"Ankylosing spondylitis" without sacroiliitis in a woman without the HLA B27 antigen.
An elderly woman with otherwise typical ankylosing spondylitis for 45 years lacked radiologic evidence of sacroiliitis and the HLA B27 antigen. The illness was complicated by renal tuberculosis requiring a left nephrectomy 23 years after the onset of low back pain, and 20 years after an episode of severe iritis. After the eradication of the tuberculosis by surgery and chemotherapy, she has continued to have symptomatic spondylitis. The case seems to be an exception to the rule that sacroiliitis is a sine qua non for ankylosing spondylitis. Women with ankylosing spondylitis tend to have milder disease with an apparently lower frequency of roentgenographic changes in sacroiliac joints.


Functional characterization of human NBC4 as an electrogenic Na+-HCO cotransporter (NBCe2).
We have functionally characterized Na+-driven bicarbonate transporter (NBC)4, originally cloned from human heart by Pushkin et al. (Pushkin A, Abuladze N, Newman D, Lee I, Xu G, and Kurtz I. Biochem Biophys Acta 1493: 215-218, 2000). Of the four NBC4 variants currently present in GenBank, our own cloning efforts yielded only variant c. We expressed NBC4c (GenBank accession no. AF293337) in Xenopus laevis oocytes and assayed membrane potential (Vm) and pH regulatory function with microelectrodes. Exposing an NBC4c-expressing oocyte to a solution containing 5% CO2 and 33 mM HCO elicited a large hyperpolarization, indicating that the transporter is electrogenic. The initial CO2-induced decrease in intracellular pH (pH(i)) was followed by a slow recovery that was reversed by removing external Na+. Two-electrode voltage clamp of NBC4c-expressing oocytes revealed large HCO- and Na+-dependent currents. When we voltage clamped V(m) far from NBC4c's estimated reversal potential (E(rev)), the pH(i) recovery rate increased substantially. Both the currents and pH(i) recovery were blocked by 200 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). We estimated the transporter's HCO:Na+ stoichiometry by measuring E(rev) at different extracellular Na+ concentration ([Na+]o) values. A plot of E(rev) against log[Na+]o was linear, with a slope of 54.8 mV/log[Na+]o. This observation, as well as the absolute E(rev) values, are consistent with a 2:1 stoichiometry. In conclusion, the behavior of NBC4c, which we propose to call NBCe2-c, is similar to that of NBCe1, the first electrogenic NBC.


Commercial discharge packs and breast-feeding counseling: effects on infant-feeding practices in a randomized trial.
A randomized controlled trial was conducted to evaluate two interventions for prolonging the duration of breast-feeding in a multiethnic sample of 343 low-income urban women. One intervention compared research breast-feeding bedside counseling by a trained counselor, who also made eight telephone calls during the first 3 months of the infant's life, with the routine breast-feeding counseling provided in the hospital by nurses. The other intervention compared commercial discharge packs provided by formula companies with research discharge packs designed to be consistent with the WHO Code of Marketing of Breastmilk Substitutes. When infants were 4 months old, a telephone interviewer unaware of treatment status contacted 95% (324/343) of the women to determine the infants' feeding and health histories. Compared with routine counseling, research counseling delayed the first introduction of solid foods to the infant's diet (P = .03, one-tailed) but did not exert a statistically significant effect on breast-feeding by 4 months' postpartum. Women who received the research discharge pack, compared with those who received the commercial pack, were more likely to prolong exclusive breast-feeding (P = .004, one-tailed), to be partially breast-feeding at 4 months postpartum (P = .04, one-tailed), and to delay the daily use of solid foods in the infant's diet (P = .017, one-tailed). Among the women who received research counseling, the research discharge pack was associated with lower rates of rehospitalization of infants than was the commercial pack (1% v 14%; P = .014, two-tailed). We conclude that in high-risk maternity populations, commercial discharge materials for breast-feeding women should be replaced by materials consistent with the WHO Code.


Effects of low-level laser therapy after nerve reconstruction in rat denervated soleus muscle adaptation.
Peripheral nerve injury (PNI) rehabilitation remains a challenge for physical therapists because PNI effects are very disabling. Low-level laser therapy (LLLT) has been described as a physical resource that is able to influence enzymes called metallopeptidases (MMPs) associated with extracellular matrix (ECM) turnover, thus accelerating neuromuscular recovery after nerve crush injuries. However, the effects of LLLT in the treatment of severe nerve injuries and denervated slow-twitch muscles are still inconclusive. The aim of this study was to evaluate the effects of different wavelengths and energy densities of LLLT irradiation, applied to a severe nerve injury after reconstruction, on denervated slow-twitch skeletal muscle adaptation. Rats were submitted to a neurotmesis of the sciatic nerve followed by end-to-end neurorrhaphy. They received transcutaneous LLLT irradiation at the lesion site. The LLLT parameters were: wavelengths--660 or 780 nm; energy densities--10, 60 or 120 J/cm²; power--40 mW; spot--4 mm². Sciatic functional index (SFI), histological, morphometric, and zymographic analyses were performed. One-way ANOVA followed by Tukey's test was used (p≤0.05). An atrophic pattern of muscle fibers was observed in all injured groups. The MMP activity in the soleus muscle reached normal levels. On the other hand, SFI remained below normality after PNI, indicating incapacity. No difference was found among PNI groups submitted or not to LLLT in any variable. LLLT applied to the nerve post-reconstruction was ineffective in delaying degenerative changes to the slow-twitch denervated muscles and in functional recovery in rats. New studies on recovery of denervated slow-twitch muscle are necessary to support clinical practice.


Population dynamics of an invasive bird parasite, Philornis downsi (Diptera: Muscidae), in the Galapagos Islands.
The invasive parasitic fly, Philornis downsi (Muscidae), is one of the greatest threats to the avifauna of the Galapagos Islands. The larvae of this fly feed on the blood and tissues of developing nestlings of at least 18 endemic and native birds. The aim of the current study was to investigate biotic and abiotic factors that may influence the population dynamics of this invasive parasite. To study the influence of vegetation zone and related climatic factors on fly numbers, a bi-weekly monitoring program using papaya-baited traps was carried out at a dry, lowland site and at a humid, highland site on Santa Cruz Island between 2012-2014. Female flies, a large proportion of which were inseminated and gravid, were collected throughout the year at both sites, indicating females were active during and between the bird breeding seasons. This is the first evidence that female flies are able to persist even when hosts are scarce. On the other hand, catch rates of male flies declined between bird breeding seasons. Overall, catch rates of P. downsi were higher in the drier, lowland habitat, which may be a consequence of host or resource availability. Time was a stronger predictor of adult fly numbers than climate, further suggesting that P. downsi does not appear to be limited by its environment, but rather by host availability. Seasonal catch rates suggested that populations in both habitats were continuous and multivoltine. Numbers of adult female flies appeared to be regulated chiefly by simple direct density dependence, and may be governed by availability of bird nests with nestlings. Nevertheless, confounding factors such as the existence of reservoir hosts that perpetuate fly populations and changes in behavior of P. downsi may increase the vulnerability of bird hosts that are already IUCN red-listed or in decline.


Results after two years of non-operative treatment of occlusal surface in children with high caries prevalence.
The aim of this study was to describe the 2-year results of an individualized treatment program designed to control occlusal caries in erupting first permanent molars. The sample consisted of 145 five-to-six-year-old students divided into a control group (n = 71) and a test group (n = 74). All test children received a biannual basic preventive program and a recall system according to individual disease activity. The basic program consisted of 3 (March) and 2 (August) sessions of oral hygiene orientation and toothbrushing with fluoride gel. The analysis of the baseline and 1-2-year data showed a significant reduction in the number of active lesions in the test group. In the control group, there were initially 70 active lesions and after two years 68 surfaces remained with disease and 24 surfaces had been filled. The children in the test group had 80 surfaces with active lesions initially and after two years only 3 surfaces with disease remained. From the 15 cavitated lesions, only 5 surfaces needed to be filled. This program showed that care of erupting teeth on an individualized basis can control occlusal caries.


Splenic injury due to colonoscopy: analysis of the world literature, a new case report, and recommendations for management.
Splenic injury is a rare complication of colonoscopy. Most literature on the topic is case-report based. Our objective was to perform a comprehensive analysis of characteristics of splenic injury due to colonoscopy from available published reports in the world literature, to compare and contrast this entity with that of traumatic splenic injury, and provide recommendations for management based on the analysis. We reviewed the PubMed database without restrictions using the terms splenic trauma after colonoscopy, splenic rupture from colonoscopy, splenic injury following colonoscopy, and splenic complications of colonoscopy, and also reviewed the references from the resulting publications. Retrieved manuscripts (case reports, reviews, and abstracts) were reviewed by two authors, and data extracted for 15 specific characteristics of each patient reported using a standardized data collection tool. Data were analyzed using descriptive statistics. Splenic injury due to colonoscopy is extremely rare as reported in published literature. The majority of patients that seek medical attention have delayed symptoms, and most require splenectomy. Subcapsular hematoma is the most common injury pattern seen. Selection criteria for operative management may be extrapolated from management guidelines for traumatic splenic injury, although nonoperative failure rates are higher for splenic injury due to colonoscopy than for trauma.


