The influence of environment: Experiences of users of myoelectric arm prosthesis-a qualitative study.
Prostheses are used to varying degrees; however, little is known about how environmental aspects influence this use. To describe users' experiences of how environmental factors influence their use of a myoelectric arm prosthesis. Qualitative and descriptive. A total of 13 patients previously provided with a myoelectric prosthetic hand participated. Their age, sex, deficiency level, etiology, current prosthesis use, and experience varied. Semi-structured interviews were audiotaped, transcribed, and analyzed through inductive content analysis. Four categories were created from the data: "Prosthesis function," "Other people's attitudes," "Support from family and healthcare," and "Individual's attitude and strategies." The overarching theme, "Various degrees of embodiment lead to different experiences of environmental barriers and facilitators," emerged from differences in individual responses depending on whether the individual was a daily or a non-daily prosthesis user. Environmental facilitators such as support from family and healthcare and good function and fit of the prosthesis seemed to help the embodiment of the prosthesis, leading to daily use. This embodiment seemed to reduce the influence of environmental barriers, for example, climate, attitudes, and technical shortcomings. Embodiment of prostheses seems to reduce the impact of environmental barriers. Support and training may facilitate the embodiment of myoelectric prosthesis use. Clinical relevance For successful prosthetic rehabilitation, environmental factors such as support and information to the patient and their social network about the benefits of prosthesis use are important. Local access to training in myoelectric control gives more people the opportunity to adapt to prosthesis use and experience less environmental barriers.


Errors and mistakes in breast ultrasound diagnostics.
Sonomammography is often the first additional examination performed in the diagnostics of breast diseases. The development of ultrasound imaging techniques, particularly the introduction of high frequency transducers, matrix transducers, harmonic imaging and finally, elastography, influenced the improvement of breast disease diagnostics. Nevertheless, as in each imaging method, there are errors and mistakes resulting from the technical limitations of the method, breast anatomy (fibrous remodeling), insufficient sensitivity and, in particular, specificity. Errors in breast ultrasound diagnostics can be divided into impossible to be avoided and potentially possible to be reduced. In this article the most frequently made errors in ultrasound have been presented, including the ones caused by the presence of artifacts resulting from volumetric averaging in the near and far field, artifacts in cysts or in dilated lactiferous ducts (reverberations, comet tail artifacts, lateral beam artifacts), improper setting of general enhancement or time gain curve or range. Errors dependent on the examiner, resulting in the wrong BIRADS-usg classification, are divided into negative and positive errors. The sources of these errors have been listed. The methods of minimization of the number of errors made have been discussed, including the ones related to the appropriate examination technique, taking into account data from case history and the use of the greatest possible number of additional options such as: harmonic imaging, color and power Doppler and elastography. In the article examples of errors resulting from the technical conditions of the method have been presented, and those dependent on the examiner which are related to the great diversity and variation of ultrasound images of pathological breast lesions.


Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time.
Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.


Conus medullaris schistosomiasis.
The authors performed a study to investigate the clinical manifestations, treatment strategies, and possible pathogenesis of conus medullaris schistosomiasis. Six cases collected from the authors' experience and four cases reported in the literature were studied retrospectively for clinical manifestations, treatment outcomes, and prognosis. All patients experienced progressive lower-extremity weakness and functional bowel and bladder impairment. Although the magnetic resonance (MR) imaging results suggested the presence of a conus medullaris tumor, schistosomiasis was diagnosed based on pathological results obtained in the 10 patients. The results of surgery followed by pyquiton and hormone treatment confirmed the diagnosis, and the patients' prognoses were good. This pathological entity is predominantly found in adults, and the clinical manifestations have no specificity, although the MR imaging may provide some clues. As a form of ectopic schistosomiasis, conus medullaris schistosomiasis deserves special consideration and further exploration. If an early diagnosis can be made and pyquiton and hormone therapy is given, surgery can be avoided and the prognosis will remain good.


Factors affecting the degree of penile deformity in Peyronie disease: an analysis of 1001 patients.
Only a few studies have investigated the association between the severity of Peyronie disease (PD) and clinical parameters such as age and associated comorbidities. The aim of this study was to report the relationship between the degree of curvature of the penis and the clinical parameters among patients with PD. A total of 1001 patients with PD were evaluated retrospectively in terms of penile deformity, erectile status, and risk factors for systemic vascular diseases. The degree of curvature was assessed with a protractor during maximum erection in response to a combined injection and stimulation test and/or vacuum device. A modified Kelami classification was used to categorize penile deformities as follows: patients with deformities without curvature (notching, hourglass, and swan neck deformity, group 1), with mild curvature (≤ 30 degrees, group 2), with moderate curvature (31-60 degrees, group 3), or with severe curvature (> 60 degrees, group 4). Chi-square tests, 1-way analysis of variance, and univariate and multiple ordinal regression analyses were used for statistical analysis. Penile deformity without curvature was detected in 12.3% of the patients, whereas the curvature was less than 30 degrees in 39.5%, 30 to 60 degrees in 34.5%, and more than 60 degrees in 13.5% of the patients. Multiple ordinal regression analysis identified age (P = .013), side of deformity (P = .007), erectile dysfunction (P < .0001), and diabetes mellitus (P = .001) as significant independent predictors of the severity of penile curvature. In conclusion, patients' age, side of deformity, erectile function, and diabetes were significantly associated with the degree of curvature.


Private inhibitory systems for the X and Y pathways in the dorsal lateral geniculate nucleus of the cat.
1. Inhibitory connections of X- and Y-type principal cells in the cat's dorsal lateral geniculate nucleus were studied with intracellular recording techniques in barbiturate-anaesthetized animals. Cells were identified as principal cells by antidromic activation from the visual cortex and as X or Y types by their responses to visual stimulation. 2. Graded electrical stimulation was used to obtain selective activation of X and Y ganglion cell axons. The optic nerves were stimulated through ring electrodes behind the eye bulbs and the evoked nerve volley was monitored by an optic tract electrode. The nerve volley consisted of two well-segregated components, an early, low-threshold Y component and a late, high-threshold X component. 3. All principal cells received monosynaptic excitation and disynaptic feed-forward inhibition from optic nerve fibres. The excitatory and inhibitory postsynaptic potentials were evoked by Y axons in Y cells and by X axons in X cells. Thus, the feed-forward inhibitory pathway to principal cells is type selective. 4. Recurrent inhibition was evoked in all cells by antidromic activation of principal cell axons in the visual cortex. The recurrent inhibitory potentials had significantly shorter latencies in Y than in X cells but with considerable overlap between the two samples. This overlap presumably reflects a similar overlap in antidromic conduction times for X and Y principal cell axons. 5. Recurrent inhibitory potentials evoked in the orthodromic direction by optic nerve stimulation originated from Y axons in Y principal cells and from X axons in X cells as would be expected for a type-selective recurrent inhibitory pathway. 6. It is concluded that X and Y principal cells in the dorsal lateral geniculate nucleus have similar but functionally separate inhibitory circuits.


Effects of Watermelon Powder and l-arginine Supplementation on Azoxymethane-Induced Colon Carcinogenesis in Rats.
Diets high in fruits and vegetables may help prevent colorectal cancer (CRC). Watermelon consumption may reduce CRC risk due to its concentration of l-citrulline and its role in endothelial nitric oxide (NO) production. Research suggests that increased NO levels have tumoricidal effects. The purpose of this study was to determine the effects of watermelon powder supplementation on aberrant crypt foci (ACF) formation, precancerous lesions, and expression of genes associated with colon carcinogenesis. Thirty-two male Sprague-Dawley rats were assigned into three groups: control, 0.36% l-arginine, or 0.5% watermelon powder and injected with azoxymethane (15 mg/kg body weight). Both l-arginine and watermelon powder groups exhibited lower total numbers of ACF and high multiplicity ACF (P < 0.01). The watermelon powder group exhibited higher NO levels and lower 8-hydroxyguanosine DNA damage (P < 0.05). Watermelon powder and l-arginine downregulated 8-oxoguanine DNA glycosylase gene expression and upregulated O6-methylguanine DNA methyltransferase gene expression (P < 0.05). Cyclooxgenase-2 gene expression was lower for rats fed with watermelon powder (P < 0.05). These results suggest that watermelon powder or l-arginine supplementation may reduce the risk of colon cancer by suppressing ACF formation through lowering oxidative DNA damage and inflammation, modulating DNA repair enzyme expression, and/or enhancing NO production.


