Gender differences in risk of bloodstream and surgical site infections.
Identifying patients most at risk for hospital- and community-associated infections is one essential strategy for preventing infections. To investigate whether rates of community- and healthcare-associated bloodstream and surgical site infections varied by patient gender in a large cohort after controlling for a wide variety of possible confounders. Retrospective cohort study. All patients discharged from January 1, 2006 through December 31, 2008 (133,756 adult discharges and 66,592 pediatric discharges) from a 650-bed tertiary care hospital, a 220-bed community hospital, and a 280-bed pediatric acute care hospital within a large, academic medical center in New York, NY. Data were collected retrospectively from various electronic sources shared by the hospitals and linked using patients' unique medical record numbers. Infections were identified using previously validated computerized algorithms. Odds of community-associated bloodstream infections, healthcare-associated bloodstream infections, and surgical site infections were significantly lower for women than for men after controlling for present-on-admission patient characteristics and events during the hospital stay [odds ratios (95 % confidence intervals) were 0.85 (0.77-0.93), 0.82 (0.74-0.91), and 0.78 (0.68-0.91), respectively]. Gender differences were greatest for older adolescents (12-17 years) and adults 18-49 years and least for young children (<12 years) and older adults (≥ 70 years). In this cohort, men were at higher risk for bloodstream and surgical site infections, possibly due to differences in propensity for skin colonization or other anatomical differences.


Efficacy and Safety of Second-line Treatments in Patients with Advanced Hepatocellular Carcinoma after Sorafenib Failure: A Meta-analysis.
In the last decade, several second-line therapies followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC) have been reported. But the outcomes were different from each other. This meta-analysis aimed to evaluate the efficacy and safety of the second-line therapies followed by sorafenib in patients with advanced HCC. Embase (1974 to October 2019) and Ovid MEDLINE (1946 to October 2019) were searched for randomized clinical trials on second-line therapies followed by sorafenib in patients with advanced HCC. The quality of each study was assessed by the modified Jadad scale. Statistical analysis was carried out by RevMan5.3 software. Efficacy and safety were analyzed. Efficacy included overall survival (OS), disease control rate, time to progression, and progression-free survival. Eight studies involving 3,173 patients were eligible. No difference in OS was found between the second-line treatment group and the control group (HR=0.87, 95% CI: 0.74-1.01, p=0.06). Disease control rate (relative risk (RR)=1.36, 95% CI: 1.16-1.60, p=0.0002), time to progression (HR=0.64, 95% CI: 0.51-0.81, p=0.0002) and progression-free survival (HR=0.60, 95% CI: 0.46-0.77, p<0.0001) were significantly improved by the second-line therapies. There was a slight difference in adverse events of any grade (RR=1.07, 95% CI: 1.00-1.14, p=0.03) between the two groups. These second-line therapies followed by sorafenib may potentially improve the prognosis in patients with advanced HCC. Compared with other second-line therapies, regorafenib seemed to be more effective.


A Rare Case of Bertolotti's Syndrome in a Young Patient: A Case Report and Literature Review.
Bertolotti's syndrome is a congenital condition characterized by the sacralization of the lower lumbar vertebrae or the lumbarization of the sacral vertebrae. The cause of pain in Bertolotti's syndrome is multifactorial. This lumbosacral transitional vertebra has a prevalence of 4% to 30%. Rarely, it is considered in the differential diagnosis of low back pain in young people. Therefore, every aspect of Bertolotti's syndrome needs to be meticulously addressed, and it should be included in the differential diagnosis of chronic back pain. Herein, we present a case of Bertolotti's syndrome presented with chronic lower back pain, confirmed on X-ray and magnetic resonance imaging (MRI). He was managed with analgesics and steroids injection with regular follow-up.


Ancestral Sequence Reconstruction of the Ribosomal Protein uS8 and Reduction of Amino Acid Usage to a Smaller Alphabet.
Understanding the origin and early evolution of proteins is important for unveiling how the RNA world developed into an RNA-protein world. Because the composition of organic molecules in the Earth's primitive environment was plausibly not as diverse as today, the number of different amino acids used in early protein synthesis is likely to be substantially less than the current 20 proteinogenic residues. In this study, we have explored the thermal stability and RNA binding of ancestral variants of the ribosomal protein uS8 constructed from a reduced-alphabet of amino acids. First, we built a phylogenetic tree based on the amino acid sequences of uS8 from multiple extant organisms and used the tree to infer two plausible amino acid sequences corresponding to the last bacterial common ancestor of uS8. Both ancestral proteins were thermally stable and bound to an RNA fragment. By eliminating individual amino acid letters and monitoring thermal stability and RNA binding in the resulting proteins, we reduced the size of the amino acid set constituting one of the ancestral proteins, eventually finding that convergent sequences consisting of 15- or 14-amino acid alphabets still folded into stable structures that bound to the RNA fragment. Furthermore, a simplified variant reconstructed from a 13-amino-acid alphabet retained affinity for the RNA fragment, although it lost conformational stability. Collectively, RNA-binding activity may be achieved with a subset of the current 20 amino acids, raising the possibility of a simpler composition of RNA-binding proteins in the earliest stage of protein evolution.


[Chemotherapy activity and pharmacokinetics of the fluoroquinolones generics Ofloxacin-PhPO and Pefloxacin-genova].
Therapeutic activity, pharmacokinetic and bioavailability on animals (inbred white mouse, rabbits) were evaluated for Ofloxacin-PhPO and Pefloxacin-genova in comparison with innovator products--Tarivid and Abaktal. The results of the experiments demonstrate that investigated generics by their therapeutic efficacy in animals and by bioavailability are similar to original products.


Seed size and emergence time within a stand of wild radish (Raphanus raphanistrum L.): the establishment of a fitness hierarchy.
To determine the role of seed size in creating adult plants of different reproductive success, individual seedlings were marked and periodically censused in a natural stand of wild radish (Raphanus raphanistrum L.) in Hamden, Connecticut. Maximum cotyledon witdth is a useful field estimator of seed weight in this species, although dramatic variation in the availability of water can modify this relationship. Using maximum cotyledon width as a linear estimate of seed weight showed that an increase in seed weight gives rise to a disproportionately large increase in an individual's total reproductive output. Analysis of covariance demonstrated that reproductive output is influenced more heavily by seed weight (maximum cotyledon width) than by emergence time. Genetic variation for seed size has been maintained in this population, suggesting that selection favoring large seeds during the seedling stage may be counteracted by selection for large numbers of seeds.


Global and local diet popularity rankings, their secular trends, and seasonal variation in Google Trends data.
The Internet has become the main source of health-related information including nutrition. The aim of this study was to rank the most popular diets among Google users globally and regionally in addition to secular and seasonal trends in the years 2004 to 2019. We used Google Trends (GT) to identify and analyze course over time and regional interest of 47 topics related to diets. We analyzed secular trends using the Seasonal Mann-Kendall test and seasonal variation using time-series decomposition. The topic "Mediterranean diet" (MedD) was used as a benchmark. We calculated the interest of all topics in proportion to the relative search volume (RSV) of MedD. Globally, Google users were particularly interested in veganism (19.54 times higher than MedD), vegetarianism (15.09 times higher than MedD), and gluten-free diet (11.11 times higher than MedD). Veganism was the most frequently searched diet type in 23 countries followed by vegetarianism (14), ketogenic diet (7), and low-carbohydrate diet (7). Whereas an increase of RSV over time was observed for 23 diets, a decrease was noted for 20. The most dynamic increase was found for FODMAP (6.12 RSV/year), gluten-free diet (5.95 RSV/year), and raw veganism (5.72 RSV/year). Sharp declines concerned negative-calorie food (-4.34 RSV/year), macrobiotic diet (-3.89 RSV/year), and cabbage soup diet (-3.50 RSV/year). The interest in most diets falls in December but peaks in January. Veganism, vegetarianism, and gluten-free diet attract the largest public interest globally. Both secular trends and seasonal variation shape the ever-changing landscape of diet popularity. GT holds promise as a valuable tool in local and international nutrition research.


Mox homeobox expression in muscle lineage of the gastropod Haliotis asinina: evidence for a conserved role in bilaterian myogenesis.
Mox homeobox genes are expressed during early vertebrate somitogenesis. Here we describe the expression of Has-Mox, a Mox gene from the gastropod Haliotis asinina. Has-Moxis expressed in the trochophore larva in paraxial mesodermal bands. During larval development, Has-Mox expression remains restricted to mesodermal cells destined to form adult muscle in the foot. This restricted expression of Has-Mox in Haliotis is similar to that observed for vertebrate Mox genes, suggesting a conserved role in myogenesis in deuterostomes and lophotrochozoans. In contrast, Mox is not expressed in muscle lineages in the ecdysozoan representatives Caenorhabditis elegans or Drosophila; the C. elegansgenome has lost Mox altogether. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00427-002-0223-6.


Continence mechanism of the ileal neobladder in women: a urodynamics study.
We undertook this study to evaluate the mechanism of continence in women who underwent modified radical cystectomy and creation of an ileal neobladder. Our surgical technique was modified in accordance with detailed anatomic dissection of female pelvises with attention to the innervation of the pelvic musculature and urethral sphincter. Ten women aged 41-71 years (mean 64.3 years) underwent nerve-sparing radical cystectomy and creation of an orthotopic neobladder with detubularized ileum. Videourodynamic evaluation was performed 6 months postoperatively to evaluate sphincteric and reservoir function. Seven of the ten patients were totally continent after the procedure, requiring no protective pad. Of these, one requires intermittent self-catheterization. Videourodynamic evaluation revealed a low-pressure reservoir with a mean capacity of 467 ml, and leakage did not occur during Valsalva maneuver. Three patients reported significant incontinence (more than one pad per day) after orthotopic reconstruction. These patients demonstrated intrinsic sphincteric deficiency with a low mean abdominal leak-point pressure of 48.3 cmH2O. Two of these women had stress incontinence preoperatively. In conclusion, continence can be preserved in most women after modified radical cystectomy and orthotopic bladder replacement. Success results from preservation of the intrinsic sphincteric mechanism and the creation of a low-pressure, compliant reservoir. A history of stress incontinence preoperatively appears to predispose to sphincteric weakness postoperatively.