Integrity of the DNA and Cellular Ultrastructure of Cryptoendolithic Fungi in Space or Mars Conditions: A 1.5-Year Study at the International Space Station.
The black fungi Cryomyces antarcticus and Cryomyces minteri are highly melanized and are resilient to cold, ultra-violet, ionizing radiation and other extreme conditions. These microorganisms were isolated from cryptoendolithic microbial communities in the McMurdo Dry Valleys (Antarctica) and studied in Low Earth Orbit (LEO), using the EXPOSE-E facility on the International Space Station (ISS). Previously, it was demonstrated that C. antarcticus and C. minteri survive the hostile conditions of space (vacuum, temperature fluctuations, and the full spectrum of extraterrestrial solar electromagnetic radiation), as well as Mars conditions that were simulated in space for a 1.5-year period. Here, we qualitatively and quantitatively characterize damage to DNA and cellular ultrastructure in desiccated cells of these two species, within the frame of the same experiment. The DNA and cells of C. antarcticus exhibited a higher resistance than those of C. minteri. This is presumably attributable to the thicker (melanized) cell wall of the former. Generally, DNA was readily detected (by PCR) regardless of exposure conditions or fungal species, but the C. minteri DNA had been more-extensively mutated. We discuss the implications for using DNA, when properly shielded, as a biosignature of recently extinct or extant life.


Rib Osteoblastoma as a Cause of Neurogenic Thoracic Outlet Syndrome: A Case Report.
BACKGROUND Osteoblastoma is a very rare bone tumor accounting for 1% of all bone tumors. Most of the time it involves the spine and long bones and it involves the ribs very rarely. While osteoblastoma occurrence in the first rib has been reported, causing neurogenic thoracic outlet syndrome (TOS) has never been reported. CASE REPORT A 23-year-old woman presented with a left cervical mass associated with pain and paresthesia in the medial aspect of the left upper extremity and 4th and 5th fingers for the previous 3 months. The patient denied any previous illness or trauma in her history. Physical examination revealed a hard mass in the posterior triangle of the left neck with altered sensation in the left 4th and 5th fingers. The patient was investigated by a chest roentgenogram, nerve conduction study, computer tomography (CT) of the chest, and magnetic resonance image (MRI), as well as incisional biopsy. Although all radiological investigations were suggesting osteochondroma with a differential diagnosis of chondrosarcoma, the incisional biopsy showed osteoblastoma. Radical surgical excision of the lesion followed through a left supraclavicular approach. The patient's preoperative symptoms were relieved completely and there was no recurrence of the tumor at 2 years. CONCLUSIONS Osteoblastoma of the first rib is very rare tumor and to present with TOS is extremely rare. The nonspecific radiological characteristics of the tumor, especially on CT, makes the preoperative certainty of the diagnosis unlikely.


Short communication: Effectiveness of tools provided by a dairy company on udder health in Dutch dairy farms.
A Dutch dairy company initiated a quality system to support dairy farmers to improve sustainability on their farm. Improvement of udder health is defined by the dairy company as one of the sustainability items. A part of that quality system is to offer farmers 3 tools to improve the udder health status of the herd. The first tool is an Udder Health Workshop at which farmers make a farm-specific action plan to improve the udder health situation in their herd. The second tool is the Udder Health Navigator, which is an internet-based program to gain insight in the actual udder health situation at the farm. The third tool is the Udder Health Checklist, which is available on the internet and it identifies farm-specific risks for udder health problems. The aim of this study was to evaluate the effectiveness of these tools in improving udder health. The bulk milk somatic cell count (BMSCC) was used as the measure of herd udder health performance. In total, 605 farms attended the Udder Health Workshop, 988 farms completed the Udder Health Navigator, and 1,855 farms completed the Udder Health Checklist in 2012. Information on BMSCC records (2 records per month) was available for 12,782 Dutch dairy farms during the years 2011 and 2012. For every farm, the average BMSCC of all months during the years 2012 and 2011 were calculated. This resulted in 306,768 average monthly observations of the BMSCC. Subsequently, all months after the completion of one of the tools were assigned a 1, and all other months were assigned a 0. A statistical analysis was carried out to compare the average monthly BMSCC of the farms that completed one or more tools with farms that did not complete one of the tools. Both completing the Udder Health Navigator and the Udder Health Checklist had a significant association with a lower average monthly BMSCC. The effect of the Udder Health Navigator and Udder Health Checklist on the BMSCC were greater in herds with a BMSCC in 2011 of 200,000 to 250,000 cells/mL and even greater for herds with a BMSCC above 250,000 cells/mL compared with herds with a BMSCC in 2011 of 150,000 to 200,000 cells/mL or less than 150,000 cells/mL. It is difficult to draw conclusions on the effect of the Udder Health Workshop due to overlap in participation between the tools. The results suggest that completing the web tools is associated with a reduction in the BMSCC of the herd.


Toothbrushing habits and risk indicators of severe early childhood caries among aboriginal Taiwanese.
The purpose of this study was to investigate the toothbrushing habits and risk indicators among aboriginal children with severe early childhood caries (S-ECC). This was a cross-sectional purposive sampling study that included 281 aboriginal children aged 2 to 5 years living in remote regions in southern Taiwan. Participant received dental examinations and questionnaires that were completed by caretakers. From among the 281 participants, 238 children (84%) presented with S-ECC. A low-frequency toothbrushing habit among the children with S-ECC was associated with caretakers with low-frequency toothbrushing (P = .001). The odds ratio of a child using improper toothbrushing methods having a caretaker with a low brushing frequency was 3.45 (P = .0157). Low-frequency toothbrushing and improper toothbrushing methods were associated with S-ECC. The caretakers' brushing frequency was a risk indicator associated with the children's poor oral hygiene.


A comparison of US- versus MR-based 3-D Prostate Shapes Using Radial Basis Function Interpolation and Statistical Shape Models.
This paper presents a comparison of three-dimensional (3-D) segmentations of the prostate, based on two-dimensional (2-D) manually segmented contours, obtained using ultrasound (US) and magnetic resonance (MR) imaging data collected from 40 patients diagnosed with localized prostate cancer and scheduled to receive brachytherapy treatment. The approach we propose here for 3-D prostate segmentation first uses radial basis function interpolation to construct a 3-D point distribution model for each prostate. Next, a modified principal axis transformation is utilized for rigid registration of the US and MR images of the same prostate in preparation for the following shape comparison. Then, statistical shape models are used to capture the segmented 3-D prostate geometries for the subsequent cross-modality comparison. Our study includes not only cross-modality geometric comparisons in terms of prostate volumes and dimensions, but also an investigation of interchangeability of the two imaging modalities in terms of automatic contour segmentation at the pre-implant planning stage of prostate brachytherapy treatment. By developing a new scheme to compare the two imaging modalities in terms of the segmented 3-D shapes, we have taken a first step necessary for building coupled US-MR segmentation strategies for prostate brachytherapy pre-implant planning, which at present is predominantly informed by US images only.


Characterizing spatial distributions of astrocytes in the mammalian retina.
In addition to being involved in retinal vascular growth, astrocytes play an important role in diseases and injuries, such as glaucomatous neuro-degeneration and retinal detachment. Studying astrocytes, their morphological cell characteristics and their spatial relationships to the surrounding vasculature in the retina may elucidate their role in these conditions. Our results show that in normal healthy retinas, the distribution of observed astrocyte cells does not follow a uniform distribution. The cells are significantly more densely packed around the blood vessels than a uniform distribution would predict. We also show that compared with the distribution of all cells, large cells are more dense in the vicinity of veins and toward the optic nerve head whereas smaller cells are often more dense in the vicinity of arteries. We hypothesize that since veinal astrocytes are known to transport toxic metabolic waste away from neurons they may be more critical than arterial astrocytes and therefore require larger cell bodies to process waste more efficiently. A 1/8th size down-sampled version of the seven retinal image mosaics described in this article can be found on BISQUE (Kvilekval et al., 2010) at http://bisque.ece.ucsb.edu/client_service/view?resource=http://bisque.ece.ucsb.edu/data_service/dataset/6566968.


Identification of a Bitter-Taste Receptor Gene Repertoire in Different Lagomorphs Species.
The repertoires of bitter-taste receptor (T2R) gene have been described for several animal species, but these data are still scarce for Lagomorphs. The aim of the present work is to identify potential repertoires of T2R in several Lagomorph species, covering a wide geographical distribution. We studied these genes in Lepus timidus, L. europaeus, Oryctolagus cuniculus algirus, Romerolagus diazi, and Sylvilagus floridanus, using O. cuniculus cuniculus as control species for PCR and DNA sequencing. We studied the identities of the DNA sequences and built the corresponding phylogenetic tree. Sequencing was successful for both subspecies of O. cuniculus for all T2R genes studied, for five genes in Lepus, and for three genes in R. diazi and S. floridanus. We describe for the first time the partial repertoires of T2R genes for Lagomorphs species, other than the common rabbit. Our phylogenetic analyses indicate that sequence proximity levels follow the established taxonomic classification.


Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies.
Recent developments in genomic analysis have unveiled the key signaling pathways in human cancer. However, only a limited number of molecular-targeted drugs are applicable for clinical use in gynecologic malignancies. TP53 signaling and phosphatidylinositol 3 kinase pathways are frequently mutated in cancer, and have received much attention as molecular targets in human cancers. In this review, we mainly focus on the functions of these pathways, and discuss the molecular-targeted drugs under clinical trials. The molecular-targeted drugs described in this review include dual phosphatidylinositol 3 kinase/mTOR inhibitors (NVP-BEZ235, DS-7423, SAR245409), an mTOR inhibitor (everolimus), an MEK inhibitor (pimasertib), an autophagy inhibitor (chloroquine), a cyclin-dependent kinases 4/6 inhibitor (PD0332991), and a poly (ADP-ribose) polymerase inhibitor (olaparib).


Cylindrical Inclusion Protein of Turnip Mosaic Virus Serves as a Docking Point for the Intercellular Movement of Viral Replication Vesicles.
Plant viruses move from the initially infected cell to adjacent cells through plasmodesmata (PDs). To do so, viruses encode dedicated protein(s) that facilitate this process. How viral proteins act together to support the intercellular movement of viruses is poorly defined. Here, by using an infection-free intercellular vesicle movement assay, we investigate the action of CI (cylindrical inclusion) and P3N-PIPO (amino-terminal half of P3 fused to Pretty Interesting Potyviridae open reading frame), the two PD-localized potyviral proteins encoded by Turnip mosaic virus (TuMV), in the intercellular movement of the viral replication vesicles. We provide evidence that CI and P3N-PIPO are sufficient to support the PD targeting and intercellular movement of TuMV replication vesicles induced by 6K2, a viral protein responsible for the generation of replication vesicles. 6K2 interacts with CI but not P3N-PIPO. When this interaction is impaired, the intercellular movement of TuMV replication vesicles is inhibited. Furthermore, in transmission electron microscopy, vesicular structures are observed in connection with the cylindrical inclusion bodies at structurally modified PDs in cells coexpressing 6K2, CI, and P3N-PIPO. CI is directed to PDs through its interaction with P3N-PIPO. We hypothesize that CI serves as a docking point for PD targeting and the intercellular movement of TuMV replication vesicles. This work contributes to a better understanding of the roles of different viral proteins in coordinating the intercellular movement of viral replication vesicles.


Concurrent chemoradiotherapy followed by L-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study.
We conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by 2 cycles of L-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma (ENKTL). CCRT consisted of 40-44 Gy of radiotherapy with weekly administration of 30 mg/m(2) of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m(2)), ifosfamide (1,200 mg/m(2)), and dexamethasone (40 mg) from days 1 to 3, and L-asparaginase (4,000 IU/m(2)) every other day from days 8 to 20) were administered sequentially. CCRT yielded a 90 % overall response rate without significant side effects in 30 patients, including 20 patients with complete response (CR); however, two patients showed distant disease progression. After CCRT, VIDL chemotherapy showed an 87 % final CR rate (26/30). Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy, no treatment-related mortality was observed, and L-asparaginase-associated toxicity was manageable. With a median follow-up of 44 months, 11 patients showed local (n = 4) and distant (n = 7) relapse or progression. The estimated 5-year progression-free and overall survival rates were 73 and 60 %, respectively. In conclusion, CCRT followed by L-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL.


[Nuclear medicine methods for the diagnosis of adrenal tumors].
Adrenal scintigraphy using 131I-6-beta-iodomethyl-19-norcholesterol or 6-methyl-75Se-methyl-19-norcholesterol is a function-dependent imaging method which, in association with high-resolution spatial imaging techniques, plays an essential role in the study of adrenocortical hyperfunction. It can distinguish between bilateral cortical hyperplasia and monolateral adenoma or carcinoma and can lateralise the adenoma. In patients with Cushing syndrome, in addition to allowing a distinction to be made between ACTH-dependent forms and independent forms, adrenocortical scintigraphy is particularly appropriate to identify non-common forms of adenomatous hyperplasia. Adrenocortical scintigraphy, performed during dexamethasone administration, is an accurate mean of differentiating bilateral adrenal hyperplasia from monolateral forms (adenoma or carcinoma) in patients with Conn's syndrome. Owing to the gradual spread of high-resolution spatial imaging techniques, the problem of the diagnostic classification of so-called "incidentalomas" (clinically silent masses discovered by chance) is a subject of considerable interest. Adreno-cortical scintigraphy appears to be able to provide an important contribution to identifying the functional behaviour of these tumours. Since the early 80s meta-iodobenzyl-guanidine (MIBG), marked with 131I or 123I, with a structure similar to norepinephrine and characterized by selective tropism for sympathetic and chromaffin tissue, has been used for the scintigraphic study of adrenal medulla. MIBG scintigraphy has been found to be particularly appropriate for the study of intra- and extra-adrenal, single and multiple, benign and malignant pheochromocytomas. This method has a high overall sensitivity and specificity. Lastly, MIBG scintigraphy is useful in the study of neuroblastoma.


Repair of an Endoscopic Retrograde Cholangiopancreatography-Related Large Duodenal Perforation Using Double Endoscopic Band Ligation and Endoclipping.
Endoscopic closure techniques have been introduced for the repair of duodenal wall perforations that occur during endoscopic retrograde cholangiopancreatography (ERCP). We report a case of successful repair of a large duodenal wall perforation by using double endoscopic band ligation (EBL) and an endoclip. Lateral duodenal wall perforation occurred during ERCP in a 93-year-old woman with acute calculous cholangitis. We switched to a forward endoscope that had a transparent band apparatus. A 2.0-cm oval-shaped perforation was found at the lateral duodenal wall. We repaired the perforation by sequentially performing double EBL and endoclipping. The first EBL was performed at the proximal edge of the perforation orifice, and two-thirds of the perforation were repaired. The second EBL, which also included the contents covered under the first EBL, repaired the defect almost completely. Finally, to account for the possible presence of a residual perforation, an endoclip was applied at the distal end of the perforation. The detection and closure of the perforation were completed within 10 minutes. We suggest that double EBL is an effective method for closure.


Diversity, Ecology, Biogeography, and Evolution of the Prevalent Brown Algal Genus Lobophora in the Greater Caribbean Sea, Including the Description of Five New Species1.
Distributed in tropical and warm-temperate waters worldwide, Lobophora species are found across the Greater Caribbean (i.e., Caribbean sensu stricto, Gulf of Mexico, Florida, the Bahamas, and Bermuda). We presently discuss the diversity, ecology, biogeography, and evolution of the Greater Caribbean Lobophora species based on previous studies and an extensive number of samples collected across the eastern, southern, and to a lesser extent western Caribbean. A total of 18 Lobophora species are now documented from the Greater Caribbean, of which five are newly described (L. agardhii sp. nov., L. dickiei sp. nov., L. lamourouxii sp. nov., L. richardii sp. nov., and L. setchellii sp. nov.). Within the Greater Caribbean, the eastern Caribbean and the Central Province are the most diverse ecoregion and province (16 spp.), respectively. Observed distribution patterns indicate that Lobophora species from the Greater Caribbean have climate affinities (i.e., warm-temperate vs. tropical affinities). In total, 11 Lobophora species exclusively occur in the Greater Caribbean; six are present in the western Atlantic; two in the Indo-Pacific; and one in the eastern Pacific. Biogeographic analyses support that no speciation occurred across the Isthmus of Panama, and that the Greater Caribbean acted as a recipient region for species from the Indo-Pacific and as a region of diversification as well as a donor region to the North-eastern Atlantic. The Greater Caribbean is not an evolutionary dead end for Lobophora, but instead generates and exports diversity. Present results illustrate how sampling based on DNA identification is reshaping biogeographic patterns, as we know them.


Vitamin E inhibition of hamster buccal pouch carcinogenesis. A gross, histologic, and ultrastructural study.
Sixty-four young adult male and female golden hamsters (Mesocricetus auratus) were divided into four equal experimental groups of sixteen animals. In Group 1 animals the left buccal pouch was painted three times weekly with a 0.25 percent solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in heavy mineral oil. In Group 2 animals the left buccal pouch was similarly painted with DMBA, but the animals also received 7 I.U. of vitamin E (alpha tocopherol) twice weekly on days alternate to the DMBA painting. The vitamin E was administered orally via a fine pipette. Group 3 animals were similarly painted with DMBA and received vitamin E vehicle by pipette. Group 4 animals served as untreated controls. Four animals in each group (two male, two female) were killed at 8, 10, 12, and 14 weeks. Buccal pouches were photographed and excised. Tumors were noted and measured in the left buccal pouches. The buccal pouches as well as major organs were fixed in formalin, sectioned in paraffin, and stained with hematoxylin and eosin. In the Group 2 animals receiving vitamin E, there was a significant delay in tumor formation so that by 12 to 14 weeks there were fewer tumors and their average size was smaller than those in the Group 1 and Group 3 animals painted with DMBA but receiving no vitamin E supplement. Microscopic examination revealed that there was less invasion of underlying tissues and less surface necrosis. The tumors in both control and vitamin E groups were well-differentiated epidermoid carcinomas. No differences in the nature of the cellular patterns of the carcinomas in control and vitamin E groups were revealed by electron microscopic studies.


