetheless, we found that motoneuron persistent inward currents activated by the EPSCs were increased in chronic SCI. These findings suggest that changes in motoneuron excitability and synaptic inhibition, rather than excitation, contribute to spasms and are better suited for more effective therapeutic interventions.Significance Statement Neural plasticity following spinal cord injury is crucial for recovery of motor function. Unfortunately, this process is blemished by maladaptive changes that can cause muscle spasms. Pharmacological alleviation of spasms without compromising the recovery of motor function has proven to be challenging. Here, we investigated changes in fundamental spinal mechanisms that can cause spasms post-injury. Our data suggest that the current management strategy for spasms is misdirected towards suppressing excitatory inputs, a mechanism that we found unaltered after injury, which can lead to further motor weakness. Instead, this study shows that more promising approaches might involve restoring synaptic inhibition or modulating motoneuron excitability.


Immunity to whole varicella-zoster virus antigen and glycoproteins I and p170: relation to the immunizing regimen of live attenuated varicella vaccine.
Humoral and cellular immune responses to whole varicella-zoster virus (VZV) antigen and the VZV proteins glycoprotein I (gpI) and nonglycosylated protein p170 were evaluated in healthy children and adults given lyophilized live-attenuated varicella vaccine. Children received one dose of vaccine containing 950 pfu, whereas adults received two doses of 2500 pfu. After one year, the antibody titers of adult vaccinees to whole VZV and to gpI were significantly higher than those of children. Antibody titers to whole VZV, gpI, and p170 were lower among both vaccine populations than titers in naturally immune individuals, but vaccinees who seroconverted initially retained detectable VZV antibodies. Using T lymphocyte proliferation to measure cellular immunity, we found the mean (+/- SE) transformation index to whole VZV antigen to be 4.1 +/- 0.96 in children tested at one year, a mean significantly lower than the mean of 12.7 +/- 3.39 in adults and 13.0 +/- 1.67 in naturally immune subjects. These observations suggest that the vaccine dose affects vaccine-induced immunity to VZV.


New perspectives on the diversification of the RNA interference system: insights from comparative genomics and small RNA sequencing.
Our understanding of the pervasive involvement of small RNAs in regulating diverse biological processes has been greatly augmented by recent application of deep-sequencing technologies to small RNA across diverse eukaryotes. We review the currently known small RNA classes and place them in context of the reconstructed evolutionary history of the RNA interference (RNAi) protein machinery. This synthesis indicates that the earliest versions of eukaryotic RNAi systems likely utilized small RNA processed from three types of precursors: (1) sense-antisense transcriptional products, (2) genome-encoded, imperfectly complementary hairpin sequences, and (3) larger noncoding RNA precursor sequences. Structural dissection of PIWI proteins along with recent discovery of novel families (including Med13 of the Mediator complex) suggest that emergence of a distinct architecture with the N-terminal domains (also occurring separately fused to endoDNases in prokaryotes) formed via duplication of an ancestral unit was key to their recruitment as primary RNAi effectors and use of small RNAs of certain preferred lengths. Prokaryotic PIWI proteins are typically components of several RNA-directed DNA restriction or CRISPR/Cas systems. However, eukaryotic versions appear to have emerged from a subset that evolved RNA-directed RNAi. They were recruited alongside RNaseIII domains and RNA-dependent RNA polymerase (RdRP) domains, also from prokaryotic systems, to form the core eukaryotic RNAi system. Like certain regulatory systems, RNAi diversified into two distinct but linked arms concomitant with eukaryotic nucleocytoplasmic compartmentalization. Subsequent elaboration of RNAi proceeded via diversification of the core protein machinery through lineage-specific expansions and recruitment of new components from prokaryotes (nucleases and small RNA-modifying enzymes), allowing for diversification of associating small RNAs.


ABA activation of an MBP kinase in Pisum sativum epidermal peels correlates with stomatal responses to ABA.
In-gel protein kinase assays using myelin basic protein (MBP) as substrate have been used to demonstrate that abscisic acid (ABA) activates an MBP kinase (AMBP kinase) in epidermal peels prepared from leaves of the Argenteum mutant of pea, Pisum sativum L. AMBP kinase has the characteristics of a mitogen-activated protein kinase (MAPK): it utilizes MBP preferentially as an artificial substrate, it is rapidly and transiently activated, it is of the appropriate size (molecular weight c. 45 kDa), requires tyrosine phosphorylation for activity and is tyrosine phosphorylated upon activation. Reverse transcription-PCR was used to generate a previously-cloned MAPK from guard cells, epidermis and mesophyll and immunoblotting using an antibody raised against a mammalian MAPK detected MAPK-related proteins, including one of 45 kDa, in epidermal peels, mesophyll and guard cells. Inhibition of AMBP kinase activation by PD98059, a specific inhibitor of MAPK kinase, and thus MAPK activation, correlated with PD98059-inhibition of ABA-induced stomatal closure and dehydrin gene expression, suggesting that ABA effects in pea epidermal peels require MAPK activation. AMBP kinase was not activated by ABA in guard cells isolated by enzyme treatment. However, a protein kinase of c. 43 kDa was activated by ABA in isolated guard cells, but not in mesophyll or epidermal tissue.


Diesel-enriched particulate matter functionally activates human dendritic cells.
Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust-derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate-dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-gamma (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-gamma production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material.


Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice.
The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801-induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders.


Understanding Mechanisms of Synergy between Acidification and Ultrasound Treatments for Activated Sludge Dewatering: From Bench to Pilot-Scale Investigation.
Enhancing activated sludge dewaterability is of scientific and engineering importance in the face of accelerated urbanization and stringent environmental regulations. In this study, we investigated the integration of acidification and ultrasound (A/US) treatment for improving sludge dewaterability at both bench- and pilot-scales. Our results showed that the A/US process exhibited significantly improved sludge dewatering performance, characterized by capillary suction time, cake moisture, and water/solid content of sludge cake. Synergistic dewatering mechanisms were elucidated with a suite of macro and spectroscopic evidence. Characterization of treated sludge revealed that US-induced thermal, mechanical shearing force, and radical oxidation effects disrupts floc cells and accelerates the decomposition of extracellular polymeric substances (EPS), releasing bound water into the bulk phase. In addition to enhancing hydrolysis of EPS, the acidic pH environment caused the protonation of functional groups on EPS, facilitating the reflocculation of US decomposed sludge for improved filterability. Our bench-scale and pilot-scale investigations provide a mechanistic basis for better understanding of the A/US process, and enable development of a viable and economical dewatering technology.


Electrophysiology of neuromuscular junction disease: an appreciation of the contributions of Edward H. Lambert.
As the muscle fiber action potential is "all or none" and is not of constant voltage recorded in volume from remote electrodes, there are serious limitations on assessment of the "safety factor" for neuromuscular transmission by stimulus-response recording from surface electrodes, or by single fiber EMG. Lambert's use of biopsied intercostal muscle with microelectrode recording of spontaneous and evoked end-plate potentials has permitted more accurate analysis of transmission disorders. His personal and collaborative studies on experimental myasthenia gravis, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and the Lambert-Eaton myasthenic syndrome are reviewed. It is suggested that studies of acetylcholine receptor agonists require reevaluation as indicating inadequacies of present models.


Extracting semantics from audio-visual content: the final frontier in multimedia retrieval.
Multimedia understanding is a fast emerging interdisciplinary research area. There is tremendous potential for effective use of multimedia content through intelligent analysis. Diverse application areas are increasingly relying on multimedia understanding systems. Advances in multimedia understanding are related directly to advances in signal processing, computer vision, pattern recognition, multimedia databases, and smart sensors. We review the state-of-the-art techniques in multimedia retrieval. In particular, we discuss how multimedia retrieval can be viewed as a pattern recognition problem. We discuss how reliance on powerful pattern recognition and machine learning techniques is increasing in the field of multimedia retrieval. We review the state-of-the-art multimedia understanding systems with particular emphasis on a system for semantic video indexing centered around multijects and multinets. We discuss how semantic retrieval is centered around concepts and context and the various mechanisms for modeling concepts and context.


Alternative splicing of amino-terminal Tau mRNA in rat spinal cord during development and following axonal injury.
Tau is a family of microtubule-associated phosphoproteins in which isoform variation is produced by alternative splicing of a single gene and posttranslational modifications. Tau isoforms that include exon 10 are overexpressed in frontotemporal dementia and progressive supranuclear palsy. Therefore, we examined the expression of tau mRNA splice variants during axonal regeneration and abortive regeneration. Previous work in our laboratory demonstrated that expression of exon 10 tau isoforms during regeneration and abortive regeneration was altered and partially recapitulated the developmental patterns of tau isoform expression. Using RT-PCR, we examined the alternative splicing of exons 2 and 3 in tau during early postnatal development and regeneration in the rat spinal cord. The levels of tau lacking exons 2 and 3 were high on the day of birth and rapidly declined. Conversely, tau isoforms containing exon 2 or exons 2 and 3 first appeared at low levels and steadily increased. During axonal regeneration, the levels of all three tau mRNA isoforms were significantly lower 7 days after injury. In a model of abortive regeneration, all of the tau isoforms were elevated 14 and 42 days postinjury. The relative levels of exon 2 and 3 tau splice variants were not altered during regeneration or abortive regeneration as occurred during development. These results suggest that tau isoform expression following neuronal injury does not recapitulate the developmental pattern and is not independently regulated as in development. Our previous results together with these data suggest that alterations in tau mRNA isoform expression that occur in neurodegeneration are not secondary to axonal injury but may be a more primary event underlying cytoskeletal derangement.


Schizophrenia, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and number needed to treat: how can CATIE inform clinicians?
The schizophrenia medication study conducted as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provided a large quantity of data. However, placing these data into a clinically meaningful context for the individual practitioner has been challenging. Effectiveness and safety outcome data were extracted from the three principal publications that documented the results of phases 1 and 2 of the CATIE schizophrenia study. Number needed to treat (NNT) and number needed to harm (NNH) were calculated from the categorical results, together with their confidence intervals. Olanzapine and clozapine demonstrated advantages over comparators in terms of all-cause discontinuation, largely driven by efficacy advantages. NNT for olanzapine compared with perphenazine, quetiapine, risperidone and ziprasidone ranged from 5.5 to 10.1 in phase 1. NNT for clozapine compared with risperidone or quetiapine was approximately 3 in phase 2. There were marked differences in association with weight gain and metabolic effects, with olanzapine demonstrating a NNH ranging from 12.4 to 17.7 in terms of discontinuation of treatment in phase 1 because of these effects. Results from phase 2 reflect phase 1 in this regard, and demonstrated an advantage for ziprasidone in terms of discontinuation because of weight gain or metabolic effects, with NNT ranging from 10.6 to 20.8. However, these notable differences in association with weight gain and metabolic effects did not seem to drive the differences in overall time to all-cause discontinuation. NNT and NNH can help place the wide array of CATIE results into clinical context, and permits quantification of the differences observed between the antipsychotics that were tested.


