[Temporal mesial sclerosis syndrome in epilepsy].
Mesial temporal sclerosis is a frequent cause of epilepsy. Patients with mesial temporal sclerosis usually have an early brain insult, a febrile convulsion in most cases, and a seizure free interval of variable duration. This is followed by complex partial seizures with stereotypic semiology. Histological analysis of the hippocampal formation demonstrates a well defined pattern of cell loss and axonal proliferation. This pattern indicates selective cell vulnerability to the excitotoxic process that causes mesial temporal sclerosis, and synaptic and axonal reorganization, which are involved in the pathogenesis of this disorder. Epilepsy associated with mesial temporal sclerosis is not a static process, neurons in this region of the temporal lobe are physiologically and biochemically active, participating in the pathophysiology of the disease by facilitating the recurrence of seizures. There are no pathognomonic findings in mesial temporal sclerosis, but its confident diagnosis can be achieved by convergence of different lines of evidence, including clinical, morphological, and functional findings. Complex partial seizures are often resistant to antiepileptic medication, while surgical resection of the epileptic focus provides seizure freedom in a large number of patients.


Three-year maintenance of a teacher-led programme targeting motor competence in early adolescent girls.
Motor competence (MC) in youth is associated with positive health outcomes, yet few achieve their developmental capability. Although numerous MC studies address initial intervention effectiveness, fewer consider intervention sustainability. This study aimed to investigate whether teachers continued to implement an effective MC programme targeting girls (mean age 12.4 ± 0.3 years), three years post-intervention. Ongoing implementation was examined using three domains of the UK Medical Research Council's framework: (i) implementation, (ii) mechanisms of impact, and (iii) context. Teachers (n = 18) completed self-report questionnaires and participated in focus group discussions (FGs). Descriptive statistics analysed questionnaires. FGs were audio recorded, transcribed verbatim and analysed in NVivo 11 using a framework approach. All teachers had continued to implement the programme, or elements thereof, three years post-intervention. The intervention structure, in particular alignment to the physical education context and curriculum, most notably influenced ongoing programme implementation. Improvement, both teacher practice and student performance, emerged as a driver of sustained impact. The programme demand appeared to be the most important facilitator of programme sustainability. Adaptations made to enhance contextual fit of the programme, post-intervention, extended the programme reach. Framed by implementation science, these findings provide valuable insight into programme sustainability and potential scalability.


Modular Nanoparticulate Prodrug Design Enables Efficient Treatment of Solid Tumors Using Bioorthogonal Activation.
Prodrug strategies that facilitate localized and controlled activity of small-molecule therapeutics can reduce systemic exposure and improve pharmacokinetics, yet limitations in activation chemistry have made it difficult to assign tunable multifunctionality to prodrugs. Here, we present the design and application of a modular small-molecule caging strategy that couples bioorthogonal cleavage with a self-immolative linker and an aliphatic anchor. This strategy leverages recently discovered in vivo catalysis by a nanoencapsulated palladium compound (Pd-NP), which mediates alloxylcarbamate cleavage and triggers release of the activated drug. The aliphatic anchor enables >90% nanoencapsulation efficiency of the prodrug, while also allowing >104-fold increased cytotoxicity upon prodrug activation. We apply the strategy to a prodrug formulation of monomethyl auristatin E (MMAE), demonstrating its ability to target microtubules and kill cancer cells only after selective activation by Pd-NP. Computational pharmacokinetic modeling provides a mechanistic basis for the observation that the nanotherapeutic prodrug strategy can lead to more selective activation in the tumor, yet in a manner that is more sensitive to variable enhanced permeability and retention (EPR) effects. Combination treatment with the nanoencapsulated MMAE prodrug and Pd-NP safely blocks tumor growth, especially when combined with a local radiation therapy regimen that is known to improve EPR effects, and represents a conceptual step forward in prodrug design.


Epidemiology of gastric cancer in Jos University Teaching Hospital Jos a 20 year review of cases.
Gastric cancer believed to be rare in the past in Africa, is now one of the leading cancer morbidity and mortality. It is now known gastric cancer is 2-3 times higher in males than females living in the same environment. We aim to describe the comprehensive histological characteristics of gastric cancer with age and sex distribution. The study site was Jos University Teaching Hospital situated in the capital of Plateau State. The hospital has a bed capacity of 530. The study materials were obtained from all stained specimens of gastric cancer recorded in the histopathology laboratory of the teaching hospital between 1985 to 2004. The biopsy site was noted. These were divided into the following groups: Cardia, body and an thrum/pyloric regions respectively. Or the information included age and sex of the patients. There were a total of 205 gastric cancer histological confirmed, out of 5705 malignant tumours recorded in the same period. There were a total of 145 cases in male and 60 in females giving a male: female ratio 2.4:1. The highest frequencies of gastric cancers were located in the anthral and cardia regions which accounted for 79% of all the tumours. Well differentiated adenocarcinoma (intestinal type) was the most frequent histological subtypes 51.2%), this was followed by poorly and diffusely infiltrating carcinoma. Other cancers included signet ring carcinoma, Non-Hodgkin's lymphoma and leiomyosarcoma in that order. The study has also demonstrated H pylori at the background of intestinal type adenocarcinoma which was seen in the body and an thrum. The study has shown that gastric cancer is not only common but it occur more males than females. The high proportion of H pylori in our environment might indicate a possible aetiological association. Therefore eradication of H pylori might reduce the prevalence of gastric carcinoma.


Incorporating problem based learning into medical curriculum: An experience from a medical college in Mangalore.
The Medical Council of India (MCI) has envisioned a change in the undergraduate medical curriculum by encouraging integrated teaching and Problem Based Learning (PBL). In this cross-sectional study 110 medical teachers of Kasturba Medical College, Mangalore were assessed regarding their perception on PBL. Independent t-test was applied to find out the difference in the mean perception scores regarding PBL among the teachers in pre/para-clinical and clinical departments and P < 0.05 was considered statistically significant. PBL as a teaching method was preferred by 65.2% medical teachers. The teachers from clinical departments (Mean 4.1, SD 0.8) perceived PBL sessions to be more effective than the traditional methods than those from the pre-clinical and para clinical departments (Mean 3.7, SD 3.7) and this difference was found to be statistically significant. (P =0.028). PBL can complement integrated teaching and motivates students towards self-learning, and apply the learnt concepts of basic specialties to clinical problem solving.


Hybridized electromagnetic-triboelectric nanogenerator for scavenging biomechanical energy for sustainably powering wearable electronics.
We report a hybridized electromagnetic-triboelectric nanogenerator for highly efficient scavenging of biomechanical energy to sustainably power wearable electronics by human walking. Based on the effective conjunction of triboelectrification and electromagnetic induction, the hybridized nanogenerator, with dimensions of 5 cm × 5 cm × 2.5 cm and a light weight of 60 g, integrates a triboelectric nanogenerator (TENG) that can deliver a peak output power of 4.9 mW under a loading resistance of 6 MΩ and an electromagnetic generator (EMG) that can deliver a peak output power of 3.5 mW under a loading resistance of 2 kΩ. The hybridized nanogenerator exhibits a good stability for the output performance and a much better charging performance than that of an individual energy-harvesting unit (TENG or EMG). Furthermore, the hybridized nanogenerator integrated in a commercial shoe has been utilized to harvest biomechanical energy induced by human walking to directly light up tens of light-emitting diodes in the shoe and sustainably power a smart pedometer for reading the data of a walking step, distance, and energy consumption. A wireless pedometer driven by the hybrid nanogenerator can work well to send the walking data to an iPhone under the distance of 25 m. This work pushes forward a significant step toward energy harvesting from human walking and its potential applications in sustainably powering wearable electronics.


Permeabilization-free en bloc immunohistochemistry for correlative microscopy.
A dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization-free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions from mice while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D EM.


Retinotopic organization of the developing retinotectal projection in the zebrafish embryo.
Developing retinal axons in the zebrafish embryo were stained with HRP or with the fluorescent dyes dil and diO to study the formation of the retinotectal projection. Retinal axons leave the eye at 34-36 hr postfertilization (PF), invade the tectum at 46-48 hr PF, and innervate the tectal neuropil at 70-72 hr PF. Dorsal and ventral axons occupy separate aspects of the optic nerve and tract and pass into their retinotopically appropriate ventral and dorsal hemitectum, respectively. Nasal and temporal axons are segregated in the nerve, mixed in the tract, and are coextensive over the rostral half of tectum until 56 hr PF. They then segregate again, due to the progression of nasal axons into the open caudal tectum. Thus, at 70-72 hr PF, dorsal and ventral as well as temporal and nasal axons occupy their retinotopically appropriate tectal quadrants. After ablation of the temporal retina prior to the time of axonal outgrowth, the nasal axons bypass the vacant rostral tectum to terminate in the caudal tectal half. Temporal axons in the absence of nasal axons remain restricted to their appropriate rostral tectal half, suggesting that nasal and temporal axons possess a preference for their retinotopically appropriate tectal domains. Measurements of individual terminal arbors and the tectal areas in embryos and in adult zebrafish showed that individual arbors are large with respect to the embryonic tectum but are about 14-15 times smaller than in the adult. However, the proportion of tectum covered by embryonic arbors is about 7 times larger than in the adult, suggesting that a higher precision of the adult projection is achieved as a result of a greater enlargement of the tectum than of the arbors.