Mesenteric venous thrombosis after appendicectomy in a child: clinical case and review of the literature.
Mesenteric venous thrombosis (MVT) after appendicectomy has not been reported in the pediatric literature. This complication is associated with significant morbidity and mortality rates in adults. The report of this case attempts to analyze the features found in an appendicectomized child documented by radiological examination and surgery before and after starting heparin therapy. Anticoagulation treatment should be started as soon as possible and continued for a long time to decrease the risk of relapse.


Acute pyogenic iliopsoas abscess in Taiwan: clinical features, diagnosis, treatments and outcome.
To study the variations of aetiology in the patients with acute pyogenic iliopsoas abscess and identify the appropriate diagnostic modalities as well as therapeutic alternatives (e.g. extraperitoneal or retrofascial percutaneous catheter drainage, PCD) other than surgery. We carried out a retrospective review and analysis of 25 patients with acute pyogenic iliopsoas abscess in our institution from August 1988 to July 1998. Blood and urine cultures, imaging studies of the plain films of the abdomen (KUB), ultrasonography (echo) and computed tomography (CT scan) were performed in all patients. The therapeutic regimens included antibiotics only, PCD or aspiration, and surgery. The male to female ratio was 7: 18. The mean age was 64 years old. Diabetes mellitus (64%) was the dominant predisposing or associated factor. The most common aetiological source was urinary tract infection (52%) with enteric micro-organisms (Escherichia coli: 44% and Klebsiella spp.: 24%). Nineteen patients (76%) had pain in the abdomen, flank or back. Six cases (24%) were classified as 'primary' abscess, and only two patients survived. Nine cases were treated with antibiotics alone, only four responded and the others expired. Of the 15 cases receiving PCD or aspiration, five cases received subsequent surgical drainage or nephrectomy and survived. Another one case of Clostridia gas gangrene received emergency fasciotomy and expired. The total mortality was extremely high (11/25, 44%). We concluded that: (i) the aetiology of iliopsoas abscess may vary with the country of origin, with a preponderance of urinary tract infection in our Taiwanese series; (ii) a high index of suspicion is mandatory to enable early diagnosis of acute pyogenic iliopsoas abscess, particularly for older diabetic patients with fever, pain in the abdomen or flank, limp or flexion of the ipsilateral hip; (iii) CT scan can confirm the diagnosis and define the extent of the abscess; (iv) effective management should include appropriate antibiotic therapy and drainage of the abscess; (v) image-guided PCD should be tried first because of its low morbidity. However, should it fail, subsequent surgical drainage should be performed.


Parietal and hippocampal contribution to topokinetic and topographic memory.
This paper reviews the involvement of the parietal cortex and the hippocampus in three kinds of spatial memory tasks which all require a memory of a previously experienced movement in space. The first task compared, by means of positron emission tomography (PET) scan techniques, the production, in darkness, of self-paced saccades (SAC) with the reproduction, in darkness, of a previously learned sequence of saccades to visual targets (SEQ). The results show that a bilateral increase of activity was seen in the depth of the intraparietal sulcus and the medial superior parietal cortex (superior parietal gyrus and precuneus) together with the frontal sulcus but only in the SEQ task, which involved memory of the previously seen targets and possibly also motor memory. The second task is the vestibular memory contingent task, which requires that the subject makes, in darkness, a saccade to the remembered position of a visual target after a passively imposed whole-body rotation. Deficits in this task, which involves vestibular memory, were found predominantly in patients with focal vascular lesions in the parieto-insular (vestibular) cortex, the supplementary motor area-supplementary eye field area, and the prefrontal cortex. The third task requires mental navigation from the memory of a previously learned route in a real environment (the city of Orsay in France). A PET scan study has revealed that when subjects were asked to remember visual landmarks there was a bilateral activation of the middle hippocampal regions, left inferior temporal gyrus, left hippocampal regions, precentral gyrus and posterior cingulate gyrus. If the subjects were asked to remember the route, and their movements along this route, bilateral activation of the dorsolateral cortex, posterior hippocampal areas, posterior cingulate gyrus, supplementary motor areas, right middle hippocampal areas, left precuneus, middle occipital gyrus, fusiform gyrus and lateral premotor area was found. Subtraction between the two conditions reduced the activated areas to the left hippocampus, precuneus and insula. These data suggest that the hippocampus and parietal cortex are both involved in the dynamic aspects of spatial memory, for which the name 'topokinetic memory' is proposed. These dynamic aspects could both overlap and be different from those involved in the cartographic and static aspects of 'topographic' memory.


Approaches to dog health education programs in Australian rural and remote Indigenous communities: four case studies.
Dog health in rural and remote Australian Indigenous communities is below urban averages in numerous respects. Many Indigenous communities have called for knowledge sharing in this area. However, dog health education programs are in their infancy, and lack data on effective practices. Without this core knowledge, health promotion efforts cannot progress effectively. This paper discusses a strategy that draws from successful approaches in human health and indigenous education, such as dadirri, and culturally respectful community engagement and development. Negotiating an appropriate education program is explored in its practical application through four case studies. Though each case was unique, the comparison of the four illustrated the importance of listening (community consultation), developing and maintaining relationships, community involvement and employment. The most successful case studies were those that could fully implement all four areas. Outcomes included improved local dog health capacity, local employment and engagement with the program and significantly improved dog health.


Pretreatment of aripiprazole and minocycline, but not haloperidol, suppresses oligodendrocyte damage from interferon-γ-stimulated microglia in co-culture model.
Recent imaging studies have indicated that the pathophysiology of schizophrenia is closely related to white matter abnormalities and microglial activation. Additionally, recent clinical trials have suggested that atypical antipsychotics may have brain protective properties and that minocycline, an antibiotic with inhibitory effects on microglial activation, improves symptoms of schizophrenia. We have reported that not only atypical antipsychotics with dopamine D2 receptor (D2R) antagonism but also aripiprazole, a unique antipsychotic drug with D2R partial agonism, inhibit microglial activation in vitro. Thus, atypical antipsychotics may exert a beneficial influence on both microglia and oligodendrocytes, while the underlying mechanisms have not been clarified. Here, we investigated whether antipsychotics suppress oligodendrocyte damage by inhibiting microglial activation utilizing a co-culture model with microglia and oligodendrocytes. Pretreatment of aripiprazole and minocycline suppressed apoptosis of oligodendrocytes in the co-culture model with interferon-γ (IFN-γ)-activated microglia, while haloperidol, a traditional antipsychotic drug, did not. Aripiprazole and minocycline inhibited the production of tumor necrosis factor-alpha (TNF-α) from IFN-γ-activated microglia. Moreover, aripiprazole and minocycline attenuated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in microglia. Overall, our results suggest that aripiprazole and minocycline may have antipsychotic effects through reducing oligodendrocyte damage caused by microglial activation. These results put forward a novel therapeutic hypothesis in schizophrenia research. Future in vivo studies to confirm the present results should be performed.


Shewanella algicola sp. nov., a marine bacterium isolated from brown algae.
A Gram-stain-negative, aerobic, rod-shaped bacterium motile by means of a single polar flagella, strain ST-6T, was isolated from a brown alga (Sargassum thunbergii) collected in Jeju, Republic of Korea. Strain ST-6T was psychrotolerant, growing at 4-30 °C (optimum 20 °C). Phylogenetic analysis based on 16S rRNA and gyrB gene sequences revealed that strain ST-6T belonged to a distinct lineage in the genus Shewanella. Strain ST-6T was related most closely to Shewanella basaltis J83T, S. gaetbuli TF-27T, S. arctica IT12T, S. vesiculosa M7T and S. aestuarii SC18T, showing 96-97 % and 85-70 % 16S rRNA and gyrB gene sequences similarities, respectively. DNA-DNA relatedness values between strain ST-6T and the type strains of two species of the genus Shewanella were <22.6 %. The major cellular fatty acids (>5 %) were summed feature 3 (comprising C16:1ω7c and/ or iso-C15:0 2-OH), C16:0, iso-C13:0 and C17:1ω8c. The DNA G+C content of strain ST-6Twas 42.4 mol%, and the predominant isoprenoid quinones were menaquinone MK-7 and ubiquinones Q-7 and Q-8. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain ST-6T is considered to represent a novel species of the genus Shewanella, for which the name Shewanella algicola sp. nov. is proposed. The type strain is ST-6T (= KCTC 23253T = JCM 31091T).


Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice.
Acylcarnitine accumulation has been linked to perturbations in energy metabolism pathways. In this study, we demonstrate that long-chain (LC) acylcarnitines are active metabolites involved in the regulation of glucose metabolism in vivo. Single-dose administration of palmitoylcarnitine (PC) in fed mice induced marked insulin insensitivity, decreased glucose uptake in muscles, and elevated blood glucose levels. Increase in the content of LC acylcarnitine induced insulin resistance by impairing Akt phosphorylation at Ser473. The long-term administration of PC using slow-release osmotic minipumps induced marked hyperinsulinemia, insulin resistance, and glucose intolerance, suggesting that the permanent accumulation of LC acylcarnitines can accelerate the progression of insulin resistance. The decrease of acylcarnitine content significantly improved glucose tolerance in a mouse model of diet-induced glucose intolerance. In conclusion, we show that the physiological increase in content of acylcarnitines ensures the transition from a fed to fasted state in order to limit glucose metabolism in the fasted state. In the fed state, the inability of insulin to inhibit LC acylcarnitine production induces disturbances in glucose uptake and metabolism. The reduction of acylcarnitine content could be an effective strategy to improve insulin sensitivity. © 2017 BioFactors, 43(5):718-730, 2017.


Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.
The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG's antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.


Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse.
Synapsin I and calcium/calmodulin-dependent protein kinase II were pressure-injected into the preterminal digit of the squid giant synapse to test directly the possible regulation of neurotransmitter release by these substances. Neurotransmitter release was determined by measuring the amplitude, rate of rise, and latency of the postsynaptic potential generated in response to presynaptic depolarizing steps under voltage clamp conditions. Injection of dephosphosynapsin I decreased the amplitude and rate of rise of the postsynaptic potential, whereas injection of either phosphosynapsin I or heat-treated dephosphosynapsin I was without effect. Conversely, injection of calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, increased the rate of rise and amplitude and decreased the latency of the postsynaptic potential. The effects of these proteins were observed without any detectable change in the initial phase of the presynaptic calcium current. A synapsin I-like protein and calcium/calmodulin-dependent protein kinase II were demonstrated by biochemical and immunochemical techniques to be present in squid nervous tissue. The data support the hypothesis that synapsin I regulates the availability of synaptic vesicles for release; we propose that calcium entry into the nerve terminal activates calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, dissociating it from the vesicles and thereby removing a constraint in the release process.


Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities.
Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of succinate dehydrogenase (SDH), can cause some forms of MD. SDHA is a crucial contributor to MRC function. In order to expand the range of MD animal models available, we attempted to generate a Sdha knockout rat. Since homozygous Sdha-/- rats could neither be identified in newborn litters, nor as early as embryonic day 14, we evaluated wild-type (WT) and heterozygous Sdha+/- genotypes. No differences in behavioral, biochemical, or molecular evaluations were observed between WT and Sdha+/- rats at 6 weeks or 6 months of age. However, 30% of Sdha+/- rats displayed mild muscle fiber atrophy with rare fibers negative for cytochrome oxidase and SDH on histochemical staining. Collectively, our data provide additional evidence that modeling SDH mutations in rodents may be challenging due to animal viability, and heterozygous rats are insufficiently symptomatic at a phenotypic and molecular level to be of significant use in the study of SDH deficiency.


Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model.
Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (+/-4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (+/-4.2%) after direct coaptation, and 25% (+/-6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration.


Effect of granulocyte colony-stimulating factor treatment at a low dose but for a long duration in patients with coronary heart disease.
In animal models, granulocyte colony-stimulating factor (G-CSF) improves post-infarct cardiac function. However, in pilot studies involving patients with angina and acute myocardial infarction (AMI), G-CSF at a high dose frequently induced coronary occlusion or restenosis, but those at a low dose showed no significant beneficial effect. We hypothesized that a low dose but long duration of G-CSF will have a beneficial effect without serious complications to patients with coronary heart disease. Forty-six patients with angina or AMI were randomly assigned into G-CSF and non-G-CSF control groups, respectively. Recombinant G-CSF was subcutaneously injected once a day for 10 days. The leukocyte counts in the peripheral blood were controlled at approximately 30,000/microl. One month later, a Thallium-201 single photon emission computed tomography revealed the increased percentage uptake and the reduced extent and severity scores in the G-CSF angina group. In the G-CSF AMI group, the curve between the ejection fraction and peak creatine kinase shifted significantly upward, compared with that of the non-G-CSF AMI group. Serious complications were not observed during the 6 months of observation. A low dose but long duration of G-CSF treatment may have a beneficial effect without any serious complications in patients with coronary heart disease.


Comparison of patency between radial artery and saphenous vein in a coronary artery bypass grafting post operative with return of the symptoms.
To compare the radial artery and saphenous vein's patency in patients with recurrence of symptoms in a coronary artery bypass grafting (CABG). Retrospective study. From January 1998 to December 2005, 469 CABGs were performed using the radial artery as a graft, in Vera Cruz Hospital in Belo Horizonte/ MG. Among the patients who underwent those surgeries, 94 presented ischemic changes in early or late postoperative period, which led them to be re-evaluated by coronary angiography. The grafts were divided in three groups: internal thoracic artery (ITA), radial artery (RA) and saphenous vein (SV), and they were stratified according to the severity of injury: uninjured or patent (< 70%), severe obstruction (70 to 99%) and occlusion. For the 94 patients in the study, 86 grafts of ITA, 94 of RA and 111 of SV were used. For the 86 ITA grafts, 73 (84.88%) were found patent. For the 94 RA grafts, 55 (58.51%) were found patent, and for the 111 SV grafts, 73 (65.76%) were uninjured. A statistically significant difference (P= 0.001) was found between RA and SV grafts, with a higher patency found for VS graft. For the RA grafts, women presented a worse result concerning the RA patency (65.7% and 40.7%), with P = 0.006. Concerning coronary revascularization, a statistically significant difference was found only for the grafts used for the right coronary, with a better result for the SV (P = 0.036). Radial artery (RA) presented worse results when compared to Saphenous vein (SV) as a second graft in a CABG, especially in women who were anastomosed in the right coronary artery.


Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms.
The yeast proteins TUP1 and SSN6 form a transcription repressor complex that is recruited to different promoters via pathway-specific DNA-binding proteins and regulates the expression of a variety of genes. TUP1 is functionally related to invertebrate and vertebrate transcriptional repressors of the Groucho/transducin-like Enhancer of split (TLE) family. The aim was to examine whether similar mechanisms underlie the transcription repression functions of TUP1 and Groucho/TLEs by determining whether TLE family members can interact with yeast SSN6 and mammalian SSN6-like proteins. It is shown in the present work that SSN6 binds to TLE1 and mediates transcriptional repression when expressed in mammalian cells. Moreover, TLE1 and TLE2 interact with two mammalian proteins related to SSN6, designated as the products of the ubiquitously transcribed tetratricopeptide-repeat genes on the Y (or X) chromosomes (UTY/X). These findings suggest that mammalian TLE and UTY/X proteins may mediate repression mechanisms similar to those performed by TUP1-SSN6 in yeast.


Increasing infantile hypertrophic pyloric stenosis? Experience in an overseas military hospital.
Fifty-four children with proven infantile hypertrophic pyloric stenosis (IHPS) were treated by Ramstedt's pyloromyotomy during a 14-year period. Between the years 1986 and 1989 the mean incidence of the disease was noted to have risen by 2.72 per 1000 live births over the preceding 10 years. Statistical analysis confirmed a significant upward trend between the years 1976 and 1989. Analysis of the majority of the cases revealed comparable perioperative morbidity rates with other UK district general hospitals. There was no operative mortality. The character of IHPS in military personnel overseas has more in common with UK than international trends. The incidence in this subgroup may be rising.


Cognitive Change After Cardiac Surgery Versus Cardiac Catheterization: A Population-Based Study.
Despite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery. Participants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently. Of 3,105 participants, 1,921 (62%) underwent catheterization and 1,184 (38%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95% confidence interval: -0.046 to 0.005 memory units, p = 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26% or 0.19% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95% confidence interval: 0.74 to 1.18). In this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.


High-fat diets and fecal level of reductase and colon mucosal level of ornithine decarboxylase, beta-glucuronidase, 5'-nucleotidase, ATPase, and esterase in mice.
In one experiment Swiss mice were maintained on a 16 or 23% fat diet (laboratory chow with added fat, principally corn oil) or on laboratory chow alone (5.5% fat). In another experiment C57BL/1 mice were given a 23% fat diet (as above) or a low-fat diet (67% laboratory chow, 1.9% corn oil, and 31% starch; 5.5% fat). Colon mucosal samples were analyzed for several enzyme activities. In Swiss mice the analyses revealed the following: 1) Ouabain-insensitive ATPase was unaltered in male mice, but it rose significantly in females fed a high-fat diet (this effect was seen when a resuspended high-speed pellet was analyzed but not seen with the initial homogenate); 2) 5'-nucleotidase activity showed a significant stepwise increase with dietary fat; 3) nonspecific esterase activity tended to rise with a high-fat diet (not significant); 4) beta-glucuronidase levels were not altered by diet fat; and 5) ornithine decarboxylase levels were not altered by diet fat. In C57BL/1 mice analyses were done on ouabain-insensitive ATPase, 5'-nucleotidase, nonspecific esterase, and beta-glucuronidase, but no diet effects were seen. Fecal reductase activity was measured with the use of 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride hydrate). A high-fat diet did not affect the activity in C57BL/1 mice, but it caused a significant rise in Swiss mice.


Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals.
The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Male Wistar albino rats weighing 250-300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.