Diet and the human intestinal bacterial flora.
In this review, the factors thought to be important in determining the composition of the gut bacterial flora are discussed. In the light of these, the effects of various dietary manipulations on the composition and metabolic activity of the gut flora are described. In general, the main effects of diet would be expected to be manifested in the right colon, whereas the material available for investigation is feces. Consequently, the data that are available tend to underestimate the effects of diet.


Building Bridges: Describing a Process for Indigenous Engagement in Epidemiology.
Processes for epidemiology embedded with Indigenous methodology are needed. Building Bridges was developed to engage Indigenous peoples in epidemiology to address health issues relevant to them. We describe our process for meaningfully engaging Indigenous leaders and peoples living with human immunodeficiency virus (HIV) in epidemiology research. As a community-based research (CBR) project, Indigenous methodologies and leadership ensured the quality and relevance of findings. Study phases included 1) advisory board formation, 2) recruitment, 3) research question identification, 4) data analysis from the Canadian HIV Observational Cohort (CANOC) collaboration, 5) data interpretation and contextualization, and 6) knowledge translation and exchange. Support and guidance from Indigenous team members, Spiritual Leaders and Elders along with meaningful relationships with allied academic researchers were pivotal. Expertise and lived experiences in Indigenous culture, HIV, epidemiology and services enabled multidirectional learning. Building Bridges' success hinged on ongoing co-learning and engagement of Indigenous peoples, service providers and researchers.


Efficient reversible watermarking based on adaptive prediction-error expansion and pixel selection.
Prediction-error expansion (PEE) is an important technique of reversible watermarking which can embed large payloads into digital images with low distortion. In this paper, the PEE technique is further investigated and an efficient reversible watermarking scheme is proposed, by incorporating in PEE two new strategies, namely, adaptive embedding and pixel selection. Unlike conventional PEE which embeds data uniformly, we propose to adaptively embed 1 or 2 bits into expandable pixel according to the local complexity. This avoids expanding pixels with large prediction-errors, and thus, it reduces embedding impact by decreasing the maximum modification to pixel values. Meanwhile, adaptive PEE allows very large payload in a single embedding pass, and it improves the capacity limit of conventional PEE. We also propose to select pixels of smooth area for data embedding and leave rough pixels unchanged. In this way, compared with conventional PEE, a more sharply distributed prediction-error histogram is obtained and a better visual quality of watermarked image is observed. With these improvements, our method outperforms conventional PEE. Its superiority over other state-of-the-art methods is also demonstrated experimentally.


Blindness in children with neuroblastoma.
Neuroblastoma is the most common extracranial solid tumor among pediatric patients, and orbital metastatic disease is not uncommon in these children. Physical signs as a consequence of orbital metastases, such as proptosis and periorbital ecchymosis, frequently are encountered. However, subsequent blindness is rare. A retrospective study was conducted to determine the incidence, related physical findings, treatment, and outcome of children who developed visual loss during treatment for neuroblastoma. Medical records for a 24-year period (1971-1994) were reviewed to identify these patients. The charts, diagnostic imaging studies, and autopsy material of these patients were reviewed. Of the 450 patients treated for neuroblastoma at the study institution during this period, 47 presented with abnormalities in physical examination of the eye. Eight of these 47 patients and 7 others developed visual loss in at least 1 eye during the first week after diagnosis (n = 5), during primary therapy (n = 6), at recurrence (n 2), or after completion of therapy (n = 2). In ten patients the visual loss was a direct consequence of the primary disease process, whereas a direct relationship between loss of vision and neuroblastoma could not be identified in the remaining five patients. Proptosis and periorbital ecchymosis were the most common associated physical findings. Although ten patients received steroids and eight received radiation, visual loss could not be prevented or reversed in these patients. Early initiation of effective, multiagent chemotherapy remains the primary approach for the treatment of neuroblastoma and its ophthalmologic complications. Radiation therapy and steroids may have benefit but failed to show good effect in this series. The prevention and treatment of blindness is probably most relevant in infants and children age < 2 years because they have the best chance for cure.


[Importance of the microbiological confirmation in an outbreak of human leptospirosis in the city of Villa Clara].
A multidisciplinary group was created to confirm the existance of human leptospirosis in the province of Villa Clara where by the end of June, 1977, there was a considerable increase of febrile cases with symptoms and signs consistent with diseases such as hemorrhagic dengue and human leptospirosis. The National Laboratory of Reference of Leptospires from "Pedro Kouri" Institute, organized a set of direct and indirect diagnostic techniques as a working strategy that would serve to confirm this health problem. As a final result, it was observed that the Ballum, Pomona, Canicola and icterohaemorrhagiae serogroups showed the highest percentage of appearance among the studied cases. A total of 7 cases had active infection, since they were positives by the passive hemoagglutination method. The four severe cases studied by passive hemoagglutination and microagglutination were positive. Sera from the 3 patients with febrile syndrome of unknown ethiology were negative by these 2 techniques. The 3 samples obtained from the autopsy of a dead were positive by direct exam in dark field and staining of immunoperoxidase. The monosera of the dead subjects were highly reactive by passive hemagglutination (titers from 1-10 and up to 1-640). 2 hemocultures were typified as Ballum; 2 urines and 1 hemoculture were positive by polymerase chain reaction. In this way, a fast answer was given to the health public authorities from the Viceministry of Hygiene and Epidemiology of Cuba on confirming microbiologically the existance of the disease. lt was sugggested to administer the Cuban vax SPIRAL vaccine in the affected area.