CXXC5 Associates with Smads to Mediate TNF-α Induced Apoptosis.
Apoptosis is a widespread phenomenon and its dysregulation may result in a variety of human pathologies, such as cancer, autoimmune diseases and neurodegenerative disorders. CXXC-type zinc finger protein 5 (CXXC5) is commonly considered as a tumor suppressor undergoing deregulation or deletion in hematonosis. But it has implied involvement in apoptosis indirectly and the molecular mechanism remains unknown. In this study, we investigated CXXC5-induced apoptosis as well as its underlying mechanism. A fluorescence resonance energy transfer (FRET) assay suggested that CXXC5 induced cell death and caspase-3 activity in primary rat cortical neurons. Further colorimetric TUNEL assay, Hoechst staining and flow cytometric assay indicated a time-dependent apoptosis in which the activities of caspase-8 and caspase-3 were both regulated via CXXC5 according to enzymatic activity assay, Hoechst staining and Western blotting. Transcription reporter assay and Western blotting showed that CXXC5 resulted in activation of tumor necrosis factor-α (TNF-α), initiated the extrinsic apoptosis pathway and cross-linked with the intrinsic mitochondrial pathway. Being a bone morphogenetic protein 4 (BMP-4) downstream regulator, and also a transcription factor, cellular co-localization and co-immunoprecipitation results indicate that CXXC5 co-localized and interacted with Smads. Western blotting and nuclear fraction extraction implied that CXXC5 facilitated Smad3 phosphorylation and Smad4 nuclear translocation, and that co-expression of Smad together with CXXC5 resulted in higher TNF-α reporter activity. In sum, CXXC5 appears to regulate the TNF-α apoptosis pathway by associating with Smads.


Family investments in low-income children's achievement and socioemotional functioning.
Family processes and parenting practices help explain developmental differences between children in low- versus higher-income households. There are, however, few studies addressing the question of: what are the key family processes and parenting practices for promoting low-income children's growth? We address this question in the present study, following conceptual work framing family processes and parenting practices as investments in children. Using secondary analyses of longitudinal data on low-income children from birth to age 15 (n = 528), we estimate several potential family investments in achievement and socioemotional outcomes during early childhood, middle childhood, and adolescence. For achievement outcomes, family investments in learning stimulation were consistently the strongest predictors. For socioemotional outcomes, investments in an orderly household and close parental supervision were the most consistent and strongest predictors, even more so than sensitive parenting. (PsycINFO Database Record


Diagnosis of chronic pancreatitis by using apparent diffusion coefficient measurements at 3.0-T MR following secretin stimulation.
To prospectively measure pancreatic apparent diffusion coefficient (ADC) before and after secretin administration in subjects with and without chronic pancreatitis (CP) who underwent magnetic resonance (MR) cholangiopancreatography with diffusion-weighted (DW) imaging at 3.0 T. Institutional review board approval of this HIPAA-compliant study was obtained. Healthy volunteers, and patients with suspected and/or known CP who were scheduled for MR cholangiopancreatography, were recruited and gave written informed consent. All subjects underwent 3.0-T MR cholangiopancreatography, including serial DW imaging sequences (b = 0, 200, and 400 sec/mm(2)) acquired for 15 minutes after secretin administration. The referring gastroenterologist then classified subjects as healthy or with mild or severe CP, given endoscopic retrograde cholangiopancreatographic and/or clinical findings. CP severity was analyzed for sex and age. Mean presecretin and maximum postsecretin ADCs were compared between groups. Pairwise mean ADCs for healthy versus mild CP patient groups, healthy versus severe CP patient groups, and mild versus severe CP patient groups were compared. Presecretin ADC threshold levels for CP discrimination were calculated (P < .05). Thirty-two subjects were imaged; four CP patients were excluded owing to severe artifact, and the remaining 28 (15 healthy patients, five with mild CP, and eight with severe CP) comprised the study population. All CP patients had endoscopic retrograde cholangiopancreatographic confirmation of CP. Mild or severe CP patients were older than healthy patients; sex distribution did not vary among groups. Mean presecretin and maximum postsecretin ADCs were higher in healthy patients than in either mild or severe CP groups (P < .01), but did not vary between mild and severe CP groups (P = .25-0.28). An ADC of less than 220 x 10(-5) mm(2)/sec was optimal for delineating between healthy and CP patients. Pancreatic ADC obtained with DW imaging at 3.0 T prior to secretin administration may help diagnose CP; postsecretin ADC response does not distinguish CP severity.


INTENSIVE CARE UNIT PRESCRIPTIONS MUST FIT RISK FACTORS TO PREVENT STRESS ULCER BLEEDING.
The physiological stress of critically ill patients can trigger several complications, including digestive bleeding due to stress ulcers (DBSU). The use of acid secretion suppressants to reduce their incidence has become widely used, but with the current understanding of the risks of these drugs, their use, as prophylaxis in critically ill patients, is limited to the patients with established risk factors. To determine the appropriateness of the use of prophylaxis for stress ulcer bleeding in acutely ill patients admitted to intensive care units and to analyze the association of risk factors with adherence to the prophylaxis guideline. Retrospective, analytical study carried out in three general adult intensive care units. Electronic medical records were analyzed for epidemiological data, risk factors for DBSU, use of stress ulcer prophylaxis, occurrence of any digestive bleeding and confirmed DBSU. The daily analysis of risk factors and prophylaxis use were in accordance with criteria based on the Guidelines of the Portuguese Society of Intensive Care for stress ulcer prophylaxis. One hundred and five patients were included. Of the patient days with the opportunity to prescribe prophylaxis, compliance was observed in 95.1%. Of the prescription days, 82.35% were considered to be of appropriate use. Overt digestive bleeding occurred in 3.81% of those included. The occurrence of confirmed DBSU was identified at 0.95%. Multivariate analysis by logistic regression did not identify risk factors independently associated with adherence to the guideline, but identified risk factors with a negative association, which were spinal cord injury (OR 0.02 p <0.01) and shock (OR 0.36 p=0.024). The present study showed a high rate of adherence to stress ulcer prophylaxis, but with inappropriate use still significant. In the indication of prophylaxis, attention should be paid to patients with spinal cord injury and in shock.


Artificial Intelligence-Driven Single-Shot PET Image Artifact Detection and Disentanglement: Toward Routine Clinical Image Quality Assurance.
Medical imaging artifacts compromise image quality and quantitative analysis and might confound interpretation and misguide clinical decision-making. The present work envisions and demonstrates a new paradigm PET image Quality Assurance NETwork (PET-QA-NET) in which various image artifacts are detected and disentangled from images without prior knowledge of a standard of reference or ground truth for routine PET image quality assurance. The network was trained and evaluated using training/validation/testing data sets consisting of 669/100/100 artifact-free oncological 18 F-FDG PET/CT images and subsequently fine-tuned and evaluated on 384 (20% for fine-tuning) scans from 8 different PET centers. The developed DL model was quantitatively assessed using various image quality metrics calculated for 22 volumes of interest defined on each scan. In addition, 200 additional 18 F-FDG PET/CT scans (this time with artifacts), generated using both CT-based attenuation and scatter correction (routine PET) and PET-QA-NET, were blindly evaluated by 2 nuclear medicine physicians for the presence of artifacts, diagnostic confidence, image quality, and the number of lesions detected in different body regions. Across the volumes of interest of 100 patients, SUV MAE values of 0.13 ± 0.04, 0.24 ± 0.1, and 0.21 ± 0.06 were reached for SUV mean , SUV max , and SUV peak , respectively (no statistically significant difference). Qualitative assessment showed a general trend of improved image quality and diagnostic confidence and reduced image artifacts for PET-QA-NET compared with routine CT-based attenuation and scatter correction. We developed a highly effective and reliable quality assurance tool that can be embedded routinely to detect and correct for 18 F-FDG PET image artifacts in clinical setting with notably improved PET image quality and quantitative capabilities.


Trace elements and some extracellular antioxidant proteins levels in serum of patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic progressive autoimmune disorder with a wide spectrum of clinical and immunological abnormalities. In this study, we aimed to investigate the levels of serum zinc (Zn), copper (Cu), magnesium (Mg), manganese (Mn), iron (Fe), ceruloplasmin (Cp), transferrin (Trf), and albumin (Alb) in SLE and whether it is related to the severity of the clinical condition of this chronic disease. Cp and Cu levels were higher, while Trf, Alb, Zn, Mg, Mn, and Fe levels were lower in serum of patients with SLE (n = 27) compared with healthy controls (n = 20). The mechanisms by which these alterations occur in certain inflammatory conditions need to be elucidated. It is also obscure whether these alterations are a cause or a consequence of the inflammation. As a conclusion, alterations in the levels of the parameters in SLE may not be a reason for, but in fact a consequence of the disease itself.