Preparation and bioavailability assessment of SMEDDS containing valsartan.
A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance diffusion rate and oral bioavailability of valsartan. The solubility of valsartan was checked in different oils, surfactants, and cosurfactants and ternary phase diagrams were constructed to evaluate the microemulsion domain. The valsartan SMEDDS was prepared using Capmul MCM (oil), Tween 80 (surfactant), and polyethylene glycol 400 (cosurfactant). The particle size distribution, zeta potential, and polydispersity index were determined and were found to be 12.3 nm, -0.746, and 0.138, respectively. Diffusion rate of valsartan was measured by in vitro dialysis bag method using phosphate buffer pH 6.8 as diffusion media. Developed high-performance liquid chromatography method was used to determine drug content in diffusion media. Oral bioavailability of valsartan SMEDDS was checked by using rabbit model. Results of diffusion rate and oral bioavailability of valsartan SMEDDS were compared with those of pure drug solution and of marketed formulation. Diffusion of valsartan SMEDDS showed maximum drug release when compared to pure drug solution and marketed formulation. The area under curve and time showed significant improvement as the values obtained were 607 ng h/mL and 1 h for SMEDDS in comparison to 445.36 and 1.36 h for market formulation suggesting significant increase (p < 0.01) in oral bioavailability of valsartan SMEDDS.


Cellular neurothekeoma: detailed characterization in a series of 133 cases.
Cellular neurothekeomas are distinctive benign cutaneous tumors of uncertain histogenesis. As relatively few cases have been reported, their clinical features and morphologic spectrum remain incompletely defined, and the significance of atypical histologic features is uncertain. This study examined the clinicopathologic and immunohistochemical features of 133 cellular neurothekeomas received between 1987 and 2003. There was a 1.8:1 female predominance, with a mean age of 25 years (84% <40 y). Mean tumor size was 1.1 cm (range: 0.3 to 6 cm; 90% <2 cm). The tumors arose most often on the upper limb (35%) or head and neck (33%). Fifty-two percent of the tumors were limited to the dermis, and 48% also involved superficial subcutaneous tissue. In 30% of cases, neurothekeoma was suggested by the referring pathologist; the most common other diagnoses offered were plexiform fibrohistiocytic tumor, benign fibrous histiocytoma, and a low-grade sarcoma. Histologically, most cases were poorly marginated; 33 (25%) infiltrated fat, and 10 (8%) entrapped skeletal muscle (all but 1 situated on the face). Nearly all tumors had a lobulated or micronodular architecture and were composed of nests and bundles of epithelioid to spindled cells with palely eosinophilic cytoplasm, often separated by dense hyaline collagen; 17 (13%) showed focally sheetlike areas, and 5 (4%) were notably plexiform. Myxoid stroma was observed in 38 (29%) tumors; 11 (8%) were predominantly myxoid. Five (4%) showed marked stromal hyalinization. Osteoclastic giant cells were seen in 20 (15%) cases. The mean mitotic rate was 3 per 10 high power fields; 28 (21%) had > or =5 per 10 high power fields. Most tumors showed mild cytologic atypia in the form of nuclear variability and small nucleoli; 33 (25%) contained notably pleomorphic cells. All tumors were reactive for NKI-C3, 110/123 (89%) expressed neuron-specific enolase, 73/127 (57%) showed at least focal staining for smooth muscle actin, and only 1 was focally desmin positive. All tumors were negative for S-100 protein. Follow-up ranged from 5 to 146 months (mean 44 mo). Ten tumors recurred locally (7 situated on the face), after a mean of 18 months; tumor had been marginally excised or had involved excision margins in all cases with available information. No other clinical or pathologic features correlated with recurrence. Cellular neurothekeomas have a predilection for the upper limbs and head and neck of pediatric and young adult females and rarely recur following incomplete excision. There is no good evidence that these lesions show nerve sheath differentiation and the nomenclature will likely change when the tumor cell lineage is better defined. Atypical histologic features (including pleomorphism, infiltration of subcutis, and a high mitotic rate) seem to have no clinical significance.


Using low-protein diet in egg production for win-win of productivity and environmental benefits should be prudent: Evidence from pilot test.
A shortage of feed protein resources restricts poultry productivity. Key strategies to alleviate this problem include improvements to the structure of the gut microbiota by the appropriate intake of high-quality protein, improvements to the comprehensive protein utilization rate, and reducing the consumption of protein raw materials. In addition, damage to the environment caused by nitrogen emissions needs to be reduced. The aim of the study was to evaluate the effects of dietary protein levels on laying performance, host metabolism, ovarian health, nitrogen emissions, and the gut microbial structure and function of laying hens. In total, 360 hens at the age of 38 weeks were randomly allotted four treatments. Each of the groups consisted of nine replicates, with 10 birds per replicate, used for 12 weeks of study. Dietary protein levels of the four groups were 13.85 %, 14.41 %, 15.63 %, and 16.30 %. Results revealed that, compared with the 13.85 % crude protein (CP) group, the 15.63 % CP group experienced significantly enhanced final body weight, average daily gain, egg production, and egg mass. Compared with the 16.30 % CP group, the other groups' serum concentrations of immunoglobulin G (IgG) and immunoglobulin M (IgM) were significantly reduced. Compared with the 16.30 % CP group, the 13.85 % and 15.63 % groups had increased CP utilization rates but reduced nitrogen emission rate, and daily per egg and per kilogram egg nitrogen emissions rose with increased dietary protein levels. Compared to the 13.85 % and 14.41 % CP groups, the 16.30 % CP group exhibited a significant increase in the expression of genes related to amino acids and carbohydrate metabolic pathways. According to the linear discriminant analysis effect size diagram, the predominant bacteria in the 15.63 % CP group (e.g., Subdoligranulum, and Ruminococcaceae_UCG-013) were significantly related to CP utilization. The results of this study emphasize that production performance is significantly reduced when protein levels are too low, whereas too high protein levels lead to gut microbiota imbalance and a reduction in the utilization efficiency of nutrients. Therefore, on the premise of ensuring the health of hens, the structure of the gut microbiota can be improved by appropriately reducing protein levels, which helps to balance the relationships among host health, productivity, resources, and the environment.


Patients' knowledge on cardiovascular risk factors and associated lifestyle behaviour in Ethiopia in 2018: A cross-sectional study.
Cardiovascular disease (CVD) is posing a major public health challenge globally. Evidence reports significant gaps in knowledge of cardiovascular risk factors among patients with CVD. Despite the growing burden of cardiovascular disease in developing countries, there is limited data available to improve the awareness of this area, which is crucial for the implementation of prevention programs. A cross-sectional survey was conducted in two referral hospitals in Eastern Ethiopia from June-September 2018. Outpatients with a confirmed diagnosis cardiovascular conditions were eligible for participation in the study. A convenience sampling technique was used. The primary outcome of the study was knowledge of cardiovascular risk factors among patients with cardiovascular disease. The knowledge of cardiovascular disease risk factors was measured using a validated instrument (heart disease fact questionnaire). A score less than 70% was defined as suboptimal knowledge. Multivariable linear regression was used to examine the relationship between knowledge of cardiovascular risk factors and explanatory variables. A total of 287 patients were enrolled in the study. Mean age was 47±11yrs and 56.4% of patients were females. More than half of patients (54%) had good knowledge on cardiovascular risk factors (scored>70%), whilst 46% demonstrated suboptimal knowledge levels in this area. Urban residency was associated with higher cardiovascular risk factors knowledge scores, whereas, never married and no formal education or lower education were identified as predictors of lower knowledge scores. There was no statistically significant association between knowledge of cardiovascular risk factors and actual cumulative risk behaviour. Almost half of CVD patients in Ethiopia have suboptimal knowledge regarding cardiovascular risk factors. Residence, education level and marital status were associated with knowledge of cardiovascular risk factors. Implementation of innovative interventions and structured, nurse-led lifestyle counselling would be required to effectively guide patients in developing lifestyle modification and achieve sustainable behaviour change.


Quadruple cancer in a single patient: a report of four cases.
Multiple primary neoplasia was once considered a rare curiosity but is now a well recognized phenomenon. Only a few papers have been published in the English literature with regard to occurrence of four or more primary malignancies in a single patient. We report four cases of quadruple cancer; a review of the literature about this topic is discussed.


Validation of 5 key colonoscopy-related data elements from Ontario health administrative databases compared to the clinical record: a cross-sectional study.
Colonoscopy is used widely, but its quality is highly variable, which may adversely affect patients. Research and quality-improvement initiatives in a variety of jurisdictions have sought to address this issue, often supported by the use of health administrative data. As these data are generally not collected for these purposes, it is critical to measure their validity before use. The aim of this study was to validate health administrative data definitions for 5 key colonoscopy elements through comparison to the clinical record. In a cross-sectional study, we randomly sampled 1968 colonoscopy and noncolonoscopy procedures performed at 23 hospitals and 5 nonhospital endoscopy clinics between April 2008 and March 2009 in Ontario. We compared definitions for 5 key colonoscopy elements (colonoscopy case, colonoscopy setting, colonoscopy completeness, anesthesiologist assistance and polypectomy) derived from the health administrative data to the clinical record. We calculated weighted and unweighted sensitivity, specificity and positive predictive value, adjusted for clustering of patients within physicians, for each definition relative to the reference standard. We abstracted 1845 records; in 1282 cases (69.5%), colonoscopy was intended or performed. The weighted sensitivity and specificity of colonoscopy case, nonhospital colonoscopy setting and anesthesiologist assistance exceeded 95%. The weighted sensitivity for colonoscopy completeness and polypectomy exceeded 95%, but specificity was less than 90%. Ontario health administrative data definitions for 5 key colonoscopy data elements performed well, with sensitivity and specificity values acceptable for use in research and quality-improvement initiatives. In jurisdictions where health administrative data are similarly used for research or quality improvement, similar studies could be considered.


Thrombospondin 2 regulates cell proliferation induced by Rac1 redox-dependent signaling.
Thrombospondin 2 (TSP2) is a matricellular protein controlling the apoptosis-proliferation balance in endothelial cells. Little is known about its transcriptional regulation compared with that of TSP1. We found that overexpression of a constitutively active mutant of Rac (Rac(V12)) specifically increases TSP2 mRNA levels without affecting TSP1 in human aortic endothelial cells (HAEC). Moreover, TSP2 induction by Rac(V12) is dependent upon reactive oxygen species (ROS) production, as gp91ds-tat peptide, an inhibitor of NADPH oxidase, and the flavoprotein inhibitor diphenylene iodinium (DPI) block TSP2 synthesis. Furthermore, we found that increasing Rac(V12) expression results in a biphasic proliferative curve, with proliferation initially increasing as Rac(V12) expression increases and then returning to levels less than that of control cells at higher expression. This growth inhibition is mediated by TSP2, as either DPI treatment, which blocks TSP2 synthesis, or pan-TSP blocking antibodies restore the proliferative ability of HAEC with high expression. Mechanistically, we show that the effect of TSP2 on cell proliferation is independent of the antiangiogenic TSP2 Hep1 sequence, which is capable of altering actin cytoskeletal reorganization but not proliferation in our experimental conditions. Finally, we show in vivo that Rac-induced TSP2 expression is observed in the aorta of transgenic mice selectively expressing Rac(V12) in smooth muscle cells. These results identify Rac-induced ROS as a new pathway involved in the regulation of TSP2 expression.


Acupuncture for the treatment of cancer pain: a systematic review of randomised clinical trials.
Controlling cancer-related pain is an important component in the palliative care of cancer patients. The objective of this review was to assess the effectiveness of acupuncture for treating cancer pain. Fourteen databases were searched from their inception through April 2011. Randomised clinical trials (RCTs) were included if acupuncture was used as the sole treatment or as a part of a combination therapy for cancer pain. Studies were included if they were controlled with a placebo or controlled against a drug-therapy or no-treatment group. The Cochrane criteria were used to assess the risk of bias. A total of 15 RCTs met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The majority of acupuncture treatments or combination therapies with analgesics exhibited favourable effects compared with conventional treatments in individual studies. However, a meta-analysis suggested that acupuncture did not generate a better effect than drug therapy (n = 886; risk ratio (RR), 1.12; 95% CI 0.98 to 1.28; P = 0.09). The comparison between acupuncture plus drug therapy and drug therapy alone demonstrated a significant difference in favour of the combination therapy (n = 437; RR, 1.36; 95% CI 1.13 to 1.64; P = 0.003). The results of this systematic review provide no strong evidence for the effectiveness of acupuncture in the management of cancer pain. The total number of RCTs included in the analysis and their methodological quality were too low to draw firm conclusions. Future rigorous RCTs will be necessary to assess the clinical efficacy of acupuncture in this area.


TOD-CNN: An effective convolutional neural network for tiny object detection in sperm videos.
The detection of tiny objects in microscopic videos is a problematic point, especially in large-scale experiments. For tiny objects (such as sperms) in microscopic videos, current detection methods face challenges in fuzzy, irregular, and precise positioning of objects. In contrast, we present a convolutional neural network for tiny object detection (TOD-CNN) with an underlying data set of high-quality sperm microscopic videos (111 videos, > 278,000 annotated objects), and a graphical user interface (GUI) is designed to employ and test the proposed model effectively. TOD-CNN is highly accurate, achieving 85.60% AP50 in the task of real-time sperm detection in microscopic videos. To demonstrate the importance of sperm detection technology in sperm quality analysis, we carry out relevant sperm quality evaluation metrics and compare them with the diagnosis results from medical doctors.


Effect of refractive error on the risk of ocular hypertension and open angle glaucoma.
From a case-control study of out-patients attending an ophthalmic clinic no relationship (relative risk = 1) was found between refractive error and ocular tension. The deconfounded effect of refractive error on open angle glaucoma (field loss) increased at higher levels of myopia (relative risk = 1.18; refractive error -0.2) The combined effects of myopia and severe ocular hypertension were found to be synergistic (interactive risk ratio = 2.2).


The contingent smile: a meta-analysis of sex differences in smiling.
The authors present a meta-analysis of sex differences in smiling based on 448 effect sizes derivedfrom 162 research reports. There was a statistically significant tendency for women and adolescent girls to smile more than men and adolescent boys (d = 0.41). The authors hypothesized that sex differences in smiling would be larger when concerns about gender-appropriate behavior were made more conspicuous, situational constraints were absent or ambiguous, or emotion (especially negative) was salient. It was also predicted that the size of the sex difference in smiling would vary by culture and age. Moderator analysis supported these predictions. Although men tend to smile less than women, the degree to which this is so is contingent on rules and roles.


Linkage map construction in the outcrossing species Lolium perenne.
Genetic maps have proven useful tools in several fields of application. First of all, they allow to get insight into the genome organization of a species, and to compare the genome structures of different species. Genetic maps are also useful for the identification of genomic regions involved in physiological processes, and are valuable tools for the positional cloning of genes. In the framework of a project with the aim of identifying genomic regions involved in disease resistance in Lolium spp., we constructed genetic maps using different marker systems. In the ryegrass species L. perenne and L. multiflorum self-pollination is prevented by a very efficient self incompatibility system. This has clear implications in mapping studies: inbred lines and double haploids are difficult to produce, and if produced low seed yields are obtained. For this reason, we created several mapping populations by crossing two highly heterozygous unrelated plants. This implies that at any given locus, up to four different alleles might be segregating in the offspring. Different marker systems were used for the construction of the genetic maps. In first instance, AFLP was used as a high throughput marker system. This allowed to generate a high number of DNA-markers useful for map construction in a quick way. The drawback of the AFLP technique is twofold: AFLP markers are 'anonymous', and are dominant (not all alleles at a locus can be detected). Co-dominant marker systems, which allow to detect all alleles present at any locus, are much more informative and are required for the construction of detailed linkage maps in outcrossers. In this study, we used three co-dominant marker systems: SSR, STS and RFLP. The RFLP markers were generated using heterologous probes derived from other monocots, what should allow to analyze the syntenic relationships between ryegrass and other monocots. Using these markers generated with different techniques, a genetic map of ryegrass has been constructed suitable for QTL analysis and comparative genetics.


Hazard identification of pharmaceutical wastewaters using biodegradability studies.
A reliable wastewater characterization is an integral part of treatment and management strategies for industrial effluents. This is especially true for the pharmaceutical industry, which exhibits significant differences in its line of activity, generating effluents of very specific and complex natures. Any hazard or risk assessment of wastewater and/or determination of its treatability must include an evaluation of its degradability. Usually various non-standardized laboratory or pilot-scale long-term tests are run by measuring summary parameters for several days to determine the biodegradation potential of the effluent. A complex approach, based on stabilization studies, was proposed to determine the hazardous impact of wastewaters in terms of biodegradable and persistent toxicity. The objective of our work was to carry out complex hazard evaluation of pharmaceutical wastewaters. Whole effluent toxicity was determined using two different toxicity tests. First, we measured the inhibition of oxygen consumption by activated sludge. The test indicated toxicity of the wastewater and thus we performed an additional acute toxicity test with luminescent bacteria Vibrio fisheri. The next step was the determination of whole effluent ready biodegradability. It was determined with simultaneous measurement of oxygen consumption (ISO 9804) and carbon dioxide production (ISO 9439) in a closed respirometer, accompanied by DOC/IC measurements. The pharmaceutical wastewater degraded readily (83%, lag phase was 2 days, biodegradation rate was 0.33999 day(-1)) on the basis of O2 measurements. The biodegradation, calculated from the CO2 measurements, was comparable. We also applied mass balances of DOC/IC at the beginning and at the end of biodegradation experiments to confirm the extent and rate of biodegradation. The determination of hazardous impact and treatability of the effluent was concluded with aerobic stabilization studies. Biodegradation of the wastewater during the study was followed by relevant biochemical analysis and DOC/IC mass balance.


Effects of inversion and negation on social inferences from faces.
Judgments about personality and other social characteristics based on facial appearance are remarkably consistent across individuals. However, whereas the facial cues that underpin age and sex judgments are already well understood, the physical bases for judgments of characteristics such as intelligence or trustworthiness are still unknown. Inversion and photographic negation are used here to investigate the visual processes underlying social inferences from the face and to explore whether various judgments might rely on different perceptual representations. In experiment 1, the perceptions of age, sex, attractiveness, approachability, intelligence, and trustworthiness, but not distinctiveness, were affected by inversion, and all these characteristics were affected by negation. The effects of inversion and negation were independent, suggesting that they impaired the encoding of different types of information. Moreover, an independent manipulation of hue and luminance in experiment 2 showed that the effects of negation were mainly due to the reversal of luminance values. These results are consistent with the view that information about the configuration of features (the processing of which is impaired by inversion) and information about surface properties (the processing of which is impaired by brightness negation) are both used in the perception of social characteristics from faces. In addition, the fact that there was a similar pattern of impairment across most judgments suggests that there is an initial common perceptual representation of the face, from which most characteristics are inferred.