Evidence that intergenic spacer repeats of Drosophila melanogaster rRNA genes function as X-Y pairing sites in male meiosis, and a general model for achiasmatic pairing.
In Drosophila melanogaster males, X-Y meiotic chromosome pairing is mediated by the nucleolus organizers (NOs) which are located in the X heterochromatin (Xh) and near the Y centromere. Deficiencies for Xh disrupt X-Y meiotic pairing and cause high frequencies of X-Y nondisjunction. Insertion of cloned rRNA genes on an Xh- chromosome partially restores normal X-Y pairing and disjunction. To map the sequences within an inserted, X-linked rRNA gene responsible for stimulating X-Y pairing, partial deletions were generated by P element-mediated destabilization of the insert. Complete deletions of the rRNA transcription unit did not interfere with the ability to stimulate X-Y pairing as long as most of the intergenic spacer (IGS) remained. Within groups of deletions that lacked the entire transcription unit and differed only in length of residual IGS material, pairing ability was proportional to the dose of 240-bp intergenic spacer repeats. Deletions of the complete rRNA transcription unit or the 28S sequences alone blocked nucleolus formation, as determined by binding of an antinucleolar antibody, yet did not interfere with pairing ability, suggesting that X-Y pairing may not be mechanistically related to nucleolus formation. A model for achiasmatic pairing in Drosophila males based upon the combined action of topoisomerase I and a strand transferase is proposed.


Microbial nanowires: a new paradigm for biological electron transfer and bioelectronics.
The discovery that Geobacter sulfurreducens can produce protein filaments with metallic-like conductivity, known as microbial nanowires, that facilitate long-range electron transport is a paradigm shift in biological electron transfer and has important implications for biogeochemistry, microbial ecology, and the emerging field of bioelectronics. Although filaments in a wide diversity of microorganisms have been called microbial nanowires, the type IV pili of G. sulfurreducens and G. metallireducens are the only filaments that have been shown to be required for extracellular electron transport to extracellular electron acceptors or for conduction of electrons through biofilms. Studies of G. sulfurreducens pili preparations and intact biofilms under physiologically relevant conditions have provided multiple lines of evidence for metallic-like conduction along the length of pili and for the possibility of pili networks to confer high conductivity within biofilms. This mechanism of electron conduction contrasts with the previously known mechanism for biological electron transfer via electron tunneling or hopping between closely associated molecules, a strategy unlikely to be well adapted for long-range electron transport outside the cell. In addition to promoting electron exchange with abiotic electron acceptors, microbial nanowires have recently been shown to be involved in direct interspecies electron transfer between syntrophic partners. An improved understanding of the mechanisms for metallic-like conductivity in microbial nanowires, as well as engineering microorganisms with desirable catalytic abilities with nanowires, could lead to new applications in microbial electrosynthesis and bioelectronics.


Adjuvants and antibody production: dispelling the myths associated with Freund's complete and other adjuvants.
Adjuvants have been used for more than 70 yr to enhance the immune response of the host animal to an antigen. Among the mechanisms that adjuvants use to enhance the immune response are the "depot" effect, antigen presentation, antigen targeting, immune activation/modulation, and cytotoxic lymphocyte induction. The immunostimulatory properties of adjuvants result in inflammation, tissue destruction, and the potential for resulting pain and distress in the host animal. The inflammatory lesions produced by adjuvants such as Freund's complete adjuvant (FCA) have led some to conclude that pain and distress are present, even in cases where the scientific evidence fails to support this conclusion. Recommendations and regulations in the literature, based on available scientific evidence, provide guidance on total adjuvant volumes, volumes per site, routes of injection, booster injections, and adjuvants used for antibody production. Among the numerous adjuvants that are used for experimental antibody production reviewed in this article, many claim to be less inflammatory, tissue destructive, and painful than FCA while producing equal or superior antibody responses. Although no adjuvant surpasses FCA for experimental antibody production against a wide range of antigenic molecules, many produce excellent antibody responses with less inflammation and tissue destruction. Balancing the requisite degree of immuno-stimulation and the extent of inflammation, necrosis, and potential pain and distress requires consideration of the nature of the antigen, the host immune responsiveness, the adjuvant's mechanisms of action, and the desired end-product. In cases where the antigen is a weak immunogen or has a very limited availability, the type and role of adjuvant becomes a critical component in producing an acceptable immune response and humoral antibody response.


Evolutionary pathways in shorebird breeding systems: sexual conflict, parental care, and chick development.
Sexual selection, mating opportunities, and parental behavior are interrelated, although the specific nature of these relationships is controversial. Two major hypotheses have been suggested. The parental investment hypothesis states that the relative parental investment of the sexes drives the operation of sexual selection. Thus, the sex that invests less in offspring care competes more intensely and monopolizes access to mates. The sexual conflict hypothesis proposes that sexual selection (the competition among both males and females for mates), mating opportunities, and parental behavior are interrelated and predicts a feedback loop between mating systems and parental care. Here we test both hypotheses using a comprehensive dataset of shorebirds, a maximum-likelihood statistical technique, and a recent supertree of extant shorebirds and allies. Shorebirds are an excellent group for these analyses because they display unique variation in parental care and social mating system. First, we show that chick development constrains the evolution of both parental care and mate competition, because transitions toward more precocial offspring preceded transitions toward reduced parental care and social polygamy. Second, changes in care and mating systems respond to one another, most likely because both influenced and are influenced by mating opportunities. Taken together, our results are more consistent with the sexual conflict hypothesis than the parental investment hypothesis.


A monoclonal antibody (AE3.d3) with mitogenic properties for murine B cells.
A monoclonal antibody, AE3.d3, derived from the fusion of rat splenocytes immunized against mouse brain with the myeloma SP2, has been produced, which has the property of inducing the proliferation of mouse lymphocytes. The mitogenic effect is highest in spleen and lymph node cells, where up to a 10-fold stimulation of 3H-TdR incorporation is observed. B lymphocytes are the most susceptible to this proliferative stimulus, and they are induced to differentiate into plaque-forming cells. T lymphocytes and "null" cells (defined by the absence of Thy-1 or Ig on their surface) do proliferate, although to a smaller extent. The T cell subpopulation, isolated from either spleen or thymus, requires additional "helper factors" in order to proliferate. The mitogenic response is not genetically restricted by H-2 type, and strains such as C3H/HeJ and CBA/N, in which B cell function is defective, as well as T cell-deficient strains such as BALB/c nude mice, are capable of responding to the stimulus of AE3.d3. Using immunofluorescence, we also examined the distribution of AE3.d3-positive cells in various lymphoid organs. The highest percentage of stained cells is found in the spleen (approximately 28%) and lymph node (18%), whereas only 14% of the bone marrow and 5% of the cells of the thymus are brightly stained with AE3.d3.


A proposed method of bias adjustment for meta-analyses of published observational studies.
Interpretation of meta-analyses of published observational studies is problematic because of numerous sources of bias. We develop bias assessment, elicitation and adjustment methods, and apply them to a systematic review of longitudinal observational studies of the relationship between objectively measured physical activity and subsequent change in adiposity in children. We separated internal biases that reflect study quality from external biases that reflect generalizability to a target setting. Since published results were presented in different formats, these were all converted to correlation coefficients. Biases were considered as additive or proportional on the correlation scale. Opinions about the extent of each bias in each study, together with its uncertainty, were elicited in a formal process from quantitatively trained assessors for the internal biases and subject-matter specialists for the external biases. Bias-adjusted results for each study were combined across assessors using median pooling, and results combined across studies by random-effects meta-analysis. Before adjusting for bias, the pooled correlation is difficult to interpret because the studies varied substantially in quality and design, and there was considerable heterogeneity. After adjusting for both the internal and external biases, the pooled correlation provides a meaningful quantitative summary of all available evidence, and the confidence interval incorporates the elicited uncertainties about the extent of the biases. In the adjusted meta-analysis, there was no apparent heterogeneity. This approach provides a viable method of bias adjustment for meta-analyses of observational studies, allowing the quantitative synthesis of evidence from otherwise incompatible studies. From the meta-analysis of longitudinal observational studies, we conclude that there is no evidence that physical activity is associated with gain in body fat.


To trade or not to trade: firm-level analysis of emissions trading in Santiago, Chile.
Whether tradable permits are appropriate for use in transition and developing economies--given special social and cultural circumstances, such as the lack of institutions and lack of expertise with market-based policies--is much debated. We conducted interviews and surveyed a sample of firms subject to emissions trading programs in Santiago, Chile, one of the first cities outside the OECD that has implemented such trading. The information gathered allows us to study what factors affect the performance of the trading programs in practice and the challenges and advantages of applying tradable permits in less developed countries.


Imaging of Individual Anatomical Risk Factors for Patellar Instability.
This review article presents several pitfalls and limitations of image interpretation of anatomical risk factors for patellar instability. The most important imaging examinations for the work-up of patients with patellar instability are the true lateral radiograph and transverse computed tomography (CT) or MR images of the knee. Primary anatomical risk factors are an insufficient medial patellofemoral ligament (MPFL), patella alta, trochlear dysplasia, increased distance from the tibial tuberosity to the trochlear groove (TTTG), and torsional limb parameters. Limitations of the Caton-Deschamps index are related to the clear identification of the patellar and tibial articular margin. Classification of trochlear dysplasia according to the Dejour system on radiographs and MR images revealed a weak reliability. The comparability of TTTG values obtained on CT and MR images at various flexion angles and different varus alignments of the knee is limited. Thus MRI performed with a dedicated knee coil may underestimate the TTTG distance compared with CT images. Increased lateral patellar tilt is a consequence of primary anatomical risk factors rather than an independent anatomical risk factor for patellar instability. The pretest likelihood of a torn MPFL on MR images is very high after an acute episode of lateral patellar dislocation. Surgical restoration of the patellofemoral joint stability addresses the complex multifactorial biomechanics by a custom-made management such as MPFL reconstruction, sulcus-deepening trochleoplasty, as well as medialization and distalization of the tibial tubercle. Quantification of anatomical risk factors for patellar instability in each person is important for highly individual treatment.