Reconsidering perfect: a qualitative study of the experiences of internet-based cognitive behaviour therapy for perfectionism.
Internet-based cognitive behaviour therapy (ICBT) is a promising format for treating different psychiatric disorders. In addition, several clinical trials have found positive results when using it to target transdiagnostic processes, such as perfectionism. However, few qualitative investigations have been conducted on the experiences of clients undergoing such treatments. In the current study, clients completing 12-week guided ICBT for perfectionism responded to open-ended questions at post-treatment. In total, 30 out of 62 (48.4%) described their impressions of its content and the support provided by their guide. The results were analysed qualitatively using thematic analysis. Five themes were found in the responses: Learning how to do things differently, Noticing the positives, Feeling safe to be honest, A comfortable treatment format and Barriers to treatment. The results suggest that many clients were able to achieve a change in perspective in relation to their perfectionism and started facing their fears. They were also able to report the benefits of doing things differently as part of treatment, such as an improvement in their interpersonal relationships. Most clients were also positive about the treatment format, enjoying its flexibility and the encouragement offered by their therapist. However, obstacles such as conflicting commitments, personal difficulties, time-consuming and comprehensive treatment modules, and a desire for more support were brought up by some, suggesting that there are aspects that could be considered in the future.


Application research on reducing radiation-induced lung injury with a trigger operator based on overlap volume histogram (OVH) in breast cancer postoperative radiotherapy.
This study aims to develop a trigger operator based on the Overlap Volume Histogram (OVH) and examined its effectiveness in enhancing plan quality to minimize radiation-induced lung injury in postoperative radiotherapy for breast cancer. This trigger operator was applied for plan re-optimization to the previous Volumetric Modulated Arc Therapy (VMAT) plans of 16 left breast conserving surgery cases. These cases were categorized into a Contiguous Group (CG) and a Separated Group (SG) based on the relative position between the target and the Left-Lung (L-Lung). We investigated the changes in Vx, mean dose, and Normal Tissue Complication Probability (NTCP) values of organs-at-risk (OARs) before and after using the trigger operator. The Pairwise Sample T test was employed to evaluate the differences in indices between the two groups before and after optimizations. The trigger operator effectively initiated plan re-optimization. The values of V5, V10, V20, V30, and V40 of the L-Lung, as well as the mean dose of the heart, all decreased after re-optimization. The Pairwise Sample T test results showed statistically significant differences in the V20, V30, and V40 of the L-Lung in the CG (P < 0.01), and in the V5, V10, V20, V30, and V40 of the L-Lung in the SG (P < 0.01). Our findings suggest that the proposed trigger operator can improve plan quality, thereby reducing radiation-induced lung injury in postoperative radiotherapy for breast cancer.


Evaluation of Surface Characteristics of Denture Base Using Organic-Inorganic Hybrid Coating: An SEM Study.
Despite the numerous positive features of acrylic denture base, there are a number of undeniable associated disadvantages. The properties of denture base have been improved through various interventions including application of different types of filler and coatings. This study aimed to evaluate the surface roughness, thickness and coating quality of organic-inorganic coating on the denture base through scanning electron microscopy. Moreover, the colour change was evaluated visually. The organic-inorganic hybrid coatings were prepared. Acrylic discs of 10×10 mm were fabricated. The test discs were dipped in the hybrid coating and cured. In order to evaluate the surface roughness and coating thickness, the surface and cross-section of the samples in both coated and control groups were subjected to scanning electron microscopy. The colour change and transparency were visually evaluated with naked eyes. The data were statistically analyzed by student's t test. The hybrid materials perfectly covered all the surfaces of acrylic resin and established proper thickness. The coated group seemed smoother and flatter than the control group; however, the difference was not statistically significant ( for all parameters p > 0.05). It was quite a thin coating and no perceptible colour change was observed. The hybrid coating maintained good binding, caused no noticeable discoloration, and thoroughly covered the acrylic resin surface with uniform delicate thickness. It also slightly improved the acrylic resin surface roughness.


Efficient evaluation functions for evolving coordination.
Abstract This paper presents fitness evaluation functions that efficiently evolve coordination in large multi-component systems. In particular, we focus on evolving distributed control policies that are applicable to dynamic and stochastic environments. While it is appealing to evolve such policies directly for an entire system, the search space is prohibitively large in most cases to allow such an approach to provide satisfactory results. Instead, we present an approach based on evolving system components individually where each component aims to maximize its own fitness function. Though this approach sidesteps the exploding state space concern, it introduces two new issues: (1) how to create component evaluation functions that are aligned with the global evaluation function; and (2) how to create component evaluation functions that are sensitive to the fitness changes of that component, while remaining relatively insensitive to the fitness changes of other components in the system. If the first issue is not addressed, the resulting system becomes uncoordinated; if the second issue is not addressed, the evolutionary process becomes either slow to converge or worse, incapable of converging to good solutions. This paper shows how to construct evaluation functions that promote coordination by satisfying these two properties. We apply these evaluation functions to the distributed control problem of coordinating multiple rovers to maximize aggregate information collected. We focus on environments that are highly dynamic (changing points of interest), noisy (sensor and actuator faults), and communication limited (both for observation of other rovers and points of interest) forcing the rovers to evolve generalized solutions. On this difficult coordination problem, the control policy evolved using aligned and component-sensitive evaluation functions outperforms global evaluation functions by up to 400%. More notably, the performance improvements increase when the problems become more difficult (larger, noisier, less communication). In addition we provide an analysis of the results by quantifying the two characteristics (alignment and sensitivity discussed above) leading to a systematic study of the presented fitness functions.


Tobacco world: evaluation of a tobacco cessation training program for third-year medical students.
Training in tobacco cessation counseling is deficient in medical schools. Tobacco World, a tobacco cessation training program, was implemented in a family medicine clerkship and subsequently evaluated. In the pilot year, students were assigned to either standard clerkship training (comparison group) or a group that also received Tobacco World training (intervention group). All students received intervention training in the second year of the study. A 35-item questionnaire was administered before and after the four-week clerkship to assess knowledge, attitude, and confidence regarding tobacco cessation counseling. Intervention training was highly rated. Students in the intervention group from both years demonstrated significant improvements in some key measurements of knowledge, attitude, confidence, and increased frequency of tobacco cessation counseling. This smoking cessation training program addresses an underrepresented area of medical school education and has the potential to translate into improved smoking cessation counseling by future physicians.


Impaired polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis.
This study has investigated the chemotactic activity of polymorphonuclear cells (PMNs) isolated from the blood of patients with either articular rheumatoid arthritis (RA) or RA with extra-articular manifestations. A double fluorochrome immunofluorescent staining test has been employed to identify cell-associated immunoglobulins, probably immune complexes. The results suggest an inverse relationship between PMN chemotaxis and staining for cell-associated immunoglobulins, either surface bound or internalised. PMNs from RA patients showed reduced chemotaxis, and this was further reduced when RA PMNs were incubated for 30 minutes in autologous serum. A similar reduction in chemotaxis of normal PMNs occurred after incubation in RA sera. Preincubation of both RA and normal PMNs in RA serum (but not normal serum) resulted in an increase in the number of cells in which cell-associated immunoglobulins were demonstrable. This further reduction in RA PMN chemotaxis after exposure to autologous serum, together with an increase in immunoglobulin staining, may indicate selection of certain PMNs at the time of venepuncture due to cell margination. Such a selection process would call for a re-evaluation of previous studies of RA PMN function in relation to the disease process.


How commercial actors used different types of power to influence policy on restricting food marketing: a qualitative study with policy actors in Thailand.
There is limited research focused explicitly on understanding how commercial actors use different forms of power to influence policy decision making in Thailand. This study aimed to identify how the food industry has used structural, instrumental and discursive power to influence policy on restricting food marketing in Thailand. Qualitative study using in-depth semistructured interviews SETTINGS: Thailand. The interviews were conducted with 20 participants (of a total of 29 invited actors) from government, civil society, technical experts, international organisation and the food and advertising industry. Interview data were identified in the transcripts and analysed using abductive methods. Non-commercial actors perceived the commercial actors' structural power (its economic influence and structurally privileged position) as central to understanding the government having not implemented policy to restrict food marketing. The commercial actors' instrumental power was observed through sponsorship, campaign and lobbying activities. Discursive power was used by the industry to shift responsibility away from the food companies and onto their customers, by focusing their messaging on freedom of consumer choice and consumer health literacy. This study examined different types of power that commercial actors were perceived to use to influence policy to restrict food marketing in Thailand. The study showed arguments and institutional processes used to enhance commercial actors' ability to shape the policy decision for nutrition, public opinion and the broader regulatory environment. The findings help governments and other stakeholders to anticipate industry efforts to counter policy. The findings also suggest the need for governance structures that counter industry power, including comprehensive monitoring and enforcement in policy implementation.