Risk Prediction Models for Invasive Mechanical Ventilation in Patients with Autoimmune Encephalitis: A Retrospective Cohort Study.
A multivariate predictive nomogram model was developed using the risk factors identified by LASSO regression and assessed by receiver operator characteristics (ROC) curve, calibration curve, and decision curve analysis. The risk factors predictive of severe respiratory failure were male gender, impaired hepatic function, elevated intracranial pressure, and higher neuron-specific enolase. The final nomogram achieved an AUC of 0.770. After validation by bootstrapping, a concordance index of 0.748 was achieved. Our nomogram accurately predicted the risk of developing respiratory failure needing IMV in AE patients and provide clinicians with a simple and effective tool to guide treatment interventions in the AE patients.


Effectiveness of lurasidone in patients with schizophrenia or schizoaffective disorder switched from other antipsychotics: a randomized, 6-week, open-label study.
To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week. ClinicalTrials.gov identifier: NCT01143077.


Unmasked Brugada pattern by ajmaline challenge in patients with myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1) generates missplicing of the SCN5A gene, encoding the cardiac sodium channel (Nav 1.5). Brugada syndrome, which partly results from Nav 1.5 dysfunction and causes increased VF occurrence, can be unmasked by ajmaline. We aimed to investigate the response to ajmaline challenge in DM1 patients and its potential impact on their sudden cardiac death risk stratification. Among 36 adult DM1 patients referred to our institution, electrophysiological study and ajmaline challenge were performed in 12 patients fulfilling the following criteria: (1) PR interval >200 ms or QRS duration >100 ms; (2) absence of complete left bundle branch block; (3) absence of permanent ventricular pacing; (4) absence of implantable cardioverter-defibrillator (ICD); (5) preserved left-ventricular ejection fraction >50%; and (6) absence of severe muscular impairment. Of note, DM1 patients with ajmaline-induced Brugada pattern (BrP) were screened for SCN5A. In all the 12 patients studied, the HV interval was <70 ms. A BrP was unmasked in three patients but none carried an SCN5A mutation. Ajmaline-induced sustained ventricular tachycardia occurred in one patient with BrP, who finally received an ICD. The other patients did not present any cardiac event during the entire follow-up (15 ± 4 months). Our study is the first to describe a high prevalence of ajmaline-induced BrP in DM1 patients. The indications, the safety, and the implications of ajmaline challenge in this particular setting need to be determined by larger prospective studies.


Diagnostic Criteria of Postoperative Cognitive Dysfunction: A Focused Systematic Review.
Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is increasingly addressed in research studies. However, a uniform definition of POCD seems to be lacking, which is a major threat to clinical research in this area. We performed a focused systematic review to determine the current degree of heterogeneity in how POCD is defined across studies and to identify those diagnostic criteria that are used most commonly. The search identified 173 records, of which 30 were included. Neurocognitive testing was most commonly performed shortly before surgery and at 7 days postoperatively. A variety of neurocognitive tests were used to test a range of cognitive domains, including complex attention, language, executive functioning, perceptual-motor function, and learning and memory. The tests that were used most commonly were the Mini-Mental State Examination, the digit span test, the trail making test part A, and the digit symbol substitution test, but consensus on which test result would be considered "positive" for POCD was sparse. The results of this systematic review suggest the lack of a consistent approach towards defining POCD. However, commonalities were identified which may serve as a common denominator for deriving consensus-based diagnostic guidelines for POCD.


[Piroplasms of ruminants in Switzerland and zoonotic significance of Babesia].
Piroplasms are tick-transmitted blood parasites belonging to the genera Babesia and Theileria. In western and southern Switzerland, B. divergens, a small Babesia species, has been known for a long time as a parasite of cattle. Recent investigations have revealed the autochthonous occurrence of this parasite also in central and eastern Switzerland. On the occasion of an outbreak of anaplasmosis in the canton of Grisons, however, B. bigemina, a large Babesia species, and Theileria of the buffeli/sergenti/orientalis species complex were for the first time identified; the epidemiology of these two piroplasms in Switzerland remains unknown until now. The recent identification by genetic analyses of B. divergens in wild ruminants contradicts the hitherto postulated strict host specificity of this Babesia species for cattle. B. divergens as well as the closely related Babesia spp. genotype EU1 have in single cases also been identified in splenectomized humans. The rodent babesia B. microti which causes a human infection that is considered an "emerging tick-borne disease" in the U.S.A., is widespread in rodent populations in Switzerland, but seems to be of minor relevance as zoonotic pathogen here. Reasons for this could be differences in virulence of the parasites or in the transmission by the respective tick-vectors on the two continents.


Topical agents or dressings for pain in venous leg ulcers.
Venous leg ulcers affect up to 1 per cent of people at some time in their lives. The main treatments are compression bandages and dressings. As these ulcers are often painful some clinicians choose particular dressings and topical treatments (analgesia/ local anaesthetic) to reduce the pain both during and between dressing changes. To assess the effectiveness of dressings, local anaesthetics or topical analgesia for pain relief in venous leg ulceration. For this update the search strings were revised and the following databases were searched: The Cochrane Wounds Group Specialised Register (Searched 16/12/09) The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 4 2009; Ovid MEDLINE - 1950 to November Week 3 2009; Ovid EMBASE - 1980 to 2009 Week 50; EBSCO CINAHL - 1982 to December 16 2009. No date or language restrictions were applied. Randomised controlled trials which evaluated local interventions used to relieve venous leg ulcer pain were considered. Pain was defined as either persistent pain or pain at dressing changes or debridement. Ulcer healing and reported adverse events were also considered as further outcomes. Eligibility for inclusion was confirmed by two review authors who independently assessed the potential trials. Two trials evaluating interventions for persistent venous leg ulcer pain were identified for this review update. Both studies evaluated ibuprofen slow release foam dressings; one comparing it with local best practice and the other with an identical foam comparator. The primary end point for both studies was "pain relief achieved". When compared with a foam dressing alone, there was no evidence of a statistically significant effect of the ibuprofen foam dressing in terms of achieving some pain relief the first evening after treatment: 74% in the ibuprofen group (46/62) had pain relief compared with 58% (35/60) in the foam group (no significant difference: RR 1.27, 95%CI 0.98 to 1.65). In the second study 100% (32/32) of people with venous ulcers achieved some pain relief with the ibuprofen dressing on the first evening of treatment compared with 93% (26/28) in the local best practice group (no significant difference: RR 1.08, 95% CI 0.96 to 1.21). Pooling these studies in a meta-analysis (using a random effects model as significant heterogeneity present (p=0.1), I(2) = 64%) there is no evidence that ibuprofen dressings increase the pain relief experienced by the first evening of use (RR 1.15, 95% CI 0.91 to 1.44). We were not able to extract sufficient data to combine other pain outcomes from these trials. There was no difference in healing rates but slightly more adverse events with ibuprofen dressings than with a similar foam dressing without ibuprofen.Six trials evaluated interventions for the pain associated with debridement and were considered sufficiently similar to pool. There was a statistically significant reduction in debridement pain scores with 5% Eutectic Mixture of Local Anaesthetics (EMLA): lidocaine-prilocaine cream; the difference in means (measured on a 100 mm scale) was 20.6 mm (95% CI 12.19 to 29.11). Of these six trials, only one small trial measured healing as an outcome and found no difference in the numbers of ulcers healed at the end of the study. There is no evidence that ibuprofen dressings offer pain relief, as measured at the first evening of use, to people with painful venous leg ulcers compared with foam dressings or best practice.EMLA appears to provide effective pain relief for venous leg ulcer debridement but the effect (if any) of EMLA on ulcer healing remains unknown.


Dysprosium-doped cadmium oxide as a gateway material for mid-infrared plasmonics.
The interest in plasmonic technologies surrounds many emergent optoelectronic applications, such as plasmon lasers, transistors, sensors and information storage. Although plasmonic materials for ultraviolet-visible and near-infrared wavelengths have been found, the mid-infrared range remains a challenge to address: few known systems can achieve subwavelength optical confinement with low loss in this range. With a combination of experiments and ab initio modelling, here we demonstrate an extreme peak of electron mobility in Dy-doped CdO that is achieved through accurate 'defect equilibrium engineering'. In so doing, we create a tunable plasmon host that satisfies the criteria for mid-infrared spectrum plasmonics, and overcomes the losses seen in conventional plasmonic materials. In particular, extrinsic doping pins the CdO Fermi level above the conduction band minimum and it increases the formation energy of native oxygen vacancies, thus reducing their populations by several orders of magnitude. The substitutional lattice strain induced by Dy doping is sufficiently small, allowing mobility values around 500 cm(2) V(-1) s(-1) for carrier densities above 10(20) cm(-3). Our work shows that CdO:Dy is a model system for intrinsic and extrinsic manipulation of defects affecting electrical, optical and thermal properties, that oxide conductors are ideal candidates for plasmonic devices and that the defect engineering approach for property optimization is generally applicable to other conducting metal oxides.