Trichloroethylene vapours do not produce dominant lethal mutations in male mice.
Exposure of male mice to trichloroethylene vapours during 24 h at levels or 50, 202 and 450 ppm did not reveal mutagenic effects in the dominant lethal assay. The following parameters were registered and evaluated: Fertilization rate, post-implantation loss, preemplantation loss and dominant lethal mutations.


The niche in single-cell technologies.
The niche is the microenvironment in which each cell exists and is able to keep its own peculiar characteristics. The importance of the niche has been intensively studied especially in the context of stem cells, as it is responsible for both the maintenance of stemness and activation of differentiation. In the past few years, a variety of single-cell technologies have shed light on the extraordinary variability that characterizes different stem cell populations both in vitro and in vivo, but in most cases positional information is lost. Recent developments of new technologies aim to integrate both the transcriptomic profiling of cells and their spatial location. In this review I will discuss the state of the art of these technologies and the integration with others approaches that will be important in the study of stem cell populations.


Differences in the gut microbiome across typical ageing and in Parkinson's disease.
The microbiota-gut-brain axis' role in Parkinson's disease (PD) pathophysiology, and how this differs from typical ageing, is poorly understood. Presently, gut-bacterial diversity, taxonomic abundance and metabolic bacterial pathways were compared across healthy young (n = 22, 18-35 years), healthy older (n = 33, 50-80 years), and PD groups (n = 18, 50-80 years) using shotgun sequencing and compositional data analysis. Associations between the gut-microbiome and PD symptoms, and between lifestyle factors (fibre intake, physical activity, and sleep) and the gut-microbiome were conducted. Alpha-diversity did not differ between PD participants and older adults, whilst beta-diversity differed between these groups. Lower abundance of Butyricimonas synergistica, a butyrate-producer, was associated with worse PD non-motor symptoms in the PD group. Regarding typical ageing, Bifidobacterium bifidum, was greater in the younger compared to older group, with no difference between the older and PD group. Abundance of metabolic pathways related to butyrate production did not differ among the groups, while other metabolic pathways differed among the three groups. Sleep efficiency was positively associated with Roseburia inulinivorans in the older group. These results highlight the relevance of gut-microbiota to PD and that reduced butyrate-production may be involved with PD pathophysiology. Future studies should account for lifestyle factors when investigating gut-microbiomes across ageing and in PD. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".


Targeting the p53 signaling pathway in cancer therapy - the promises, challenges and perils.
Research over the past three decades has identified p53 as a multi-functional transcription factor. p53 influences myriad, highly diverse cellular processes, and represents one of the most important and extensively studied tumor suppressors. Activated by various stresses, p53 blocks cancer progression by provoking transient or permanent growth arrest, by enabling DNA repair, or by advancing cellular death programs. This anti-cancer activity profile, together with genomic and mutational analyses documenting inactivation of p53 in more than 50% of human cancers, motivated drug development efforts to (re-) activate p53 in established tumors. The complexities of p53 signaling in cancer are summarized, including current strategies and challenges to restore p53's tumor suppressive function in established tumors, to inactivate p53 inhibitors, and to restore wild type function of p53 mutant proteins. p53 represents an attractive target for the development of anti-cancer therapies. Whether p53 is 'druggable', however, remains an area of active research and discussion, as p53 has pro-survival functions and chronic p53 activation accelerates aging, which may compromise the long-term homeostasis of an organism. The complex biology and dual functions of p53 in cancer prevention and age-related cellular responses pose significant challenges to the development of p53-targeting cancer therapies.


Failure of glucose infusion to suppress the exaggerated GH response to GHRH in patients with anorexia nervosa.
The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) test under basal conditions (saline infusion) and during steady-state hyperglycemia (200 mg/dl, induced by the intravenous administration of 8 mg/min.kg of glucose) in 6 adolescent girls with acute-stage AN (as diagnosed by psychopathological, hormonal, and nutritional criteria) and in 5 age-matched female controls. In control subjects, GHRH stimulated GH release during saline, but not glucose, infusion. In the anorectic patients, the GH response to GHRH was exaggerated during both saline infusion (2.97 +/- 0.79 versus 0.52 +/- 0.22 micrograms.120 min.ml-1, p less than 0.02) and under hyperglycemic conditions (4.61 +/- 0.56 versus 0.33 +/- 0.10, p less than 0.001). We conclude that the inhibitory action of hyperglycemia on GHRH-induced GH release is lost in the acute phase of AN.


The impact of Meth A fibrosarcoma derived EMAP II on dendritic cell migration.
Studies have suggested that tumors are capable of modulating dendritic cell (DC) phenotype. A soluble protein produced by certain tumors, endothelial monocyte-activating polypeptide II (EMAP II) has been suggested as an anti-tumor agent based on its anti-angiogenic activity. However, this factor has not been evaluated for effects on DC. In this study, we analyzed the effect of Meth A fibrosarcoma supernatant and recombinant human EMAP II on DC migration. This included the migration of Langerhans cells from mouse ear skin sections and the migration of cells of a dendritic cell line (JAWS II) in a transwell culture system. The results of these studies indicated that EMAP II stimulates the migration of DC. Additional studies showed that the presence of the ascites form of the Meth A tumor led to a decrease in Langerhans cell (LC) numbers in the skin, and this decrease could be partially blocked by neutralizing antibody specific for EMAP II. Subcutaneous injection at the base of the ear of recombinant human EMAP II also led to a decrease in epidermal LC similar to that observed in tumor bearing mice. Together, these results suggest novel roles for EMAP II in modulating the migration of DC and suggest that these effects may modify Meth A tumor/host interactions.


Segmental auxiliary liver transplantation: a new approach to an old problem.
Long-term results after a new technique of partial heterotopic auxiliary liver transplantation carried out in pigs are presented. There are three main characteristics of this technique: (1) hemihepatectomy on the bench to solve the problem of space, (2) laterolateral vena cava anastomosis through which it is possible to fix the graft to the host's inferior vena cava. The above anastomosis is fashioned as close as possible to the right atrium and (3) partial diversion of the portal blood through the graft, while maintaining adequate portal blood for the host liver. Of the four animals that underwent transplants, three survived for more than 12 hr. One animal died after 1 day and another was sacrificed after 82 days. At this time, one animal is still alive, 8 months following transplantation and appears to enjoy a normal life. The present technique appears to anticipate the problem of space, of graft congestion, of graft atrophy, and mainly, the problem of functional competition between the graft and the host liver.


[Bioavailability and elimination of various digoxin preparations in the beagle dog and their possible sex dependence (author's transl)].
The glycoside serum levels were investigated in two healthy male and two healthy female Beagles after oral administration of four different galenic preparations of digoxin. Serum samples were taken at defined intervals and examined by radioimmunology for their glycoside content. Female Beagles eliminated orally administered digoxin considerably more rapidly than did male animals as observed by the disappearance rates of glycoside from the serum. Sex-linked differences in the bioavailability of different galenic preparations of digoxin were not confirmed statistically in this trial. No differences between sexes regarding maximum serum levels were detectable with similar preparations. These results suggest that the serum elimination rate of digoxin is different in male and female Beagles. Possible causes for these findings are discussed.


The macrophage migration inhibitory factor protein superfamily in obesity and wound repair.
The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.


Hematopoietic stem cell deficiency resulting from cytomegalovirus infection of bone marrow stroma.
Cytomegalovirus (CMV) recurrence from latency is a major risk factor in bone marrow transplantation (BMT). Owing to the immunodepletive treatment, ablation of the immune control of latent CMV is responsible for recurrence and cytopathogenic spread of the virus in vital tissues. There is increasing evidence for reconstituting bone marrow being itself a target tissue of CMV. By inhibiting post-transplantation hematopoiesis, CMV is causal for maintenance of the immunocompromised state, which leads to a prolonged phase of persistent virus replication. Based on results in a murine model of BMT and concurrent CMV infection, we discuss possible mechanisms of CMV-mediated bone marrow graft failure. It is concluded that an irremediable damage of bone marrow stroma by CMV is responsible for a reduced rate of regeneration of the marrow-repopulating, pluripotent stem cell.


Corrigendum: Plants in vitro propagation with its applications in food, pharmaceuticals and cosmetic industries; current scenario and future approaches.
[This corrects the article DOI: 10.3389/fpls.2022.1009395.].


Oxytocin decreases aversion to angry faces in an associative learning task.
Social and financial considerations are often integrated when real life decisions are made, and recent studies have provided evidence that similar brain networks are engaged when either social or financial information is integrated. Other studies, however, have suggested that the neuropeptide oxytocin can specifically affect social behaviors, which would suggest separable mechanisms at the pharmacological level. Thus, we examined the hypothesis that oxytocin would specifically affect social and not financial information in a decision making task, in which participants learned which of the two faces, one smiling and the other angry or sad, was most often being rewarded. We found that oxytocin specifically decreased aversion to angry faces, without affecting integration of positive or negative financial feedback or choices related to happy vs sad faces.