Recurrent disc herniation and long-term back pain after primary lumbar discectomy: review of outcomes reported for limited versus aggressive disc removal.
It remains unknown whether aggressive disc removal with curettage or limited removal of disc fragment alone with little disc invasion provides a better outcome for the treatment of lumbar disc herniation with radiculopathy. We reviewed the literature to determine whether outcomes reported after limited discectomy (LD) differed from those reported after aggressive discectomy (AD) with regard to long-term back pain or recurrent disc herniation. A systematic MEDLINE search was performed to identify all studies published between 1980 and 2007 reporting outcomes after AD or LD for a herniated lumbar disc with radiculopathy. The incidence of short- and long-term recurrent back or leg pain and recurrent disc herniation was assessed from each reported LD or AD cohort and the cumulative incidence compared. Fifty-four studies (60 discectomy cohorts) met the inclusion criteria, reporting the outcomes of 13 359 patients after lumbar discectomy (LD, 6135 patients; AD, 7224 patients). The reported incidence of short-term recurrent back or leg pain was similar after LD (mean, 14.5%; range, 7-16%) and AD (mean, 14.1%; range, 6-43%) (P < 0.01). However, more than 2 years after surgery, the reported incidence of recurrent back or leg pain was 2.5-fold less after LD (mean, 11.6%; range, 7-16%) compared with AD (mean, 27.8%; range, 19-37%) (P < 0.0001). The reported incidence of recurrent disc herniation after LD (mean, 7%; range, 2-18%) was greater than that reported after AD (mean, 3.5%; range, 0-9.5%) (P < 0.0001). Review of the literature demonstrates a greater reported incidence of long-term recurrent back and leg pain after AD but a greater reported incidence of recurrent disc herniation after LD. Prospective, randomized trials are needed to firmly assess this possible difference.


Bacterial nucleoid-associated protein uncouples transcription levels from transcription timing.
The histone-like nucleoid-structuring (H-NS) protein binds to horizontally acquired genes in the bacterium Salmonella enterica serovar Typhimurium, silencing their expression. We now report that overcoming the silencing effects of H-NS imposes a delay in the expression of genes activated by the transcriptional regulator PhoP. We determine that PhoP-activated genes ancestral to Salmonella are expressed before those acquired horizontally. This expression timing reflects the in vivo occupancy of the corresponding promoters by the PhoP protein. These results are surprising because some of these horizontally acquired genes reached higher mRNA levels than ancestral genes expressed earlier and were transcribed from promoters harboring PhoP-binding sites with higher in vitro affinity for the PhoP protein. Our findings challenge the often-made assumption that for genes coregulated by a given transcription factor, early genes are transcribed to higher mRNA levels than those transcribed at later times. Moreover, they provide a singular example of how gene ancestry can impact expression timing. Importance: We report that gene ancestry dictates the expression behavior of genes under the direct control of the Salmonella transcriptional regulator PhoP. That is, ancestral genes are transcribed before horizontally acquired genes. This reflects both the need to overcome silencing by the H-NS protein of the latter genes and the architecture of the corresponding promoters. Unexpectedly, transcription levels do not reflect transcription timing. Our results illustrate how a bacterium can exhibit an elaborate temporal expression behavior among genes coregulated by a transcription factor even though the products encoded by the target genes do not participate in a morphological or developmental pathway.


Inhibition of Rho-kinase Attenuates Left Ventricular Remodeling Caused by Chronic Intermittent Hypoxia in Rats via Suppressing Myocardial Inflammation and Apoptosis.
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. This study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms. Adult male Sprague-Dawley rats suffered from CIH or normoxia stimulus and were intervened with vehicle or fasudil (10 mg·kg·d, intraperitoneal injection) for 6 weeks. In this study, treatment with fasudil significantly reversed intermittent hypoxia-induced histopathological transformations and ultrastructural changes in rat myocardium. Moreover, fasudil downregulated the protein levels of RhoA and phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1), thus effectively inhibited the activation of RhoA/ROCK signaling pathway. Simultaneously, activity of nuclear factor (NF)-kB was suppressed by fasudil, which was accompanied by reduced NF-kB downstream inflammatory genes including interleukin-6, tumor necrosis factor-a and monocyte chemotactic protein-1, and apoptosis. These results suggest that fasudil attenuates myocardial remodeling in CIH rats, at least partly by suppressing activation of NF-kB. Inhibition of the RhoA/ROCK pathway could become an important therapeutic target in the prevention of OSAS-related cardiomyopathy.


Methanocalculus pumilus sp. nov., a heavy-metal-tolerant methanogen isolated from a waste-disposal site.
A mesophilic hydrogenotrophic methanogen, strain MHT-1T, was isolated from the leachate of a sea-based site for solid waste disposal (the port of Osaka, Japan). Strain MHT-1T was found to be an irregular coccus and was able to use H2/CO2 and formate as energy sources. Acetate was required for growth. The optimum temperature and pH for growth were 35 degrees C and 6.5-7.5, respectively. Strain MHT-1T was resistant to high concentrations of several heavy metals such as CdCl2 and CuSO4. The G+C content of the DNA was 51.9 mol%. Analysis of the 16S rRNA gene revealed that the isolate was a member of the genus Methanocalculus but distinct from its nearest neighbour, Methanocalculus halotolerans, there being a sequence similarity of 98.9%. DNA-DNA hybridization analysis revealed 51% relatedness with the DNA of M. halotolerans strain SEBR 4845T. The optimum NaCl concentration was 1.0%, whereas the optimum in M. halotolerans was 5.0%. A new species, Methanocalculus pumilus, is proposed for strain MHT-1T. The type strain is MHT-1T (= DSM 12632T = JCM 10627T).


The methylation pattern of tRNA genes in Xenopus laevis.
The methylation sensitive restriction enzymes Hha I and Hpa II were used to analyse the methylation pattern of a tRNA gene cluster in germ line and somatic DNA of Xenopus laevis. A single tDNA repeat containing 8 tRNA genes was studied and all copies were found to be fully modified in sperm DNA. In the DNA from erythroid cells, hepatocytes, kidney and brain, most tDNA repeats were found to be fully modified. However, in a fraction of the repeats, specific demethylated sites can be detected, giving rise to a pattern which does not vary significantly from one tissue to another. Although our results do not allow a straightforward correlation between hypomethylation and tRNA gene transcription, they are in agreement with the observation that hypomethylation accompanies differentiation and development.


Effective handling of nonlinear distortions in CO-OFDM using affinity propagation clustering.
We experimentally demonstrate a system-agnostic and training-data-free nonlinearity compensator, using affinity propagation (AP) clustering in single- and multi-channel coherent optical OFDM (CO-OFDM) for up to 3200 km transmission. We show that AP outperforms benchmark deterministic and clustering algorithms by effectively tackling stochastic nonlinear distortions and inter-channel nonlinearities. AP offers up to almost 4 dB power margin extension over linear equalization in single-channel 16-quadrature amplitude-modulated CO-OFDM and a 1.4 dB increase in Q-factor over digital back-propagation in multi-channel quaternary phase-shift keying CO-OFDM. Simulated results indicate transparency to higher modulation format orders and better efficiency when a multi-carrier structure is considered.


Study on alcohol dependence and factors related to erectile dysfunction among aborigines in Taiwan.
Relatively few studies have addressed the risk factors of erectile dysfunction (ED) in Taiwanese- most have described ED and medical problems in the general population. In this study, the cardiovascular risk factors of ED among aborigines in Taiwan were investigated. However, alcohol dependence (AD) was prevalent in Taiwan's aborigine population. So this study also focused on the relationship among AD, the cardiovascular risk factors and ED. A cross-sectional study was conducted, and data was obtained from a baseline survey of 192 aboriginal adults (35-75 years of age). The participants' demographic data, AD, markers of endothelial function, serum testosterone, and ED status were assessed. Ninety-four (49%) of the 192 participants had a history of alcoholism and 79 (84%) of those with alcoholism had ED. The study reported that AD and hyperlipidemia, metabolic syndrome (MetS), ED, abnormality of testosterone, and high-sensitivity C-reactive protein are highly prevalent among the aborigines. Factors that may affect ED included age, AD, central obesity, diabetes mellitus, hyperlipidemia, hypertension, MetS, and testosterone. ED is highly prevalent among aborigines with the risk factors of AD, MetS, old age, and abnormal testosterone serum level. MetS, atherosclerosis, and ED are risk factors for cardiovascular diseases. Hence, an increased focus on Taiwanese aborigines with ED is necessary.


Stereospecific analysis of triglycerides: an alternative method.
A new method for the stereospecific analysis of triglycerides is demonstrated on a corn oil which had been analyzed by an earlier method. The triglyceride (1,2,3-triacyl L-glycerol) was partially degraded by means of methyl magnesium bromide. The 1,3-diglyceride was then isolated, and converted into l-2-phosphatidyl phenol, from which phospholipase A cleaved the fatty acids from position 1. The remaining lysophosphatide was analyzed to yield the fatty acids at position 3 of the original triglyceride. The fatty acid composition of position 2 was determined after hydrolysis of the corn oil with pancreatic lipase. This method has the advantage over the one reported previously of yielding direct analyses of the fatty acids in each of the three positions.