Mangroves shelter coastal economic activity from cyclones.
Mangroves shelter coastlines during hazardous storm events with coastal communities experiencing mangrove deforestation are increasingly vulnerable to economic damages resulting from cyclones. To date, the benefits of mangroves in terms of protecting coastal areas have been estimated only through individual case studies of specific regions or countries. Using spatially referenced data and statistical methods, we track from 2000 to 2012 the impact of cyclones on economic activity in coastal regions inhabited by nearly 2,000 tropical and subtropical communities across 23 major mangrove-holding countries. We use nighttime luminosity to represent temporal trends in coastal economic activity and find that direct cyclone exposure typically results in permanent loss of 5.4-6.7 mo for a community with an average mangrove extent (6.3 m per meter of coastline); whereas, a community with more extensive mangroves (25.6 m per meter of coastline) experiences a loss equivalent to 2.6-5.5 mo. These results suggest that mangrove restoration efforts for protective benefits may be more cost effective, and mangrove deforestation more damaging, than previously thought.


Structure of component B (7-mercaptoheptanoylthreonine phosphate) of the methylcoenzyme M methylreductase system of Methanobacterium thermoautotrophicum.
Component B, the heat-stable low-molecular-weight cofactor required for methane production by dialyzed cell-free extracts of Methanobacterium thermoautotrophicum, has been purified to homogeneity and its structure assigned. Results of low-resolution fast-atom-bombardment and field-desorption mass spectrometry indicated a molecular weight of 419, and high-resolution fast-atom-bombardment mass spectrometry agreed with the molecular formula C13H26NO8PS2. Evidence from fast-atom-bombardment and field-desorption mass spectrometry and 360-MHz 1H NMR in deuterium oxide argued that the compound was isolated as a mixed disulfide with 2-mercaptoethanol; so the proposed elemental formula of the free acid, free thiol would be C11H22NO7PS (molecular weight, 343). The proposed structure for an active form of the coenzyme is 7-mercaptoheptanoylthreonine phosphate.


Significance of maternal periodontal health in preeclampsia.
The aim of the present case-control study was to evaluate the association between maternal periodontitis and preeclampsia. Association studies between maternal periodontitis and elevated risk for preeclampsia have shown conflicting results. Periodontal maintenance is necessary to reduce the risk of adverse pregnancy outcomes like preeclampsia. Periodontal parameters [bleeding on probing, probing depth (PD), and clinical attachment level (CAL)] of 1320 women were assessed, followed by retrieval of their demographic and medical data from the medical records. Based on the medical records, 80 women were excluded from the study, leaving 1240 females as the eligible sample for the study. The women were divided into control group (1120 non-preeclamptic women who gave birth to infants with adequate gestational age) and case group (120 preeclamptic women). Logistic regression analysis revealed that primiparity and maternal periodontitis were the two significant variables causing preeclampsia. Further analysis was carried out by matching the two groups for primiparity to find the significance of maternal periodontitis. Maternal periodontitis was defined as PD ≥4 mm and CAL ≥3 mm at the same site in at least four teeth. The results showed that maternal periodontitis (odds ratio 19.8) was associated with preeclampsia. Maternal periodontitis also remained associated with preeclampsia after matching for primiparity, which was another significant confounding factor in the study (odds ratio 9.33). Maternal periodontitis is a risk factor associated with preeclampsia, emphasizing the importance of periodontal care in prenatal programs.


A patient with myasthenia gravis and a large arachnoid cyst - report of a case.
Myasthenia gravis is a chronic autoimmune disease characterized by weakening of voluntary muscles during the day and a marked restitution of function during the night and after rest. The symptoms may worsen over days or weeks, sometimes even in a few hours, and are usually well controlled by appropriate therapy. Arachnoid cysts are congenital or acquired deformities of the arachnoid membrane and are usually too small to cause distinct clinical symptomatology. We describe a case of a 76-year-old myasthenia gravis patient with an arachnoid cyst. To the best of our knowledge this is the first reported case of these two comorbidities together.


The effect of carbohydrate-electrolyte beverage drinking strategy on 10-mile running performance.
The purpose of the current study was to investigate the influence of ingesting a carbohydrate-electrolyte (CHO-E) beverage ad libitum or as a prescribed volume on 10-mile run performance and gastrointestinal (GI) discomfort. Nine male recreational runners completed the 10-mile run under the following 3 conditions: no drinking (ND; 0 ml, 0 g CHO), ad libitum drinking (AD; 315 ± 123 ml, 19 ± 7 g CHO), and prescribed drinking (PD; 1,055 ± 90 ml, 64 ± 5 g CHO). During the AD and PD trials, drinks were provided on completion of Miles 2, 4, 6, and 8. Running performance, speed (km/hr), and 10-mile run time were assessed using a global positioning satellite system. The runners' ratings of perceived exertion and GI comfort were recorded on completion of each lap of the 10-mile run. There was a significant difference (p < .10) in performance times for the 10-mile race for the ND, AD, and PD trials, which were 72:05 ± 3:36, 71:14 ± 3:35, and 72:12 ± 3.53 min:s, respectively (p = .094). Ratings of GI comfort were reduced during the PD trial in comparison with both AD and ND trials. In conclusion, runners unaccustomed to habitually drinking CHO-E beverages during training improved their 10-mile race performance with AD drinking a CHO-E beverage, in comparison with drinking a prescribed volume of the same beverage or no drinking.


Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa.
Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations in West Africa. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species A, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species A. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species A but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.


Initial community perspectives on the Health Service Extension Programme in Welkait, Ethiopia.
The Health Service Extension Programme (HSEP) is an innovative approach to addressing the shortfall in health human resources in Ethiopia. It has developed a new cadre of Health Extension Workers (HEWs), who are charged with providing the health and hygiene promotion and some treatment services, which together constitute the bedrock of Ethiopia's community health system. This study seeks to explore the experience of the HSEP from the perspective of the community who received the service. A random sample of 60 female heads-of-household in a remote area of Tigray participated in a structured interview survey. Although Health Extension Workers (HEWs) had visited them less frequently than planned, participants generally found the programme to be helpful. Despite this, their basic health knowledge was still quite poor regarding the major communicable diseases and their vectors. Participants felt the new HESP represented an improvement on previous health provision. HEWs were preferred over Traditional Birth Attendants for assistance with labour While the introduction of HEWs has been a positive experience for women living at the study site, the frequency of visits, extent of effectively imparted health knowledge and affects of HEWs on other health providers needs to be further explored.


Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum.
The de novo pyrimidine-biosynthesis pathway of Plasmodium falciparum is a promising target for antimalarial drug discovery. The parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. Direct (or indirect) inhibition of de novo pyrimidine biosynthesis via dihydroorotate dehydrogenase (PfDHODH), the fourth enzyme of the pathway, has already been shown to be lethal to the parasite. In the second step of the plasmodial pyrimidine-synthesis pathway, aspartate and carbamoyl phosphate are condensed to N-carbamoyl-L-aspartate and inorganic phosphate by aspartate transcarbamoylase (PfATC). In this paper, the 2.5 Å resolution crystal structure of PfATC is reported. The space group of the PfATC crystals was determined to be monoclinic P21, with unit-cell parameters a = 87.0, b = 103.8, c = 87.1 Å, α = 90.0, β = 117.7, γ = 90.0°. The presented PfATC model shares a high degree of homology with the catalytic domain of Escherichia coli ATC. There is as yet no evidence of the existence of a regulatory domain in PfATC. Similarly to E. coli ATC, PfATC was modelled as a homotrimer in which each of the three active sites is formed at the oligomeric interface. Each active site comprises residues from two adjacent subunits in the trimer with a high degree of evolutional conservation. Here, the activity loss owing to mutagenesis of the key active-site residues is also described.


Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.
The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.


Prostate cancer among pesticide applicators: a meta-analysis.
To analyse data from peer-reviewed, case-referent and cohort studies, studying the occurrence of prostate cancer in pesticide applicators and in some other, related, occupational categories, in order to determine a possible relationship of cancer of the prostate with pesticide exposure; to calculate a meta-rate ratio and to compare it with the meta-rate ratios obtained in a previous meta-analysis performed over a shorter time (1995-2001) in a broader exposure category, including many pesticide-related agricultural and non-agricultural occupations. Medline was searched for the years between 1966 and 2003, and relevant studies were identified from 1986 on. We conducted a meta-analysis of 22 studies complying with the inclusion criteria in order to pool their relative risk (RR) estimates. Studies were summarised and assessed for homogeneity and publication bias. The meta-rate ratio, based on 22 estimates of RR, is 1.24 [95% confidence interval (95% CI) 1.06-1.45]. This pooled risk estimate for the occupational categories selected is higher than the one previously calculated for farmers in general over a shorter period of publication. Substantial heterogeneity of rate ratios exists between the different studies. The major source of heterogeneity identified is geographic location. Increased meta-rate ratios are observed for studies derived from North America as well as from Europe, the meta-rate ratios from Europe being lower than those from North America. There is no obvious indication of publication bias. The increased meta-rate ratio for prostate cancer in agricultural pesticide applications provides additional evidence for a possible relationship between pesticide exposure and prostate cancer. The homogeneity observed between the individual rate ratios, after we had regrouped the data according to geographic location, tends to increase the consistency of the association. However, the data available from the individual studies do not provide sufficient exposure information for firm conclusions to be drawn about pesticide exposure as the cause of prostate cancer, independently from other factors.