Clinical study of precision analysis and deviation control of a domestic guide plate-assisted edentulous implant surgery.
To evaluate the accuracy of a domestic digital implant guide plate to assist edentulous implant surgery, analyze the sources of deviation, and reduce the deviation of the guide plate. In total, 14 edentulous patients were selected, and 100 implant sites were measured. The preoperative cone beam computerized tomography (CBCT) data were imported into the software to design and fabricate the guide plate. After implant surgery,the data were imported for 3D reconstruction and alignment model was exported into the Geomagic Studio software for deviation measurement. Analysis of the overall accuracy of the domestic guide plate showed deviation of the implant neck center, horizontal direction, implant base center, depth, and angle of 0.83 ± 0.27 mm, 0.39 ± 0.17 mm, 1.11 ± 0.35 mm, 0.45 ± 0.19 mm, and 3.16 ± 1.73°. There were not statistically significant difference (p>0.05) between the tooth/mucosa-supported guide plate and the mucosa-supported, mandibular guide plate and maxillary, vertical implantation and inclined, anterior implant sites and posterior teeth. There was a statistically significant difference (p<0.05) between the use of the modified non-pressure plate tool box and the pressure plate tool box. First, the domestic implant guide plate can significantly improve the accuracy and efficiency in edentulous implant surgery. Second, the accuracy of the tooth/mucosa-supported guide plate is higher than mucosa-supported guide plate. Third, the accuracy of the new tool box without pressure plate is improved.


Association of Benign Paroxysmal Positional Vertigo with Depression and Anxiety-A Systematic Review and Meta-Analysis.
To evaluate the extent to which Benign Paroxysmal Positional Vertigo (BPPV) is associated with a higher prevalence of depression and anxiety in patients. Three databases including PubMed, Embase, and The Cochrane Library were searched by two independent authors from inception to June 12, 2022 for observational studies and randomized controlled trials investigating the association between BPPV and depression and anxiety. We included studies published as full-length articles in peer-reviewed journals with an adult population aged at least 18 years who have BPPV, detected through validated clinical methods like clinical diagnosis, interview and Dix-Hallpike test. A total of 23 articles met the final inclusion criteria and 19 articles were included in the meta-analysis. BPPV was associated with a 3.19 increased risk of anxiety compared to controls, and 27% (17%-39%) of BPPV patients suffered from anxiety. Furthermore, the weighted average Beck's Anxiety Inventory score was 18.38 (12.57; 24.18), while the weighted average State-Trait Anxiety Index score was 43.08 (37.57; 48.60). There appears to be some association between BPPV and anxiety, but further studies are required to confirm these associations. Laryngoscope, 2023.


Orthogonal-view Microscope for the Biomechanics Investigations of Aquatic Organisms.
Microscopes are essential for the biomechanical and hydrodynamical investigation of small aquatic organisms. We report a do-it-yourself microscope (GLUBscope) that enables the visualization of organisms from two orthogonal imaging planes - top and side views. Compared to conventional imaging systems, this approach provides a comprehensive visualization strategy of organisms, which could have complex shapes and morphologies. The microscope was constructed by combining custom 3D-printed parts and off-the-shelf components. The system is designed for modularity and reconfigurability. Open-source design files and build instructions are provided in this report. Additionally, proof-of-use experiments (particularly with Hydra) and other organisms that combine the GLUBscope with an analysis pipeline were demonstrated to highlight the system's utility. Beyond the applications demonstrated, the system can be used or modified for various imaging applications.


Microplastics in aquatic species of Anzali wetland: An important freshwater biodiversity hotspot in Iran.
Coastal wetlands are sensitive ecosystems that give habitat to large number of species. The extent of the impact of microplastic pollution in the aquatic system and humans is not known. In this study, the occurrence of microplastics (MPs) was assessed in 7 aquatic species from the Anzali Wetland (40 fish and 15 shrimp specimens), a listed wetland on the Montreux record. Specifically, the tissues analyzed were gastrointestinal (GI) tract, gills, skin, and muscles. The total frequency of MPs (all detected MPs in the GI tract, gill and skin samples) varied from 5.2 ± 4.2 MPs/specimen for Cobitis saniae to 20.8 ± 6.7 MPs/specimen for Abramis brama. Among all tissues studied, the GI tract of the Chelon saliens, a herbivorous demersal species, had the greatest level of MPs (13.6 ± 10 MPs/specimen). Significant differences (p < 0.05) were found between the abundance of MPs in different species, tissues, living domains and feeding habit types. The findings support that fish may uptake MPs through adherence in gills (respiration) in addition to ingestion. White/transparent and black/grey polyamide (PA) fibers were the most common type of MP which may be originated from municipal wastewater and intensive fishing activities. About 34% of the MPs were in the range of 250 μm-500 μm, and those >100 μm were not detected in muscles from the study fish. All species had unhealthy weight according to the Fulton's condition index (K). Positive relationships existed between biometric properties (total length and weight) of species and the total frequency of uptaken MPs, pointing to detrimental impact of MPs in the wetland.


Competition in bistable vision is attribute-specific.
We employ ambiguous figures and rivalrous stimuli that have multiple ambiguous properties to show that the different attributes of an ambiguous stimulus can undergo independent switching dynamics. This suggests that competition is distributed and attribute-specific, consistent with the known functional segregation of visual processing. Conflicting evidence that binocular rivalry is an early or late visual process may be better understood as evidence for attribute-specific competition occurring at multiple stages of visual processing. Specifically, we show that whether perceptual selection during binocular rivalry is early and eye-based or late and percept-based depends on the particular ambiguous attributes of the rivalrous stimulus.


A T-bet gradient controls the fate and function of CCR6-RORγt+ innate lymphoid cells.
At mucosal surfaces, the immune system should not initiate inflammatory immune responses to the plethora of antigens constantly present in the environment, but should remain poised to unleash a potent assault on intestinal pathogens. The transcriptional programs and regulatory factors required for immune cells to switch from homeostatic (often tissue-protective) function to potent antimicrobial immunity are poorly defined. Mucosal retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) innate lymphoid cells (ILCs) are emerging as an important innate lymphocyte population required for immunity to intestinal infections. Various subsets of RORγt(+) ILCs have been described but the transcriptional programs controlling their specification and fate remain largely unknown. Here we provide evidence that the transcription factor T-bet determines the fate of a distinct lineage of CCR6(-)RORγt(+) ILCs. Postnatally emerging CCR6(-)RORγt(+) ILCs upregulated T-bet and this was controlled by cues from the commensal microbiota and interleukin-23 (IL-23). In contrast, CCR6(+)RORγt(+) ILCs, which arise earlier during ontogeny, did not express T-bet. T-bet instructed the expression of T-bet target genes such as interferon-γ (IFN-γ) and of the natural cytotoxicity receptor NKp46. Mice genetically lacking T-bet showed normal development of CCR6(-)RORγt(+) ILCs, but they could not differentiate into NKp46-expressing RORγt(+) ILCs (that is, IL-22-producing natural killer (NK-22) cells) and failed to produce IFN-γ. The production of IFN-γ by T-bet-expressing CCR6(-)RORγt(+) ILCs was essential for the release of mucus-forming glycoproteins required to protect the epithelial barrier during Salmonella enterica infection. Salmonella infection also causes severe enterocolitis that is at least partly driven by IFN-γ. Mice deficient for T-bet or depleted of ILCs developed only mild enterocolitis. Thus, graded expression of T-bet in CCR6(-)RORγt(+) ILCs facilitates the differentiation of IFN-γ-producing CCR6(-)RORγt(+) ILCs required to protect the epithelial barrier against Salmonella infections. Co-expression of T-bet and RORγt, which is also found in subsets of IL-17-producing T-helper (T(H)17) cells, may be an evolutionarily conserved transcriptional program that originally developed as part of the innate defence against infections but that also confers an increased risk of immune-mediated pathology.


[Fractures of the coxal femur end. Development of surgical treatment and rehabilitation (1973-1978)].
734 fractures of the proximal femur end treated between 1973 and 1978 are presented in order to demonstrate the progress of surgical treatment and rehabilitation as well as the advantages of certain methods.


A comparision of normal submaxillary gland proteins with proteins obtained from a transplantable murine salivary gland carcinoma (myoepithelioma).
A new transplantable murine salivary gland carcinoma (myoepithelioma) was further characterized by comparing total protein patterns with normal submaxillary gland proteins. Analysis by isoelectric focussing or by labelling studies with radioactive leucine showed considerable differences between tumour and normal proteins. In contrast, analysis of staining patterns after electrophoresis in sodium dodecyl sulphate containing gels revealed a striking similarity between normal proteins, tumour proteins and proteins obtained from metastatic growths. It thus appears that tumour proteins closely resemble the normal proteins from the tissue of origin with respect to molecular size as determined by electrophoretic mobility, while significant differences occur in charge and labelling kinetics.


Correction of Non-Linear Propagation Artifact in Contrast-Enhanced Ultrasound Imaging of Carotid Arteries: Methods and in Vitro Evaluation.
Non-linear propagation of ultrasound creates artifacts in contrast-enhanced ultrasound images that significantly affect both qualitative and quantitative assessments of tissue perfusion. This article describes the development and evaluation of a new algorithm to correct for this artifact. The correction is a post-processing method that estimates and removes non-linear artifact in the contrast-specific image using the simultaneously acquired B-mode image data. The method is evaluated on carotid artery flow phantoms with large and small vessels containing microbubbles of various concentrations at different acoustic pressures. The algorithm significantly reduces non-linear artifacts while maintaining the contrast signal from bubbles to increase the contrast-to-tissue ratio by up to 11 dB. Contrast signal from a small vessel 600 μm in diameter buried in tissue artifacts before correction was recovered after the correction.


Prognostic significance of preoperative plasma fibrinogen levels in primary gastrointestinal stromal tumours: a retrospective cohort study.
Improved prediction of prognosis for gastrointestinal stromal tumours (GISTs) has become increasingly important since the introduction of targeted therapy. Here, we aimed to evaluate the prognostic significance of preoperative plasma fibrinogen (Fib) levels in patients with primary GISTs and to analyse their correlations with clinicopathological characteristics. A total of 201 previously untreated patients with primary GISTs who had undergone radical surgery at our institution between October 2004 and July 2018 were enrolled. The optimal cut-off value for Fib levels was calculated using time-dependent receiver-operating characteristic curve analysis. RFS, the primary endpoint, was calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox regression models were calculated. High preoperative plasma Fib levels were detected as an independent adverse prognostic factor (p = 0.008, hazard ratio 3.136, 95% CI 1.356‒7.256). Furthermore, high preoperative plasma Fib levels also indicated a poor prognosis within the modified National Institutes of Health (mNIH) high-risk subgroup (p = 0.041). In addition, preoperative plasma Fib levels showed a positive correlation with several prognostic factors and even a linear relationship with tumour size (Spearman correlation coefficient [r] = 0.411, p < 0.001). Our results suggest that high preoperative plasma Fib levels may indicate a poor prognosis in patients with primary GISTs. As a cost-effective biomarker, preoperative assessment of plasma Fib levels may help to further risk stratify patients with mNIH high-risk GISTs and instruct the application of targeted therapy.


Intermittent blood flow in solid tumours--an under-appreciated source of 'drug resistance'.
As the search for improved anti-cancer drugs continues, new paradigms concerning the reasons for clinical failures in common human solid tumours are also evolving. Classical drug resistance is now perhaps less often invoked to explain lack of treatment efficacy than are newer concepts, including 'contact resistance', 'tumour heterogeneity', 'regrowth resistance', and 'physiological barriers' to drug delivery. This commentary will explore the resistance of solid tumours to chemotherapy from yet another, largely ignored perspective: that of tumour-specific fluctuations in blood flow. Transient decreases in blood flow have significant implications for delivery of chemotherapeutic agents, cellular responsiveness to those agents, and the regrowth potential of the surviving tumour cells.


Use of polytetrafluoroethylene grafts for renal bypass.
Fifty-six revascularizations of the renal arteries were performed in 52 patients with renovascular hypertension with the use of polytetrafluorethylene grafts between June 1979 and October 1984, with an average follow-up of 25.0 +/- 7.7 months. Ninety-two percent of the patients were considered to have good results (30% cured and 62% improved). Four patients were classified as unsuccessfully treated; one died postoperatively of myocardial infarction. All patients underwent late angiographic studies, with only one graft thrombosis being identified. No evidence of anastomotic stenosis, graft dilatation, or false aneurysm occurred during the follow-up period. From this experience, we believe polytetrafluoroethylene grafts are a valuable alternative to other graft materials for renal artery bypass and may be the preferred graft in the management of atheromatous lesions.


Multi-atlas Based Segmentation Editing with Interaction-Guided Constraints.
We propose a novel multi-atlas based segmentation method to address the editing scenario, when given an incomplete segmentation along with a set of training label images. Unlike previous multi-atlas based methods, which depend solely on appearance features, we incorporate interaction-guided constraints to find appropriate training labels and derive their voting weights. Specifically, we divide user interactions, provided on erroneous parts, into multiple local interaction combinations, and then locally search for the training label patches well-matched with each interaction combination and also the previous segmentation. Then, we estimate the new segmentation through the label fusion of selected label patches that have their weights defined with respect to their respective distances to the interactions. Since the label patches are found to be from different combinations in our method, various shape changes can be considered even with limited training labels and few user interactions. Since our method does not need image information or expensive learning steps, it can be conveniently used for most editing problems. To demonstrate the positive performance, we apply our method to editing the segmentation of three challenging data sets: prostate CT, brainstem CT, and hippocampus MR. The results show that our method outperforms the existing editing methods in all three data sets.


Ethical considerations of the new reproductive technologies. By the Ethics Committee (1986-87) of The American Fertility Society in light of Instruction on the Respect for Human Life in its Origin and on the Dignity of Procreation issued by the Congregation for the Doctrine of the Faith.
In September 1986, The American Fertility Society issued a report, Ethical Considerations of the New Reproductive Technologies, setting forth the then-held ethical position of the Society on the various new reproductive technologies. In 1987, the Congregation for the Doctrine of the Faith issued the Instruction on the Respect for Human Life and Its Origin and on the Dignity of Procreation. While both documents state that very similar moral criteria were used to derive ethical positions with respect to various reproductive procedures, the conclusions as to the ethical acceptability of the various procedures differ sharply in the two documents. The question can be raised about the procedure used by the Congregation of the Faith to derive its conclusions from the stated premises. Thus, while stating that "the individual integrally and adequately considered" is to be the basis of the moral judgment, the fact is that most conclusions are based on and referenced to past Catholic statements. While the difference in conclusion from similar premises may be troubling to society, it can be especially paralyzing to four groups: (1) those who face problems that might be solved by one or another of the new reproductive technologies; (2) those who are involved in applying them; (3) those who are responsible for institutional policies where such techniques may be applied; and (4) those who are in a position to influence public policy in a legislative or regulatory way. Because of the conflicting conclusions of the two documents, the present Ethics Committee (1986-87) of The American Fertility Society was convened and considered these guidelines in the light of the Instruction.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential effects of hypothermal stress on lactate metabolism in fresh water- and seawater-acclimated milkfish, Chanos chanos.
The milkfish Chanos chanos, an economically important cultured marine species in Southeast Asia, exhibits stenothermal and euryhaline characteristics and huge mortality usually occurs during extreme cold weather in winter. Under conditions beyond optimal temperatures, ectothermic species experience an increase in anaerobic glycolysis. To better understand the hypothermal acclimation response of this tropical species, the lactate metabolic profiles of freshwater (FW)- and seawater (SW)-acclimated milkfish were compared under control (optimal temperature; 28 °C) and hypothermal treatment (18 °C) conditions. In this study, the lactate dehydrogenase (LDH) isoform genes, ldha and ldhb, were identified in milkfish livers and muscles, respectively. The LDH is a bidirectional enzyme that triggered the conversion of pyruvate to lactate via anaerobic glycolysis as LDH exhibits the reductase activity (LDH-R), while via the reverse direction as LDH exhibits the oxidase activity (LDH-O). The hypothermal stress significantly upregulated the LDH-R activity in the muscles and the monocarboxylate transporter activity in both muscles and livers, of SW- and FW-acclimated milkfish. The levels of blood lactate, however, decreased in SW-acclimated milkfish. Under hypothermal stress, anaerobic metabolism increased in the muscles of both FW and SW individuals, whereas the liver of SW-acclimated milkfish showed better acute phase capacity to utilize blood lactate than FW-acclimated milkfish. Taken together, in the present study, the major functions of the bidirectional enzyme LDH were identified according to its LDH-O and LDH-R activities. Furthermore, environmental salinities were found to affect the acute anaerobic metabolic strategies of euryhaline teleosts under hypothermal stress and were correlated with their hypothermal tolerance ability.


Quality of life in adult congenital heart disease: what do we already know and what do we still need to know?
Quality of life (QOL) is a key outcome in patients with congenital heart disease (CHD) because CHD has become a chronic condition accompanied by lifelong impairments. Recently, published studies on QOL in adults with CHD have reported inconsistent findings. Patients' QOL seems to depend on multiple factors and is not solely determined by their heart defect and various medical or demographic characteristics. For instance, evidence suggests that a strong sense of coherence might be an important pathway to improve QOL. However, studies on QOL and its determinants are characterized by important methodological differences and limitations, making it impossible to draw firm conclusions. To fill the gaps in the current evidence base, longitudinal and international research is needed. Furthermore, the research field on QOL in CHD should move on from observational studies to interventional research to guide health professionals in improving QOL.


The use of the non-specific immunological factors, conglutinin, immunoconglutinin and heterophile antibody, in the serodiagnosis of bovine brucellosis.
The changes in the titres of immunoconglutinin (IK), conglutinin and heterophile antibodies were measured in calves vaccinated with Br. abortus Strain 19. The IK titres rose rapidly following vaccination but returned to normal within ten weeks. A survey of the sera of over 300 cattle showed no significant correlation between the Brucella STA titre and any of these "non-specific' indicators. It is concluded that they are of little assistance in the serodiagnosis of brucellosis.


Transporters for amino acids in plant cells: some functions and many unknowns.
Membrane proteins are essential to move amino acids in or out of plant cells as well as between organelles. While many putative amino acid transporters have been identified, function in nitrogen movement in plants has only been shown for a few proteins. Those studies demonstrate that import systems are fundamental in partitioning of amino acids at cellular and whole plant level. Physiological data further suggest that amino acid transporters are key-regulators in plant metabolism and that their activities affect growth and development. By contrast, knowledge on the molecular mechanisms of cellular export processes as well as on intracellular transport of amino acids is scarce. Similarly, little is known about the regulation of amino acid transporter function and involvement of the transporters in amino acid signaling. Future studies need to identify the missing components to elucidate the importance of amino acid transport processes for whole plant physiology and productivity.


Enzyme immunoassay, complement fixation and hemagglutination inhibition tests in the diagnosis of influenza A and B virus infections. Purified hemagglutinin in subtype-specific diagnosis.
The efficacy of enzyme immunoassay (EIA) in detecting diagnostic antibody rises to influenza A and B viruses was compared with complement fixation (CF) and hemagglutination inhibition (HI) tests in 455 patients with an acute respiratory infection. EIA and HI detected significantly more diagnostic antibody rises against influenza A than the CF method (96 and 87 vs. 47, respectively). In the case of influenza B significantly more diagnostic influenza B antibody rises were observed by EIA than by CF or HI (59 vs. 37 and 40, respectively). In most of the cases antibody rises in EIA were found in both IgG and IgA isotypes whereas increases in IgM antibodies were seen less frequently. Purified hemagglutinins (HA) were prepared from influenza A HI- and H3-subtypes and from influenza B viruses and used as antigens in EIA and the results were compared with those of HI. Infections caused by influenza A HI-subtype showed good homologous antibody responses in EIA but heterologous antibody responses to H3-subtype and influenza B HAs were frequently observed. Heterologous responses were clearly less frequent in patients with infections caused by the H3-subtype. Influenza B infections occasionally raised HA antibodies against influenza A H1-subtype but not to the H3-subtype. Interestingly, HI detected these heterologous responses at least as frequently as EIA. When whole viruses were used as antigens in EIA, subtype specificity was not observed and cross-reactions between influenza A and B virus antibodies were found. These observations suggest that, although EIA can show greater diagnostic efficacy over HI and CF methods, HI is still the serological method of choice in determining the causative subtype of influenza A virus infection.


The primary structure of phospholipase A2 from porcine pancreas. A reinvestigation.
The primary structure of porcine pancreatic phospholipase A2 (EC 184.108.40.206) has been reinvestigated. A number of modifications have been introduced including the addition of a 7th disulfide bridge. The structure which is presented here shows a high degree of homology with the amino acid sequence of snake venom and horse pancreas phospholipase A2.


Effect of acetoxycycloheximide and dibutyryladenosine cyclic 3':5'-monophosphate on axonal regeneration in the goldfish optic nerve.
Acetoxycycloheximide (AXM) or dibutyryl cyclic AMP (dbcAMP) was injected unilaterally into the vitreous humor of the eye beginning 5-6 days after bilateral optic nerve crush. Injections were repeated every 12-24 h for a total of 3-5 days; goldfish were sacrificed 10 days after lesioning the nerves. At a low dosage of AXM (0.1 microgram daily for 5 days), the mean outgrowth distance in treated neurons was 60% less than in contralateral control neurons. At a high dosage (0.3 microgram daily for 4 days), outgrowth was immediately blocked in both treated and contralateral control axons. Dibutyryl cyclic AMP, in a dose of 5 microM every 12 h for 3 days, produced a 38% reduction in outgrowth distance, associated with a 30% reduction in protein synthesis by the retinal ganglion cells and a 73% reduction in the amount of protein carried by the fast component of axonal transport.


[Screening the trans-action factors binding to the enhancer element of rat GST-P by yeast one-hybrid system].
To investigate the diversity of the mechanisms of rat glutathione S-transferase P (GST-P) gene expression regulation and the relation between rat GST-P gene expression and carcinogenesis. To search the trans-action factors binding to the enhancer element of rat GST-P (glutathione S-transferase P enhancer, GPE I). We searched the trans-action factors binding to GPE I using yeast one-hybrid system, and analyzed the DNA sequence by sequencing and computer search. Two positive clones pYGPE1 and pYGPE2 were obtained. The homologies of the insert sequence of pYGPE1 nucleotide and amino acid sequences with rat c-jun cDNA were 99% and 100% respectively; the homologies of the insert sequence of pYGPE2 nucleotide and amino acid sequences with rat mitochondrial adenine nucleotide translocase cDNA were 99% and 100% respectively. Rat c-Jun and mitochondrial adenine nucleotide translocase can bind to the GPE I core sequence, and they perhaps are the trans-action factors of GPE I.


Embolization of experimental aneurysms using a heparin-loaded stent graft with micropores.
For percutaneous transluminal angioplasty (PTA), a heparin-loaded stent graft, composed of a commercially available metallic stent with a microporous and surface-modified thin film, has been developed. Early controlled endothelialization is promoted by a regular array of micropores produced by an excimer laser ablation technique. Early thrombus is prevented by a drug delivery system established by impregnation of photoreactive gelatin with heparin. Our stent grafts were used for embolization of experimental carotid aneurysms with an autologous external jugular vein patch in dogs. At 1 month after formation, the aneurysms were occluded with stent grafts. Affected arteries were removed with the aneurysms, immediately (two aneurysms in one dog), 1 week (four aneurysms in two dogs), 1 month (three aneurysms in two dogs) and 3 months (four aneurysms in two dogs) after embolization, and were studied histologically to evaluate patency and endothelialization over the intraluminal surface of the thin film. Treated carotid arteries were all patent with occluded aneurysms completely at any periods. Even at 1 week after embolization, endothelialization was confirmed on the surface of the stent graft on the lumen side. At 1 and 3 months, all treated aneurysms with enough patent parent arteries were filled with organized tissues and completely occluded. Our developed stent graft appears to be promising for the treatment of aneurysms, especially with respect to immediate termination of blood inflow and early endothelialization in the neck of the aneurysm.


[Compliance of age related macular degeneration patients undergoing anti-VEGF therapy : Analysis and suggestions for improvement].
Activity-based treatment regimens with anti-vascular endothelial growth factor (anti-VEGF) are currently the gold standard for treatment of exudative age-related macular degeneration (nAMD). Whereas injection frequencies of approximately seven injections in the first year and six in the second year are expected with a pro re nata (PRN) regimen, retrospective real life observations have recorded significantly reduced numbers of injections. This study was carried out to investigate the reasons for the reduction in follow-up control appointments and to find out whether a telemedicine network could influence the motivation and compliance for regular control examinations and treatment. The patient collective included 210 eyes from 191 patients with nAMD treated by anti-VEGF therapy in 2010 and 2011. The activity-based anti-VEGF treatment, control examinations and treatment intervals were performed according to the guidelines over a mean follow-up of 2 years. In another collective of 100 eyes from 100 patients with treatment of nAMD 2 groups were observed: 1 group with patients for whom control examinations were carried out close to home including an online transmission of the results to the treating retinal center and another group in which the patients had to be examined in the treatment center. After 140 weeks 50 % of the patients in the first collective regularly attended control examinations and after 1 year the number was 79 %. After 2 years the probability of continuous supervision is given for only 62 % of the patients, whereas in 38 % the treatment was terminated. Of these patients treatment was terminated in 8 % due to valid criteria, whereas in 30 % of the patients the termination was unintentional. The main reason (38 %) for an unintentional termination of examination and treatment was the frequent and long journey. Patients in the second collective had a significantly higher compliance with respect to the control examinations (p < 0.001) and number of injections (p = 0.02) over the period of nearly 2 years due to the introduction of electronic transmission of images. A long-term therapy of nAMD in the clinical routine can be achieved by a close relationship with the ophthalmologist, continuous follow-up controls and therapy cycles. A close telemedical networking between the ophthalmologist and the treatment center can lead to better patient compliance. Furthermore, the construction of such platforms represents a challenge not only for the treatment of nAMD but also for other diseases.


Body fat distribution and breast cancer risk: findings from the Nigerian breast cancer study.
The relationship between overall obesity and breast cancer risk has been well recognized, but the role of central obesity in breast cancer development is uncertain. Between 1998 and 2009, 1,233 invasive breast cancer cases and 1,101 community controls were recruited into the Nigerian Breast Cancer Study at Ibadan, Nigeria. Logistic regressions were used to calculate multivariate odds ratio (OR) and 95% confidence intervals (CI), adjusting for age, body mass index (BMI), and other known risk factors for breast cancer. The OR for the highest quartile group of waist circumference relative to the lowest was 2.39 (95% CI, 1.59-3.60; P-trend < 0.001). Comparing women with waist/hip ratio (WHR) in the lowest quartile group, the OR for women in the highest quartile category was 2.15 (95% CI, 1.61-2.85; P-trend < 0.001). An inverse association was observed between hip circumference and breast cancer, with an OR of 0.36 for the highest quartile (95% CI, 0.24-0.55; P-trend < 0.001). The effects of these three measures existed in both pre- and postmenopausal women. Of note, we found a significant interaction between WHR and BMI (P-interaction = 0.016): the OR comparing the highest to the lowest WHR quartile was 2.81 (95% CI, 1.90-4.16) for women with BMI < 25 kg/m2 and 1.70 (95% CI, 1.11-2.61) for women with BMI ≥ 25 kg/m2. These results suggest that central adiposity, measured by waist circumference and waist/hip ratio, was an important risk factor for breast cancer in Nigerian women, and the effect of central adiposity was strong in normal-weight women.


Assessment of functional mobility and gait during a timed up and go test in adults with total blindness.
The loss of vision leads to behavioral and motor adaptations that do not necessarily translate to good functioning with regards to daily tasks. To investigate differences in functional mobility in adults with total blindness, and analyze differences in spatiotemporal gait variables with and without the use of a cane, and wearing shoes or barefoot. We used an inertial measurement unit to assess the spatiotemporal parameters of the gait and functional mobility in seven subjects with total blindness and four sighted participants during the timed up and go test (TUG) test performed under conditions: barefoot/shod; and with/without a cane (blind subjects). Significant differences between groups were found in total TUG test time and in the sub-phases when the blind subjects executed the TUG barefoot and without a cane (p < .01). Other differences were found in trunk movement during sit-to-stand, and stand-to-sit where blind subjects when without cane and barefoot, they had a greater range of motion than sighted subjects (p < .01). Also, BMI has a moderate to strong influence in the execution of the TUG in blind subjects (p < .05) CONCLUSION: This study showed that, when using a gait-assistance device and wearing shoes, blind subjects have similar functional mobility and gait as sighted subjects, suggesting that an external haptic reference can compensate for the lack of vision. Knowledge of these differences can provide a better understanding of the adaptive behavior in this population, thereby assisting in minimizing the occurrence of trauma and falls.


Exploring the connectedness of rural auxiliary midwives to social networks in Koutiala, Mali.
rural auxiliary midwives are central to clinical maternal care in Mali. However, little is known about their social role within the villages they serve. Exploring the social connectedness of midwives in their communities can reveal areas in which they need additional support, and ways they could benefit their communities beyond their clinical role. to examine rural auxiliary midwives' social connectedness to the communities they serve. embedded, mixed methods design combining social network case studies with semi-structured interviews. midwives were recruited for semi-structured interviews during technical trainings held in Koutiala in southern Mali. Social network analyses were conducted among all adult women in two small villages purposively sampled from the Koutiala region. 29 interviews were conducted, transcribed, and coded using NVivo (Version 9) to qualitatively assess social connectedness. In two villages, the complete social networks of women's friendships were analysed using UCINET Version 6 (n=142; 74). Rank-orders of actors according to multiple measures of their centrality within the network were constructed to assess the midwives' position among village women. both local and guest midwives reported feeling high levels of social integration, acceptance, and appreciation from the women in their communities. Specific challenges existed for guest or younger midwives, and in midwives' negotiations with men. In the two sociometric analyses, both the local and guest midwives ranked among the most influential social actors in their respective villages. though they hold a unique position among other rural women, this study suggests that midwives in Koutiala are well connected socially, and may be capable of becoming effective agents of network based-behavioural health interventions. Additional support is warranted to help midwives affirm a credible professional status in a male-dominated society, especially those of local status and younger age. Programme planners and policy-makers should consider the potential of midwives in communication when designing behaviour change interventions for women in similarly underserved areas.


A multicenter phase II study of TSU-68, an oral multiple tyrosine kinase inhibitor, in combination with docetaxel in metastatic breast cancer patients with anthracycline resistance.
TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, and fibroblast growth factor receptor. This open-label, non-comparative, multicenter phase II study evaluated TSU-68 in combination with docetaxel in patients with metastatic breast cancer that had relapsed within 1 year despite prior treatment with an anthracycline-containing regimen. TSU-68 was orally administered on days 1-21, and docetaxel was intravenously delivered on day 1. The regimen was repeated every 21 days. Primary endpoint was objective response rate according to the RECIST guidelines version 1.0. TSU-68 in combination with docetaxel produced objective responses in 21.1% and clinical benefits in 42.1% of the patients, respectively (1 complete response, 3 partial response, and 4 stable disease for at least 24 weeks, n = 19). Median time to progression was 148 days, and median overall survival was 579 days. The common adverse drug reactions were leukopenia, neutropenia, nail disorder, malaise, dysgeusia, alopecia, and edema. TSU-68 in combination with docetaxel showed a promising antitumor response with manageable toxicity in patients with anthracycline-resistant metastatic breast cancer. Further studies are warranted in a different population of breast cancer or other solid cancers.


Water pollution incidents and their influencing factors in China during the past 20 years.
There is an urgent need to explore the current situation of China's water pollution incidents for policymaking, accident prevention, and risk mitigation. This study analyzed 1528 water pollution incidents in China from 2001 to 2020 and explored the spatiotemporal characteristics and causes of incidents and consequent damage. The frequency of water pollution accidents increased in 2004, peaked in 2006, and decreased thereafter with a significant decline in 2016. Due to the developed river networks, high population densities, and increasing environmental awareness, pollution incidents were mostly concentrated in China's relatively industrially developed eastern coastal regions. Illegal emission is the major cause, accounting for 51% of all incidents, but with pipeline construction gradually approaching a peak, pipeline leakage poses a noteworthy risk in the future. Although the severity of accidents has reduced recently, it is still necessary to strengthen the risk prevention strategies for general and major accidents. Furthermore, three key factors, including economic development, regulations and legal system, and public participation in pollution supervision and control, which affect the trends and characteristics of water pollution incidents in China, were discussed. This paper offers valuable insights and suggestions that may have useful implications for policymaking and the prevention of water pollution.


Correction: A Revised Time Tree of the Asterids: Establishing a Temporal Framework For Evolutionary Studies of the Coffee Family (Rubiaceae).
[This corrects the article DOI: 10.1371/journal.pone.0126690.].


Derivation and characterization of chondrocytes from embryonic stem cells in vitro.
The model system of embryonic stem (ES) cell differentiation in vitro via cellular aggregates (embryoid bodies, EBs) can be used to analyze cell differentiation from a pluripotent stem cell via progenitor cells up to terminally differentiated cell types. ES cells are known to be pluripotent; they have the capacity to differentiate into any cell lineage of the three germ layers. Using various ES cell lines, we characterized chondrogenic and osteogenic differentiation in EBs by histochemical staining, immunostaining, mRNA-in situ hybridization, and reverse transcriptase polymerase chain reaction analysis. Here, we describe in detail our established protocols to analyze chondrogenic differentiation of ES cells. We summarize different ways to modulate ES cell-derived chondrogenic differentiation.


Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas.
Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3+, 3+ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.


Translating fathers' support for breastfeeding into practice.
Breastfeeding has numerous health benefits for the mother and child. For breastfeeding to be successful and continue for longer, women need adequate support. Fathers/partners play an important role in providing this support to women, but research suggests that fathers/partners often feel inadequately informed and supported by health professionals. Midwives and health visitors are in ideal positions to offer women and their partner's timely and relevant breastfeeding information and support throughout the perinatal period. This article discusses the benefits of breastfeeding, presents research evidence of the crucial role fathers/partners play in promoting and supporting breastfeeding, and recommends ways in which health professionals can provide breastfeeding information and support to fathers/partners.


[Mechanism of paradoxical resistance of the digastric muscle to the action of tetanus toxin].
Excitability parameters of m. masseter and m. digastricus fibers (resting minute potential--MP, action potential--AP, critical level of depolarization--CLD and rheobase currents) were determined in anesthetized rats (nembutal, 40 mg/kg) on days 3-4 and 10-15 after local intramuscular tetanus toxin injection (20 and 40 mouse Dlm, respectively). The development of local tetanus in m. masseter was characterized by typical excitability changes--a decrease in MP and AP. Local spasm in m. digastricus under analogous conditions of tetanus toxin injection was absent, while excitability tests demonstrated MP, AP and CLD augmentation. As m. digastricus motoneurons are devoid of inhibitory synaptic regions, these nervous cells are not affected by tetanus toxin.


[Radiofrequency ablation - is a technique finished?].
According to current scientific investigations radiofrequency ablation (RFA) as a local ablative tumor therapy for unresectable liver malignancies is currently accepted as the best therapeutic choice. The results of randomized trials justify RFA for small hepatocellular carcinomas (HCC) and RFA is considered to be a viable alternative to resection for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer (CRC LM). However, surgical resection still remains the gold standard for resectable CRC LM. The intraprocedural image guidance modality of choice is computed tomography (CT) alongside CT fluoroscopy. Contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) are used for preprocedural lesion detection and differentiation as well as for follow-up and can be used to perform RFA procedures as well. This article highlights new developments in RFA.


Occurrence of CGRP receptors on dedifferentiated smooth muscle cells from media of rat thoracic aorta.
Autoradiographic studies with [125I]-CGRP did not demonstrate receptors on sections from two different regions of 5-week-old rat aorta (of both sexes). By contrast, cultured smooth muscle cells isolated from similar aortic media and passaged 5 to 7 times exhibited specific binding.


Probability of myopia in children with high refined carbohydrates consumption in France.
Evaluate risk factors for paediatric myopia in a contemporary French cohort taking into account consumption of refined carbohydrates (starches and sugars). An epidemiological cross-sectional study was conducted between May 2017 and May 2018. Two hundred sixty-four children aged 4 to 18 years attending the Centre Hospitalier Universitaire Gui de Chauliac in Montpellier were recruited. Ophthalmologic or optometric cycloplegic refraction were measured. Evaluated risk factors for myopia were collected, including family history of myopia, outdoor time, reading time, screen time, physical activity, and consumption of refined carbohydrates. Association between the probability of at least one eye showing myopia (defined as < 0 D) and frequency of refined carbohydrates consumption adjusted for risk factors and control factors was tested. Overall, 86/264 (32.6%) children investigated showed myopia in at least one eye. We included 180 children exhibiting refraction < 3 D in both eyes: 88 (48.9%) girls and 92 (51.1%) boys. The consumption of refined carbohydrates significantly increased the probability of myopia for girls (odds ratio [OR] = 1.07; 95% confidence interval [CI], 1.02-1.13; P = 0.009) but decreased it for boys (OR = 0.94; 95% CI, 0.89-0.98; P = 0.011). The probability of myopia was marginally increased with increased screen time (OR = 2.32; 95% CI, 0.94-6.47; P = 0.083). Outdoor time seemed marginally protective (OR = 0.74; 95% CI, 0.54-1.01; P = 0.057). Refined carbohydrates consumption could be associated with child myopia, with increased probability for girls and unexpected reduced probability for boys, possibly due to the fact that frequency of carbohydrates consumption do not really capture boy's chronic hyperglycemia, boys being more physically active than girls at all ages. Some known risk/protective factors of myopia were marginally significant: screen time (risk) and outdoor time (protective). This study reinforces the belief that modifiable risk factors for myopia could be targets for future public health actions.


Optical character recognition reading aid for the visually impaired.
An optical character recognition (OCR) reading machine is a significant help for visually impaired patients. An OCR reading machine is used. This instrument can provide a significant help in order to improve the quality of life of patients with low vision or blindness.


Lack of Lymphocyte Recovery After Esophagectomy Predicts Overall and Recurrence-Free Survival.
Lymphocytes have become the target of cancer interventions through engineering or immune checkpoint antibodies. We previously found decreased lymphocyte counts to be a predictor of mortality and complications in trauma and cardiac surgery patients. We hypothesized lack of lymphocyte count recovery postoperatively would predict outcomes in esophagectomy patients. A retrospective review of all patients undergoing esophagectomy for adenocarcinoma performed over 13 y at our center by a single surgeon after institutional review board approval was performed. Patients were grouped by postoperative lymphocytes counts: never low, low with recovery, and low without recovery. Resolution of lymphopenia was assessed by day 4. Primary end points were overall and recurrence-free survival. In total, 198 patients were included with a minimum 6-mo follow-up. Collectively the 5-y recurrence and overall survival rates were 36% and 50%, respectively. Recurrence was significantly higher at 5 y in patients with persistent lymphopenia (43%) compared with those who recovered (14% P = 0.0017) and those who never dropped (0% P = 0.0009). The persistent lymphopenia group had significantly lower survival (45%) compared with the two other groups (67% P = 0.0232). There is a significant decrease in the overall and recurrence-free survival in those patients whose lymphocyte count drops without recovery after their esophagectomy. These data imply differences in immune responses to the stress of surgery that can be measured with routine postoperative laboratory values and are indicative of overall outcomes.


Argyrogrammana Strand (Lepidoptera: Riodinidae) from Parque Nacional da Serra do Divisor, Acre, Brazil, with the description of four new species.
The species of Argyrogrammana Strand, 1932 collected at the Parque Nacional da Serra do Divisor, Acre, Brazil (PNSD) are listed and detailed with behavioral notes. In total, 17 species were recorded, including 13 new records for Brazil (marked with an asterisk): A. alstonii (Smart, 1979)*, A. nurtia ludibunda Brévignon & Gallard, 1995*, A. pulchra (Talbot, 1929)*, A. bonita Hall & Willmott, 1995*, A. amalfreda (Staudinger, [1877])*, A. physis phyton (Stichel, 1911), A. halli Dolibaina & Dias, sp. nov.*, A. celata Hall & Willmott, 1995*, A. gallardi Dolibaina & Dias, sp. nov.*, A. aparamilla Hall & Willmott, 1995*, A. praestigiosa (Stichel, 1929), A. johannismarci Brévignon, 1995*, A. brevignoni Dolibaina & Dias, sp. nov.*, A. rameli (Stichel, 1930), A. willmotti Dolibaina & Dias, sp. nov.*, A. iracyi P. Jauffret & J. Jauffret, 2007 and A. saulensis tunari Gallard, 2008, comb. nov.*. Four new species are described, two from "amalfreda complex": A. halli Dolibaina & Dias, sp. nov. and A. gallardi Dolibaina & Dias, sp. nov.; one from "trochilia complex": A. brevignoni Dolibaina & Dias, sp. nov.; and one from "stilbe complex": A. willmotti Dolibaina & Dias, sp. nov. Argyrogrammana iracyi saulensis Gallard, 2008 is recognized as a valid species, A. saulensis saulensis, stat. nov., and a new combination is proposed to A. saulensis tunari Gallard, 2008, comb. nov. The females of A. iracyi P. Jauffret & J. Jauffret, 2007 and A. saulensis tunari are recognized and figured for the first time. The taxonomy of the species found at the PNSD is discussed and adults are figured, including illustrations of the genitalia.


In vitro acetylation of the liver HMG non-histone proteins and its modulation by spermine and dexamethasone during aging of rats.
The in vitro acetylation of HMG proteins was studied using liver slices of young (18-week) and old (138-week) male rats. Acetylation of total HMG proteins is lower in old age. The incorporation of (14C) acetate into individual HMG proteins varies remarkably with advancing age. Whereas acetylation of high mol. wt. proteins (HMG 1 and 2) is higher, that of low mol. wt. proteins (HMG 14 and 17) is lower in the liver of young rats as compared to the old ones. Spermine stimulates the acetylation of HMG 1 and 14 in young and HMG 1, 2 and 14 in old age. It inhibits the acetylation of HMG 17 in both ages. Dexamethasone decreases the level of incorporation of (14C) into HMG 1 and 17 in young and HMG 14 and 17 in old rats. On the other hand, it stimulates the acetylation of HMG 14 by two-fold in young and that of HMG 1 and 2 by more than three-fold in old rats. Such alteration in the acetylation of HMG proteins may account for age-related changes in the structure and function of chromatin.


Aptamer-based colorimetric detection of proteins using a branched DNA cascade amplification strategy and unmodified gold nanoparticles.
A branched DNA amplification strategy was employed to design a colorimetric aptameric biosensor using unmodified gold nanoparticles (AuNPs). First, a programmed DNA dendritic nanostructure was formed using two double-stranded substrate DNAs and two single-stranded auxiliary DNAs as assembly components via a target-assisted cascade amplification reaction, and it was then captured by DNA sensing probe-stabilized AuNPs. The release of sensing probes from AuNPs led to the formation of unstable AuNPs, promoting salt-induced aggregation. By integrating the signal amplification capacity of the branched DNA cascade reaction and unmodified AuNPs as a sensing indicator, this amplified colorimetric sensing strategy allows protein detection with high sensitivity (at the femtomole level) and selectivity. The limit of detection of this approach for VEGF was lower than those of other aptamer-based detection methods. Moreover, this assay provides modification-free and enzyme-free protein detection without sophisticated instrumentation and might be generally applicable to the detection of other protein targets in the future.


Imbalance in the activities of alkaline phosphatase and Na+-K+-ATPase in the brain of experimentally induced phenylketonuric squirrels (Funambulus palmarum).
Phenylketonuric squirrels have shown marked inhibition of alkaline phosphatase in the olfactory lobes and cerebral hemispheres, whereas the Na+-K+-ATPase remained less altered. In the pathogenesis of phenylketonuria inhibition of alkaline phosphatase at the level of "Blood-Brain Barrier" (BBB), leads transport system to impaired functioning.


Initiation of antidepressant use among refugee and Swedish-born youth after diagnosis of a common mental disorder: findings from the REMAIN study.
The objective of this study was to compare the initiation and type of antidepressant use between refugees and matched Swedish-born youth after a diagnosis of a common mental disorder (CMD) and assess sociodemographic and clinical factors associated with the initiation. The study cohort included youth aged 16-25 years, with an incident diagnosis of CMD based on specialized health care registers in Sweden 2006-2016, without prior antidepressant use during 1 year. One Swedish-born person was matched for each identified refugee youth (N = 3936 in both groups). Initiation of antidepressant use and factors associated with the initiation, were investigated with logistic regression yielding Odds ratios, OR, and 95% Confidence Intervals, CI. Refugees were less likely to initiate antidepressant use compared with Swedish-born (40.5% vs. 59.6%, adjusted OR 0.43, 95% CI 0.39-0.48). Selective serotonin reuptake inhibitors (SSRIs) were less frequently initiated for refugees than Swedish-born (71.2% vs. 81.3% of initiations, p < 0.0001). Sertraline was the most commonly initiated antidepressant both for refugees (34.3%) and Swedish-born individuals (40.3%). Among refugees, factors associated with increased odds of antidepressant initiation were previous use of anxiolytics or hypnotics, previous sickness absence of < 90 days, cancer and older age (OR range 1.07-2.72), and less than 5 years duration of residency in Sweden was associated with decreased odds (OR 0.76, 95% CI 0.63-0.92). Young refugees with a CMD seem to initiate antidepressants in general and those most effective considerably less often than their Swedish-born counterparts.


Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis.
The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine.


Reconstruction of traumatic medial malleolus loss using the bone sliding technique: A case report.
Open injury of the medial malleolus is relatively rare, and it can cause instability of the ankle joint and affect the walking function of the lower extremity. We describe an original plan for the reconstruction of medial malleolus defects using the bone sliding technique and report as follows. A 48-year-old female presented with an isolated open injury to her right ankle by a traffic accident. The skin of the medial ankle was severely contaminated with mud, and the medial malleolus, part of the Talus's cartilage and soft tissue, were defective. The anterior tibial artery was cut, and the anterior and posterior tibial tendons were ruptured. We describe the reconstruction of the medial malleolus using a bone sliding technique. At two years follow-up, she had a good outcome with a nearly painless, stable ankle with functional plantarflexion but restricted dorsiflexion. The original method is a new choice for the reconstruction of the medial malleolus.


Neutrophil to lymphocyte ratio as a prognostic marker of deep neck space infections secondary to odontogenic infection.
Neutrophil to lymphocyte ratio (NLR) is a marker of infection and is used as a prognostic marker for cancer and cardiovascular disease. There is little application of NLR as a biomarker for odontogenic infection. C-reactive protein (CRP) is a commonly used marker for odontogenic infection that correlates with length of stay (LOS). The aim of this study was to assess the clinical utility of NLR as a prognostic marker of deep neck space infections secondary to odontogenic infection and to analyse its correlation with admission CRP and LOS. Data from January 2019 to December 2019 were retrospectively examined for patients admitted with a deep neck space infection of odontogenic cause. Data on admission CRP, NLR, sex, age, site of infection, LOS, treatment, ICU admission, and presence of comorbidities were analysed. A total of 161 patients were included, 89 (52.7%) of whom were male, and 72 (42.6%) female. Mean (SD) age was 38.4 (16.8) years (range: 5-86 years). Mean (SD) admission CRP and NLR were 105.9 (93.1) mg/L and 7.5 (7.7). Mean (SD) LOS was 2.9 (3.2) days (range: 0.5-35 days). Both admission CRP (p≤0.01) and admission NLR (p≤0.01). were significantly associated with LOS. Receiver operating characteristics analysis for LOS≥2 days produced an area under the curve for CRP and NLR of 0.666 and 0.639. The optimum cut-off value of NLR for LOS≥2 days was 4.65. In conclusion, NLR can be used as a prognostic marker for patients admitted with deep neck space infection secondary to odontogenic infection. Patients with NLR≥4.65 are likely to require LOS≥2 days.


miR395-regulated sulfate metabolism exploits pathogen sensitivity to sulfate to boost immunity in rice.
MicroRNAs (miRNAs) play important roles in plant physiological activities. However, their roles and molecular mechanisms in boosting plant immunity, especially through the modulation of macronutrient metabolism in response to pathogens, are largely unknown. Here, we report that an evolutionarily conserved miRNA, miR395, promotes resistance to Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), two destructive bacterial pathogens, by regulating sulfate accumulation and distribution in rice. Specifically, miR395 targets and suppresses the expression of the ATP sulfurylase gene OsAPS1, which functions in sulfate assimilation, and two sulfate transporter genes, OsSULTR2;1 and OsSULTR2;2, which function in sulfate translocation, to promote sulfate accumulation, resulting in broad-spectrum resistance to bacterial pathogens in miR395-overexpressing plants. Genetic analysis revealed that miR395-triggered resistance is involved in both pathogen-associated molecular pattern-triggered immunity and R gene-mediated resistance. Moreover, we found that accumulated sulfate but not S-metabolites inhibits proliferation of pathogenic bacteria, revealing a sulfate-mediated antibacterial defense mechanism that differs from sulfur-induced resistance. Furthermore, compared with other bacteria, Xoo and Xoc, which lack the sulfate transporter CysZ, are sensitive to high levels of extracellular sulfate. Accordingly, miR395-regulated sulfate accumulation impaired the virulence of Xoo and Xoc by decreasing extracellular polysaccharide production and biofilm formation. Taken together, these results suggest that rice miR395 modulates sulfate metabolism to exploit pathogen sensitivity to sulfate and thereby promotes broad-spectrum resistance.


Isolated cochlear nerve hypoplasia with various internal auditory meatus deformities in children.
We report neuro-otological findings in isolated congenital cochlear nerve hypoplasia with various bony deformities and evaluate relationships between functional impairment and the radiologic dimensions of the internal auditory meatus (IAM). We performed imaging and functional analyses on consecutive juvenile or adolescent patients between 2001 and 2005 with "isolated" unilateral hypoplasia of the cochlear nerve, without inner ear anomaly or other deformities. Among 20 patients with unilateral profound deafness who underwent imaging studies, 10 (50%) passed the inclusion criteria. In all affected ears, auditory brain stem responses were absent and the speech discrimination score was very poor (0% to 5%). Distortion product otoacoustic emissions were good in 2 ears, fair in 1 ear, and poor in 7 ears. Caloric responses were absent in 2 ears, reduced in 3 ears, and normal in 5 ears. Inferior vestibular nerve function and facial nerve function were normal in all ears. Distortion product otoacoustic emissions and caloric responses tended to be better in ears with less severe narrowing of the IAM. The risk of co-involvement of the inner ear and superior vestibular nerve functions is higher in the presence of a narrower bony IAM. Cochlear nerve hypoplasia is proposed as one of the most important causes of juvenile unilateral deafness because of its unexpectedly high incidence.


In vitro models of differentiated Sertoli cell structure and function.
Primary cultures of Sertoli cells maintained in conventional cultures on plastic culture vessels do not retain many of the structural and functional properties of their in vivo counterparts. Sertoli cell phenotype is better maintained by incorporating certain environmental parameters, intrinsic to the testis, into the Sertoli cell culture system. These environmental parameters include a) high cell density, b) a unique extracellular matrix, c) a semipermeable support between the basal plasma membrane of the cells and blood-derived nutrients in the interstitium, d) chemically distinct microenvironments at the apical and basal surfaces of the cells, and e) cell-to-cell interactions among Sertoli cells and other testicular cell types. Using three variations of Sertoli cell culture we have demonstrated the importance of each of these environmental parameters in obtaining a better Sertoli cell culture model.


Defective trafficking of rhodopsin and its role in retinal degenerations.
Retinitis pigmentosa is a retinal degeneration transmitted by varied modes of inheritance and affects approximately 1 in 4000 individuals. The photoreceptors of the outer retina, as well as the retinal pigmented epithelium which supports the outer retina metabolically and structurally, are the retinal regions most affected by the disorder. In several forms of retinitis pigmentosa, the mislocalization of the rod photoreceptor protein rhodopsin is thought to be a contributing factor underlying the pathophysiology seen in patients. The mutations causing this mislocalization often occur in genes coding proteins involved in ciliary formation, vesicular transport, rod outer segment disc formation, and stability, as well as the rhodopsin protein itself. Often, these mutations result in the most early-onset cases of both recessive and dominant retinitis pigmentosa, and the following presents a discussion of the proteins, their degenerative phenotypes, and possible treatments of the disease.


Effects of Lumbriculus variegatus (Annelida, Oligochaete) bioturbation on zinc sediment chemistry and toxicity to the epi-benthic invertebrate Chironomus tepperi (Diptera: Chironomidae).
Classical laboratory-based single-species sediment bioassays do not account for modifications to toxicity from bioturbation by benthic organisms which may impact predictions of contaminated sediment risk to biota in the field. This study aims to determine the effects of bioturbation on the toxicity of zinc measured in a standard laboratory bioassay conducted with chironomid larvae (Chironomus tepperi). The epi-benthic chironomid larvae were exposed to two different levels of sediment contamination (1600 and 1980 mg/kg of dry weight zinc) in the presence or absence of annelid worms (Lumbriculus variegatus) which are known to be tolerant to metal and to have a large impact on sediment properties through bioturbation. Chironomids had 5-6x higher survival in the presence of L. variegatus which shows that bioturbation had a beneficial effect on the chironomid larvae. Chemical analyses showed that bioturbation induced a flux of zinc from the pore water into the water column, thereby reducing the bioavailability of zinc in pore water to the chironomid larvae. This also suggested that pore water was the major exposure path for the chironomids to metals in sediment. During the study, annelid worms (Oligochaetes) produced a thin layer of faecal pellets at the sediment surface, a process known to: (i) create additional adsorption sites for zinc, thus reducing its availability, (ii) increase the microbial abundance that in turn could represent an additional food source for opportunistic C. tepperi larvae, and (iii) modify the microbial community's structure and alter the biogeochemical processes it governs thus indirectly impact zinc toxicity. This study represents a contribution in recognising bioturbating organisms as "ecological engineers" as they directly and indirectly influence metal bioavailability and impact other sediment-inhabiting species. This is significant and should be considered in risk assessment of zinc levels (and other metals) in contaminated sediment when extrapolating from laboratory studies to the field.


Intrauterine devices: results of a separate clinical and ultrasound follow-up study.
A separate clinical and ultrasound study was carried out in 20 unselected patients receiving an IUD (ML Cu 250 or Cu T-200). Clinical adverse effects were studied in relation to ultrasound findings after 0, 2 and 6 months of insertion. Using both the sound length and initial ultrasound measurements, it was possible to calculate that none of the 20 IUDs reached the fundal wall of the uterine cavity (distance 0.1-2.4 cm). The mean initial distance between the top of the uterine fundal wall and the top of the IUD (TOP) was 2.0 cm (range 1.3-2.4 cm). A downward displacement of more than 0.5 cm in consecutive measurements was observed in 3 patients. Malposition of one or two arms of the IUD was found in 8 patients. In 6 of these patients clinical complaints were present.


Cholesterol-associated lysosomal disorder triggers cell death of hematological malignancy: Dynamic analysis on cytotoxic effects of LW-218.
The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth in vivo. Thus, the necessary impact of integral lysosomal function in cell rescue and death were illustrated.


An Algorithmic Approach to Triaging Facial Trauma on the Sidelines.
On-the-field evaluation of facial trauma requires a focused initial assessment of the patient's airway and breathing with a knowledge of the critical associated injuries. The initial triage in facial trauma involves assessing and protecting the athlete's airway, breathing, and cervical spine. The algorithm then requires a repeat evaluation for subtle causes of airway obstruction and aspiration risks. Final steps include control of hemorrhage, recognition of neurologic and ophthalmologic disability, and complete exposure of the athlete to examine for other associated injury. The ABC repeat ABCDE mnemonic allows providers to avoid missing critical injuries that require immediate intervention.


Systematic investigation of sequence and structural motifs that recognize ATP.
Interaction between ATP, a multifunctional and ubiquitous nucleotide, and proteins initializes phosphorylation, polypeptide synthesis and ATP hydrolysis which supplies energy for metabolism. However, current knowledge concerning the mechanisms through which ATP is recognized by proteins is incomplete, scattered, and inaccurate. We systemically investigate sequence and structural motifs of proteins that recognize ATP. We identified three novel motifs and refined the known p-loop and class II aminoacyl-tRNA synthetase motifs. The five motifs define five distinct ATP-protein interaction modes which concern over 5% of known protein structures. We demonstrate that although these motifs share a common GXG tripeptide they recognize ATP through different functional groups. The p-loop motif recognizes ATP through phosphates, class II aminoacyl-tRNA synthetase motif targets adenosine and the other three motifs recognize both phosphates and adenosine. We show that some motifs are shared by different enzyme types. Statistical tests demonstrate that the five sequence motifs are significantly associated with the nucleotide binding proteins. Large-scale test on PDB reveals that about 98% of proteins that include one of the structural motifs are confirmed to bind ATP.