Surgical Considerations in the Treatment of Ankle Instability.
OBJECTIVE: To review the surgical indications, techniques, biomechanical testing, and clinical results reported for the most common surgical techniques used to treat ankle instability. DATA SOURCES: We searched MEDLINE from 1960-2001 using the terms ankle instability, functional ankle instability, mechanical ankle instability, ankle ligament surgery, Broström, Chrisman-Snook, and Evans. DATA SYNTHESIS: Although 80% to 85% of acute ankle sprains are successfully treated with a functional ankle-rehabilitation program, the remaining 15% to 20% have recurrent ankle instability and reinjury, necessitating surgical intervention. The fundamentals of the surgical approach to lateral ankle instability are based on the anatomy of the lateral ankle ligaments, the anterior talofibular ligament, and the calcaneofibular ligament. Ankle-instability surgery has been broadly divided into an anatomic repair consisting of an imbrication of the lateral ligamentous complex and an ankle-ligament reconstruction. An ankle-ligament reconstruction weaves a harvested tendon graft, most commonly the peroneus brevis, to augment the lateral ligaments of the ankle. Goals of surgery are to reestablish ankle stability and function without compromising motion and without complications. Anatomic repair and imbrication of the lateral ligament complex with the Gould modification has an 85% to 95% success rate, and the risk of associated nerve injuries is low. This approach provides increased stability by reinforcing local host tissue, preserving subtalar and talocrural motion, eliminating the comorbidity associated with tendon-graft harvest, and offering a quicker functional recovery. One concern in using the anatomic approach is the resultant strength of the repair, although the literature does not support this concern. Ankle-reconstruction procedures that sacrifice tendons are thought to provide a stronger construct, and hence, more stability. This increased stability results in loss of talocrural and subtalar range of motion, prolonging recovery and decreasing sport performance. Adjacent nerve injury is more common with ankle-ligament reconstruction. CONCLUSIONS/RECOMMENDATIONS: Based on the literature, we believe that a modified Broström lateral-ligament repair should be considered the first choice for persistent ankle instability refractory to a functional ankle-rehabilitation protocol. Ankle reconstruction with tendon augmentation should be reserved for patients with generalized ligamentous laxity or long-standing ligamentous insufficiency or as a salvage procedure in a patient with a failed modified Broström lateral-ligament repair.


Adenine nucleotides and magnesium ions in relation to control of mammalian cerebral-cortex hexokinase.
1. The kinetics of inhibition of brain soluble cytoplasmic hexokinase by ADP were examined in relation to variations in the concentrations of Mg(2+) and ATP. The type of inhibition observed was dependent on the Mg(2+)/ATP ratio. 2. ADP at Mg(2+)/ATP ratios 2:1 exhibited inhibition of the ;mixed' type; at Mg(2+)/ATP ratios 1:1 the inhibition appeared to be competitive with regard to ATP. 3. Inhibition by free ATP was observed when the Mg(2+)/ATP ratio was less than 1:1. The inhibition was also of the ;mixed' type with respect to MgATP(2-). 4. The inhibitions due to ADP and to free ATP were not additive. The results suggested that there may be up to four sites in the soluble enzyme: for glucose, glucose 6-phosphate, ADP and MgATP(2-). 5. The ;free' non-particulate intracellular Mg(2+) concentration was measured and concluded to be about 1.5mm. 6. The concentrations in vivo of Mg(2+) and ATP likely to be accessible to a cytoplasmic enzyme are suggested to be below those that yield maximum hexokinase rates in vitro. The enzymic rates were measured at relevant suboptimum concentrations of Mg(2+) and ATP in the presence of ADP. Calculations that included non-competitive inhibition due to glucose 6-phosphate (56-65% at 0.25mm) resulted in net rates very similar to the measured rates for overall glycolysis. This system may therefore provide a basis for effective control of cerebral hexokinase.


SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis.
SPOC1 (PHF13) is a recently identified protein that has been shown to dynamically associate with somatic chromatin, to modulate chromatin compaction and to be important for proper cell division. Here, we report on the expression of SPOC1 in promyelocytic leukaemia zinc finger (PLZF)-positive undifferentiated spermatogonial stem cells (SSCs) of the mouse testis. To investigate further the biological function of SPOC1 in germ cells we generated Spoc1 mutant mice from a gene-trap embryonic stem cell clone. Postpubertal homozygous Spoc1(-/-) animals displayed a pronounced progressive loss of germ cells from an initially normal germ epithelium of the testis tubules leading to testis hypoplasia. This loss first affected non-SSC stages of germ cells and then, at a later time point, the undifferentiated spermatogonia. Remarkably, successive loss of all germ cells (at >20 weeks of age) was preceded by a transient increase in the number of undifferentiated A(aligned) (A(al)) spermatogonia in younger mice (at >10 weeks of age). The number of primary Spoc1(-/-) gonocytes, the proliferation of germ cells, and the initiation and progression of meiosis was normal, but we noted a significantly elevated level of apoptosis in the Spoc1(-/-) testis. Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis.


Dietary choices are influenced by genotype, mating status, and sex in Drosophila melanogaster.
Mating causes many changes in physiology, behavior, and gene expression in a wide range of organisms. These changes are predicted to be sex specific, influenced by the divergent reproductive roles of the sexes. In female insects, mating is associated with an increase in egg production which requires high levels of nutritional input with direct consequences for the physiological needs of individual females. Consequently, females alter their nutritional acquisition in line with the physiological demands imposed by mating. Although much is known about the female mating-induced nutritional response, far less is known about changes in males. In addition, it is unknown whether variation between genotypes translates into variation in dietary behavioral responses. Here we examine mating-induced shifts in male and female dietary preferences across genotypes of Drosophila melanogaster. We find sex- and genotype-specific effects on both the quantity and quality of the chosen diet. These results contribute to our understanding of sex-specific metabolism and reveal genotypic variation that influences responses to physiological demands.


Treatment of hip fractures in elderly and senile patients.
Hip fractures in elderly and senile patients are associated with a high incidence of morbidity and mortality. For this reason, restoration of function rather than restoration of the hip must be the first concern. In senile patients with intertrochanteric fractures, condylocephalic fixations is preferred because of the decreased infection rate. In patients with severe osteoporosis, bed rest with traction as needed for comfort may be preferable. Fractures of the femoral neck in this group are best treated with percutaneous pin fixation. In the elderly ambulatory patient with no more than minimal confusion, compression screw fixation with severe osteoporosis in these patients should have adjunctive use of methylmethacrylate. In this group, fractures of the femoral neck in our experience are better treated with a cemented endoprosthesis or total hip arthroplasty.


How alpha-crystallin prevents the aggregation of insulin.
Using steady-state, polarized, and phase-modulation fluorometry, the dithiothreitol-induced denaturation of insulin and formation of its complex with alpha-crystallin in solution were studied. Prevention of the aggregation of insulin by alpha-crystallin is due to formation of chaperone complexes, i.e. interaction of chains of the denatured insulin with alpha-crystallin. The conformational changes in alpha-crystallin that occur during complex formation are rather small. It is unlikely that N-termini are directly involved in the complex formation. The 8-anilino-1-naphthalenesulfonate (ANS) is not sensitive to the complex formation. ANS emits mainly from alpha-crystallin monomers, dimers, and tetramers, but not from oligomers or aggregates. The possibility of highly sensitive detection of aggregates by light scattering using a spectrofluorometer with crossed monochromators is demonstrated.


Artificial liver support systems in the management of complications of cirrhosis.
Acute-on-chronic liver failure (ACLF) is associated with multiorgan dysfunction requiring intensive care support and carries an exceptionally high risk of mortality. Decompensation of liver cirrhosis is triggered by different precipitating events but the final common pathway is hypothesized to be unregulated systemic inflammation. The concept of an artificial liver that may impact favorably upon the inflammatory response and provide liver function to prevent complications seems to be promising. This article aims to describe the currently available artificial and bioartificial systems and reviews their effect on different complications of cirrhosis, such as liver function and hepatic hemodynamics, renal function and systemic hemodynamics, hepatic encephalopathy, inflammation/infection, and coagulation. Due to the difficulties in studying large patient numbers with ACLF and the heterogeneity of this patient group, only limited data on survival are available. The currently available studies indicate that there is a survival benefit for artificial and bioartificial liver support in certain subgroups of patients; however, further studies are warranted. At present several studies in this field are under way. In this review several of the companies interested in the manufacture of the respective devices provide an up-to-date report of ongoing trials. In summary, artificial and bioartificial liver support are already playing important roles in the treatment of complications of ACLF. Better understanding of the pathophysiology of ACLF, further development of the current systems, and their evaluation in appropriately controlled clinical studies are necessary to translate their application to improvement in outcome of patients with ACLF.


Phosphine-gold(I) compounds as anticancer agents: general description and mechanisms of action.
Gold complexes have been explored as metallodrugs with great potential applications as antitumoral agents. In particular, gold-phosphine derivatives seemed quite promising since the use of the antiarthritic auranofin drug (thiolate-Au-PEt3 complex) presented also biological activity against different cancer cells. So, different auranofin analogues have been explored within this context and for this reason, the main number of phosphine-gold complexes developed with this goal contain thiolate ligands. Other complexes have been also studied such as tetrahedral bis(phosphine)gold(I) and phosphine-gold-halides. Very recently, phosphine-gold-alkynyl complexes have also shown very interesting biological activities although few reports are published related to them. Their mechanism of action seems to be clearly different that the used by platinum drugs (DNA intercalating processes) and recent studies point to be related to the inhibition of Trx reductase. Cellular uptake and biodistribution studies are well reported in the original works but the use of luminescence techniques is relatively less explored. For this, the use of these techniques is also specifically reported in this review.