Lidars: a key component of urban biodefense.
A biological aerosol attack in a city could infect tens of thousands of people. In the absence of announcements by the attacker or detection by present point detection systems, victims would be unaware of their exposure prior to developing symptoms. Since infections are most effectively countered before the onset of symptoms, detection technologies that provide early awareness of an attack should be given high priority. Current biological point detection (BPD) systems collect environmental air samples and then analyze them in laboratories so as to permit detection within 12-36 hours of an attack. Improvements in the pipeline may reduce this lag time to as little as a few hours. However, BPD systems have inherent weaknesses when used to detect and respond to an aerosol attack. The likelihood of a limited number of BPD systems intercepting an aerosol plume in a vast attack space may be low. Moreover, BPD systems do not provide critical information needed for response, such as the source location, precise time, and geographic reach of an attack. The missing information would invaluably guide prophylaxis distribution, identification of contaminated areas, and criminal apprehension. This article describes how lidars used for real-time observation of aerosol plumes could complement BPD systems by providing fine-scale spatial and temporal information. A lidar system also could be used to corroborate positive BPD system results, to improve reaction to positive results, and/or to provide an independent basis for low-regret protective steps. Lidar systems can resolve key biodefense challenges, and this article describes three compatible concepts of operations. Leveraging lessons from a lidar system now operating at the Pentagon, a test of an expanded lidar network would provide immediate protection for key Washington, DC, assets, demonstrate the synergy of BPD systems and lidars, and provide a test bed for research to improve lidar's shortcomings.


Growth hormone retesting during puberty: a cohort study.
To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty. Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 μg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.


Timeliness and factors associated with rotavirus vaccine uptake among Australian Aboriginal and non-Aboriginal children: A record linkage cohort study.
Rotavirus vaccines (RV), included in Australia's National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children. Birth records for 681,456 children born in two Australian states in 2007-2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV. Compared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9-16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27-0.34) among Aboriginal, and 0.53 (95%CI: 0.51-0.55) among non-Aboriginal children. Prematurity (<33 weeks), low birthweight (<1500 g), maternal age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake. Aboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.


The accuracy of volumetric bone density measurements in dual x-ray absorptiometry.
New developments in dual x-ray absorptiometry (DXA) allow the performance of high precision anteroposterior (AP) and lateral scans of spinal bone mineral density (BMD, units: g/cm2) without the patient moving from the supine position. Data from both projections may be combined to give an estimate of the true volumetric bone mineral density (VBMD, units: g/cm3) of the lumbar vertebral bodies. This report presents a cadaver study designed to validate DXA measurements of volumetric bone density. Sections of whole lumbar spine were scanned in AP and lateral projections in a water tank to simulate soft tissue. Individual vertebrae were then divided to separate the vertebral body from the neural arch, and vertebral body volume was measured using the displacement of sand. The bone mineral content (BMC) of vertebral bodies and neural arches was measured by ashing at 250 degrees C for 60 hours followed by 500 degrees C for a further 24 hours. The results showed that DXA scanning systematically underestimated ashing data by 14% for AP BMC, 33% for vertebral body BMC, 23% for vertebral body volume, and 12% for VBMD. Despite these significant systematic errors, the DXA measurements and ashing values were highly correlated (r = 0.979-0.992). The results suggested that after allowing for the systematic errors, lateral DXA parameters related closely to true BMC, volume, and VBMD.


Clinical Features and Prognosis in ANCA Associated Vasculitis Patients with Acute Kidney Injury.
Renal involvement in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) often presents as acute kidney injury (AKI), which is closely related to the prognosis of critically ill patients. Nevertheless, there are few researches on the subgroup of AVV patients with AKI. The study aimed to explore clinical features and prognosis in AAV patients with AKI. A retrospective analysis of AAV patients was conducted. The enrolled patients were grouped according to whether AKI on admission occurred or not. Demographic, clinical data and follow-up records were gathered from medical histories. Survival rates of AAV patients with AKI and risk factors of all AAV patients were studied. (1) In the AKI group, the levels of hemoglobin, evaluated glomerular filtration rate (eGFR), serum albumin and complement 3 were significantly lower (P<0.05); the proportions of microscopic polyangiitis (MPA) and levels of serum creatinine (SCr) on admission, red blood cell (RBC) counts in urine, 24-hour urine protein excretion (UPE) and Birmingham Vasculitis Activity Score (BVAS) were significantly higher (P<0.05). There was a significantly lower incidence of otorhinolaryngologic involvement in the AKI group (P<0.05). (2) There were significantly lower survival rates and renal survival rates in the AKI group (P<0.05). (3) Higher creatinine and AKI were risk factors for poor prognosis in AAV patients. AAV patients with AKI have more severe kidney damage, higher disease activity and worse prognosis. More attention should be paid to AAV patients with AKI for both remission induction and infection prevention.


Exploring the structure and activity of haloalkane dehalogenase from Sphingomonas paucimobilis UT26: evidence for product- and water-mediated inhibition.
The hydrolysis of haloalkanes to their corresponding alcohols and inorganic halides is catalyzed by alpha/beta-hydrolases called haloalkane dehalogenases. The study of haloalkane dehalogenases is vital for the development of these enzymes if they are to be utilized for bioremediation of organohalide-contaminated industrial waste. We report the kinetic and structural analysis of the haloalkane dehalogenase from Sphingomonas paucimobilis UT26 (LinB) in complex with each of 1,2-dichloroethane and 1,2-dichloropropane and the reaction product of 1-chlorobutane turnover. Activity studies showed very weak but detectable activity of LinB with 1,2-dichloroethane [0.012 nmol s(-1) (mg of enzyme)(-1)] and 1,2-dichloropropane [0.027 nmol s(-1) (mg of enzyme)(-1)]. These activities are much weaker compared, for example, to the activity of LinB with 1-chlorobutane [68.2 nmol s(-1) (mg of enzyme)(-1)]. Inhibition analysis reveals that both 1,2-dichloroethane and 1,2-dichloropropane act as simple competitive inhibitors of the substrate 1-chlorobutane and that 1,2-dichloroethane binds to LinB with lower affinity than 1,2-dichloropropane. Docking calculations on the enzyme in the absence of active site water molecules and halide ions confirm that these compounds could bind productively. However, when these moieties were included in the calculations, they bound in a manner similar to that observed in the crystal structure. These data provide an explanation for the low activity of LinB with small, chlorinated alkanes and show the importance of active site water molecules and reaction products in molecular docking.


Transcriptome sequencing and de novo analysis for Yesso scallop (Patinopecten yessoensis) using 454 GS FLX.
Bivalves comprise 30,000 extant species, constituting the second largest group of mollusks. However, limited genetic research has focused on this group of animals so far, which is, in part, due to the lack of genomic resources. The advent of high-throughput sequencing technologies enables generation of genomic resources in a short time and at a minimal cost, and therefore provides a turning point for bivalve research. In the present study, we performed de novo transcriptome sequencing to first produce a comprehensive expressed sequence tag (EST) dataset for the Yesso scallop (Patinopecten yessoensis). In a single 454 sequencing run, 805,330 reads were produced and then assembled into 32,590 contigs, with about six-fold sequencing coverage. A total of 25,237 unique protein-coding genes were identified from a variety of developmental stages and adult tissues based on sequence similarities with known proteins. As determined by GO annotation and KEGG pathway mapping, functional annotation of the unigenes recovered diverse biological functions and processes. Transcripts putatively involved in growth, reproduction and stress/immune-response were identified. More than 49,000 single nucleotide polymorphisms (SNPs) and 2,700 simple sequence repeats (SSRs) were also detected. Our data provide the most comprehensive transcriptomic resource currently available for P. yessoensis. Candidate genes potentially involved in growth, reproduction, and stress/immunity-response were identified, and are worthy of further investigation. A large number of SNPs and SSRs were also identified and ready for marker development. This resource should lay an important foundation for future genetic or genomic studies on this species.