Design of amino acid aldehydes as transition-state analogue inhibitors of arginase.
Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino acids bearing aldehyde side chains have been synthesized in which the electrophilic aldehyde C=O bond is isosteric with the C=N bond of L-arginine. This substitution is intended to facilitate nucleophilic attack by the metal-bridging hydroxide ion upon binding to the arginase active site. Syntheses of the amino acid aldehydes have been accomplished by reduction, oxidation, and Wittig-type reaction with a commercially available derivative of L-glutamic acid. Amino acid aldehydes exhibit inhibition in the micromolar range, and the X-ray crystal structure of arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution. In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and donates a hydrogen bond to D128, and the second hydroxyl group donates a hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic the binding of the neutral tetrahedral intermediate and its flanking transition states in arginase catalysis.


Radio frequency radiation (RFR): the nature of exposure and carcinogenic potential.
Epidemiologic evidence on the relation between radio-frequency radiation (RFR) and cancer is reviewed. Radio-wave communications are used extensively in modern society; thus, we are all subject to RFR created by radio, television, wireless telephony, emergency communications, radar, etc. Interest in the health effects of RFR has been motivated by the rapid growth in wireless communications and by media reports expressing concern that specific diseases may be caused by RFR exposure, e.g., from cellular telephone handsets. Due to the ubiquitous presence of RFR, the public health implication of any connection between RFR and cancer risk is potentially significant. (It is important to keep RFR distinct from power-line electromagnetic fields.) Comparison of potential risks from RFR exposure with other occupational and environmental health risks requires evaluating the level of support from available epidemiology, from studies with laboratory animals, and from mechanistic or biophysical information about the interaction of RFR with living tissues. A large number of studies have been done with laboratory animals and with in vitro systems; a more limited set of epidemiologic studies is available. Effects from RFR exposure that lead to temperature increases have been consistently reported, but 'non-thermal' effects have not been substantiated. Also, there are no mechanistic theories that support 'non-thermal' interactions with biology. Evidence to support a causal relationship between exposure to RFR and human cancers is scant. Our present state of knowledge about exposure, mechanisms, epidemiology, and animal studies does not identify significant cancer risks.


Contrasting behavior between two populations of an ice-obligate predator in East Antarctica.
The Austral autumn-winter is a critical period for capital breeders such as Weddell seals that must optimize resource acquisition and storage to provision breeding in the subsequent spring. However, how Weddell seals find food in the winter months remains poorly documented. We equipped adult Weddell seals after their annual molt with satellite-relayed data loggers at two sites in East Antarctica: Dumont D'Urville (n = 12, DDU) and Davis (n = 20). We used binomial generalized mixed-effect models to investigate Weddell seals' behavioral response (i.e., "hunting" vs. "transit") to physical aspects of their environment (e.g., ice concentration). Weddell seal foraging was concentrated to within 5 km of a breathing hole, and they appear to move between holes as local food is depleted. There were regional differences in behavior so that seals at Davis traveled greater distances (three times more) and spent less time in hunting mode (half the time) than seals at DDU. Despite these differences, hunting dives at both locations were pelagic, concentrated in areas of high ice concentration, and over areas of complex bathymetry. There was also a seasonal change in diving behavior from transiting early in the season to more hunting during winter. Our observations suggest that Weddell seal foraging behavior is plastic and that they respond behaviorally to changes in their environment to maximize food acquisition and storage. Such plasticity is a hallmark of animals that live in very dynamic environments such as the high Antarctic where resources are unpredictable.


Laparoscopic omentectomy for peritoneal dialysis catheter flow obstruction: a case report and review of the literature.
Peritoneal dialysis catheter outflow dysfunction frequently is caused by omentum or epiploic appendices blocking the side holes of the catheter tubing. Laparoscopy has been utilized increasingly to remedy mechanical blockage of the peritoneal device. This obviates the need for catheter replacement, permits early return to dialysis, and lowers the patient dropout rate from peritoneal dialysis as a modality for renal replacement therapy. We report a case of laparoscopic subtotal omentectomy to successfully resolve recurrent catheter obstruction that failed previous omentolysis and omentopexy. Using four port sites, the omental resection was accomplished using the harmonic scalpel. The procedure was performed on an ambulatory basis, dialysis was resumed after 1 week, and there were no infectious complications or port site leaks. We define terminology to standardize reporting of omentectomy. Our technique of laparoscopic omentectomy is described and compared to those of previously published reports. The role of laparoscopic omentectomy relative to other commonly used laparoscopic approaches to the obstructed peritoneal dialysis catheter is reviewed.