Adipokines demonstrate the interacting influence of central obesity with other cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults.
Metabolic syndrome (MetS) or prediabetes is a complex disorder that is defined by a clustering of cardiometabolic risk factors, including obesity, hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance. Among cardiometabolic risk factors, central obesity plays a key role in the development of MetS through alterations in the secretion of adipokines and interacts with other MetS risk factors to unfavorably influence overall cardiometabolic risk. Obesity has grasped epidemic proportions in Asia, which has the highest number of people with diabetes in the world. But, the importance of central obesity in the clustering of all four MetS risk factors or vice versa in predicting severity of MetS has not yet been investigated in Asian population. Therefore, the present study examined the influence of central obesity on circulating levels of adipokines through its interaction with the clustering of cardiometabolic risk factors of MetS including hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension in Hong Kong Chinese adults. Blood samples from 83 Hong Kong Chinese adults, who were previously screened for MetS according to the guideline of the United States National Cholesterol Education Program Expert Panel Adult Treatment Panel III criteria were selected. Insulin and adipokines, including visfatin, chemerin, plasminogen activator inhibitor-1 (PAI-1), resistin, C-C motif chemokine ligand 2 (CCL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), leptin and adiponectin were assessed. The interacting effect of central obesity with all of the other four MetS risk factors increased the proinflammatory status of adipokines (TNF-α, leptin) and decreased the anti-inflammatory status of adipokine (adiponectin). Our results indicate that the inflammatory status of MetS may be more severe in the presence of central obesity. Adipokines, as biomarkers for pathophysiological changes, may help to improve early patient identification and to predict MetS-associated morbidity and mortality.


Thermogenesis in the avian body and the role of the pineal in thermoregulation.
In the absence of the brown adipose tissue, maintenance of body temperature (Tb) in birds is generally believed to be by shivering thermogenesis (ST), though evidence for nonshivering thermogenesis (NST) is becoming available. In ST, glycogen utilization by the anaerobic white muscle fibers forms the main energy process, while the aerobic red fibers appear to be largely involved in NST. Winter pigeons maintained on a 12 h photophase (PP) and 12 h scotophase (SP) had higher Tb during PP in both warm (25 degrees C) and cold (3 degrees C) acclimated birds. In pinealectomized (Px) pigeons Tb was higher than in controls during PP and SP without affecting the circadian thermal rhythm. This hyperthermic effect (HE) of pinealectomy was nullified with subcutaneous implantation of melatonin. These warm acclimated winter Px pigeons when examined for Tb next winter, did not show HE. Summer Px pigeons did not show HE as did the winter Px pigeons, indicating seasonal difference. No significant difference in circulating levels of T3 and T4 was seen in the summer as well as winter warm acclimated Px pigeons. These results suggest that the HE observed in warm acclimated Px winter pigeons was not mediated by the thyroid and that the pineal has no influence on the thyroid in the warm acclimated birds. The slightly higher HE seen in cold (3 degree C) acclimated Px pigeons may well be due to the influence of the thyroid.


Uptake of metronidazole and its effect on viability in trichomonads and Entamoeba invadens under anaerobic and aerobic conditions.
[(14)C]metronidazole used at the chemotherapeutic concentration of 10 mug/ml is taken up rapidly by the anaerobic protozoa Tritrichomonas foetus, Trichomonas vaginalis, and Entamoeba invadens kept under anaerobic conditions. It can be calculated that within 30 to 60 min the intracellular concentration of the label is 50 to 100 times higher than in the medium. The presence of air markedly suppresses the uptake in the trichomonads and abolishes it in E. invadens. The suppression disappears after anaerobic conditions are established. The rate of uptake in T. foetus is dependent on the concentration of the drug in the range studied (1 to 200 mug/ml). Analysis of double reciprocal plots suggests that the drug enters the cells predominantly or exclusively by diffusion. The major factor driving the uptake is most likely the intracellular biotransformation of the compound. If less than 3 mug of drug per mg of protein is taken up by T. foetus no decrease in viability is observed. Above this level the cytotoxic activity corresponds roughly to the amount accumulated in the cell, irrespective of whether the conditions are anaerobic or aerobic.


Image analysis using a dual-tree M-band wavelet transform.
We propose a two-dimensional generalization to the M-band case of the dual-tree decomposition structure (initially proposed by Kingsbury and further investigated by Selesnick) based on a Hilbert pair of wavelets. We particularly address: 1) the construction of the dual basis and 2) the resulting directional analysis. We also revisit the necessary pre-processing stage in the M-band case. While several reconstructions are possible because of the redundancy of the representation, we propose a new optimal signal reconstruction technique, which minimizes potential estimation errors. The effectiveness of the proposed M-band decomposition is demonstrated via denoising comparisons on several image types (natural, texture, seismics), with various M-band wavelets and thresholding strategies. Significant improvements in terms of both overall noise reduction and direction preservation are observed.


Matrix metalloproteinases involvement in pathologic conditions.
Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.


A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis.
Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥ 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase > 3 × baseline and greater than the upper limit of normal range, and eight patients had serum creatinine > 33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to < 250 ng/mL. Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population.


Eating disorders in older women: does late onset anorexia nervosa exist?
The objective of this study is to determine whether eating disorders can present for the first time in older people. This is a descriptive study of patients above the age of 50 years who have presented to a national eating disorder center within the last 10 years. Thirty-two patients were identified; data were available for 26 of these patients and 11 agreed for further interview and questionnaire completion. There were no cases where the eating disorder had its onset late in life. Of the 11 interviewed, six participants retained a diagnosis of anorexia nervosa, four had Eating Disorder Not Otherwise Specified and only one was recovered. Comorbid depression was universal in those still suffering with an eating disorder diagnosis, and their level of social functioning was impaired. Anorexia nervosa is a chronic and enduring mental illness that, although rare, can be found in older people. In our sample, we found no evidence of late-onset disorders; all described cases were lifelong.


Persistence of group B Streptococcus vaginal colonization and prevalence of hypervirulent CC-17 clone correlate with the country of birth: a prospective 3-month follow-up cohort study.
To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.


Case reports. 2. Accidental strangulation: a case report.
Accidental strangulation, though reported, is uncommon. We report a case of an unusual accidental strangulation in which the floating end of the 'saree' of the pillion rider of a two-wheeler motorcycle got entangled in the moving rear wheel and constricted her neck. To our knowledge this is the first case of its type involving a two-wheeler motorcycle. Comments are also given on traditional Indian wear and safety measures required in two-wheelers to prevent such incidents.


The epidemiology of methicillin-resistant Staphylococcus aureus colonisation and infection.
Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common nosocomial pathogen in health care facilities throughout the world. Overall, approximately two-thirds of nosocomial cases and outbreaks have occurred in critical care units. Major risk factors for colonisation and infection in nursing homes include age, underlying conditions, nasal colonisation and the presence of indwelling devices such as catheters, tracheostomies and nasogastric tubes. In general, patients with MRSA infections in an acute care facility are more likely to have had a prolonged hospital stay, to have received prior antibiotics and to have severe underlying disease, than patients infected with methicillin-susceptible S. aureus. Risk factors for MRSA bacteraemia include: a higher frequency of severe underlying disease, poorer underlying prognosis, prior antibiotic therapy, prolonged hospitalisation, intravascular catheterisation, and intensive care unit location. Risk factors for developing MRSA postoperative wound infections include: prior antimicrobial therapy, prolonged hospitalisation and severity of underlying disease. Little data are available to identify specific risk factors for colonisation or infection of burn wounds by MRSA.


Abnormal brown adipose composition and beta-adrenoceptor binding in obese Zucker rats.
The composition, morphology, beta-adrenergic receptor binding, and in vitro lipolysis were examined in lean and obese, 5- to 6-mo-old male Zucker rat interscapular brown adipose tissue (IBAT). IBAT pads from obese rats were heavier (283%), had more lipid (700%), and more (75%)( and larger (83%) adipocytes than those from lean rats. Also, IBAT from obese rats had no multiloculated cells, and 50% of their IBAT adipocytes were the size of white fat cells. High affinity binding for (-)-[3H]dihydroalprenolol (KD, 15-18 nM), as well as the estimated KD values for binding and the 1/2 Vmax values for adrenergic agonist-induced lipolysis were similar in isolated IBAT cells from lean and obese rats. However, adipocytes from IBAT in obese rats had 75% fewer high affinity beta-adrenergic binding sites per cell (Bmax) compared to those in lean rats. These findings are most compatible with the infiltration of IBAT by white adipocytes. Such infiltration would be expected to reduce the overall thermogenic capacity of IBAT in obese Zucker rats and thereby contribute to the maintenance of their obesity.