Substance use, resistance skills, decision making, and refusal efficacy among Mexican and Mexican American preadolescents.
This article examines the relationships among resistance skills, refusal efficacy, decision-making skills, and substance use for a sample of Mexican and Mexican American 5th grade students who were attending public schools in Phoenix, Arizona. An analysis of self-report questionnaire data indicated that the likelihood that male students reported ever having used one or more substances increased as they reported a greater willingness to use passive decision-making (e.g., going along) and decreased as they reported greater refusal efficacy and a greater willingness to utilize active decision making (e.g., thoughtful processing). No significant relationships emerged between the 4 predictors and lifetime substance use among the girls. These findings support the role of social skills in substance use prevention, shed light on an understudied group, and suggest the importance of continuing to examine gender differences in skills-based interventions.


Comparison of tire and road wear particle concentrations in sediment for watersheds in France, Japan, and the United States by quantitative pyrolysis GC/MS analysis.
Impacts of surface runoff to aquatic species are an ongoing area of concern. Tire and road wear particles (TRWP) are a constituent of runoff, and determining accurate TRWP concentrations in sediment is necessary in order to evaluate the likelihood that these particles present a risk to the aquatic environment. TRWP consist of approximately equal mass fractions of tire tread rubber and road surface mineral encrustations. Sampling was completed in the Seine (France), Chesapeake (U.S.), and Yodo-Lake Biwa (Japan) watersheds to quantify TRWP in the surficial sediment of watersheds characterized by a wide diversity of population densities and land uses. By using a novel quantitative pyrolysis-GC/MS analysis for rubber polymer, we detected TRWP in 97% of the 149 sediment samples collected. The mean concentrations of TRWP were 4500 (n = 49; range = 62-11 600), 910 (n = 50; range = 50-4400) and 770 (n = 50; range = 26-4600) μg/g d.w. for the characterized portions of the Seine, Chesapeake and Yodo-Lake Biwa watersheds, respectively. A subset of samples from the watersheds (n = 45) was pooled to evaluate TRWP metals, grain size and organic carbon correlations by principal components analysis (PCA), which indicated that four components explain 90% of the variance. The PCA components appeared to correspond to (1) metal alloys possibly from brake wear (primarily Cu, Pb, Zn), (2) crustal minerals (primarily Al, V, Fe), (3) metals mediated by microbial immobilization (primarily Co, Mn, Fe with TOC), and (4) TRWP and other particulate deposition (primarily TRWP with grain size and TOC). This study should provide useful information for assessing potential aquatic effects related to tire service life.


Effects of the posterior cruciate ligament reconstruction on the biomechanics of the knee joint: a finite element analysis.
Previous experimental studies have been conducted to evaluate the biomechanical effects of posterior cruciate ligament reconstruction; but no consensus has been reached on the preferred method of reconstruction. The 3D finite element mesh of a knee joint was reconstructed from computed tomography and magnetic resonance images. The ligaments were considered as hyperelastic materials. The tibiofemoral and patellofemoral joints were modeled with large sliding contact elements. The 3D model was used to simulate knee flexion from 0 degrees to 90 degrees in four cases: a knee with a "native" posterior cruciate ligament, a resected posterior cruciate ligament, a reconstructed single graft posterior cruciate ligament, and a reconstructed double graft posterior cruciate ligament. A resected posterior cruciate ligament induced high compressive forces in the medial tibiofemoral and patellofemoral compartments. The pressures generated in the tibiofemoral and patellofemoral compartments were nearly the same for the two reconstruction techniques (single graft and double graft). The single graft resulted in lower tensile stresses inside the graft than for the double graft. Firstly, a resected posterior cruciate ligament should be replaced to avoid excessive compressive forces, which are a source of cartilage degeneration. Secondly, the two types of posterior cruciate ligament reconstruction techniques partially restored the biomechanics of the knee in flexion, e.g. contact pressures were restored for pure flexion of the knee. The reconstruction techniques therefore partially restore the biomechanics of the knee in flexion. A double graft reconstruction is subjected to the highest tensile stresses.


Rolling ribbons.
We present the results of a combined experimental and theoretical investigation of rolling elastic ribbons. Particular attention is given to characterizing the steady shapes that arise in static and dynamic rolling configurations. In both cases, above a critical value of the forcing (either gravitational or centrifugal), the ribbon assumes a two-lobed, peanut shape similar to that assumed by rolling droplets. Our theoretical model allows us to rationalize the observed shapes through consideration of the ribbon's bending and stretching in response to the applied forcing.


One year outcome in first episode schizophrenia. Predictors of relapse.
The aim of this study was to identify the predictors of outcome at one year follow-up after the first psychotic episode of schizophrenia. Seventy-nine first-episode schizophrenia patients were assessed monthly with the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms (SAPS), and Scale for Assessment of Negative Symptoms (SANS) after discharge from their first hospitalization. Outcome measures were presence of relapse and rehospitalization, level of global functioning, employment status and severity of symptoms at one year. A total of 33% of the patients had a relapse, and 12.1% were rehospitalized during one year follow-up. Premorbid childhood functionality was worse in patients who had relapse, but there was no correlation between premorbid adjustment scores and BPRS, SANS and SAPS scores at one year. There was no difference in duration of untreated psychosis (DUP) between patients who had relapse and not; however, the patients who had double relapse, had longer DUP than those without relapse. The time period between discharge and rehospitalization was shorter in patients with longer DUP. Functionality in childhood and noncompliance to the treatment independently contributed to the relapse rate. Functionality in late adolescence independently contributed to the Global Assessment of Functioning (GAF) scale score at one year and the GAF score at discharge appeared as a predictor of employment. The results of the present study suggest that treatment compliance and early premorbid adjustment level seem to be important predictors of relapse rate in first episode schizophrenia.


The extended use of modular knee endoprostheses.
Modular knee prostheses have been used since the 1980's. Their goal was to offer an alternative to reconstructing large bony defects without using bone grafting. Initially, they were used for reconstruction after resection of tumours about the knee. Their success encouraged their use in the treatment of some failed total knee arthroplasties, with large bony defects and severe ligamentous instability. We have implanted 7 modular knee prostheses between July 2006 and January 2009. There were 4 tumoral cases, 1 case of desarthrodhesis after a Campanacci procedure and two cases of failed total knee arthroplasties. We have achieved encouraging results using these implants with all but one patient surviving at two years after surgery. All the implants were considered to function normally regarding range-of motion, muscle strength and gait. The surgical and medical management of patients with bone sarcomas has advanced greatly during the last 20 years, improving their overall survival. Thus, the surgeons are provided with increased abilities to perform limb-sparing or joint-mobility sparing surgery.


The effect of microvascular decompression in patients with multiple sclerosis and trigeminal neuralgia.
Trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) is thought to be caused by demyelinating plaques within the nerve root entry zone, the trigeminal nucleus, or the trigeminal tracts. To review our experience of microvascular decompression (MVD) in patients with MS and symptomatic TN. All first-time MVDs for symptomatic trigeminal neuralgia in patients with MS performed by the senior author during an 8-year period (1999-2007) in this department were reviewed. The preoperative pain components were differentiated as being 100% episodic pain, > 50% episodic pain, or > 50% constant pain. At follow-up, pain relief was assessed with a standard mail questionnaire; those still having residual pain were further examined in the outpatient clinic or interviewed by phone. Of the 19 MS patients, 15 were available for follow-up. The median observation period was 55 months (range, 17-99 months). At follow-up, 7 of 15 patients (47%) were completely free of their episodic pain, and an additional 4 (27%) had significant relief of episodic pain (ie, worst pain marked as 0 to 3 cm on a 10-cm visual analog scale). Among the subgroup of 8 patients with a constant pain component, all were free of their constant pain, and 4 (50%) were free of their episodic pain. In our 8-year experience of doing MVD in MS patients with TN, we found complete and significant relief of episodic TN in a large proportion of patients. Even those with a constant pain component before MVD were completely relieved of their constant pain. Thus, in patients with TN (with or without a constant pain component), the presence of MS should not prevent patients from being offered MVD.


Transcriptomic response of the red tide dinoflagellate, Karenia brevis, to nitrogen and phosphorus depletion and addition.
The role of coastal nutrient sources in the persistence of Karenia brevis red tides in coastal waters of Florida is a contentious issue that warrants investigation into the regulation of nutrient responses in this dinoflagellate. In other phytoplankton studied, nutrient status is reflected by the expression levels of N- and P-responsive gene transcripts. In dinoflagellates, however, many processes are regulated post-transcriptionally. All nuclear encoded gene transcripts studied to date possess a 5' trans-spliced leader (SL) sequence suggestive, based on the trypanosome model, of post-transcriptional regulation. The current study therefore sought to determine if the transcriptome of K. brevis is responsive to nitrogen and phosphorus and is informative of nutrient status. Microarray analysis of N-depleted K. brevis cultures revealed an increase in the expression of transcripts involved in N-assimilation (nitrate and ammonium transporters, glutamine synthetases) relative to nutrient replete cells. In contrast, a transcriptional signal of P-starvation was not apparent despite evidence of P-starvation based on their rapid growth response to P-addition. To study transcriptome responses to nutrient addition, the limiting nutrient was added to depleted cells and changes in global gene expression were assessed over the first 48 hours following nutrient addition. Both N- and P-addition resulted in significant changes in approximately 4% of genes on the microarray, using a significance cutoff of 1.7-fold and p ≤ 10-4. By far, the earliest responding genes were dominated in both nutrient treatments by pentatricopeptide repeat (PPR) proteins, which increased in expression up to 3-fold by 1 h following nutrient addition. PPR proteins are nuclear encoded proteins involved in chloroplast and mitochondria RNA processing. Correspondingly, other functions enriched in response to both nutrients were photosystem and ribosomal genes. Microarray analysis provided transcriptomic evidence for N- but not P-limitation in K. brevis. Transcriptomic responses to the addition of either N or P suggest a concerted program leading to the reactivation of chloroplast functions. Even the earliest responding PPR protein transcripts possess a 5' SL sequence that suggests post-transcriptional control. Given the current state of knowledge of dinoflagellate gene regulation, it is currently unclear how these rapid changes in such transcript levels are achieved.