Factors affecting motorcycle helmet use: size selection, stability, and position.
One of the main requirements of a protective helmet is to provide and maintain appropriate and adequate coverage to the head. A helmet that is poorly fitted or fastened may become displaced during normal use or even ejected during a crash. Observations and measurements of head dimensions, helmet position, adjustment, and stability were made on 216 motorcyclists. Helmet details were recorded. Participants completed a questionnaire on helmet usability and their riding history. Helmet stability was assessed quasistatically. Differences between the dimensions of ISO headforms and equivalent sized motorcyclists' heads were observed, especially head width. Almost all (94%) of the helmets were labeled to be compliant with AS/NZS 1698 (2006). The majority of riders were satisfied with the comfort, fit, and usability aspects of their helmets. The majority of helmets were deemed to have been worn correctly. Using quasistatic pull tests, it was found that helmet type (open-face or full-face) and the wearing correctness were among factors that affected the loads at which helmets became displaced. The forces required to displace the helmet were low, around 25 N. The size of the in-use motorcycle helmets did not correspond well to the predicted size based on head dimensions, although motorcyclists were generally satisfied with comfort and fit. The in vivo stability tests appear to overpredict that helmets will come off in a crash, based on the measured forces, tangential forces measured in the oblique impact tests, and the actual rate of helmet ejection.


Three-dimensional quantification of vorticity and helicity from 3D cine PC-MRI using finite-element interpolations.
We propose a 3D finite-element method for the quantification of vorticity and helicity density from 3D cine phase-contrast (PC) MRI. By using a 3D finite-element method, we seamlessly estimate velocity gradients in 3D. The robustness and convergence were analyzed using a combined Poiseuille and Lamb-Ossen equation. A computational fluid dynamics simulation was used to compared our method with others available in the literature. Additionally, we computed 3D maps for different 3D cine PC-MRI data sets: phantom without and with coarctation (18 healthy volunteers and 3 patients). We found a good agreement between our method and both the analytical solution of the combined Poiseuille and Lamb-Ossen. The computational fluid dynamics results showed that our method outperforms current approaches to estimate vorticity and helicity values. In the in silico model, we observed that for a tetrahedral element of 2 mm of characteristic length, we underestimated the vorticity in less than 5% with respect to the analytical solution. In patients, we found higher values of helicity density in comparison to healthy volunteers, associated with vortices in the lumen of the vessels. We proposed a novel method that provides entire 3D vorticity and helicity density maps, avoiding the used of reformatted 2D planes from 3D cine PC-MRI. Magn Reson Med 79:541-553, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Interstitial lung disease and CDK4/6 inhibitors in the treatment of breast cancer.
CDK4/6 inhibitors have changed the treatment paradigm of many patients living with metastatic and early-stage high-risk hormone receptor (HR)-positive breast cancer. Even though patients and clinicians are aware and learning how to manage common adverse events, such as bone marrow suppression and gastrointestinal toxicities, there are less common and potentially severe adverse events, such as interstitial lung disease (ILD), that require special consideration. In this narrative review, we discuss the incidence, mechanism, and treatment of CDK4/6 inhibitor associated ILD. CDK4/6 inhibitors in combination with endocrine therapy (ET) are standard treatment for HR-positive, HER2-negative metastatic breast cancer and for selected patients with early stage HR-positive breast cancer. Common toxicities of these medications are often controlled with dose reductions, dose interruptions, and/or prophylactic medications, such as antidiarrheals. However, there are a small subset of patients at risk for less common and potentially severe toxicities, such as ILD. Individualized risk should be considered, including underlying lung disease, thrombosis risk and drug-drug interactions, in order to counsel patients about the risk of ILD.


Death of Parents and Adult Psychological and Physical Well-Being: A Prospective U.S. National Study.
Guided by a life course perspective, attachment theory, and gender theory, this study aims to examine the impact of death of a father, a mother, or both parents, as well as continuously living with one or both parents dead (in contrast to having two parents alive) on multiple dimensions of psychological well-being (depressive symptoms, happiness, self-esteem, mastery, and psychological wellness), alcohol abuse (binge drinking), and physical health (self-assessed health). Analyses of longitudinal data from. 8,865 adults in the National Survey of Families and Households 1987-1993 reveal that a father's death leads to more negative effects for sons than daughters and a mother's death leads to more negative effects for daughters than sons. Problematic effects of parent loss are reflected more in men's physical health reports than women's. This study's results suggest that family researchers and practitioners working with aging families should not underestimate the impact of filial bereavement on adult well-being.


Expression of bioactive single-chain murine IL-12 in transgenic plants.
Interleukin-12 (IL-12), an important immunomodulator for cell-mediated immunity, shows significant potential as a vaccine adjuvant and anticancer therapeutic. However, its clinical application is limited in part by lack of an effective bioproduction system for this complex heterodimeric glycoprotein. Transgenic plants show promise as scalable bioproduction platforms for challenging biopharmaceutical proteins. To test the potential of plants to effectively produce bioactive IL-12, we developed transgenic tobacco plant lines and derived root cultures yielding high levels of mouse IL-12 (MuIL-12). Functional IL-12 is a heterodimer consisting of two disulfide-linked subunits, p35 and p40. To ensure the stoichiometric expression and assembly of p35 and p40, we expressed a single-chain version of MuIL-12. Plant-derived single-chain MuIL-12 was characterized and purified for in vitro bioactivity assays. Our results demonstrated precise cleavage of the endogenous mouse p40 signal peptide in plants as well as addition of N-linked glycans. Plant-derived MuIL-12 triggered induction of interferon-gamma (IFN-gamma) secretion from mouse splenocytes and stimulated splenocyte proliferation with comparable activities to those observed for commercially available animal cell-derived MuIL-12. These studies indicate that plants produce fully functional MuIL-12 at levels compatible with commercial production and may serve as an effective bioproduction platform for bioactive IL-12s from other species for human or veterinary vaccine and therapeutic applications.


Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women-2 years of screening experience from Denmark.
Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening. Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies. The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%. The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance.


[Non-pharmacological therapy of decompensated heart failure: cardiac resynchronization therapy].
Cardiac resynchronization therapy (CRT) is a novel and effective therapy for patients with heart failure. The aim of CRT is to improve the heart's pumping efficiency by the resynchronization of the chambers. Electrical dyssynchrony shows itself as bundle branch block with prolongation of QRS >120 ms. Mechanical dyssynchrony (atrioventricular, interventricular and intraventricular) is evidenced by echocardiographic parameters. A cardioverter-defibrillator function can be included with the pulse generator in patients with high risk of sudden death. The estimate of perioperative death associated with CRT was 0.3% with a low rate of complications, similar to that seen in standard pacemaker placement. In 10% of patients there was an implant failure due to the difficulty in accessing the coronary sinus. Approximately one third of patients are non-responder with no significant improvement after implantation. The beneficial effect of CRT on soft endpoints and mortality (symptoms, NYHA class, 6-min walking test, quality of life score, ejection fraction) was demonstrated in the earliest randomized clinical trials. Current guidelines for CRT are based on inclusion and exclusion criteria in the large randomized trials that have been performed and patients with chronic atrial fibrillation are included. Unresolved issues are the identification of non-responders and the efficacy of CRT in patients with mechanical dyssynchrony without electrical dyssynchrony and in NYHA functional class I/II patients with ejection fraction < or = 35%.


Language impairments in youths with traumatic brain injury: implications for participation in criminal proceedings.
As many as 30% of incarcerated juveniles have a history of traumatic brain injury (TBI). Moderate or severe TBI is associated with a high risk of impairment in language comprehension and expression, which may have profound effects on juveniles' ability to understand and express themselves in criminal proceedings. In this article, we review common language impairments in youths with TBI and discuss potential effects of these impairments on 3 stages of US criminal proceedings: (1) initial encounter with law enforcement; (2) interrogation and Miranda rights; and (3) competence to undergo trial proceedings. We then describe language assessment tools and procedures that may be helpful in legal contexts. Our aim was to inform clinicians and legal staff working with juvenile defendants with TBI, with the long-term goal of developing empirically based guidelines to ensure that juvenile defendants with TBI can fully and effectively participate in criminal proceedings.


A protocol for cell therapy infusion in neonates.
Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-μm filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2 mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose. Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery. Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.


Tempo-spatially resolved cellular dynamics of human immunodeficiency virus transacting activator of transcription (Tat) peptide-modified nanocargos in living cells.
Understanding the cellular uptake mechanism and intracellular fate of nanocarriers in living cells is of great importance for the rational design of efficient drug delivery cargos as well as the development of robust biomedical diagnostic probes. In present study, with a dual wavelength view darkfield microscope (DWVD), the tempo-spatially resolved dynamics of Tat peptide-functionalized gold nanoparticles (TGNPs, with size similar to viruses) in living HeLa cells were extensively explored. It was found that energy-dependent endocytosis (both clathrin- and caveolae-mediated processes were involved) was the prevailing pathway for the cellular uptake of TGNPs. The time-correlated dynamic spatial distribution information revealed that TGNPs could not actively target the cell nuclei, which is contrary to previous observations based on fixed cell results. More importantly, the inheritance of TGNPs to the daughter cells through mitosis was found to be the major route to metabolize TGNPs by HeLa cells. These understandings on the cellular uptake mechanism and intracellular fate of nanocargos in living cells would provide deep insight on how to improve and controllably manipulate their translocation efficiency for targeted drug delivery.


Postoperative Patient- and Parent-Reported Outcomes for Children with Congenital Hand Differences: A Systematic Review.
Patient- and parent-reported outcomes are increasingly considered as measures of treatment effectiveness for congenital conditions. The authors' specific aim was to review the use of patient- and parent-reported outcomes of quality of life, activities of daily living, perception of hand appearance, and satisfaction after reconstruction for congenital hand differences. The authors reviewed articles addressing congenital hand differences from PubMed, MEDLINE, and EMBASE published between January of 1966 and October of 2016. The authors excluded studies that did not include reconstruction or lacked patient- or parent-reported outcomes. Investigators reviewed 48 studies and extracted the following: study type, level of evidence, type of congenital hand differences, sample size, procedure performed, length of follow-up, and domains and results of patient-satisfaction questionnaires. Multiple studies across several types of congenital hand differences showed that a majority of patients and parents report improvements and are satisfied with postoperative outcomes. However, there were several patient cohorts (e.g., thumb duplication, thumb hypoplasia, radial longitudinal deficiency) who expressed dissatisfaction with outcomes and continue to experience decreased health-related quality of life. Overall, patient satisfaction and reports of health-related quality of life among children with congenital hand differences are favorable. Patients seem to cope and adapt well, but teasing and social relationships remain problematic, particularly as children enter school. This article highlights addressing these concerns before embarking on reconstruction.