Predicting Adherence and Persistence with Oral Bisphosphonate Therapy in an Integrated Health Care Delivery System.
Examining drug exposure is essential to pharmacovigilance, especially for bisphosphonate (BP) therapy. To examine differences in 4 measures of oral BP exposure: treatment discontinuation, adherence, persistence, and nonpersistence. Among women aged ≥ 50 years who initiated oral BP therapy during 2002-2007 with at least 3 years of health plan membership follow-up, discontinuation was defined by evidence of no further treatment during the study observation period. Among those with at least 2 filled BP prescriptions during the study period, adherence was calculated for each year of follow-up using the (modified) proportion of days covered (mPDC) metric that allows for stockpiling of prescription/refills overlap ≤ 30 days supply. Persistence was quantified by treatment duration, allowing a gap of up to 60 days between prescription/refill days covered. Nonpersistence was quantified by the periods without drugs outside this allowable gap. Multivariable logistic regression was used to compare age and race groups and the relationships of early adherence (adherence during the first year) with subsequent adherence. Among 48,390 women initiating oral BP therapy and followed for 3 years, 26.7% discontinued in year 1, and 14.7% of the remaining 35,456 women discontinued in year 2. Discontinuation rates were slightly higher (29.4%, P < 0.001) for women aged ≥ 75 years and somewhat lower (21.1%, P < 0.001) for Asian women. During the first year, 60.4% of the women achieved an mPDC of ≥ 75%, with demographic differences in adherence similar to that seen for treatment discontinuation. Over the 3 years, the median mPDC levels for BP therapy were 86%, 84%, and 85% in years 1, 2, and 3, respectively, for those receiving treatment. Cumulative persistence was 2.3 years (median, IQR = 1.0-3.0) overall and slightly greater for Asian versus white women and lower for older women. There were 18,174 (42.9%) women with at least 1 period of nonpersistence during 3 years follow-up in excess of the 60-day allowable gap between prescription/refills (median cumulative nonpersistence = 0.65, IQR = 0.30-1.25 years). Women with mPDC ≥ 75% during the first year had a 12-fold and 6-fold increased odds of mPDC ≥ 75% during year 2 and year 3, respectively. BP discontinuation rates are highest for women during the first year. Among those continuing treatment in subsequent years, adherence rates were relatively stable. Persistence and adherence varied slightly by age and was somewhat higher in Asians, contributing to differences in cumulative BP exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent 1-2 years. Hence, subgroups of patients receiving oral BP drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use. This study was supported by grants from the Kaiser Permanente Northern California Community Benefit Program and the National Institutes of Health, 1R01AG047230-01A1. The opinions expressed in this publication are solely the responsibility of the authors and do not represent the official views of Kaiser Permanente or the National Institutes of Health. Hui, Yi, and Chandra have received past research funding from Amgen not related to the current study. Adams has received research funding from Amgen, Merck, and Otsuka not related to the current study. Niu has received research funding from Bristol-Myers Squibb not related to the current study. Ettinger has received past legal fees in litigation involving Fosamax. Lo has received past research funding from Amgen and current research funding from Sanofi not related to the current study. The data from this study were presented at the Academy of Managed Care Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Hui and Lo, along with Adams, Niu, Yi, and Ettinger. Hui took the lead in data collection, along with Chandra, and data interpretation was performed by Niu, Yi, and Lo, along with the other authors. The manuscript was written by Hui, Adams, and Lo, along with Niu, Yi, and Ettinger, and revised by Ettinger, Hui, Lo, and Niu, along with the other authors.


Adherence to oral migraine-preventive medications among patients with chronic migraine.
Chronic migraine (CM) is a disabling disorder characterized by ≥15 headache days per month that has been shown to significantly reduce quality of life. Migraine-prevention guidelines recommend preventive medications as the standard of care for patients with frequent migraine. The aim of this study was to assess adherence to 14 commonly prescribed oral migraine-preventive medications (OMPMs) among patients with CM. Retrospective claims analysis of a US claim database (Truven MarketScan® Databases) was queried to identify patients who were at least 18 years old, diagnosed with CM, and initiated an OMPM (antidepressants, beta blockers, or anticonvulsants) between January 1, 2008 and September 30, 2012. Medication possession ratios (MPR) and proportion of days covered (PDC) were calculated for each patient. A cutoff of ≥80% was used to classify adherence. The odds of adherence between OMPMs were compared using logistic regression models. Of the 75,870 patients identified with CM, 8688 met the inclusion/exclusion criteria. Adherence ranged between 26% to 29% at six months and 17% to 20% at 12 months depending on the calculation used to classify adherence (PDC and MPR, respectively). Adherence among the 14 OMPMs was similar except for amitriptyline, nortriptyline, gabapentin, and divalproex, which had significantly lower odds of adherence when compared to topiramate. Adherence to OMPMs is low among the US CM population at six months and worsens by 12 months.


The collection and reporting of measures of deprivation in musculoskeletal research: An international survey study.
The reporting of deprivation measures is typically poor in musculoskeletal (MSK) research. To explore MSK researcher's perspectives on the deprivation indices and measures that are, or could be, collected and reported in their studies, and potential barriers and facilitators to collecting these data. An online international survey was undertaken to determine knowledge, use and reporting of deprivation indices and measures by MSK researchers and the factors which influence this. Data were analysed using descriptive statistics. 42 respondents from 16 countries completed the survey. The index of multiple deprivation was the most well-known measure (26%) although only 17% had reported data from this index. Most commonly reported markers of deprivation were: employment (60%), education (60%) and ethnicity (50%). Most common barriers to collecting these data included: uncertainty on perceived importance of deprivation measures (79%), what should be collected (71%), and concerns on missing data and sensitivities from participants reluctant to provide this information (33%). Consensus on necessary measures to be collected and reported (88%) and improved awareness of the relationship between deprivation and MSK health (79%) were considered key activities to improve deprivation recording in MSK research. There is poor awareness of the collection and reporting of deprivation measures in MSK research. Greater understanding on the importance of these data in reducing inequalities in MSK care is needed to facilitate improvement. This would enable greater assessment of generalisability and to assess whether interventions have different effects in people from different socio-economic groups.


Endoluminal pulmonary artery banding: technique, applications and results.
Occasionally pulmonary artery banding is necessary to reduce pulmonary arterial blood flow and pressure in patients who cannot be repaired in a single stage. Traditional extraluminal PAB can be associated with significant morbidity. We describe our technique, applications, and results of endoluminal pulmonary artery banding (EPAB) with and without creation of an aortopulmonary window (APW) for complex cardiac anomalies. Thirty-two patients underwent EPAB; 20 patients had simultaneous creation of an APW. Median patient age was 40 days (range, 2 to 3,210); median weight was 3.5 kg (range, 2.4 to 23 kg). Endoluminal pulmonary artery banding fenestrations of 2 to 8 mm were centrally placed in a Dacron patch that was attached circumferentially and intraluminally in the main pulmonary artery. Fenestrations were sized by presence of APW and patient weight. Thirty-one of 32 patients underwent associated cardiac procedures. The mean follow-up period was 2.6 years (range, 0 to 15.5). Overall early mortality was 31% (10 of 32); 8% in EPAB alone (1 of 12) and 45% for EPAB+APW (9 of 20). Of the early deaths, 7 of 10 had severe, preoperative ventricular dysfunction. There was 1 early EPAB-related complication requiring band revision for relief of partial obstruction of the APW. At hospital dismissal, the mean pressure gradient after EPAB was 55.1 +/- 8.4 mm Hg as assessed by echocardiography. No patient experienced distal pulmonary hypertension, distortion, or band occlusion. There were 6 late deaths. At late follow-up, 5 patients underwent band revision, and complete repair was accomplished in 10 patients. Endoluminal pulmonary artery banding provided a consistently effective and durable reduction in pulmonary arterial blood flow with no pulmonary artery distortion. Early mortality was low for EPAB alone. Endoluminal pulmonary artery banding alone is preferred when controlled pulmonary blood flow and cardiopulmonary bypass are required to address intracardiac abnormalities. The role of EPAB with APW needs to be defined.


Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.
Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.


Attentional state modulates the effect of an irrelevant stimulus dimension on perception.
Covariations of acoustic features provide redundancy in rapidly changing soundscapes: Hearing one feature enables a listener to infer another if these 2 features normally covary. However, it is unknown whether situational demands affect the degree to which covariations influence perceptual inferences. We exploited a perceptual interdependency between modulation rate and frequency and examined, in 6 experiments, whether challenging situations would alter the degree to which people rely on frequency information to make decisions about modulation rate. Participants listened to amplitude-modulated (AM) sounds with modulation rates (∼5 Hz) either decreasing or increasing over time and identified the direction of the rate change. Participants were instructed to ignore carrier frequency, which either decreased or increased (∼1,300 Hz) over time. We observed that participants were more likely to perceive the modulation rate as slowing down when frequency decreased and as speeding up when frequency increased (AM-rate change illusion). The magnitude of the illusion increased when uninformative cues (compared with informative cues) prohibited regulation of attention to sounds, and under distraction introduced by a concurrent visual motion-tracking task. The evidence suggests that the attentional state affects how strongly people rely on featural covariations to make perceptual inferences. (PsycINFO Database Record


Interservice Physician Assistant Program: Educators for an Expanding Profession.
The number of physician assistant (PA) programs has increased exponentially across the past decade, and the demand for PAs will likely remain strong through 2025. Because of this rapid growth, both new and established PA programs face significant challenges in recruiting experienced educators. We describe the value of using PAs trained through the Interservice Physician Assistant Program (IPAP) as civilian PA educators. The literature on IPAP and its graduates proved too limited to conduct a formal systematic review. We searched the PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for works speaking to the value that IPAP-trained PAs may bring to civilian PA training. Those findings were supplemented with informal conversations with IPAP-trained PAs currently employed in the military and those working in civilian PA education. Themes were identified supporting the potential value of IPAP-trained PAs in civilian training. Military PAs work within hierarchical organizations and may transition easily to academic settings. They leave military service not only as highly trained and proficient primary care providers but also as experienced educators. Military PAs must demonstrate professionalism across their entire military careers. They serve as leaders and work in teams, but they are also experienced in negotiating up chains of command. They are trained in and apply the latest innovations in health care delivery and have provided care with a degree of autonomy uncommon in civilian PA practice. The PAs trained through IPAP leave the service with skills and experiences valuable to civilian PA training. Employing these PAs in civilian education honors their service contributions while addressing emerging PA educator workforce demands.


Predictive factors for colonic diverticular rebleeding: a retrospective analysis of the clinical and colonoscopic features of 111 patients.
Colonic diverticular bleeding can stop spontaneously or be stopped by endoscopic hemostasis. We analyzed the clinical and colonoscopic features of patients with colonic diverticular bleeding to establish the predictive factors for rebleeding. A total of 111 patients (median age, 72 years) with colonic diverticular bleeding in Aso Iizuka Hospital between April 2007 and July 2010 were enrolled. Age, sex, body mass index (BMI), comorbidity, medication, location of bleeding, colonoscopic findings and hemostatic methods were analyzed retrospectively from the hospital records. The most common sites of bleeding were the ascending (39.6%) and sigmoid (29.7%) colon. Overt rebleeding occurred in 30 patients (27.0%). Spontaneous hemostasis was seen in 81 patients (73.0%), and endoscopic hemostatic treatment was performed in 30 patients. The BMI in the patients with colonic diverticular rebleeding was significantly higher than in patients without rebleeding. Colonoscopic findings of actively bleeding or nonbleeding visible vessels in the responsible diverticula were more frequent in the group with rebleeding. A higher BMI and colonoscopic findings of actively bleeding or nonbleeding visible vessels can be used as predictive factors for colonic diverticular rebleeding. Patients with such findings should be carefully followed up after hemostasis of the initial colonic diverticular bleeding.


Incentives for organ donation: proposed standards for an internationally acceptable system.
Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.


Reduced fiber integrity and cognitive control in adolescents with internet gaming disorder.
The association between the impaired cognitive control and brain regional abnormalities in Internet gaming disorder (IGD) adolescents had been validated in numerous studies. However, few studies focused on the role of the salience network (SN), which regulates dynamic communication among brain core neurocognitive networks to modulate cognitive control. Seventeen IGD adolescents and 17 healthy controls participated in the study. By combining resting-state functional connectivity and diffusion tensor imaging (DTI) tractography methods, we examined the changes of functional and structural connections within SN in IGD adolescents. The color-word Stroop task was employed to assess the impaired cognitive control in IGD adolescents. Correlation analysis was carried out to investigate the relationship between the neuroimaging indices and behavior performance in IGD adolescents. The impaired cognitive control in IGD was validated by more errors during the incongruent condition in color-word Stroop task. The right SN tract showed the decreased fractional anisotropy (FA) in IGD adolescents, though no significant differences of functional connectivity were detected. Moreover, the FA values of the right SN tract were negatively correlated with the errors during the incongruent condition in IGD adolescents. Our results revealed the disturbed structural connectivity within SN in IGD adolescents, which may be related with impaired cognitive control. It is hoped that the brain-behavior relationship from network perspective may enhance the understanding of IGD.


Minor physical anomalies: relation to later achievement.
A substantial number of school-age children with learning disability are characterized as being distractible, and there is a congenital contributor to distractibility that has shown relation to school achievement, and to learning disability in particular. This congenital contributor can be assessed at any time from the neonatal through the early school-age period by a 10-minute examination. It seems likely that the basis for the congenital contributor to learning disability is an information processing defect that appears as early as the first year of life in the form of a rapid waning of attention when tired, an overly slow waning when in a rested state, and a failure to form cognitive schemas from perceptual input in either case. The congenital characteristic could also affect learning disability by its association with less than optimal peer relations. The latter could, in turn, affect the child's link to the classroom learning situation.


The value of the tumor marker CA 15-3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen.
To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases.


The development of somatostatin immunoreactivity in the interpeduncular nucleus of the cat.
Somatostatin (SS) immunoreactivity was localized in a population of neurons in the interpeduncular nucleus (IPN) of the developing and adult cat. SS-immunoreactive perikarya and fibers were found in several subdivisions of the IPN, but were most heavily concentrated in the central nucleus (IPC). Some immunoreactive fibers appeared to be associated with the ventral surface of the IPN where they may come in contact with the interpeduncular cistern. Bundles of immunoreactive fibers also appeared to leave the rostral pole of the IPN bilaterally. Still other SS-positive perikarya and fibers were associated with the tegmentopeduncular tract and the medial division of the dorsal tegmental nucleus. SS was present in both perikarya and fibers of the IPN at birth. The concentration of immunoreactivity increased dramatically during the first 100 days postnatal, but by 180 days the overall intensity of immunoreactivity had decreased to adult levels. These data indicate that SS may be present in the cat IPN in a specific population of neurons that is most active during early postnatal development. The data are consistent with previous suggestions that SS plays a special role in the development of certain neuronal systems and may be particularly important in the integration of behaviors during the neonatal period.


Morphological and molecular biology identification of Cystoisospora sp. in the blue fox, Alopex lagopus (Linnaeus, 1758).
To investigate the prevalence and molecular characteristics of Cystoisospora sp. in blue fox (Alopex lagopus), Sheather's sugar floatation method was conducted to detect coccidia in 423 fresh fecal samples randomly collected from blue fox farms from three cities in China. The overall prevalence of coccidia was 1.4% (6/423), and three Cystoisospora sp. (Cystoisospora fennechi, Cystoisospora sp. I and Cystoisospora vulpina) were identified by their morphological characteristics. The 18S ribosomal RNA (rRNA) and cytochrome c oxidase subunit I (COI) locus sequences were sequenced for molecular biological identification, homology comparison, and phylogenetic analysis of Cystoisospora sp. by single-oocyst selection technology and multi-locus-nested PCR amplification. At the 18S rRNA and COI loci, C. vulpina had 99.48% and 99.59% homology, respectively, with Cystoisospora canis and Cystoisospora ohioensis from canines. Phylogenetic analysis indicated that C. vulpina was clustered in a clade with Cystoisospora sp. from Canidae, which the relatives are consistent with the hosts. To our knowledge, this is the first report on molecular identification and evolutionary analysis of C. vulpina at two different loci.


Pneumonia in US hospitalized patients with influenza-like illness: BioSense, 2007-2010.
We used data from BioSense, a national electronic surveillance system, to describe pneumonia in hospitalized patients with influenza-like illness (ILI). Ninety-five hospitals from 20 states reported ICD-9-CM-coded inpatient final diagnosis data during the study period of September 2007 to February 2010. We compared the characteristics of persons with and without pneumonia among those with ILI-related hospitalizations. BioSense captured 26 987 ILI-related inpatient hospitalizations; 8979 (33%) had a diagnosis of pneumonia. Analysis of trends showed highest counts of pneumonia during the 2007-2008 season and the second 2009 pandemic wave. Pneumonia was more common with increasing age. Microbiology and pharmacy data were available for a subset of patients; 107 (5%) with pneumonia had a bloodstream infection and 17% of patients were prescribed antiviral treatment. Our findings demonstrate the potential utility of electronic healthcare data to track trends in ILI and pneumonia, identify risk factors for disease, identify bacteraemia in patients with pneumonia, and monitor antiviral use.


Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways.
We investigated whether microtubule-interfering agents (MIAs: taxol, colchicine, nocodazole, vinblastine, vincristine, 17-beta-estradiol, 2-methoxyestradiol) altered cyclooxygenase-2 (COX-2) expression in human mammary epithelial cells. MIAs enhanced prostaglandin E(2) synthesis and increased levels of COX-2 protein and mRNA. Nuclear run-off assays revealed increased rates of COX-2 transcription after treatment with MIAs. Calphostin C, an inhibitor of protein kinase C, blocked the induction of COX-2 by MIAs. The stimulation of COX-2 promoter activity by MIAs was inhibited by overexpressing dominant negative forms of Rho and Raf-1. MIAs stimulated ERK, JNK, and p38 mitogen-activated protein kinases (MAPK); pharmacological inhibitors of MAPK kinase and p38 MAPK blocked the induction of COX-2 by MIAs. Overexpressing dominant negative forms of ERK1 or p38 MAPK inhibited MIA-mediated activation of the COX-2 promoter. MIAs stimulated the binding of the activator protein-1 transcription factor complex to the cyclic AMP response element in the COX-2 promoter. A dominant negative form of c-Jun inhibited the activation of the COX-2 promoter by MIAs. Additionally, cytochalasin D, an agent that inhibits actin polymerization, stimulated COX-2 transcription by the same signaling pathway as MIAs. Thus, microtubule- or actin-interfering agents stimulated MAPK signaling and activator protein-1 activity. This led, in turn, to induction of COX-2 gene expression via the cyclic AMP response element site in the COX-2 promoter.