Risk factors for Mycobacterium tuberculosis infection among children in Greenland.
To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents' educational level and the child's health status. Demographic data for each child--i.e. parents' place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother's age when the child was born--were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55-11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33-4.63). Self-reported TB contact modified the profile to include household crowding and low mother's education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75-35.0) than children without an infected older sibling. Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important.


Role of liver in pathophysiology of NIDDM.
Glucose homeostasis is physiologically maintained by the balance between glucose production by the liver and glucose utilization by the peripheral tissues. Insulin controls hepatic glucose production and promotes glucose utilization by the skeletal muscle. In non-insulin-dependent diabetes mellitus (NIDDM), postabsorptive hepatic glucose production is increased and exhibits a positive correlation with fasting plasma glucose concentration. This increase in hepatic glucose production is the main cause of fasting hyperglycemia in NIDDM. Between the two processes by which the liver produces glucose (gluconeogenesis and glycogenolysis), gluconeogenesis appears to be drastically increased in NIDDM. The increase in gluconeogenesis accounts for most of the increased hepatic glucose production in this condition, and a positive correlation has been found in NIDDM subjects between the rates of gluconeogenesis and fasting plasma glucose concentration. Increased production of gluconeogenic precursors (lactate, alanine, glycerol) fuels this increased gluconeogenesis, but some type of intrahepatic mechanism is also present in NIDDM that increases the hepatic conversion of these substrates into glucose. Hyperglucagonemia and increased hepatic free fatty acid oxidation might be responsible for this increase hepatic gluconeogenic efficiency in NIDDM. Reduced suppression of hepatic glucose production after carbohydrate ingestion also plays an important role in the impairment in postprandial glucose homeostasis in NIDDM. In NIDDM subjects splanchnic extraction of an oral glucose load is not decreased, but hepatic glucose production is suppressed less than in nondiabetic subjects after the load. Residual hepatic glucose production after glucose ingestion is also correlated with fasting plasma glucose in NIDDM. Preliminary data suggest that in the postprandial state increased gluconeogenesis represents the primary mechanism responsible for impaired suppression of hepatic glucose production. Given the primary role of increase hepatic gluconeogenesis in the pathogenesis of hyperglycemia in NIDDM, development of new drugs aimed at correcting the factors that might cause increased gluconeogenesis (e.g., increased free fatty acid oxidation and hyperglucagonemia) might open the way for new form of treatment of this disorder.


Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease.
The major intracytoplasmic lesion of Alzheimer's disease is the neurofibrillary tangle (NFT), which is primarily composed of paired helical filaments (PHFs). The mechanism responsible for the formation of PHFs, as well as their insolubility and apparent heterogeneity, is unknown. We found that basic fibroblast growth factor (bFGF) binds to heparinase-sensitive sites in NFTs. bFGF binding is due to a heparan sulfate proteoglycan (HSPG) immunocytochemically identified in NFTs. In the presence of polycations (e.g., Ca2+), HSPG will bind to free carboxyl groups in NFT proteins. HSPG binding may play a role in transforming normal soluble proteins into insoluble PHFs.


Eban health promotion intervention: conceptual basis and procedures.
This article concerns the health promotion intervention that served as the comparison condition in Project Eban, the NIMH Multisite HIV/STD Prevention Trial for African American Couples. Considerable research has documented the high rates of chronic diseases, including heart disease, cancer, stroke, and diabetes, among African Americans. Many of these diseases are tied to behavioral risk factors-the things that people do or do not do, their diet, the amount of exercise they get, and their substance use practices. The Eban Health Promotion Intervention was designed to increase healthful behaviors, including physical activity, healthful dietary practices, ceasing cigarette smoking and alcohol abuse, practicing early detection and screening behaviors, and improving medication adherence. As a comparison condition, the Eban Health Promotion Intervention was designed to be structurally similar to the Eban HIV/STD Risk Reduction Intervention. This article describes the intervention and how it was developed, integrating social cognitive theory with information collected in formative research to ensure that the intervention was appropriate for African Americans affected by HIV. Project Eban not only tests the efficacy of an HIV/STD risk reduction intervention for African American serodiscordant couples, but also tests the efficacy of an intervention addressing many of the other health problems common in this population.


Inadequate postgraduate training of skin and soft tissue infections in an era of community-associated methicillin-resistant Staphylococcus aureus.
Since 2002, the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) has been steadily increasing and CA-MRSA may now account for most community-based SSTIs. Although consensus remains vague, using antibiotics with MRSA coverage has shown improved rates of clinical resolution. The goal of this pilot study was to assess resident physicians' awareness and management of CA-MRSA SSTIs in the acute/ambulatory care setting. This is a prospective cross-sectional survey-design study based on clinical case scenarios approved by the university's institutional review board. The survey was distributed to residents in internal medicine, general surgery, and emergency medicine. The survey was designed to assess (1) their knowledge of MRSA prevalence in community SSTIs and (2) their choice of empiric antibiotic for community-based SSTIs. Across all residency programs, only 15.7% of residents correctly estimated prevalence of CA-MRSA in SSTIs in the acute care/ambulatory setting to be 50% or higher. In practice, 28.6% of general surgery residents, 50.0% of internal medicine residents, and 69.7% of emergency medicine residents would use an antibiotic with appropriate MRSA coverage. This pilot study reveals that a substantial number of resident physicians are unaware of the increasing prevalence of CA-MRSA SSTIs and continue to use β-lactam antibiotics for empiric pharmacotherapy of community-based SSTIs. More education is desperately needed on this crucial topic across various residency training programs.


A new perspective on Listeria monocytogenes evolution.
Listeria monocytogenes is a model organism for cellular microbiology and host-pathogen interaction studies and an important food-borne pathogen widespread in the environment, thus representing an attractive model to study the evolution of virulence. The phylogenetic structure of L. monocytogenes was determined by sequencing internal portions of seven housekeeping genes (3,288 nucleotides) in 360 representative isolates. Fifty-eight of the 126 disclosed sequence types were grouped into seven well-demarcated clonal complexes (clones) that comprised almost 75% of clinical isolates. Each clone had a unique or dominant serotype (4b for clones 1, 2 and 4, 1/2b for clones 3 and 5, 1/2a for clone 7, and 1/2c for clone 9), with no association of clones with clinical forms of human listeriosis. Homologous recombination was extremely limited (r/m<1 for nucleotides), implying long-term genetic stability of multilocus genotypes over time. Bayesian analysis based on 438 SNPs recovered the three previously defined lineages, plus one unclassified isolate of mixed ancestry. The phylogenetic distribution of serotypes indicated that serotype 4b evolved once from 1/2b, the likely ancestral serotype of lineage I. Serotype 1/2c derived once from 1/2a, with reference strain EGDe (1/2a) likely representing an intermediate evolutionary state. In contrast to housekeeping genes, the virulence factor internalin (InlA) evolved by localized recombination resulting in a mosaic pattern, with convergent evolution indicative of natural selection towards a truncation of InlA protein. This work provides a reference evolutionary framework for future studies on L. monocytogenes epidemiology, ecology, and virulence.


A facilitating role for the primary motor cortex in action sentence processing.
The involvement of the motor system in action language comprehension is a hotly debated topic in cognitive neuroscience and psychology. Recent studies suggest that primary motor cortex (M1) response to action language is context-sensitive rather than automatic and necessary. Specifically, semantic polarity (i.e. affirmative/negative valence) appears to modulate the intensity of this response, which is stronger for affirmative action sentences. The aim of our study was to examine further the context sensitivity of M1 response. More specifically, we aimed to determine whether M1 response follows semantic polarity or the core meaning of the sentence using two-part action sentences containing interacting polarities. Modulations of M1 activity were recorded using surface electromyography of the first dorsal interosseous muscle of the right hand in 22 healthy participants. Our results show an increase in M1 activity during the first part of the sentence, regardless of semantic polarity. This response was then modulated by the polarity of the second part of the sentence, which carried crucial information regarding the action. These observations suggest that M1 differentially responds to different aspects of action sentences, one response being automatic and the other following the core meaning of the sentence. Our results thus contribute to clarifying the nature of the motor response to action language, which is key to develop more comprehensive and plausible neurobiological models of language processing.


Effects of nicotine and atomoxetine on brain function during response inhibition.
The nicotinic acetylcholine receptor (nAChR) agonist nicotine and the noradrenaline transporter inhibitor atomoxetine are widely studied substances due to their propensity to alleviate cognitive deficits in psychiatric and neurological patients and their beneficial effects on some aspects of cognitive functions in healthy individuals. However, despite growing evidence of acetylcholine-noradrenaline interactions, there are only very few direct comparisons of the two substances. Here, we investigated the effects of nicotine and atomoxetine on response inhibition in the stop-signal task and we characterised the neural correlates of these effects using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Nicotine (7 mg dermal patch) and atomoxetine (60 mg per os) were applied to N = 26 young, healthy adults in a double-blind, placebo-controlled, cross-over, within-subjects design. BOLD images were collected during a stop-signal task that controlled for infrequency of stop trials. There were no drug effects on behavioural performance or subjective state measures. However, there was a pronounced upregulation of activation in bilateral prefrontal and left parietal cortex following nicotine during successful compared to unsuccessful stop trials. The effect of nicotine on BOLD during failed stop trials was correlated across individuals with a measure of trait impulsivity. Atomoxetine, however, had no discernible effects on BOLD. We conclude that nicotine effects on brain function during inhibitory control are most pronounced in individuals with higher levels of impulsivity. This finding is compatible with previous evidence of nicotine effects on stop-signal task performance in highly impulsive individuals and implicates the nAChR in the neural basis of impulsivity.


Postfire logging in riparian areas.
We reviewed the behavior of wildfire in riparian zones, primarily in the western United States, and the potential ecological consequences of postfire logging. Fire behavior in riparian zones is complex, but many aquatic and riparian organisms exhibit a suite of adaptations that allow relatively rapid recovery after fire. Unless constrained by other factors, fish tend to rebound relatively quickly, usually within a decade after a wildfire. Additionally, fire and subsequent erosion events contribute wood and coarse sediment that can create and maintain productive aquatic habitats over time. The potential effects of postfire logging in riparian areas depend on the landscape context and disturbance history of a site; however available evidence suggests two key management implications: (1) fire in riparian areas creates conditions that may not require intervention to sustain the long-term productivity of the aquatic network and (2) protection of burned riparian areas gives priority to what is left rather than what is removed. Research is needed to determine how postfire logging in riparian areas has affected the spread of invasive species and the vulnerability of upland forests to insect and disease outbreaks and how postfire logging will affect the frequency and behavior of future fires. The effectiveness of using postfire logging to restore desired riparian structure and function is therefore unproven, but such projects are gaining interest with the departure of forest conditions from those that existed prior to timber harvest, fire suppression, and climate change. In the absence of reliable information about the potential consequence of postfire timber harvest, we conclude that providing postfire riparian zones with the same environmental protections they received before they burned isjustified ecologically Without a commitment to monitor management experiments, the effects of postfire riparian logging will remain unknown and highly contentious.


Short-term outcomes after symptomatic internal carotid artery occlusion.
Previous studies concerning internal carotid artery (ICA) occlusion have focused on long-term prognosis. The purpose of the present study was to evaluate short-term outcomes of patients with symptomatic ICA occlusion. We used data from the Registry of the Canadian Stroke Network on consecutive patients presenting to 11 stroke centers in Ontario. We included patients with noncardioembolic ischemic stroke or transient ischemic attack within the anterior circulation. The resulting cohort was divided into 4 groups based on vascular imaging of the ipsilateral extracranial ICA: occlusion, severe stenosis, moderate stenosis, and mild/no stenosis. Logistic regression modeling was used to evaluate the association between the degree of stenosis/occlusion of the symptomatic ICA and a series of short-term outcome measures. Of the 4144 patients who met study criteria, 283 patients had a symptomatic ICA occlusion. Compared with patients with ICA occlusion, patients with all other degrees of stenosis had a lower risk of in-hospital death, neurological worsening, and poor functional outcome. Particularly, severe stenosis was associated with a lower risk of in-hospital death (adjusted OR, 0.40; 95% CI, 0.20 to 0.79), neurological worsening (adjusted OR, 0.52; 95% CI, 0.34 to 0.78), and poor functional outcome (adjusted OR, 0.62; 95% CI, 0.41 to 0.94) compared with the ICA occlusion group. The results of our study showed that patients with symptomatic ICA occlusion are at a high risk of adverse outcomes that is as severe, if not worse, than any other degree of ICA stenosis in the short term. Thus, more aggressive management may be warranted for patients with acute, symptomatic ICA occlusion.


Exploring the Relationship between Housing and Health for Refugees and Asylum Seekers in South Australia: A Qualitative Study.
Housing is an important social determinant of health; however, little is known about the impact of housing experiences on health and wellbeing for people from refugee and asylum-seeking backgrounds. In this paper, we outline a qualitative component of a study in South Australia examining these links. Specifically, interviews were conducted with 50 refugees and asylum seekers who were purposively sampled according to gender, continent and visa status, from a broader survey. Interviews were analysed thematically. The results indicated that housing was of central importance to health and wellbeing and impacted on health through a range of pathways including affordability, the suitability of housing in relation to physical aspects such as condition and layout, and social aspects such as safety and belonging and issues around security of tenure. Asylum seekers in particular reported that living in housing in poor condition negatively affected their health. Our research reinforces the importance of housing for both the physical and mental health for asylum seekers and refugees living in resettlement countries. Improving housing quality, affordability and tenure security all have the potential to lead to more positive health outcomes.


Calcium depletion and calmodulin inhibition affect the import of nuclear-encoded proteins into plant mitochondria.
Many metabolic processes essential for plant viability take place in mitochondria. Therefore, mitochondrial function has to be carefully balanced in accordance with the developmental stage and metabolic requirements of the cell. One way to adapt organellar function is the alteration of protein composition. Since most mitochondrial proteins are nuclear encoded, fine-tuning of mitochondrial protein content could be achieved by the regulation of protein translocation. Here we present evidence that the import of nuclear-encoded mitochondrial proteins into plant mitochondria is influenced by calcium and calmodulin. In pea mitochondria, the calmodulin inhibitor ophiobolin A as well as the calcium ionophores A23187 and ionomycin inhibit translocation of nuclear-encoded proteins in a concentration-dependent manner, an effect that can be countered by the addition of external calmodulin or calcium, respectively. Inhibition was observed exclusively for proteins translocating into or across the inner membrane but not for proteins residing in the outer membrane or the intermembrane space. Ophiobolin A and the calcium ionophores further inhibit translocation into mitochondria with disrupted outer membranes, but their effect is not mediated via a change in the membrane potential across the inner mitochondrial membrane. Together, our results suggest that calcium/calmodulin influences the import of a subset of mitochondrial proteins at the inner membrane. Interestingly, we could not observe any influence of ophiobolin A or the calcium ionophores on protein translocation into mitochondria of yeast, indicating that the effect of calcium/calmodulin on mitochondrial protein import might be a plant-specific trait.


Aciclovir or valaciclovir for Bell's palsy (idiopathic facial paralysis).
The most common disorder of the facial nerve is acute idiopathic facial paralysis or Bell's palsy and there may be significant morbidity or incomplete recovery associated with severe cases. To assess the efficacy of aciclovir or similar agents for treating Bell's palsy. We searched the Cochrane Neuromuscular Disease Group register (searched April 2003), MEDLINE (from January 1966 to April 2003), EMBASE (from January 1980 to April 2003) and LILACS (from January 1982 to April 2003). We also contacted authors of identified trials. Randomised or quasi-randomised trials of aciclovir or valaciclovir therapy, alone or in combination with any other drug, in patients with Bell's palsy. We identified six randomised trials. Three studies met our inclusion criteria, including 246 patients. One study evaluated aciclovir with corticosteroid versus corticosteroid alone, another study evaluated aciclovir alone versus corticosteroid and a further study evaluated valaciclovir with corticosteroid versus corticosteroid alone or versus placebo alone. Incomplete recovery after one year: data were not available. An analysis was performed on data reported at the end of the study period in each trial. The results from one study four months after the start of treatment significantly favoured the treatment group, whilst the results of the study three months after the start of treatment significantly favoured the control group. The results from the second study at four months showed no statistically significant difference between the three groups. Adverse events: relevant data were not reported in any of the three trials. Complete facial paralysis six months after start of treatment: only one patient had complete paralysis upon entering one of the studies. This patient was assigned to the control group and the level of recovery attained was not reported. Motor synkinesis or crocodile tears one year after start of treatment: data were available up to a maximum of four months after onset of paralysis. One study reported a significant difference between the treatment groups in favour of the aciclovir plus corticosteroid group over corticosteroid alone, another demonstrated an inconclusive result with no difference between the aciclovir and corticosteroid. The third study did not comment upon these sequelae. More data are needed from a large multicentre randomised controlled and blinded study with at least 12 months' follow up before a definitive recommendation can be made regarding the effect of aciclovir or valaciclovir on Bell's palsy.


Pharmacokinetics and metabolism of the 5-hydroxytryptamine antagonist tropisetron after single oral doses in humans.
Tropiestron is a potent and selective antagonist of 5-hydroxytryptamine receptors. Tropisetron was developed for the indication of cancer chemotherapy-induced emesis. The pharmacokinetic and metabolic dispositions of tropisetron were studied in 12 healthy male volunteers receiving a single oral dose of 62 or 312 mumol (20 or 100 mg) of [14C]tropisetron. Serial plasma samples and complete urine and feces were collected for 120 hr postdose. Whereas the absorption of oral doses of 62-312 mumol tropisetron was rapid and complete, bioavailability was estimated to be only 66% for the 312 mumol dose and 52% for the 62 mumol dose, apparently because of saturable first-pass metabolism. Maximal concentrations of tropisetron averaged 87 and 608 nM after doses of 62 and 312 mumol, respectively, and the parent drug accounted for 21 and 36% of the radioactivity in AUC0-24 hr pools. Approximately 90% of the drug was metabolized before excretion, and approximately 70% of the dose was recovered in the urine. Following both the 62 and 312 mumol doses, the terminal half-life of tropisetron averaged 6-7 hr and that of total radioactivity was 10-11 hr. Tropisetron and its metabolites in plasma and urine were separated by gradient elution reversed-phase HPLC. Structures of eight metabolites were assigned on the bases of NMR and MS data. Tropisetron was metabolized by oxidative hydroxylation of the indole ring at positions 5, 6, and 7. The hydroxylated derivatives are further conjugated with glucuronic acid and sulfate. N-Oxygenation and oxidative N-demethylation at the tropinyl nitrogen also occur in trace amounts.(ABSTRACT TRUNCATED AT 250 WORDS)


A decrease in the number and incidence of osteoporotic hip fractures among elderly individuals in Niigata, Japan, from 2010 to 2015.
We investigated the incidence of hip fracture in patients aged ≥50 years in 2015 in Niigata Prefecture, Japan. We also determined the long-term trend in hip fracture incidence from 1985 to 2015. In 2015, 3214 hip fractures occurred in Niigata Prefecture. The crude incidence rate of hip fracture was 282.7 per 100,000 persons per year (122.9 in men and 416.4 in women). The incidence of hip fracture decreased from 2010 to 2015 in all age groups except in men aged 65-69 years and women aged 60-64 years. The percentage of patients who took anti-osteoporotic medication before their hip fractures increased from 10.2% in 2010 to 14.9% in 2015. The age-specific incidence in women tended to increase until 2010, but significantly decreased from 2010 to 2015 (p < 0.001). Similarly, the incidence in men decreased from 2010 to 2015 but was not significantly different from that in 1994 (p = 0.633); this incidence had been increasing since 1999. In conclusion, a generally increasing trend was observed in the incidence of hip fractures for 30 years in both men and women in Niigata Prefecture; however, it turned into a descending trend beginning in 2010.


Incidence, Causes and Risk Factors for 30-Day Unplanned Reoperation After Gastrectomy for Gastric Cancer: Experience of a High-Volume Center.
To investigate the incidence, causes and risk factors for unplanned reoperation because of early complications within 30 days of radical gastrectomy for gastric cancer. The study cohort comprised 1,948 patients who underwent radical gastrectomy for gastric cancer between November 2010 and April 2017. The incidence, causes and outcomes of unplanned reoperation were examined and the risk factors were identified using univariate and multivariate analyses. In total, 24 patients (1.2%) underwent unplanned reoperations because of early complications after radical gastrectomy. The main causes more frequently requiring reoperation were adhesive intestinal obstruction (eight cases, 33.3%), intra-abdominal bleeding (five cases, 20.8%), wound dehiscence (five cases, 20.8%), anastomotic leakage and intra-abdominal infection (five cases, 20.8%), and iatrogenic common bile duct injury (one case). Multivariate analysis identified that only combined multi-organ resection (odds ratio (OR) = 4.060, 95% confidence interval (CI): 1.645 - 10.023, P = 0.002) was an independent risk factor. Two patients (8.3%) who underwent reoperation died from disseminated intravascular coagulation or sepsis, respectively, which was significantly higher than the remaining 1,924 patients who did not require reoperation (six cases, 0.3%, P < 0.001). Moreover, patients who underwent reoperation experienced higher morbidity rates (37.5% vs. 6.8%, P < 0.001), requiring intensive care (20.8% vs. 2.4%, P < 0.001) and longer postoperative hospital stays (33.6 days vs. 11.0 days, P < 0.001) compared with patients required no reoperation. Combined multi-organ resection was an independent risk factor for unplanned reoperation following radical gastrectomy. Avoiding multi-organ resection as possible will decrease the likelihood of patients requiring reoperation.


Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis.
Cerebral disease manifestation occurs in about two thirds of males with X-linked adrenoleukodystrophy (CALD) and is fatally progressive if left untreated. Early histopathologic studies categorized CALD as an inflammatory demyelinating disease, which led to repeated comparisons to multiple sclerosis (MS). The aim of this study was to revisit the relationship between axonal damage and myelin loss in CALD. We applied novel immunohistochemical tools to investigate axonal damage, myelin loss and myelin repair in autopsy brain tissue of eight CALD and 25 MS patients. We found extensive and severe acute axonal damage in CALD already in prelesional areas defined by microglia loss and relative myelin preservation. In contrast to MS, we did not observe selective phagocytosis of myelin, but a concomitant decay of the entire axon-myelin unit in all CALD lesion stages. Using a novel marker protein for actively remyelinating oligodendrocytes, breast carcinoma-amplified sequence (BCAS) 1, we show that repair pathways are activated in oligodendrocytes in CALD. Regenerating cells, however, were affected by the ongoing disease process. We provide evidence that-in contrast to MS-selective myelin phagocytosis is not characteristic of CALD. On the contrary, our data indicate that acute axonal injury and permanent axonal loss are thus far underestimated features of the disease that must come into focus in our search for biomarkers and novel therapeutic approaches.


Purification, properties, and partial structure elucidation of a high-molecular-weight glycoprotein from cervical mucus of the bonnet monkey (Macaca radiata).
A high-molecular-weight glycoprotein has been purified from the cervical mucus of the bonnet monkey (Macaca radiata). The glycoprotein was shown to be homogeneous by electrophoresis, sedimentation equilibrium, and N-terminal group determination, and to contain 19% protein, 19% D-galactose, 18% N-acetyl-D-galactosamine, 15% N-acetyl-D-glucosamine, 11% L-fucose, 10% sialic acid, and 1% sulfate groups, corresponding to about 1800 amino acid residues and 400 carbohydrate side chains of about 9 monosaccharides. The carbohydrate chains are linked to the peptide backbone through N-acetyl-D-galactosamine and serine (or threonine) residues. Reduction with dithiothreitol and alkylation with iodoacetic acid reduced the molecular mass from 1 to 0.5 X 10(6) daltons and produced subunits having the same size, charge, and N-terminal amino acid. Electrophoretic studies suggested the presence of disulfide bonds between two chains of the glycoprotein. Degradation with alkaline borohydride gave, after fractionation on Bio-Gel P-2, fractions containing L-fucose, D-galactose, N-acetyl-D-galactosaminitol, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, and sialic acid in the ratio of 1.0:3.0:1.0:1.0:1.3:1.0. Further fractionation by electrophoresis and paper chromatography gave a charged fraction representing 13% of the original glycoprotein. Enzymic degradation and methylation studies indicated the presence of the structure alpha-Gal-(1 leads to 3)-[Fuc(1 leads to 2)]-Gal-(1 leads to 4)-GlcNAc, linked to a core component containing N-acetyl-D-galactosaminitol.


Membrane potential modulates the activation of GABA-gated channels.
1. The activity of single gamma-aminobutyric acid (GABA)-gated Cl- channels (GABA = 0.5-2.0 microM) was recorded in inside-out patches of membrane from cultured chick cerebral neurons. 2. The distribution of open intervals of the GABA channel was described by the sum of two exponentials, which suggests the presence of at least two open states of the channel. The time constants of these two components were 0.39 +/- 0.1 and 2.1 +/- 0.9 ms (+/- SD, n = 9). 3. The distribution of shut intervals was described by the sum of either three (n = 5) or four (n = 3) exponentials. This suggests the presence of at least three or four shut states. 4. At all GABA concentrations examined, the activity of the GABA channel decreased over time. This decline in activity was most likely the result of desensitization of the GABA channels. 5. The distribution of open intervals was unchanged during desensitization of the GABA channel. Thus desensitization is not associated with an alteration in either the mean lifetime of the two open states or the relative number of transitions to these two states. Rather, desensitization results from a decrease in the probability of channel opening. 6. There was an e-fold increase in the probability of finding a GABA channel open for every 80 +/- 43 mV (n = 4) of depolarization. The degree of voltage dependence decreased as the GABA channels desensitized. 7. The depolarization-induced increase in open channel probability was not associated with any change in the distribution of open intervals. Thus depolarization does not affect the mean open time of the channel but rather increases the likelihood that it will open. 8. A simple model with three or four shut and two open states is considered for the gating of the GABA channel by the agonist. Possible sites for the voltage dependence within this proposed model are discussed.