Hybridization and postzygotic isolation promote reinforcement of male mating preferences in a diverse group of fishes with traditional sex roles.
Behavioral isolation is thought to arise early in speciation due to differential sexual and/or natural selection favoring different preferences and traits in different lineages. Instead, behavioral isolation can arise due to reinforcement favoring traits and preferences that prevent maladaptive hybridization. In darters, female preference for male coloration has been hypothesized to drive speciation, because behavioral isolation evolves before F1 inviability. However, as with many long-lived organisms, the fitness of second-generation hybrids has not been assessed because raising animals to adulthood in the laboratory is challenging. Of late, reinforcement of male preferences has been implicated in darters because male preference for conspecific females is high in sympatry but absent in allopatry in multiple species pairs. The hypothesis that reinforcement accounts for behavioral isolation in sympatry assumes that hybridization and postzygotic isolation are present. Here, we used genomic and morphological data to demonstrate that hybridization is ongoing between orangethroat and rainbow darters and used hybrids collected from nature to measure postzygotic barriers across two hybrid generations. We observed sex ratio distortion in adult F1s and a dramatic reduction in backcross survival. Our findings indicate that selection to avoid hybridization promotes the evolution of male-driven behavioral isolation via reinforcement in this system.


Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy.
Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.


Corneal Morphologic Characteristics in Patients With Down Syndrome.
Literature suggests corneal morphologic characteristics compatible with keratoconus are present in a high percentage of patients with Down syndrome (DS), suggesting the need to perform a detailed examination of the anterior segment to try to avoid serious visual impairment in this group of patients. To characterize the abnormal features of the cornea in patients with DS and compare these with a control group. Multicenter case-control study at Vissum Alicante, Alicante, Spain, and the Ophthalmology and Pediatric Department, Cairo University, Cairo, Egypt. Data collection took place between May 2013 and May 2016. Data were analyzed between June 2016 and August 2016. The study included 321 eyes of 217 participants from 2 groups: 112 participants in the DS group and 105 healthy participants in the control group. Patients were evaluated using Placido disc/Scheimpflug camera topographer (Sirius, CSO). Visual, refractive and anterior, and posterior corneal characteristics were assessed and compared in both groups. Keratoconus diagnosis. Incidence of corneal morphologic irregularities similar to keratoconus in patients with DS. In the DS group, mean (SD) age was 14.88 (15.76) years, 54 (48%) were women, 66 (59%) were white, and 46 (41%) were Arab. In the control group, mean (SD) age was 40.29 (14.66) years, 54 (51%) were women, and all were white. Clinical assessment of corneal topography showed that 71.3% (95% CI, 45.2-97.4) of patients in the DS group showed characteristics compatible with keratoconus. Differences were found in steepest keratometry of 47.35 diopters (D) in patients with DS vs 43.70 D in control individuals (difference, 3.65 D; 95% CI, 3.23-4.35 D; P <.001) and in corneal pachymetry of 503 μm in patients with DS vs 545 μm in control individuals (difference, 42 μm; 95% CI, 38.8-56.7 μm; P <.001). Patients with DS have steeper and thinner corneas and more corneal aberrations than those without genetic alterations and normal corneas. The findings suggest a detailed corneal study should be considered in such patients to detect keratoconus and implement treatment as appropriate to try to avoid serious visual impairment in this group of patients.


BRCA1 counteracts progesterone action by ubiquitination leading to progesterone receptor degradation and epigenetic silencing of target promoters.
Germ-line mutations in the BRCA1 gene increase the risk of breast cancer in women, but the precise mechanistic basis for this connection remains uncertain. One popular hypothesis to explain breast tissue specificity postulates a link between BRCA1 and the action of the ovarian hormones estrogen and progesterone. Given the relevance of progesterone for normal mammary development and breast cancer formation, we searched for a functional relationship between BRCA1 and progesterone receptor (PR) in the PR-positive breast cancer cell line T47D. Here, we report that BRCA1 inhibits the transcriptional activity of PR by at least 2 mechanisms involving the E3 ubiquitin ligase activity of BRCA1. First, BRCA1 has a direct effect on the cellular level of PR and, hence, on the extent of PR recruitment to target promoters through the promotion of its ligand-independent and -dependent degradation. Through in vitro and in vivo assays, we found that BRCA1/BARD1 may be the main E3 ubiquitin ligase responsible for ubiquitination and degradation of PR in the absence of hormone. Second, after hormone treatment of cells, the BRCA1/BARD1 complex is recruited via interaction with PR to the hormone-responsive regions of PR target genes, affecting local levels of monoubiquitinated histone H2A and contributing to epigenetic silencing of these promoters. The connections between BRCA1/BARD1 and PR activity suggested by our findings may help explain why host mutations in BRCA1 exert a tissue specificity in preferentially elevating the risk of breast cancer.


[Campylobacter in acute diarrhea of infants].
Investigation of C. jejuni, C. coli has been realised on 280 babies in Tunis, 123 of them do not present any diarrhea. The global frequency of campylobacter isolated is 4.64%. Concerning babies with diarrhea, the frequency is 4.45%, whereas it is 4.86% in the group without diarrhea. A similar frequency of C. jejuni and C. coli appears in the two groups.


