Ant assemblages in the taiga biome: testing the role of territorial wood ants.
Ants were collected with sets of pitfall traps in four coniferous-forest habitats in southern Finland. A three-level competition hierarchy concept was used to generate predictions on ant community structure. The levels of the hierarchy, and the respective predictions, from top to bottom were: (1) The dominant territorial wood ants (Formica rufa-group species), expected to exclude each other. (2) The other aggressive species, likely to be excluded by the F. rufa-group. (3) The submissive species, non-aggressive and defending only their nest, and thus likely to coexist with the dominants but in reduced numbers. As expected, the species of the F. rufa-group excluded each other, and the species number of the other aggressive ants was significantly cut down in the presence of the F. rufa-group. The aggressive species F. sanguinea and Camponotus herculeanus showed complementary occurrences with the F. rufa-group, and Lasius niger reduced occurrences. The number of the submissive species was not significantly affected by the F. rufa-group. However, pairwise correlation coefficients were significantly more often negative than positive between presence of the F. rufa-group and average proportion of pitfalls per set with a submissive species, each analyzed in turn. The result indicates that the F. rufa-group also reduced the colony densities of the submissive species. We conclude that in the taiga biome territorial wood ants are, after adjusting for physical vicissitudes of the environment, the major structuring force of ant species assemblages.


Acquired hemophilia A after vaccination against SARS-CoV-2 with the mRNA-1273 (Moderna) vaccine.
Acquired hemophilia A is a rare bleeding diathesis most typically seen in systemic rheumatic disease, solid and hematologic malignancies, and pregnancy. We present a case of this condition that occurred immediately after vaccination against SARS-CoV-2 with the mRNA-1273 (Moderna) vaccine.


Imaging of maxillofacial trauma: evolutions and emerging revolutions.
The aim of diagnostic imaging for maxillofacial trauma is to provide additional information that can positively influence medical or surgical patient management. Current advances in diagnostic imaging have come from the confluence of 3 driving forces: (1) the demand from clinicians to enhance and expand their diagnostic abilities; (2) the development of new theoretical concepts by basic scientists; and (3) the application of concepts by engineers and manufacturers to provide increasingly sophisticated imaging capabilities. The role of imaging within the health care environment is, however, also buffeted by the complex, sometimes competing, interactions of external social, political, economic, and technological pressures at the national, regional, and local levels. The purposes of this review are to provide a perspective on current imaging modalities used for maxillofacial trauma and to provide an insight into the influences, both technologic and external, on future developments and applications.


Intrahypothalamic microinfusion of corticotropin-releasing factor elevates blood glucose and free fatty acids in rats.
Three experiments examined whether intrahypothalamic microinfusions of corticotropin releasing factor (CRF) can affect circulating levels of the metabolic fuels, glucose and free fatty acids. Infusions of CRF into the paraventricular nucleus dose-dependently increased serum glucose levels; greater increases were seen in acute than in chronic preparations. The greater effectiveness could not be accounted for by anesthetization per se. CRF infusion into the ventromedial nucleus did not affect serum glucose. Infusions into both sites, however, significantly increased serum free fatty acids. Neither glucose nor free fatty acids were altered by infusions into the lateral hypothalamus or the caudate-putamen. These data suggest that the previously identified CRF binding sites and CRF neuronal terminals in the paraventricular and ventromedial nuclei may be involved in the central regulation of metabolic fuel release. Additionally, it appears that the importance of CRF in the paraventricular nucleus in regulating serum glucose may be greater under some conditions than others.


Haemostatic effects of adrenaline-lidocaine subcutaneous infiltration at donor sites.
This study sought methods in burn surgery to reduce postoperative pain and blood loss at donor sites. A prospective, randomised, controlled, blinded trial included 56 people undergoing burn surgery, divided into two groups. Both groups received subcutaneous infiltration at donor sites, with either 1:500,000 adrenaline solution containing added lidocaine or with 0.45% normal saline (controls). Outcome measurements included amount of intraoperative bleeding, need for electrocautery, days the hydrocolloid dressing remained on donor sites, percentage of re-epithelialised skin at donor sites 1 week after surgery and viability of skin grafts. Results indicated that subcutaneous adrenaline-lidocaine infiltration at donor sites reduced intraoperative bleeding, decreased postoperative pain, shortened the duration of surgery and general anaesthesia and accelerated re-epithelialisation at the donor site. The overall graft take in both groups was similar.


Surgical Treatment of Lateral Tibial Plateau Fractures Involving the Posterolateral Column.
To summarize the indications and the clinical effects of a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach in the treatment of fractures of the lateral tibial plateau involving the posterolateral column. Eleven patients with lateral tibial plateau fractures were included in the present study. The fractures were Schatzker type II or lateral platform fractures involving posterolateral column. The anterolateral combined posterolateral approach (lateral + posterolateral locking plate fixation) was applied in 7 patients and 4 patients underwent transfibular neck osteotomy (lateral + posterolateral locking plate fixation + 1/4 tubular plate edge fixation, fibular osteotomy with Kirschner wire tension band fixation, and hollow nail fixation for upper tibiofibular joint). All cases were followed up for 12-24 months, with an average follow-up of 17.5 ± 5.0 months. At the last followup, the Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation. The knee joint function was evaluated using the knee function evaluation criteria of the Hospital for Special Surgery (HSS). The Lachman test and the pivot-shift test were used to evaluate the anterior and posterior and rotational stability of the knee joint. The range of knee motion was recorded. Bone healing was achieved in all patients with fractures treated with a transfibular neck osteotomy approach and a combined anterolateral and posterolateral approach. At the last follow-up, both the Lachman test and the pivot-shift test results were negative. All patients had complete knee extension. For the combined anterolateral and posterolateral approach, the knee flexion angle was 110°-130°, with an average of 122.86° ± 7.56°. For the transfibular neck osteotomy approach, the knee flexion angle was 115°-130°, with an average of 120.00° ± 7.07°. For the patients in which the combined anterolateral and posterolateral approach was used, the Rasmussen score was 12-18 points, with an average of 16.00 ± 2.56 points. The results were excellent in 4 cases and good in 3 cases; therefore, 100% of results were excellent or good. For patients in which the transfibular neck osteotomy approach was used, the Rasmussen score was 10-18 points, with an average of 15.25 ± 3.77 points. The results were excellent in 2 cases, good in 1 case, and acceptable in 1 case; therefore, 75% of results were excellent or good. The HSS score for the combined anterolateral and posterolateral approach was 76-98 points, with an average of 88.43 ± 7.55 points. The results were excellent in 5 cases and good in 2 cases; therefore, 100% of results were excellent or good. The HSS score for the transfibular neck osteotomy approach was 74-96 points, with an average of 87.25 ± 9.43 points. The results were excellent in 3 cases and good in 1 case; therefore, 100% of results were excellent or good. There were no significant differences in operation time, surgical blood loss, fracture healing time, postoperative imaging score, and knee function evaluation between the two approaches. One patient who underwent transfibular neck osteotomy had a 3-mm step that gradually appeared, but no significant abnormalities were found in the width of the platform and the lower limb force line. One patient in whom the combined anterolateral and posterolateral approach was used showed numbness in the common peroneal nerve. No common peroneal nerve injury occurred through the transfibular neck osteotomy approach. The anterolateral combined posterolateral approach and the transfibular neck osteotomy approach are effective in the surgical treatment of lateral tibial plateau fractures involving the posterolateral column. However, the transfibular neck osteotomy approach is more suitable for the posterolateral plateau articular surface damaged with bone separation and displacement, deep collapse, cases involving a large range of the posterolateral column, especially fractures of the lateral tibial plateau in the upper tibiofibular syndesmosis area of the line connecting the anterior and posterior margin of the fibular head to the midpoint of the plateau.


[Cataract-related changes of intelligence. An innovative aspect].
On average, the intelligence level of adults decreases with age. Since loss of vision increases in parallel and, according to a review of literature, impairment of vision corresponds to cognitive deterioration, age-related reduction of intelligence could partially be explained by restricted vision. Are late-acquired cataracts closely related to reduction in intelligence levels? AIM. If it is substantiated that late-acquired cataracts cause mental impairment, a frequent disorder of vision will be identified that principally may be treated quickly and successfully. By this means ophthalmologists were able to improve intelligence, "the" key variable in modern information societies. An open controlled longitudinal study in five samples of seniors with and without cataract surgery. The actual mental efficiency and the knowledge of cataract patients reached a lower level than a "normal" population. A few weeks after an IOL implantation the actual intelligence level increased relevantly and statistically significantly in all samples, whereas controls displayed no systematic changes. Cataracts and removal by surgery can change the IQ considerably which is of great importance for the patient and for the social and medical environment.


The use of a supercooling refrigerator improves the preservation of organ grafts.
Current medical transplantation confronts major problems such as the shortage of donors and geographical restrictions that inhibit efficient utilization of finite donor organs within their storage lives. To overcome these issues, expanding organ preservation time has become a major concern. We investigated whether a strategy which best preserves organ grafts can be achieved by the use of a newly developed refrigerating chamber, which is capable of establishing a supercooled and unfrozen state stably by generating an electrostatic field in its inside. When adult rat organs such as heart, liver, and kidneys were stored in the supercooled conditions, the levels of major biochemical markers leaked from the preserved organs were significantly lower than in the ordinary hypothermic storage. No apparent tissue damages were observed histologically after the supercooled preservation. Our results suggest that the use of this supercooling refrigerator improves organ preservation and may provide an innovative technique for human organ transplantation.


Nontypeable Haemophilus influenzae-binding gangliosides of human respiratory (HEp-2) cells have a requisite lacto/neolacto core structure.
Nontypeable Haemophilus influenzae (NTHI) are a major cause of human infections. We previously demonstrated high affinity and high specificity binding of NTHI to minor gangliosides of human respiratory (HEp-2) cells and macrophages, but not to brain gangliosides. We further identified the NTHI-binding ganglioside of human macrophages as alpha2,3-sialylosylparagloboside (IV3NeuAc-nLcOse4Cer, nLM1), which possesses a neolacto core structure that is absent in brain gangliosides. This supported a hypothesis that lacto/neolacto core carbohydrates are critical for NTHI-ganglioside binding. To investigate, we determined the core carbohydrate structure of NTHI-binding gangliosides of HEp-2 cells, through multiple approaches, including specific enzymatic degradation, mass spectral analysis and gas-liquid chromatography. Our analyses denote the following critical structural attributes of NTHI-binding gangliosides: (1) a conserved lacto/neolacto core structure; (2) requisite sialylation, which may be either internal or external, with alpha2,3 (human macrophages) or alpha2,6 (HEp-2 cells) anomeric linkages; (3) internalized galactose residues. Mass spectral and gas chromatographic analyses confirm that NTHI-binding gangliosides of HEp-2 cells possess lacto/neolacto carbohydrate cores and identify the structure of the major peak as NeuAcalpha2-6Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glcbeta1-1Cer (alpha2,6-sialosylparagloboside, nLM1). Collectively, our studies denote NTHI-binding gangliosides as lacto/neolacto series structures.


Medical expenditures attributable to cerebral palsy and intellectual disability among Medicaid-enrolled children.
This study estimated medical expenditures attributable to cerebral palsy (CP) among children enrolled in Medicaid, stratified by the presence of co-occurring intellectual disability (ID), relative to children without CP or ID. The MarketScan(®) Medicaid Multi-State database was used to identify children with CP for 2003-2005 by using the International Classification of Diseases, Ninth Revision; Clinical Modification (ICD-9-CM) code 343.xx. Children with ID were identified for 2005 by using ICD-9-CM code 317.xx-319.xx. Children without CP or ID during the same period served as control subjects. Medical expenditures were estimated for case and control children for 2005. The difference between the average expenditures for children with and without CP was used as a proxy for attributable expenditures for the condition. The attributable expenditures of co-occurring ID were calculated similarly as the difference in average expenditures among children with CP with and without ID. A total of 9927 children with CP were identified. Among them, 2022 (20.3%) children had co-occurring ID recorded in medical claims. Children with CP but without ID incurred medical expenditures that were $15,047 higher than those of control children without CP or ID. By contrast, children with CP and co-occurring ID incurred costs that were $41,664 higher, compared with control children, and $26,617 more than children with CP but without ID. Administrative data from a large, multistate database demonstrated high medical expenditures for publicly insured children with CP. Expenditures approximately tripled for children with CP and co-occurring ID.


Gas6 or Mer deficiency ameliorates silica-induced autophagosomes accumulation in mice lung.
Published evidences have shown that autophagy plays an important role in silica-induced lung inflammation and collagen deposition. Our previous study found that the level of growth arrest-specific protein 6 (Gas6) in bronchoalveolar lavage fluid was increased after silica exposure. However, it is unclear whether Gas6 is involved in the regulation of silica-induced autophagy dysfunction. In this study, we observed an autophagosomes accumulation in wild-type C57BL/6 (WT) mice lung after silica intratracheal instillation and then investigated whether genetic loss of Gas6 (Gas6-/-) could ameliorate it. Our data showed that Gas6-/- mice exhibited a limited autophagosomes accumulation from days 7-84 after silica exposure, revealed by reduced induction and increased degradation of autophagosomes in mice lung tissue. Interestingly, silica particles could elevate the expression of Mer receptor, which was significantly decreased in Gas6-/- mice (P < 0.05). Furthermore, we found that Mer deficiency (Mer-/-) could also reduce the formation of autophagosomes and restore the function of impaired lysosomes in silica-treated mice. Taken together, our results indicate that genetic loss of Gas6 attenuates silica-induced autophagosomes accumulation partly through down-regulating the expression of Mer receptor. Targeting Gas6/Mer-mediated autophagy pathway may provide a novel insight into the prevention and therapy of silica-induced pulmonary fibrosis.


Utilization of a tomographic attachment for "moving band" arteriography.
By using a slit plate, scanographic arterial studies can be performed with a tomographic attachment of an X-ray unit that is normally used for routine radiographic examinations. The expense is minimal and no structural changes are necessary.


Multiple liquid crystal phases of DNA at high concentrations.
DNA packaging in vivo is very tight, with volume concentrations approaching 70% w/v in sperm heads, virus capsids and bacterial nucleoids. The packaging mechanisms adopted may be related to the natural tendency of semi-rigid polymers to form liquid crystalline phases in concentrated solutions. We find that DNA forms at least three distinct liquid crystalline phases at concentrations comparable to those in vivo, with phase transitions occurring over relatively narrow ranges of DNA concentration. A weakly birefringent, dynamic, 'precholesteric' mesophase with microscopic textures intermediate between those of a nematic and a true cholesteric phase forms at the lowest concentrations required for phase separation. At slightly higher DNA concentrations, a second mesophase forms which is a strongly birefringent, well-ordered cholesteric phase with a concentration-dependent pitch varying from 2 to 10 micron. At the highest DNA concentrations, a phase forms which is two-dimensionally ordered and resembles smectic phases of thermotropic liquid crystals observed with small molecules.


Multimodal medical image fusion algorithm based on pulse coupled neural networks and nonsubsampled contourlet transform.
Combining two medical images from different modalities is more helpful for using the resulting image in the healthcare field. Medical image fusion means combining two or more images coming from multiple sensors. This technology obtains an output image that presents more effective and useful information from two images. This paper proposes a multi-modal medical image fusion algorithm based on the nonsubsampled contourlet transform (NSCT) and pulse coupled neural networks (PCNN) methods. The input images are decomposed using the NSCT method into low- and high-frequency subbands. The PCNN is a fusion rule for integrating both low- and high-frequency subbands. The inverse of the NSCT method is to reconstruct the fused image. The results of medical image fusion help doctors with disease diagnosis and patient treatment. The proposed algorithm is tested on six groups of multi-modal medical images using 100 pairs of input images. The proposed algorithm is compared with eight fusion methods. We evaluate the performance of the proposed algorithm using the fusion metrics: peak signal to noise ratio (PSNR), mutual information (MI), entropy (EN), weighted edge information (Q[Formula: see text]), nonlinear correlation information entropy (Q[Formula: see text]), standard deviation (SD), and average gradient (AG). Experimental results show that the proposed algorithm can perform better than other medical image fusion methods and achieve promising results.


[Benign tumors--surgical indication?].
Diagnostic and therapeutic options of the benign tumors in the anal region will be discussed. There is no systematic scheme for these tumors depending on the polymorph aspects and different matrices in the borderline between ecto- and entoderma. Because of the localisation either in perianal skin, fossa ischiorectalis or in the retrorectal space there is a need of different therapeutic options and approaches.


Ion channel clustering enhances weak electric field detection by neutrophils: apparent roles of SKF96365-sensitive cation channels and myeloperoxidase trafficking in cellular responses.
We have tested Galvanovskis and Sandblom's prediction that ion channel clustering enhances weak electric field detection by cells as well as how the elicited signals couple to metabolic alterations. Electric field application was timed to coincide with certain known intracellular chemical oscillators (phase-matched conditions). Polarized, but not spherical, neutrophils labeled with anti-K(v)1.3, FL-DHP, and anti-TRP1, but not anti-T-type Ca(2+) channels, displayed clusters at the lamellipodium. Resonance energy transfer experiments showed that these channel pairs were in close proximity. Dose-field sensitivity studies of channel blockers suggested that K(+) and Ca(2+) channels participate in field detection, as judged by enhanced oscillatory NAD(P)H amplitudes. Further studies suggested that K(+) channel blockers act by reducing the neutrophil's membrane potential. Mibefradil and SKF93635, which block T-type Ca(2+) channels and SOCs, respectively, affected field detection at appropriate doses. Microfluorometry and high-speed imaging of indo-1-labeled neutrophils was used to examine Ca(2+) signaling. Electric fields enhanced Ca(2+) spike amplitude and triggered formation of a second traveling Ca(2+) wave. Mibefradil blocked Ca(2+) spikes and waves. Although 10 microM SKF96365 mimicked mibefradil, 7 microM SKF96365 specifically inhibited electric field-induced Ca(2+) signals, suggesting that one SKF96365-senstive site is influenced by electric fields. Although cells remained morphologically polarized, ion channel clusters at the lamellipodium and electric field sensitivity were inhibited by methyl-beta-cyclodextrin. As a result of phase-matched electric field application in the presence of ion channel clusters, myeloperoxidase (MPO) was found to traffic to the cell surface. As MPO participates in high amplitude metabolic oscillations, this suggests a link between the signaling apparatus and metabolic changes. Furthermore, electric field effects could be blocked by MPO inhibition or removal while certain electric field effects were mimicked by the addition of MPO to untreated cells. Therefore, channel clustering plays an important role in electric field detection and downstream responses of morphologically polarized neutrophils. In addition to providing new mechanistic insights concerning electric field interactions with cells, our work suggests novel methods to remotely manipulate physiological pathways.


Hallucinations, Delusions and Impulse Control Disorders in Parkinson Disease.
Psychotic and compulsive symptoms in Parkinson disease are highly prevalent and associated with poor outcomes and greater caregiver burden. When acute, delirium should be ruled out or treated accordingly. When chronic, comorbid systemic illnesses, dementia, and psychiatric disorders should be considered. Reduction and discontinuation of anticholinergics, amantadine, dopamine agonists, and levodopa as tolerated, as well as adjunctive clozapine or quetiapine are frequently effective to manage Parkinson disease psychosis. Pimavanserin appears effective but is not widely available, and more experience is needed. Dopamine agonist discontinuation is usually successful for impulse control disorders, but requires frequent monitoring, documentation, and caregiver involvement.


Absent left hemidiaphragm, arhinencephaly, and cardiac malformations.
An infant is reported with absent left hemidiaphragm, hydrocephalus, arhinencephaly, and cardiovascular anomalies. The parents are second cousins.


A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma.
It is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins. Formalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients. Of the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (+/-5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=or<0.001). The expression of WISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (p<0.001, Table 5) and right-sided CRC tumour (p=0.019, Table 6). Total WISP-1 score was associated with well-differentiated CRC tissues (p=0.029). Overexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by promoting cell cycle checkpoint progression, accelerating cell growth and inhibiting apoptosis. Our data may provide useful information towards the search for potent therapeutic targets towards the development of novel treatment strategies for CRC.


The eye of the tongue sole Cynoglossus bilineatus (Lacepède, 1802) (Teleostei: Pleuronectiformes).
We report the ocular features of the tongue sole, Cynoglossus bilineatus (Lacepède, 1802), a marine, bottom-dwelling flatfish. In this species, both eyes are located juxtaposed on the same side of the flat head. Histology revealed the sclera to be fibrous (collagenous) in nature. The choroid possesses the choriocapillaris, and adjacent to it, 3-4 rows of iridophores with stacks of cytoplasmic platelets. No choroidal gland is present. The retinal pigment epithelium (RPE) contains scanty melanin granules. Its vitread half is modified into a dense tapetum with lipid spheres (about 0.34 μm in diameter). In juveniles, the tapetal spheres arise by budding from the smooth endoplasmic reticulum of the RPE. There are blood vessels within the retina; the vitreal vessels penetrate the retina and ramify close to the level of the outer limiting membrane. The vessels are capillaries in nature. The photoreceptor layer contains abundant rods, and twin cones and single cones, being arranged into square mosaics. The optic disc is non-pleated and shows pan- cytokeratin immunopositivity, which is related to the bundled cytokeratin filaments detected in astrocytes by electron microscopy. The retinal tapetum and choroidal iridophores help the species to live in a muddy bottom having dim-light environment. The lack of a choroidal gland, hypoxic aquatic condition and presence of a dense retinal tapetum (that limits O2 transport to the photoreceptors) appear to have favored the proliferation of vitreal vessels within the retina in this species. The fibrous sclera has probably arisen to provide structural support to the eye in migration from the lateral to the dorsal aspect of the head during larval metamorphosis.


Infectivity of soilborne Frankia and mycorrhizae in Discaria trinervis along a vegetation gradient in Patagonian soil.
The infective capacities of the nitrogen fixing Actinomycete Frankia and arbuscular mycorrhizal fungi from soils near watercourses, along a vegetation gradient, were studied using plant bioassays. Frankia and arbuscular mycorrhizas capable of infecting Discaria trinervis were found at seventeen sites sampled. More specific enumeration of the infective capacities of both microorganisms in relation to environmental factors was performed in seven representative soils of the analysed vegetation zones (rainforest, xeric forest and steppe) using the most probable number method. The highest nodulation capacities ranged from 340 infective units g(-1 )soil, in a steppe marsh devoid of actinorhizas, to 61 in a coastal actinorhizal scrub (in xeric forest). The highest number of infective mycorrhizal units--also found in marsh--was 145. In general, rainforest soils had the lowest values for both microorganisms. Infective units of Frankia and arbuscular mycorrhizal fungi in soil were positively correlated (r = 0.89, P < 0.05). Both soilborne symbionts showed the highest infective capacity in semi-arid conditions nearby watercourse and at the valley bottom location. Tripartite symbiosis was effective in plants inoculated with steppe and xeric forest soils and plants inoculated with Frankia BCU110501 and Glomus mosseae. Interaction between both symbionts and influence of environmental conditions, in general, would contribute to define comparable trends of their infective capacities.


Aortic valve prosthesis selection in dialysis patients based on the patient's condition.
Previous studies have examined outcomes in dialysis patients undergoing cardiac surgery. However, only a few studies have solely focused on outcomes after aortic valve replacement (AVR). This study aimed to clarify independent predictors of the long-term survival of dialysis patients with AVR and to determine whether a mechanical valve or bioprosthesis is suitable based on the patient's condition. A total of 38 consecutive dialysis patients who underwent AVR at our institute were reviewed (mean age 69.1 ± 9.4 years). There were 23 bioprostheses and 15 mechanical valve replacements. The operative mortality and the long-term survival were not different between the bioprosthesis and the mechanical valve group (13.0 vs. 13.3%). The significant multivariate predictors for long-term survival were concomitant coronary artery bypass grafting (CABG) and prosthesis size. Valve types and age at operation did not affect long-term survival. Five-year survival of patients with small prosthetic valves and concomitant CABG was 0%. When the patient's quality of life is taken into account, it may be appropriate to use a bioprosthesis in a dialysis patient with a small annulus and concomitant CABG even if the patient is young.


ChildTalks+: a study protocol of a pre-post controlled, paired design study on the use of preventive intervention for children of parents with a mental illness with focus on eating disorders.
Children of parents with a mental illness are at high risk of developing a mental disorder as a result of transgenerational transmission. Without effective intervention, they could form the next generation of psychiatric patients. ChildTalks+ is a preventive intervention involving four structured psychoeducational sessions designed for parents affected by a mental disorder and their children. Its aim is to reduce the risk of mental disorders in children of parents with mental illness. This study draws on our clinical practice and involves a group of patients with eating disorders. The aim of the project, which will run in the Czech Republic, is to evaluate the effectiveness of ChildTalks+ methodology. ChildTalks+ therapists (professionals from health, social, and educational facilities) will recruit 66 families where a parent is treated for a mental disorder and the family includes children aged 6-18. Paired allocation into an intervention group (N = 33) and a control group (N = 33) will be based on the number of risk factors identified in the family. Both groups will complete questionnaires at the baseline, post-test, and follow-up assessments after six and 12 months. The intervention group will receive the ChildTalks+ intervention within 2 months of the baseline assessment; the control group after the last assessment. Questionnaires will be completed by parents and children aged 12+ and, in two cases, 15+ years. Quantitative data will be supplemented with qualitative data from ChildTalks+ therapists working with patients with eating disorders. The ChildTalks+ intervention is expected to strengthen parenting competencies and family protective factors, improve family communication, increase awareness of parental mental health issues, and improve the wellbeing of children of parents with mental illness with long-term sustainable outcomes. The study should contribute to the evidence base for the ChildTalks+ program and help identify key themes in the implementation of similar preventive interventions. ClinicalTrials.gov Identifier: NCT05554458. Registered 26 September 2022. Retrospectively registered.


Evaluation of disk susceptibility testing of cefotaxime/desacetylcefotaxime.
The susceptibility of 453 clinical bacterial isolates was determined by broth microdilution and disk diffusion methods to cefotaxime (CTX), desacetylcefotaxime (dCTX), and various combinations of CTX plus dCTX. With a 1:1 ratio of CTX/dCTX, 97% of the minimal inhibitory concentrations were within one doubling dilution of those for CTX alone. With the disk diffusion test, the 30/30 micrograms disk of CTX/dCTX produced zone diameters very similar to those of the 30 micrograms CTX disk, averaging 0.4 mm larger than the latter. Regression analysis demonstrated that the 30 micrograms CTX disk was equally predictive for CTX and a 1:1 ratio of CTX/dCTX.


Enhanced adsorption for the removal of antibiotics by carbon nanotubes/graphene oxide/sodium alginate triple-network nanocomposite hydrogels in aqueous solutions.
Large-scale abuse of antibiotics has led to serious environmental problems. Some conventional adsorbents such as several biopolymer gels have poor adsorption performance and inadequate mechanical properties. In this paper, carbon nanotubes (CNTs) and graphene oxide (GO), were combined with sodium alginate (SA) to improve the adsorption performance and other properties of traditional adsorbents. With the help of hydrogen peroxide and l-cysteine (L-cys), carbon nanotubes/l-cysteine@graphene oxide/sodium alginate (CNTs/L-cys@GO/SA) triple-network composite hydrogels were prepared. Compared with traditional hydrogels and the double-network hydrogels that are currently being developed, these triple-network composite hydrogels can exploit their three-dimensional structure to improve their adsorption capacity. The independent triple-network structure increases the three-dimensional space, so there are more pores and pollutant adsorption sites to achieve the high-efficient removal of ciprofloxacin. And the adsorption capacity of CNTs/L-cys@GO/SA hydrogels can reach 181 mg g-1 and 200 mg g-1 at 25 °C and 15 °C respectively in weak acidity environment. In fact, CNTs/L-cys@GO/SA hydrogels show better property at low temperature. In addition, the thermal stability, mechanical properties and swelling ability of the triple-network hydrogels have also been improved. The independent multilayer network can retain the excellent properties of the original materials and make the internal space of hydrogels larger. These multinetwork hydrogels have great potential for removing pollutants from wastewater. In addition, the CNTs/L-cys@GO/SA hydrogels show the higher adsorption capacity of ciprofloxacin under the conditions of weak acidity, low temperature and low inorganic salt concentration, so the removal of ciprofloxacin by hydrogels can also be promoted by changing environmental conditions.


Towards attaining SDG 6: The opportunities available for capacitive deionization technology to provide clean water to the African population.
The unavailability of clean water caused by population growth, increased industrial activities, and global climate change is a major challenge in many communities. A number of desalination technologies including distillation, reverse osmosis and electrodialysis, have been used to supplement the available water resources. However, these technologies are energy intensive and demand a significant financial commitment. Capacitive deionization (CDI) is an emerging desalination technology which is promising to provide water at a reasonable cost, especially in societies with limited incomes such as those in Africa. The opportunities for CDI to provide clean water to the African population are discussed in this paper. These opportunities include electrosorption at low potential, low energy consumption, large quantities of agricultural wastes for the production of electrode materials, high sunshine irradiation throughout the year, suitability for disinfection and defluoridation and its applications in the removal of heavy metals and emerging pollutants. Due to the existence of numerous enabling conditions, the analysis from this paper demonstrates that CDI can be a dependable method to provide clean water in Africa.


Inconsistency and low transparency were found between core outcome set protocol and full text publication: a comparative study.
The objective of the study was to assess inconsistencies between individual protocols and associated full-text publications in the development of core outcome sets (COSs). Protocols and subsequent full-text publications were retrieved by searching the following electronic databases: PubMed, Embase, Web of Science, and the Core Outcome Measures in Effectiveness Trials database from inception to October 1, 2019. We summarized changes in the general and methodological characteristics by comparing the protocols with the full-text publications and reported change as information frequency and proportion. A total of 24 protocols and 32 corresponding full-text publications that encompassed 14 study topics were identified from databases. In the identified initial list of outcomes, five COSs (20.8%) changed the included study type, none of which explained the reasons for these changes. In addition, eight COSs showed inconsistencies between the protocols and full-text publications in the searched databases, of which, only two studies explained the reasons for these changes. Compared with the protocols, three COSs changed the number of Delphi rounds, eight COSs changed the participants (stakeholder groups), and three COSs changed the consensus definition of the Delphi survey. Only two COSs explained the reason for changing the number of Delphi rounds, and none of the studies explained why the participants changed. For the face-to-face consensus meeting, we found that nine COSs changed the participants and none explained the reasons for these changes. Our study found many inconsistencies between protocols and the full-text publications concerning COS development. These inconsistencies related to the included study types, databases searched, Delphi surveys, and face-to-face consensus meetings. As it is necessary to publish protocols before developing COSs, transparency regarding any changes to the methods is needed.


Correction: Detecting rare diseases in electronic health records using machine learning and knowledge engineering: Case study of acute hepatic porphyria.
[This corrects the article DOI: 10.1371/journal.pone.0235574.].


Lipids production and nutrients recycling by microalgae mixotrophic culture in anaerobic digestate of sludge using wasted organics as carbon source.
Insufficient organics in anaerobic digestate of sludge limited algal mixotrophic culture and caused low lipids production. In this study, enhancing lipids production and pollutants removal by adding acidified starch wastewater was tested for Chlorella pyrenoidosa mixotrophic culture. The results showed that an optimal addition of acidified starch wastewater into anaerobic digestate of sludge (1:1, v/v) improved biomass and lipids production by 0.5-fold (to 2.59 g·L-1) and 3.2-fold (87.3 mg·L-1·d-1), respectively. The acidified starch wastewater addition also improved the quality of algal biodiesel with higher saturation (typically in C16:0 and C18:0). In addition, 62% of total organic carbon, 99% of ammonium and 95% of orthophosphate in mixed wastewater were effectively removed by microalgae. This study provides a promising way to improve biodiesel production and nutrients recovery from anaerobic digestate of sludge using waste carbon source.


State AIDS Drug Assistance Programs: equity and efficiency in an era of rapidly changing treatment standards.
The 54 state AIDS Drug Assistance Programs (ADAP) provide medications to HIV-infected persons with limited resources. Eligibility and coverage vary, raising concerns about health inequities. To compare the relative clinical and economic performance of ADAP programs. A state-transition simulation model of HIV disease was used to explore the clinical consequences and lifetime costs associated with selected state policies. Clinical data came from the Multicenter AIDS Cohort Study, AIDS Clinical Trials Group Protocol 320, and other published randomized trials. Cost data came from the national AIDS Cost and Services Utilization Survey, and the 1999 Red Book. ADAP data came from National Association of State and Territorial AIDS Directors reports and interviews. Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, cost-effectiveness in dollars per quality-adjusted life year (QALY) gained. ADAPs vary considerably in terms of formulary policies, health outcomes, expected costs, and cost-efficiency. Conservative projections, based on a cohort with starting mean CD4 count of 250 cells/microL, yield life expectancies ranging from 5.36 to 6.81 life years (4.69-6.01 quality-adjusted life years [QALYs]). Total per person lifetime direct medical costs range from $81,200 to $112,700; higher costs reflect increased spending on medications. Expected costs per QALY gained range from $7000 to $28,000. Under pessimistic assumptions regarding initial CD4 counts, drug efficacy, and discounting, the most comprehensive policy remains below $33,000/QALY. Even the most comprehensive ADAPs constitute a cost-effective use of HIV care resources. A uniform, national ADAP formulary warrants consideration.


Correlation between porous texture and cell seeding efficiency of gas foaming and microfluidic foaming scaffolds.
In the design of scaffolds for tissue engineering applications, morphological parameters such as pore size, shape, and interconnectivity, as well as transport properties, should always be tailored in view of their clinical application. In this work, we demonstrate that a regular and ordered porous texture is fundamental to achieve an even cell distribution within the scaffold under perfusion seeding. To prove our hypothesis, two sets of alginate scaffolds were fabricated using two different technological approaches of the same method: gas-in-liquid foam templating. In the first one, foam was obtained by insufflating argon in a solution of alginate and a surfactant under stirring. In the second one, foam was generated inside a flow-focusing microfluidic device under highly controlled and reproducible conditions. As a result, in the former case the derived scaffold (GF) was characterized by polydispersed pores and interconnects, while in the latter (μFL), the porous structure was highly regular both with respect to the spatial arrangement of pores and interconnects and their monodispersity. Cell seeding within perfusion bioreactors of the two scaffolds revealed that cell population inside μFL scaffolds was quantitatively higher than in GF. Furthermore, seeding efficiency data for μFL samples were characterized by a lower standard deviation, indicating higher reproducibility among replicates. Finally, these results were validated by simulation of local flow velocity (CFD) inside the scaffolds proving that μFL was around one order of magnitude more permeable than GF.


Synthesis of novel monodentate phosphoramidites and their application in iridium-catalyzed asymmetric hydrogenations.
New monodentate H(8)-binaphthol based phosphoramidites 6 b-i have been prepared. Starting from (S)-3,3'-dibromo-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diol 3, a general protocol for the synthesis of ligands 6 is presented. A small ligand library bearing aryl substituents in the 3,3'-position of the binaphthol core was synthesized and successfully tested in the iridium-catalyzed asymmetric hydrogenation of 2-amidocinnamates to obtain different alpha-amino acid derivatives in up to 99 % ee.


Prose memory deficits associated with schizophrenia.
Memory of contextual information is essential to one's quality of living. This study investigated if the different components of prose memory, across three recall conditions: first learning trial immediate recall, fifth learning trial immediate recall, and 30-min delayed recall, are differentially impaired in people with schizophrenia, relative to healthy controls. A total of 39 patients with schizophrenia and 39 matched healthy controls were recruited. Their prose memory, in terms of recall accuracy, temporal sequence, recognition accuracy and false positives, commission of distortions, and rates of learning, forgetting, and retention were tested and compared. After controlling for the level of intelligence and depression, the patients with schizophrenia were found to commit more distortions. Furthermore, they performed poorer on recall accuracy and temporal sequence accuracy only during the first initial immediate recall. On the other hand, the rates of forgetting/retention and recognition accuracy were comparable between the two groups. These findings suggest that people with schizophrenia could be benefited by repeated exposure to the materials to be remembered. These results may have important implications for rehabilitation of verbal declarative memory deficits in schizophrenia.


Ecology of heterotrophic dinitrogen fixation in the rhizosphere of mangrove plant community at the Ganges river estuary in India.
Heterotrophic dinitrogen fixation in root associations of successional stages of the tropical mangrove plant community at the Ganges river estuary in India was investigated by excised-root acetylene reduction assay, and enumeration and identification of diazotrophic bacteria from sediment, root and tidal water samples. High to very high rates of nitrogenase activity (64-130 nmol C2H4/g dry root/h) were associated with washed excised roots of seven common early-successional mangrove species at the inundated swamps. Declining, late-successional mangroves at the occasionally inundated ridges had considerably lower values and the "declined" mangroves and other non-littoral species at embankment protected highlands had very low to insignificant values of root nitrogenase activity. Total and inorganic nitrogen contents of the mangrove sediments were low and were positively related to the stages of physiographic succession. Plant-associated sediments of particularly the old formation swamps had very high C/N ratios. Nine isolates of nitrogen-fixing bacteria belonging to all known O2 response groups were distinguished from a large population of diazotrophs associated with roots of mangroves and other associate plant species of the community. The isolates differed with respect to their N2-fixation efficiency and halotolerance in pure culture. There was no specificity of any of the bacterial isolates to any of the plant species of the community but a higher number of efficient isolates were seen to be associated with mangroves at the swampy succession. Sediment-free tidal water also contained a large population of microaerophilic and anaerobic N2-fixing bacteria.


Enzymatic degradation and quantitative lectin labeling for characterizing glycoconjugates which act as lectin acceptors in cat submandibular gland.
Sites of binding of eight different lectins (LTA, UEA I, WGA, SBA, DBA, CON A, PNA, RCA I) to cat submandibular gland were studied after exposure of tissue sections to sialidase, alpha-fucosidase, beta-galactosidase, alpha-mannosidase, beta-N-acetylglucosaminidase. All lectins were affected by enzymatic predigestion and the labeling of individual lectins was highly dependent upon the glycosidase used to pretreat the sections. Glycoconjugates of demilunar, acinar and ductal cells exhibited a different composition of terminal sequences. For example, fucose proved to form the disaccharide fucose-galactose in demilunar and acinar cells, whereas it was present with the sequence fucose-N-acetyl-D-glucosamine in striated duct cells. Sialic acid participated both to the terminal sequence sialic acid-galactose and sialic acid-N-acetyl-D-galactosamine either in demilunar or in ductal cells. Lectin labeling combined with glycosidase digestion was also helpful in verifying the influence of neighbouring oligosaccharides on the affinity of lectins for the respective sugars.


A method for deriving homogenous population of oligodendrocytes from mouse embryonic stem cells.
There is a pressing need for new therapeutics for the generation and transplantation of oligodendrocyte to the white matter to help replace and render injured cells that are lost in demyelinating disease. There are a few protocols describing a homogenous derivation of non-manipulated mouse embryonic stem cells to oligodendrocytes (ES-OL). Moreover, protocols that are successful in producing ES-OL do so with low efficiency. Therefore, we describe clear methodology for differentiation of mouse ES cells to oligodendrocyte to a high degree of homogenity and reproducibility in vitro. In addition, taking advantage of three defined media, we can generate a defined ES to oligodendrocyte lineage while selecting against neurons and astrocytes. More specifically, (1) Glial stem cell defining media (GSCDM), supplemented with appropriate combination of SHH and RA support pro-oligodendrocyte developing neural spheres from ES cells, (2) Oligodendrocyte differentiating media, induces lineage selection of oligodendrocytes progenitors from neural stem cells, and (3) Oligodendrocyte maturation media, supports oligodendrocytes progenitor maturation. Moreover, the ES cell derived oligodendrocytes display mature properites in the prescence of rat dorsal root gangila in vitro. Thus confirming thier potential for use to invesitgate developmental pathways and future potential use of cells in transplantation towards myelin repair.


Kinetics of degradation by immobilized cells with ultrasonic irradiation.
Linear alkylbenzene sulphonate (LAS) decompositions by immobilized cells with ultrasonic irradiation were investigated at the optimized condition in order to gain insight into the kinetics of the decomposition process. Firstly, by analyzing the decomposition process of LAS theoretically, showed the kinetic model of suspending cells and immobilized cells both followed the MONOD model (namely micro=micromaxs/(ks+s) during wastewater treatment, then discussed the kinetics model of LAS degradation by immobilized cells with ultrasonic irradiation at the presupposition conditions, and then the two unknown parameters ([See text]) in the gained model were researched at the condition of laboratory. Moreover, experiments have been done to validate the parameters ([See text]) in the kinetics equation, the result shows the valid kinetics equation of LAS degradation is at the LAS concentration of 30-80 mg/L:


Swimming capability of the remopleuridid trilobite Hypodicranotus striatus: hydrodynamic functions of the exoskeleton and the long, forked hypostome.
The sophisticated hydrodynamic performance achieved by the exoskeleton and the long, forked hypostome of the remopleuridid trilobite Hypodicranotus striatus was demonstrated using image-based modelling and computational fluid dynamics simulation techniques. To understand the function of the long, forked hypostome, we examined two types of exoskeletal models, one with and one without the hypostome. We simulated the flow structures around the exoskeletal models under several ambient flow velocities to evaluate the shapes of the streamlines, the values of the drag and lift forces and the relevant coefficients acting on the models. The simulation results showed that the long, forked hypostome prevents the formation of a ventral vortex; thus, it stabilises the flow structure under all of the ambient velocities tested. Moreover, the hypostome functions to create positive lift, with stable lift coefficients observed under a wide range of velocities, and to reduce the drag coefficient as velocity increases. These results imply that the hypostome can reduce viscous drag with a modest lift force, which is an essential requirement for actively swimming animals. We conclude that the long, forked hypostome evolved to provide an active and stable swimming system, and we therefore hypothesise that Hypodicranotus exoskeletal morphology resulted from the adaptation to be a high-performance swimmer.


EP1 activation inhibits doxorubicin-cardiomyocyte ferroptosis via Nrf2.
Chemotherapeutic agents, such as doxorubicin (DOX), may cause cardiomyopathy, even life-threatening arrhythmias in cancer patients. Ferroptosis-an iron-dependent oxidative form of programmed necrosis, plays a pivotal role in DOX-induced cardiomyopathy (DIC). Prostaglandins (PGs) are bioactive signaling molecules that profoundly modulate cardiac performance in both physiologic and pathologic conditions. Here, we found that PGE2 production and its E-prostanoid 1 receptor (EP1) expression were upregulated in erastin (a ferroptosis inducer) or DOX-treated cardiomyocytes. EP1 inhibition markedly aggravated erastin or DOX-induced cardiomyocyte ferroptosis, whereas EP1 activation exerted opposite effect. Genetic depletion of EP1 in cardiomyocytes worsens DOX-induced cardiac injury in mice, which was efficiently rescued by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Mechanistically, EP1 activation protected cardiomyocytes from DOX-induced ferroptosis by promoting nuclear factor erythroid 2-related factor 2 (Nrf2)-driven anti-oxidative gene expression, such as glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). EP1 was coupled with Gαq to elicit intracellular Ca2+ flux and activate the PKC/Nrf2 cascade in ferroptotic cardiomyocytes. EP1 activation also prevents DOX-induced ferroptosis in human cardiomyocytes. Thus, PGE2/EP1 axis protects cardiomyocytes from DOX-induced ferroptosis by activating PKC/Nrf2 signaling and activation of EP1 may represent an attractive strategy for DIC prevention and treatment.


Case of right-neck tumor that appears to be ectopic thymus.
A 7-year-old female infant presented with an asymptomatic soft tissue mass in the right neck. The tumor was considered to be a benign one because it had a smooth margin and no change in its size was observed. Ultrasonography showed a 4.5-cm-diameter solid tumor with a smooth, well-defined border. Inside the tumor, flow signals were observed on color Doppler and there were numerous echogenic spots. Magnetic resonance imaging (MRI) examination showed findings consistent with an ectopic thymus, i.e., T1- and T2-weighted images showed thymus-like signals. The course of the case is being continuously followed.


Etiology of neurogenic thoracic outlet syndrome.
The anatomic problems that lead to TOS are now well known. They consist of congenital anomalies that are superimposed on some form of trauma. There are some promising technologies that offer hope of early anatomic diagnosis. Sophisticated imaging of the brachial plexus as advocated by Collins offers hope. High resolution multidetector CT scanning seems even more promising.


Tetra-kis[μ2-5-nitro-2-(phenyl-sulfan-yl)benzoato-κ2 O:O']bis-[(aceto-nitrile-κN)copper(II)].
The title compound, [Cu2(μ2-O2CC12H8NO2S)4(CH3CN)2], consists of a dinuclear and centrosymmetric complex based on two CuII atoms coordinated by four 5-nitro-2-phenyl-sulfanyl-benzoate anions and two aceto-nitrile ligands. Each benzoate anion acts as a bis-monodentate ligand while each aceto-nitrile acts as a monodentate ligand, leading to a square-pyramidal NO4 coordination environment for each CuII atom with the aceto-nitrile N atom at the apex. The intra-molecular Cu⋯Cu distance in the dimer is 2.6478 (3) Å. The cohesion of the crystal structure is ensured by (phen-yl)C-H⋯O(nitro) hydrogen bonds and (phen-yl)C-H⋯π inter-actions.


Modification of Chloroplast Antioxidant Capacity by Plastid Transformation.
As immobile organisms, green plants must be frequently challenged by a broad range of environmental stresses. During these constantly adverse conditions, reactive oxygen species (ROS) levels can rise extremely in plants, leading to cellular dysfunction and cell death presumably due to irreversible protein overoxidation. Once considered merely as deleterious molecules, cells seek to remove them as efficiently as possible. To enhance ROS scavenging capacity, genes encoding antioxidative enzymes can be directly expressed from the genome of plastid (chloroplast), a major compartment for ROS production in photosynthetic organisms. Thus, overexpression of antioxidant enzymes by plastid engineering may provide an alternative to enhance plant's tolerance to stressful conditions specifically related with chloroplast-derived ROS. Here, we describe basic procedures for expressing glutathione reductase, a vital component of ascorbate-glutathione pathway, in tobacco via plastid transformation technology.


Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli.
The kringle-2 domain (residues 176-262) of tissue-type plasminogen activator (t-PA) was cloned and expressed in Escherichia coli. The recombinant peptide, which concentrated in cytoplasmic inclusion bodies, was isolated, solubilized, chemically refolded, and purified by affinity chromatography on lysine-Sepharose to apparent homogeneity. [35S]Cysteine-methionine-labeled polypeptide was used to study the interactions of kringle-2 with lysine, fibrin, and plasminogen activator inhibitor-1. The kringle-2 domain bound to lysine-Sepharose and to preformed fibrin with a Kd = 104 +/- 6.2 microM (0.86 +/- 0.012 binding site) and a Kd = 4.2 +/- 1.05 microM (0.80 +/- 0.081 binding site), respectively. Competition experiments and direct binding studies showed that the kringle-2 domain is required for the formation of the ternary t-PA-plasminogen-intact fibrin complex and that the association between the t-PA kringle-2 domain and fibrin does not require plasmin degradation of fibrin and exposure of new COOH-terminal lysine residues. We also observed that kringle-2 forms a complex with highly purified guanidine-activated plasminogen activator inhibitor-1, dissociable by 0.2 M epsilon-aminocaproic acid. The kringle-2 polypeptide significantly inhibited tissue plasminogen activator/plasminogen activator inhibitor-1 interaction. The kringle-2 domain bound to plasminogen activator inhibitor-1 in a specific and saturable manner with a Kd = 0.51 +/- 0.055 microM (0.35 +/- 0.026 binding site). Therefore, the t-PA kringle-2 domain is important for the interaction of t-PA not only with fibrin, but also with plasminogen activator inhibitor-1 and thus represents a key structure in the regulation of fibrinolysis.


Gallstone disease is associated with rectal cancer: a meta-analysis.
Increased levels of secondary bile acids after cholecystectomy and cholelithiasis are believed to increase the risk of colorectal cancer, and several studies have suggested that the risk of colorectal cancer may be the greatest proximally. Numerous conflicting studies have been published and it remains unclear whether the risk is apparent in the rectum. This meta-analysis aims to determine the risk of developing rectal cancer following gallstone disease or cholecystectomy. The prospective protocol included a literature search of PubMed, MEDLINE, EMBASE, and Current Contents (1950-2011). Selection criteria were developed to sort for studies exploring the relationship between cholelithiasis, cholecystectomy, and rectal cancer in an adult population. A random-effects model was used to generate pooled odds ratios (OR) and 95% confidence intervals (CI). Publication bias and heterogeneity were assessed. Of the 2358 studies identified, 42 were suitable for final analysis. There were 1,547,506 subjects in total, 14,226 diagnosed with rectal cancer, and 496,552 with gallstones or cholecystectomy. There was a statistically significant risk of rectal cancer following cholelithiasis (OR = 1.33; 95% CI = 1.02-1.73), though no risk was apparent following cholecystectomy (OR = 1.14; 95% CI = 0.92-1.41). Cholelithiasis increases the risk of rectal cancer. No association exists between cholecystectomy and rectal cancer.


Genomic adaptations to chemosymbiosis in the deep-sea seep-dwelling tubeworm Lamellibrachia luymesi.
Symbiotic relationships between microbes and their hosts are widespread and diverse, often providing protection or nutrients, and may be either obligate or facultative. However, the genetic mechanisms allowing organisms to maintain host-symbiont associations at the molecular level are still mostly unknown, and in the case of bacterial-animal associations, most genetic studies have focused on adaptations and mechanisms of the bacterial partner. The gutless tubeworms (Siboglinidae, Annelida) are obligate hosts of chemoautotrophic endosymbionts (except for Osedax which houses heterotrophic Oceanospirillales), which rely on the sulfide-oxidizing symbionts for nutrition and growth. Whereas several siboglinid endosymbiont genomes have been characterized, genomes of hosts and their adaptations to this symbiosis remain unexplored. Here, we present and characterize adaptations of the cold seep-dwelling tubeworm Lamellibrachia luymesi, one of the longest-lived solitary invertebrates. We sequenced the worm's ~ 688-Mb haploid genome with an overall completeness of ~ 95% and discovered that L. luymesi lacks many genes essential in amino acid biosynthesis, obligating them to products provided by symbionts. Interestingly, the host is known to carry hydrogen sulfide to thiotrophic endosymbionts using hemoglobin. We also found an expansion of hemoglobin B1 genes, many of which possess a free cysteine residue which is hypothesized to function in sulfide binding. Contrary to previous analyses, the sulfide binding mediated by zinc ions is not conserved across tubeworms. Thus, the sulfide-binding mechanisms in sibgolinids need to be further explored, and B1 globins might play a more important role than previously thought. Our comparative analyses also suggest the Toll-like receptor pathway may be essential for tolerance/sensitivity to symbionts and pathogens. Several genes related to the worm's unique life history which are known to play important roles in apoptosis, cell proliferation, and aging were also identified. Last, molecular clock analyses based on phylogenomic data suggest modern siboglinid diversity originated in 267 mya (± 70 my) support previous hypotheses indicating a Late Mesozoic or Cenozoic origins of approximately 50-126 mya for vestimentiferans. Here, we elucidate several specific adaptations along various molecular pathways that link phenome to genome to improve understanding of holobiont evolution. Our findings of adaptation in genomic mechanisms to reducing environments likely extend to other chemosynthetic symbiotic systems.


Reproductive potential of the earthworm Eisenia foetida.
Regression equations are provided for the earthworm Eisenia foetida with respect to age at which 50% of the population became clitellate at 25° C in relation to population density in activated sludge and in horse manure. Regression equations are provided for progeny per cocoon versus weight of cocoon, and weight of cocoon in relation to weight of parent; from these an equation is derived for progeny per cocoon relative to worm weight. Regression equations are given on (a) number of cocoons produced per adult in relation to age and population density from onset of adulthood to median peak production of cocoons, age 10 weeks, and from age 10 weeks to age 27 weeks, and (b) weight of worm in relation to population density and age between ages 5 and 27 weeks. From (a) and (b) a family of equations (c) are derived giving progeny per cocoon in relation to age of adult and population density. From equations (a) and (c) two families of equations are generated giving progeny per adult in relation to ascent to, and descent from, the median week of peak cocoon production in relation to population density. Data also are provided on age at which reproduction terminates in relation to population density, optimum population density for reproduction, and hatchability.


Novel features and enhancements in BioBin, a tool for the biologically inspired binning and association analysis of rare variants.
BioBin is an automated bioinformatics tool for the multi-level biological binning of sequence variants. Herein, we present a significant update to BioBin which expands the software to facilitate a comprehensive rare variant analysis and incorporates novel features and analysis enhancements. In BioBin 2.3, we extend our software tool by implementing statistical association testing, updating the binning algorithm, as well as incorporating novel analysis features providing for a robust, highly customizable, and unified rare variant analysis tool. The BioBin software package is open source and freely available to users at http://www.ritchielab.com/software/biobin-download. email@example.com. Supplementary data are available at Bioinformatics online.


Reinvestigation of the virulence of Rhodococcus equi isolates from patients with and without AIDS.
Rhodococcus equi emerged as a zoonotic pathogen of human immunodeficiency virus-infected patients over the last three decades. Two virulence plasmid types of R. equi, pVAPA and pVAPB associated with equine and porcine isolates, have been recognized, and more recently, pVAPN, a novel host-associated virulence plasmid in R. equi, was found in bovine and caprine isolates. We reinvestigated 39 previously reported isolates of R. equi from patients with and without acquired immunodeficiency syndrome (AIDS) by detecting vapA, vapB and vapN using PCR and plasmid profiling. After excluding one isolate that could not be cultured from frozen storage, eight isolates carried a virulence plasmid encoding vapA (pVAPA), 10 carried a virulence plasmid encoding vapB (pVAPB), seven carried a virulence plasmid encoding vapN (pVAPN) and 13 were negative for those genes. Of the 29 isolates from patients with AIDS, 7, 10 and 5 harboured pVAPA, pVAPB and pVAPN respectively. Among nine isolates from patients without AIDS, one and two harboured pVAPA and pVAPN respectively. This study demonstrated that pVAPN-positive R. equi existed in human isolates before 1994 and reaffirmed that equine-associated pVAPA-positive, porcine-associated pVAPB-positive and bovine- or caprine-associated pVAPN-positive R. equi are widely spread globally. Because domestic animals might be major sources of human infection, further research is needed to reveal the prevalence of pVAPN-positive R. equi infection in cattle and goats.


Genomic regions that influence plasma levels of inflammatory markers in hypertensive sibships.
We carried out univariate and bivariate linkage analyses to identify genomic regions that may influence plasma levels of C-reactive protein (CRP) and fibrinogen and exert pleiotropic effects on both traits. Subjects included African American (AA, n=1310, mean age 62.7+/-9.4 years) and non-Hispanic white (NHW, n=796, mean age 58.4+/-9.8 years) belonging to hypertensive sibships. Plasma CRP was measured by an immunoturbidimetric assay and fibrinogen by the Clauss method. Genotyping was performed at 366 microsatellite marker loci spaced approximately 10 cM apart across the 22 autosomes. Estimation of heritability and linkage analyses was carried out using a variance components approach. Significant heritability was noted for CRP (0.38 in AA and 0.37 in NHW subjects) and fibrinogen (0.44 in AA and 0.28 in NHW subjects). Significant genetic correlation between CRP and fibrinogen was present in both AA (0.39) and NHW (0.40) subjects. In univariate linkage analysis, the maximum logarithm of odds (LOD) score for CRP was on chromosome 10q22 in NHW (LOD=1.69, 106.75 cM, P=0.0026) and for fibrinogen on chromosome 2 in AA (LOD=2.14, 55.5 cM, P=0.0009) subjects. Bivariate linkage analysis demonstrated suggestive evidence of linkage (defined as LOD score >or= 2.87) for both traits on chromosome 12 (LOD=3.44, 152.16 cM, P=0.0003) in AA and on chromosome 21 (LOD=3.03, 13.05 cM, P=0.0008) in NHW subjects. Plasma CRP and fibrinogen levels are heritable and genetically correlated. Linkage analyses identified several chromosomal regions that may harbour genes influencing CRP and fibrinogen levels and exert pleiotropic effects on both traits.


MMP-1 and ADAM10 as Targets for Therapeutic Intervention in Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF), a fatal disease characterized by excessive matrix degradation and fibrosis, destroys the lung architecture and results in the inability of the lungs to absorb oxygen. The cause(s) of IPF is unknown and current treatments are palliative. Matrix metalloproteinases (MMPs) and A Disintegrin And Metalloproteinases (ADAMs) likely play roles in IPF progression. However, specific MMPs and ADAMs in IPF have not been identified due to challenges in MMP/ADAM profiling. We employed a designer affinity resin that binds exclusively to the active forms of MMPs and ADAMs and found by mass spectrometry higher levels of active MMP-1, ADAM9, ADAM10, and ADAM17 in lung tissues of IPF patients. Inhibition of MMP-1 and ADAM10 with the small-molecule inhibitor GI254023X in an in vitro lung fibrosis assay decreased the profibrotic protein α-smooth muscle actin (α-SMA). Our results indicate that inhibition of MMP-1 and ADAM10 may hold promise in treatment of IPF.


Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.
The etiology of Autism Spectrum Disorders (ASD) includes a strong genetic component and a complicated environmental component. Recent evidence indicates that maternal diabetes, including gestational diabetes, is associated with an increased prevalence of ASD. While previous studies have looked into possible roles for maternal diabetes in neurodevelopment, there are few studies into how gestational diabetes, with no previous diabetic or metabolic phenotype, may affect neurodevelopment. In this study, we have specifically induced gestational diabetes in mice, followed by behavioral and molecular phenotyping of the mice offspring. Pregnant mice were injected with STZ a day after initiation of pregnancy. Glucose levels increased to diabetic levels between E7 and E14 in pregnancy in a subset of the pregnant animals. Male offspring of Gestational Diabetic mothers displayed increased repetitive behaviors with no dysregulation in the three-chambered social interaction test. RNA-seq analysis revealed a dysregulation in genes related to forebrain development in the frontal cortex and a dysregulation of a network of neurodevelopment and immune related genes in the striatum. Together, these results give evidence that gestational diabetes can induce changes in adulthood behavior and gene transcription in the brain.


Requirements for cDC2 positioning in blood-exposed regions of the neonatal and adult spleen.
The marginal zone (MZ) of the spleen contains multiple cell types that are involved in mounting rapid immune responses against blood-borne pathogens, including conventional dendritic cells (cDCs) and MZ B cells. MZ B cells develop later than other B cell types and are sparse in neonatal mice. Here, we show that cDC2s are abundant in the MZ of neonatal compared with adult mice. We find that conditions associated with reduced MZ B cell numbers in adult mice cause increased cDC2 occupancy of the MZ. Treatment with the S1PR1-modulating drug, FTY720, causes cDC2 movement into the MZ through the indirect mechanism of displacing MZ B cells into follicles. Splenic cDC2s express high amounts of α4β1 and αLβ2 integrins and depend on these integrins and the adaptor Talin for their retention in blood-exposed regions of the spleen. Splenic CD4 T cell activation by particulate antigens is increased in mice with higher cDC2 density in the MZ, including in neonatal mice. Our work establishes requirements for homeostatic cDC2 positioning in the spleen and provides evidence that localization in blood-exposed regions around the white pulp augments cDC2 capture of particulate antigens. We suggest that MZ positioning of cDC2s partially compensates for the lack of MZ B cells during the neonatal period.


Implementing High Dimensional Reduction Analysis on Histocytometric Data.
In a previous protocol article, we demonstrated construction of a histocytometry pipeline that is capable of both segmenting highly aggregated cell populations and retaining the original intensity data range of the input microscopy images. In the protocol presented here, using the output from the aforementioned article, we demonstrate how to phenotype the data using the high dimensional reduction analysis technique optimized t-distributed stochastic neighbor embedding (opt-t-SNE) and compare it to traditional manual gating. Additionally, we present a protocol illustrating the advantage of the inclusion of cell junction/membrane markers for accurately segmenting highly aggregated cell populations in ilastik. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Phenotyping lymph node populations using manual gating Basic Protocol 2: Phenotyping lymph node populations using t-SNE dimensional reduction Support Protocol: ilastik segmentation using a pan marker.


A new vision for distance learning and continuing medical education.
Increasing demands on continuing medical education (CME) are taking place at a time of significant developments in educational thinking and new learning technologies. Such developments allow today's CME providers to better meet the CRISIS criteria for effective continuing education: convenience, relevance, individualization, self-assessment, independent learning, and a systematic approach. The International Virtual Medical School (IVIMEDS) provides a case study that illustrates how rapid growth of the Internet and e-learning can alter undergraduate education and has the potential to alter the nature of CME. Key components are a bank of reusable learning objects, a virtual practice with virtual patients, a learning-outcomes framework, and self-assessment instruments. Learning is facilitated by a curriculum map, guided-learning resources, "ask-the-expert" opportunities, and collaborative or peer-to-peer learning. The educational philosophy is "just-for-you" learning (learning customized to the content, educational strategy, and distribution needs of the individual physician) and "just-in-time" learning (learning resources available to physicians when they are required). Implications of the new learning technologies are profound. E-learning provides a bridge between the cutting edge of education and training and outdated procedures embedded in institutions and professional organizations. There are important implications, too, for globalization in medical education, for multiprofessional education, and for the continuum of education from undergraduate to postgraduate and continuing education.


Spontaneous perirenal hemorrhage (Wunderlich syndrome) in the fetus: a case report.
Spontaneous perirenal hemorrhage (Wunderlich syndrome) in the fetus is a rare urinary system disease. Prenatal ultrasound diagnosis presents challenges due to the lack of specific clinical features. A 27-year-old Chinese woman gravida 2 para 0 found her fetus with the left Wunderlich syndrome accompanying bilateral hydronephroses and bladder dysfunction with an early diagnosis through prenatal ultrasound and postnatal magnetic resonance imaging. After a timely emergency cesarean section, the infant was administrated antimicrobial prophylaxis and an indwelling catheter treatment. Ultrasound follow-up showed his urinary system gradually developed normally. A fetus with bilateral hydronephroses accompanying bladder dysfunction should be observed because of the risk of spontaneous renal rupture with hemorrhage formation. Ultrasound and magnetic resonance imaging play a vital role in the diagnosis and follow-up of Wunderlich syndrome. Early diagnosis facilitates better pregnancy planning and appropriate care of newborns.


A road map for designing and implementing a biological monitoring program.
Designing and implementing natural resource monitoring is a challenging endeavor undertaken by many agencies, NGOs, and citizen groups worldwide. Yet many monitoring programs fail to deliver useful information for a variety of administrative (staffing, documentation, and funding) or technical (sampling design and data analysis) reasons. Programs risk failure if they lack a clear motivating problem or question, explicit objectives linked to this problem or question, and a comprehensive conceptual model of the system under study. Designers must consider what "success" looks like from a resource management perspective, how desired outcomes translate to appropriate attributes to monitor, and how they will be measured. All such efforts should be filtered through the question "Why is this important?" Failing to address these considerations will produce a program that fails to deliver the desired information. We addressed these issues through creation of a "road map" for designing and implementing a monitoring program, synthesizing multiple aspects of a monitoring program into a single, overarching framework. The road map emphasizes linkages among core decisions to ensure alignment of all components, from problem framing through technical details of data collection and analysis, to program administration. Following this framework will help avoid common pitfalls, keep projects on track and budgets realistic, and aid in program evaluations. The road map has proved useful for monitoring by individuals and teams, those planning new monitoring, and those reviewing existing monitoring and for staff with a wide range of technical and scientific skills.


TAM receptors and their ligand-mediated activation: Role in atherosclerosis.
TAM family tyrosine kinase receptors including Tyro3, Axl, and MerTK are the key efferocytosis receptors presenting on antigen-presenting cell that mediate the clearance of apoptotic cells. They are thought to regulate inflammatory diseases by modulating inflammatory response and efferocytosis. Recent studies have revealed novel roles of TAM receptors in the biosynthesis of specialized pro-resolving mediators (SPMs) and inflammation resolution. In this chapter, we discuss the central roles of TAM signaling in atherosclerosis focusing on their regulation in efferocytosis and inflammation resolution and highlight the unique therapeutic potential of SPMs in blocking the progression of atherosclerosis.


Barriers and facilitators of the return-to-school process affecting adolescent recipients of allogeneic hematopoietic cell transplantation: A qualitative interview study of caregivers.
Adolescent hematopoietic cell transplant (HCT) recipients remain out of school for a prolonged period of time; navigating their return to school after completion of therapy can be challenging for caregivers. Between August 2020 and June 2021, we conducted individual semi-structured interviews of 19 caregivers of adolescent HCT recipients (10-18 years of age at HCT; 1-7 years post HCT) to understand the challenges faced at the time of their child's return to in-person school post HCT. Conventional content analysis was used to analyze interview transcripts, and thematic analysis was used to identify and organize emerging themes. Three themes emerged from the caregivers' experiences. First, caregivers reported facing several challenges related to lack of communication between their child's healthcare and school teams, which was burdensome for them. Second, some caregivers reported receiving support from school and healthcare professionals, as well as their child's peers, which helped reduce the burden of return to school. Caregivers also reported providing motivational, emotional, and spiritual support to patients. Lastly, caregivers made several recommendations regarding the need for better communication between family, healthcare professionals, and school professionals and availability of supportive care such as mental health counseling and neuropsychological testing. Notably, the need for a return-to-school navigator emerged as a key finding from our analysis. Caregivers of adolescent HCT recipients face several challenges supporting their children's return to school post HCT, which are related to lack of communication between patients' healthcare and school teams. While some reported receiving support from school and healthcare professionals and their child's peers, the need to coordinate the return-to-school process was burdensome for several caregivers. Additional work is needed to optimize support for HCT recipients and their caregivers during their return-to-school process to minimize burden. Our study findings have the potential to serve as a framework for developing and testing supportive care interventions to improve the return-to-school experience of HCT survivors and ultimately their quality of life.


Rapid adaptive responses of rosette-type macrophyte Vallisneria natans juveniles to varying water depths: The role of leaf trait plasticity.
Rosette-type submerged macrophytes are widely distributed across a range of water depths in shallow lakes and play a key role in maintaining ecosystem structures and functions. However, little is known about the rapid adaptive responses of such macrophytes to variations in water depth, especially at the juvenile stage. Here, we conducted a short-term in situ mesocosm experiment, in which the juveniles of Vallisneria natans were exposed to a water depth gradient ranging from 20 to 360 cm. Twenty-two leaf-related traits were examined after 4 weeks of growth in a shallow lake. Most (18) traits of V. natans generally showed high plasticity in relation to water depth. Specifically, juveniles allocated more biomass to leaves and had higher specific leaf area, leaf length-to-width ratio, chlorophyll content, and carotenoids content in deep waters, displaying trait syndrome associated with high resource acquisition. In contrast, V. natans juveniles in shallow waters had higher leaf dry matter content, leaf soluble carbohydrate content, carotenoids per unit chlorophyll, and peroxidase activity, pertaining to resource conservation. Notably, underwater light intensity was found to be the key factor explaining the trait plasticity along the water depth gradient, and 1.30 mol photons m-2 d-1 (at 270 cm) could be the optimal irradiance level based on the total biomass of V. natans juveniles. The present study highlights the significance of leaf trait plasticity for rosette-type macrophytes in response to variations in water depth and sheds new light on the differences between trade-offs in deep- and shallow-water areas.


Higher order iminodiacetic acid libraries for probing protein-protein interactions.
Higher order iminodiacetic acid diamide trimer (560 compounds) and tetramer libraries (1260 compounds) are described and were assembled in a convergent multistep solution-phase synthesis for use in studying protein-protein interactions.


HRT opposed to low-dose tamoxifen (HOT study): rationale and design.
The rationale for the HOT study is mainly based on the findings of the Italian Tamoxifen Prevention Study, where 5,408 healthy hysterectomized women aged 35-70 years were randomized to 20 mg/day of tamoxifen or placebo for 5 years. After 81.2 months median follow-up, 79 breast cancers occurred (34 on tamoxifen versus 45 on placebo, p=0.215). In the subgroup of 1,580 women who used estrogen replacement therapy (ERT) at some point during the study, 23 breast cancers were observed: 17 on placebo and 6 on tamoxifen (hazard ratio=0.35, 95% CI, 0.14-0.89). Pharmacokinetic and pharmacodynamic (surrogate endpoint biomarkers) studies showed that a lower dose of tamoxifen (such as 5 mg/day) does not affect the drug's activity on several biomarkers of both cardiovascular and breast cancer risk. We therefore propose a multicenter placebo-controlled phase III trial in postmenopausal healthy women on hormone replacement therapy (HRT) to assess whether the combination of HRT and low-dose tamoxifen retains the benefits while reducing the risks of either.


Catecholamine-synthesizing enzymes in the adult and prenatal human testis.
Catecholamines play functional roles in the mature and developing mammalian testis but the cell types responsible for their local synthesis are still controversially discussed. Here, we demonstrate that four enzymes involved in the biosynthesis of catecholamines, namely, tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine- N-methyltransferase (PNMT), are expressed in Leydig cells of the human testis. Tyrosine hydroxylase, the key enzyme of the biosynthesis of catecholamines, was localized to Leydig cells both at the transcript level (by RT-PCR analyses and by in situ hybridization assays) and at the protein level (by immunoblotting and by immunohistochemistry). The other enzymes were also demonstrated in Leydig cells by RT-PCR and immunohistochemical analyses. The presence of TH, AADC, DBH, and PNMT in human Leydig cells was found, in addition, by immunohistochemical approaches carried out on sections from prenatal human testes. Thus, the present study identifies the Leydig cells as the presumed sites of catecholamine production in both the mature and fetal human testes and further supports the previously recognized neuroendocrine characteristics of this cell type.


Different aspects of the cyclops lesion following anterior cruciate ligament reconstruction: a multifactorial etiopathogenesis.
After anterior cruciate ligament (ACL) reconstruction using a patellar-tendon autograft, 65 patients underwent second-look arthroscopy in conjunction with hardware removal. In 23 patients, hypertrophic tissue was found in the anterior part of the knee. This tissue presented different aspects, from a well-synovialized nodule to a more disorganized fibrous tissue according to patients' complaints. Endoscopic resection of this offending tissue was generally sufficient to obtain a satisfactory result. In patients presenting a loss of extension, the notch frequently had to be enlarged. We have found a multifactorial pathogenesis to be likely: the nodule is a natural fibroproliferative tissue process originating either from drilling debris from the tibial tunnel or from remnants of the ACL stump and, more rarely, from broken graft fibers. Sometimes, when the graft is malpositioned, the scar tissue can result from repeated graft impingement on the notch at terminal extension. Formation of this aberrant tissue should be prevented by proper positioning of the graft, by enlargement of the narrowed notch in chronic cases, by using drills of increasing diameters to avoid production of osteocartilaginous fragments, by meticulous resection of all drilling debris and ACL remnants around the tibial tunnel, and by enlarging the notch roof if any contact with the graft is present when the knee is fully extended intraoperatively.


Shedding New Light on Ancient Glass Beads by Synchrotron, SEM-EDS, and Raman Spectroscopy Techniques.
The oxidation states of colouring elements and the pigments in ancient rare glasses have been investigated in this study. Synchrotron X-ray, SEM-EDS, and Raman techniques revealed that Cu2+plays a major role in blue and green glasses. The lead stannate pigment gives glasses a yellow colour. Copper and lead stannate can cause the green colour in glasses, and iron gives rise to the colour of black glasses. Microcomputed tomography reveals the distribution of the heavy elements, pigments, and inclusions in the glasses. The Dvaravati glasses in Southeast Asia may have been imported or technologically transferred to domestic manufacturers during trading on the Silk Road that connected the East and the West.


Design of a medical image management system: a practical cost-effective approach.
The impact of technology and economics is driving radiology departments into a digital era. There have been significant developments in the design of Medical Image Management System components. However, many important design criteria have been neglected, leading to an ineffective end product. This paper will discuss the more important design criteria. The design will be considered from the user's point of view. The implementation of a prototype Medical Image Management System (MIMS) serving a Medical Intensive Care Unit in our Institution will be presented. The structure and very preliminary results of a clinical evaluation will be discussed. Plans to expand the MIMS beyond the Department and the Hospital will also be briefly discussed. The role of the personal computer in the design of a MIMS will be reviewed.


Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease.
DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell-type-specific gene expression. Here we performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease (IBD). Results were validated using pyrosequencing, real-time PCR, and immunostaining. The functional impact of DNA methylation changes on gene expression was assessed by employing in-vitro assays in intestinal cell lines. DNA methylation analyses allowed identification of 214 genes for which expression is regulated via DNA methylation, i.e. regulatory differentially methylated regions (rDMRs). Pathway and functional analysis of rDMRs suggested a critical role for DNA methylation in regulating gene expression and functional development of the human intestinal epithelium. Moreover, analysis performed on intestinal epithelium of children newly diagnosed with IBD revealed alterations in DNA methylation within genomic loci, which were found to overlap significantly with those undergoing methylation changes during intestinal development. Our study provides novel insights into the physiological role of DNA methylation in regulating functional maturation of the human intestinal epithelium. Moreover, we provide data linking developmentally acquired alterations in the DNA methylation profile to changes seen in pediatric IBD.


STAT3 gain-of-function mutation in a patient with pulmonary Mycobacterium abscessus infection.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in cellular proliferation, apoptosis, and differentiation. Mutations in the STAT3 gene have been associated with dysregulation of the immune system giving rise to primary immunodeficiency syndromes (PID). Clinically, patients may present with very broad manifestations, and its diagnosis is usually very challenging. Proper treatment remains unclear, and limited options are available. We report an adult male patient with long-standing history of immunodeficiency, who was found to have Mycobacterium abscessus infection. Two-hundred and seven immunogenes were sequenced using next-generation sequencing technology (NGS). A STAT3 heterozygous missense pathologic variant was identified in the patient located in the transactivation domain (TA) of STAT3, associated with a gain of functionality, leading to recurrent bronchopulmonary infections, and involvement of multiple organ systems. Severe cases of autoimmunity should prompt for evaluation of PIDs in the setting of genetic mutations. Anti-IL-6 therapy may benefit patients with STAT3 GOF mutations. These patients should also be screened for lymphoproliferative disorders.


[Interest of flexible videocystoscopy in blue light (+Hexvix(®)) in consultation for the diagnosis of vesical tumor].
Estimate the feasibility and the results of the realization in consultation of a flexible videocystoscopy in blue light preceded by an instillation of Hexvix(®) (GE Healthcare) for the initial diagnosis or the surveillance of vesicals tumors (VT). The objective of this study was to compare the number of hurts seen in white light and in blue light, and to estimate in which percentage of case the use of the Hexvix(®) in consultation modified the care. Thirty consecutive patients (26 men and four women) were estimated prospectively by vesical videofibroscopy in blue light (Wolf's PD videofibroscope) realized 1 hour after an endovesical instillation of Hexvix(®). All the examinations were realized in external consultation under local anesthetic by xylocaine gel: 23 (76.6%) patients within the framework of a surveillance of VT and seven (23.4%) for the diagnosis of a hematuria with normal echography. When a suspect hurt or a VT was discovered, the patients benefited from an endoscopic resection under anesthesia with new cystoscopy in blue light. Suspect hurts were revealed in 10 out of 30 patients, five in white and blue light, five in blue light only. Among the five only visible hurts in blue light, three were urothelial tumors (any pTa of bottom-rank, less of 5 mm) and two non-specific hurts. No CIS's hurt was revealed during this study. The fibroscopy in blue light allowed to diagnose invisible hurts in white light in three patients (10%) and has modified the care of five patients (16.7%). The duration of the cystoscopy was on average of 9.5 minutes. The tolerance of the examination was good and no complication arose. The use of the flexible videocystoscopy in blue light +Hexvix(®) has allowed to improve the rate of detection of VT. Except CIS's hurts, this improvement was bound to the diagnosis of little aggressive small-sized VT. The indications must be specified by studies of bigger scale and a medical economic evaluation.


[Antibacterial and antifungal compounds. VIII. Synthesis and antifungal activity of pyrrol derivatives similar to trichostatin A].
Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.


Using autoencoders as a weight initialization method on deep neural networks for disease detection.
As of today, cancer is still one of the most prevalent and high-mortality diseases, summing more than 9 million deaths in 2018. This has motivated researchers to study the application of machine learning-based solutions for cancer detection to accelerate its diagnosis and help its prevention. Among several approaches, one is to automatically classify tumor samples through their gene expression analysis. In this work, we aim to distinguish five different types of cancer through RNA-Seq datasets: thyroid, skin, stomach, breast, and lung. To do so, we have adopted a previously described methodology, with which we compare the performance of 3 different autoencoders (AEs) used as a deep neural network weight initialization technique. Our experiments consist in assessing two different approaches when training the classification model - fixing the weights after pre-training the AEs, or allowing fine-tuning of the entire network - and two different strategies for embedding the AEs into the classification network, namely by only importing the encoding layers, or by inserting the complete AE. We then study how varying the number of layers in the first strategy, the AEs latent vector dimension, and the imputation technique in the data preprocessing step impacts the network's overall classification performance. Finally, with the goal of assessing how well does this pipeline generalize, we apply the same methodology to two additional datasets that include features extracted from images of malaria thin blood smears, and breast masses cell nuclei. We also discard the possibility of overfitting by using held-out test sets in the images datasets. The methodology attained good overall results for both RNA-Seq and image extracted data. We outperformed the established baseline for all the considered datasets, achieving an average F1 score of 99.03, 89.95, and 98.84 and an MCC of 0.99, 0.84, and 0.98, for the RNA-Seq (when detecting thyroid cancer), the Malaria, and the Wisconsin Breast Cancer data, respectively. We observed that the approach of fine-tuning the weights of the top layers imported from the AE reached higher results, for all the presented experiences, and all the considered datasets. We outperformed all the previous reported results when comparing to the established baselines.


Therapeutic endoscopic retrograde cholangiopancreatography: what the future holds.
These are exciting times for interventional endoscopists performing ERCP. The advent of noninvasive, diagnostic techniques of the pancreaticobiliary tree has resulted in a shift toward more therapeutic procedures. The combination of major technologic advances together with endoscopists' growing comfort with invasive procedures has helped to push the boundaries of endoscopic therapy. These therapies, however, should always be sanctioned by sound science and well-controlled clinical trials.