Construction of Janus structures on thin silk fabrics via misting for wet-thermal comfort and antimicrobial activity.
Owing to their small fiber diameter (10-15 μm), silk fabrics are always thin (32-90 g m-2). Therefore, construction of the Janus surfaces of silk fabrics that possess excellent multifunctionality remains a formidable challenge. Herein, first, silk fabrics were grafted using glycidyltrimethylammonium chloride to form a superhydrophilic surface (G-side). Then, a unilateral hydrophobic surface (O-side) was readily fabricated by mist coating octadecyltrichlorosilane-functionalized SiO2 nanoparticles (NPs) to produce hierarchical surface textures. To prevent NP penetration from the G-side to the O-side, a "fireproof isolation" method was employed. Consequently, Janus silk fabrics (JanSFs) bearing asymmetric wettability were prepared, and their wetting gradient could be conveniently regulated. With the mist time ranging from 4 to 7 min, the unidirectional transport index and efficiency of the unidirectional water transport increased and decreased by 13.2 and 10.4 times, respectively. Sweat could be effectively drained away from human skin to ensure that the skin was dry and comfortable. Compared with the surface temperature of the raw fabric, the raw fabric of JanSFs increased by 2.7 °C. Furthermore, the breathability of JanSF was negligibly affected, and the outer O-side of the JanSF showed substantial antibacterial activity. This study is important for designing JanSFs that exhibit unidirectional water transport.


A study of dinitro-bis-1,2,4-triazole-1,1'-diol and derivatives: design of high-performance insensitive energetic materials by the introduction of N-oxides.
In this contribution we report on the synthesis and full structural as well as spectroscopic characterization of 3,3'-dinitro-5,5'-bis-1,2,4-triazole-1,1'-diol and nitrogen-rich salts thereof. The first synthesis and characterization of an energetic 1-hydroxy-bistriazole in excellent yields and high purity is presented. This simple and straightforward method of N-oxide introduction in triazole compounds using commercially available oxone improves the energetic properties and reveals a straightforward synthetic pathway toward novel energetic 1,2,4-triazole derivatives. X-ray crystallographic measurements were performed and deliver insight into structural characteristics and strong intermolecular interactions. The standard enthalpies of formation were calculated for all compounds at the CBS-4 M level of theory, revealing highly positive heats of formation for all compounds. The energetic properties of all compounds (detonation velocity, pressure, etc.) were calculated using the EXPLO5.05 program, and the ionic derivatives show superior performance in comparison to the corresponding compounds bearing no N-oxide. All substances were characterized in terms of sensitivities (impact, friction, electrostatic) and thermal stabilities, and the ionic derivatives were found to be high thermally stable, insensitive compounds that are exceedingly powerful but safe to handle and prepare.


Importance of Lipopolysaccharide and Cyclic β-1,2-Glucans in Brucella-Mammalian Infections.
Brucella species are the causative agents of one of the most prevalent zoonotic diseases: brucellosis. Infections by Brucella species cause major economic losses in agriculture, leading to abortions in infected animals and resulting in a severe, although rarely lethal, debilitating disease in humans. Brucella species persist as intracellular pathogens that manage to effectively evade recognition by the host's immune system. Sugar-modified components in the Brucella cell envelope play an important role in their host interaction. Brucella lipopolysaccharide (LPS), unlike Escherichia coli LPS, does not trigger the host's innate immune system. Brucella produces cyclic β-1,2-glucans, which are important for targeting them to their replicative niche in the endoplasmic reticulum within the host cell. This paper will focus on the role of LPS and cyclic β-1,2-glucans in Brucella-mammalian infections and discuss the use of mutants, within the biosynthesis pathway of these cell envelope structures, in vaccine development.


Comparative mapping in loblolly and radiata pine using RFLP and microsatellite markers.
Genetic linkage maps were constructed for loblolly pine (Pinus taeda L.) and radiata pine (P. radiata D. Don) using a common set of RFLP and microsatellite markers. The map for loblolly pine combined data from two full-sib families and consisted of 20 linkage groups covering 1281 cM. The map for radiata pine had 14 linkage groups and covered 1223 cM. All of the RFLP probes readily hybridise between loblolly and radiata pine often producing similar hybridisation patterns. There were in total 60 homologous RFLP loci mapped in both species which could be used for comparative purposes. A set of 20 microsatellite markers derived from radiata pine were also assayed; however, only 9 amplified and revealed polymorphic loci in both species. Single-locus RFLP and microsatellite markers were used to match up linkage groups and compare order between species. Twelve syntenic groups were obtained each consisting of from 3 to 9 homologous loci. The order of homologous loci was colinear in most cases, suggesting no major chromosomal rearrangements in the evolution of these species. Comparative mapping between loblolly and radiata pine should facilitate genetic research in both species and provide a framework for mapping in other pine species.


[Study of mechanisms of action of amitriptyline and acupuncture using nociceptive flexor reflex in patients with chronic forms of headache].
The nociceptive flexor reflex (NFR, R3) was tried for quantitative assessment of pain in patients with various forms of primary and secondary headaches. Amitriptyline and acupuncture elevated the threshold of R3-reflex emergence, though the threshold of subjective pain sensitivity increased only in response to amitriptyline. NFR is adequate for assessing anesthesia efficacy and investigating the mechanisms of action of analgesics in patients with headache.


Fucoidan Alleviates Acetaminophen-Induced Hepatotoxicity via Oxidative Stress Inhibition and Nrf2 Translocation.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress.