Visualizing Microbial Community Dynamics via a Controllable Soil Environment.
Understanding the basic biology that underpins soil microbiome interactions is required to predict the metaphenomic response to environmental shifts. A significant knowledge gap remains in how such changes affect microbial community dynamics and their metabolic landscape at microbially relevant spatial scales. Using a custom-built SoilBox system, here we demonstrated changes in microbial community growth and composition in different soil environments (14%, 24%, and 34% soil moisture), contingent upon access to reservoirs of nutrient sources. The SoilBox emulates the probing depth of a common soil core and enables determination of both the spatial organization of the microbial communities and their metabolites, as shown by confocal microscopy in combination with mass spectrometry imaging (MSI). Using chitin as a nutrient source, we used the SoilBox system to observe increased adhesion of microbial biomass on chitin islands resulting in degradation of chitin into N-acetylglucosamine (NAG) and chitobiose. With matrix-assisted laser desorption/ionization (MALDI)-MSI, we also observed several phospholipid families that are functional biomarkers for microbial growth on the chitin islands. Fungal hyphal networks bridging different chitin islands over distances of 27 mm were observed only in the 14% soil moisture regime, indicating that such bridges may act as nutrient highways under drought conditions. In total, these results illustrate a system that can provide unprecedented spatial information about interactions within soil microbial communities as a function of changing environments. We anticipate that this platform will be invaluable in spatially probing specific intra- and interkingdom functional relationships of microbiomes within soil.IMPORTANCE Microbial communities are key components of the soil ecosystem. Recent advances in metagenomics and other omics capabilities have expanded our ability to characterize the composition and function of the soil microbiome. However, characterizing the spatial metabolic and morphological diversity of microbial communities remains a challenge due to the dynamic and complex nature of soil microenvironments. The SoilBox system, demonstrated in this work, simulates an ∼12-cm soil depth, similar to a typical soil core, and provides a platform that facilitates imaging the molecular and topographical landscape of soil microbial communities as a function of environmental gradients. Moreover, the nondestructive harvesting of soil microbial communities for the imaging experiments can enable simultaneous multiomics analysis throughout the depth of the SoilBox. Our results show that by correlating molecular and optical imaging data obtained using the SoilBox platform, deeper insights into the nature of specific soil microbial interactions can be achieved.


Prolonged survival in patients with lung cancer with diabetes mellitus.
Patients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer. We analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined. One thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41-0.75) as compared with without. Patients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus.


Nutritional Treatment in Crohn's Disease.
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) which can affect any part of the whole gastrointestinal tract (from mouth to anus). Malnutrition affects 65-75% of CD patients, and it is now well acknowledged that diet is of paramount importance in the management of the disease. In this review, we would like to highlight the most recent findings in the field of nutrition for the treatment of CD. Our analysis will cover a wide range of topics, from the well-established diets to the new nutritional theories, along with the recent progress in emerging research fields, such as nutrigenomics.


[A Case of Adult Mature Teratoma Located in Retroperitoneum].
A 35-year-old man wasreferred to our hospital for treatment of a right adrenal tumor detected by ultrasonography during a physical check-up. Contrast-enhanced abdominal computed tomography revealed a poorly enhanced 74 mm tumor situated adjacent to the upper pole of the right kidney. The tumor consisted of fat with peripheral calcification. Magnetic resonance imaging also revealed a right retroperitoneal tumor with fatty contents and well-circumscribed capsule. The endocrine examination revealed the tumor as non-functioning. These findings were suggestive of a right adrenal myelolipoma. We performed laparoscopic right adrenalectomy because of its large size and malignant potency. The pathological examination revealed the retroperitoneal tumor asa mature teratoma existing apart from the adrenal gland. Primary retroperitoneal teratomasare relatively rare. Herein, we report thiscas e of adult mature teratoma occurring in the retroperitoneum.


Environmental risk factors in siblings with Parkinson's disease.
To investigate possible risk factors in Parkinson's disease, we conducted a case-controlled study of 19 families having two or more siblings with Parkinson's disease. Demographic data were collected, including lifetime histories of places of residence; sources of drinking water; occupations, such as farming; and exposure to herbicides and pesticides. Rural living and drinking well water, but not farming and herbicide exposure, were significantly increased in 38 parkinsonians compared with 38 normal control subjects. A comparison of parkinsonian siblings with siblings with essential tremor revealed no differences in any risk factors for the years of shared environment. These data suggest that living in a rural environment and drinking well water are risk factors for Parkinson's disease and that the total life exposure to an environmental toxin may be more important than exposure in early life.


Simultaneous silencing of endo-β-1,4 xylanase genes reveals their roles in the virulence of Magnaporthe oryzae.
Due to functional redundancy, it is often difficult to genetically analyse the biological function of fungal cell wall-degrading enzymes that belong to a gene family. To overcome this difficulty, we used RNAi to knock-down (KD) multiple xylanase genes to elucidate their roles in the pathogenicity of the blast fungus, Magnaporthe oryzae. To obtain the maximum average efficiency of gene silencing for the xylanase genes, we used the 'building blocks method', in which a 40 bp sequence was chosen from an endoxylanase gene, and 10 such sequences from 10 endoxylanases were combined to make an artificial RNAi trigger by synthetic DNA. Quantitative RT-PCR analysis revealed that the transcript levels of all the expressed xylanase genes were significantly reduced in KD mutants with the artificial RNAi trigger. Even though the KD mutants did not completely lose their pathogenicity to host plants, the number of lesions, rate of penetration and extent of infected cells were all reduced in KD mutant-infected leaves. The degree of pathogenicity reduction was associated with the silencing levels of xylanase mRNA and enzymatic activity in the KD mutants. Cytological analysis indicated that xylanases play significant roles in both vertical penetration and horizontal expansion of M. oryzae in infected plants.


Simple and efficient access to N-tosyl beta-amino ketones and their conversion into 2,4-disubstituted azetidines.
Treatment of N-tosylaldimines with acetophenone at room temperature in the presence of BF(3).OEt(2) as a catalyst furnished the corresponding N-tosyl beta-amino ketones in high yields (77-86%) within 6-9 h. Subsequent reduction and cyclization of these compounds afforded 2,4-disubstituted N-tosylazetidines, comprising a three-step, high-yielding synthesis starting from aldimines.


[Neuropsychological assessment in the diagnosis and differential diagnosis of fronto-temporal dementia].
Clinical diagnosis of fronto-temporal dementia (FTD) and its rare variants (semantic dementia and primary progressive aphasia) represents a special challenge bearing in mind its difficulties and is important due to therapeutic differences with the most common Alzheimer's dementia. Of note, cholinesterase inhibitors commonly prescribed in Alzheimer's disease are not effective in FTD and a novel drug, memantine, has not been evaluated as yet. Neuropsychological evaluation is an important add-on to neurological, psychiatric and neuroimaging assessments in the clinical diagnosis of FTD. In this paper, we have described characteristics of neuropsychological deficits observed in FTD (such as attention, language, visuospatial and memory impairments) as well as tools used (tests) in clinical practice. Special attention is paid to the utility of neuropsychological examination in the differential diagnosis of FTD versus Alzheimer's disease, vascular dementia and other, less common forms of dementia.


Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects.
Intestinal absorption of the water-soluble vitamins biotin and pantothenic acid is carrier mediated and involves the sodium-dependent multivitamin transporter (SMVT; product of the SLC5A6 gene). We recently observed that intestinal-specific (conditional) knockout of the mouse Slc5a6 gene (SMVT-cKO) is associated with growth retardation, the development of spontaneous and severe inflammation, abnormal histology in the large intestine, altered gut permeability, and early death. Our aim in this study was to examine the possibility that biotin and pantothenic acid oversupplementation (BPS) of the SMVT-cKO mice could reverse the above-described abnormalities. BPS was provided in the drinking water to mice before conception, to dams during pregnancy and lactation, and to the SMVT-cKO mice throughout their life. Our findings showed that such a regimen prevents early death, as well as normalizes the growth rate, intestinal integrity, pathology, and inflammation in SMVT-cKO mice. These findings provide clear evidence for a role for biotin and/or pantothenic acid in the maintenance of normal intestinal integrity and health.


Development of a perfusion process for continuous lentivirus production using stable suspension producer cell lines.
The large-scale production of clinical-grade lentiviral vectors (LVs) for gene therapy applications is a remaining challenge. The use of adherent cell lines and methods like transient transfection are cost-intensive and hamper process scalability as well as reproducibility. This study describes the use of two suspension-adapted stable packaging cell lines, called GPRGs and GPRTGs, for the development of a scalable and serum-free LV production process. Both stable packaging cell lines are based on an inducible Tet-off system, thus requiring doxycycline removal for initiation of the virus production. Therefore, we compared different methods for doxycycline removal and inoculated three independent 5 L bioreactors using a scalable induction method by dilution, an acoustic cell washer and manual centrifugation. The bioreactors were inoculated with a stable producer cell line encoding for a LV carrying a clinically relevant gene. LV production was performed in perfusion mode using a cell retention device based on acoustic wave separation. Comparable cell-specific productivities were obtained with all three methods and cumulative functional yields up to 6.36 × 1011 transducing units per bioreactor were generated in a 234-h long process, demonstrating the usability of stable Tet-off cell lines for an easily scalable suspension process. Remarkably, cell viabilities >90% were maintained at high cell densities without compromising productivity throughout the whole process, allowing to further extend the process time. Given its low effects of toxicity during virus production, the presented cell lines are excellent candidates to develop a fully continuous LV production process to overcome the existing bottlenecks in LV manufacturing.


Gentamicin-induced spiral ganglion cell death: apoptosis mediated by ROS and the JNK signaling pathway.
Reactive oxygen species (ROS) and the c-Jun N-terminal kinase (JNK) signaling pathway may be involved in secondary apoptosis of spiral ganglion cells (SGCs) induced by intracochlear gentamicin injection. The purpose of this study was to ascertain the role of ROS and the JNK signaling pathway in secondary apoptosis of SGCs induced by intracochlear gentamicin treatment. Gentamicin (40 mg/ml) was injected into the cochlea of guinea pigs (n = 18) to destroy the hair cells and induce secondary apoptosis of SGCs. At 1 (n = 6), 2 (n = 6), and 3 (n = 6) weeks after gentamicin treatment, the cochleas were removed and stained with hematoxylin and eosin, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling to observe the morphologic changes and apoptosis of SGCs. A dihydroethidium (DHE) assay was performed to detect ROS generation, and RT-PCR and Western blot analysis were used to assess the expression of Fas ligand (FasL), JNK, and c-Jun. After gentamicin was injected into the cochlea, apoptosis and progressive loss of SGCs were observed. RT-PCR and Western blot analysis showed increased expression of FasL after gentamicin treatment. ROS generation detected by DHE fluorescence increased progressively, and the expression of JNK, phospho-JNK, c-Jun, and phospho-c-Jun also increased.


Nanoscopic mechanical anisotropy in hydrogel surfaces.
The bulk mechanical properties of soft materials have been studied widely, but it is unclear to what extent macroscopic behavior is reflected in nanomechanics. Using an atomic force microscopy (AFM) imaging method called force spectroscopy mapping (FSM), it is possible to map the nanoscopic spatial distribution of Young's modulus, i.e. "stiffness," and determine if soft or stiff polymer domains exist to correlate nano- and macro-mechanics. Two model hydrogel systems typically used in cell culture and polymerized by a free radical polymerization process, i.e. poly (vinyl pyrrolidone) (PVP) and poly(acrylamide) (PAam) hydrogels, were found to have significantly different nanomechanical behavior despite relatively similar bulk stiffness and roughness. PVP gels contained a large number of soft and stiff nanodomains, and their size was inversely related to crosslinking density and changes in crosslinking efficiency within the hydrogel. In contrast, PAam gels displayed small nanodomains occuring at low frequency, indicating relatively uniform polymerization. Given the responsiveness of cells to changes in gel stiffness, inhomogeneities found in the PVP network indicate that careful nanomechanical characterization of polymer substrates is necessary to appreciate complex cell behavior.


Comprehensive Analysis of Two H13-Type Starting Materials Used for Laser Cladding and Aerosol Particles Formed in This Process.
Laser cladding with H13 steel powders was performed and the related material transformations were studied for the particles emitted during this process. Fractions of various sizes of the aerosol particles formed during the laser cladding were collected on a cascade impactor, while the electromobility and the aerodynamic size of the particles were measured using a scanning mobility particle spectrometer and an aerodynamic particle sizer, respectively. The aerosol particles deposited onto the impactor plates were analyzed using scanning electron microscopy−energy-dispersive X-ray spectroscopy, as well as total-reflection X-ray fluorescence and X-ray absorption near-edge structure spectroscopy. Both the concentration and mean oxidation state of the major components were correlated with the aerosol particle size. The ultrafine aerosol particles (with a diameter less than about 100 nm) were predominantly oxidized and formed as the result of an evaporation−oxidation−condensation process sequence. The larger particles (>200 nm in geometric diameter) were primarily the residues of the original metal powder and exhibited a composition change as compared to the as-received metal powder. Correlations between the changes in the concentration ratio of the components were detected and explained.


Prevalence of cholera risk factors between migrant Haitians and Dominicans in the Dominican Republic.
To determine whether cholera risk factor prevalence in the Dominican Republic can be explained by nationality, independent of other factors, given the vulnerability of many Haitians in the country and the need for targeted prevention. A cross-sectional, observational household survey (103 Haitian and 260 Dominican) was completed in 18 communities in July 2012. The survey included modules for demographics, knowledge, socioeconomic status, and access to adequate water, sanitation, and hygiene (WASH) infrastructure. Logistic regression assessed differential access to WASH infrastructure and Poisson regression assessed differences in cholera knowledge, controlling for potential confounders. Dominican and Haitian households differed on demographic characteristics. Haitians had lower educational attainment, socioeconomic status, and less knowledge of cholera than Dominicans (adjusted odds ratio [aOR] = 0.66; 95% confidence interval [95%CI] = 0.55-0.81). Access to improved drinking water was low for both groups, but particularly low among rural Haitians (aOR = 0.21; 95%CI: 0.04-1.01). No differences were found in access to sanitation after adjusting for sociodemographic confounders (aOR = 1.00; 95%CI: 0.57-1.76). Urban/rural geography and socioeconomic status play a larger role in cholera risk factor prevalence than nationality, indicating that Haitians' perceived vulnerability to cholera is confounded by contextual factors. Understanding the social dynamics that lead to cholera risk can inform control strategies, leading to better targeting and the possibility of eliminating cholera from the island.


[An easy introduction to organismal and cellular mechanisms for graviperception].
In this review paper, organismal and also cellular mechanisms for perception of gravity are explained. A statolith and a number of hair cells which surround the statolith is a basic structure of statocysts for detecting the direction of gravity or tilting of the body in various animals. The vestibular system of vertebrate was explained, especially on the process from the body-tilting to impulse frequencies which travel to brain. For the cellular responses to gravity, contribution of various organella (??) and cytoskeleton are introduced. Such cellular responses may change when the gravity values become less or null. Gravity perception mechanisms of plants are also explained.


Interferon-Mediated Response to Human Metapneumovirus Infection.
Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases in infants and children worldwide. Although this pathogen infects mainly young children, elderly and immunocompromised people can be also seriously affected. To date, there is no commercial vaccine available against it. Upon HMPV infection, the host innate arm of defense produces interferons (IFNs), which are critical for limiting HMPV replication. In this review, we offer an updated landscape of the HMPV mediated-IFN response in different models as well as some of the defense tactics employed by the virus to circumvent IFN response.


Evidence-based modeling of critical illness: an initial consensus from the Society for Complexity in Acute Illness.
Given the complexity of biological systems, understanding their dynamic behaviors, such as the Acute Inflammatory Response (AIR), requires a formal synthetic process. Dynamic Mathematical Modeling (DMM) represents a suite of methods intended for inclusion within the required synthetic framework. The DMM, however, is a relatively novel approach in the practice of biomedical research. The Society for Complexity in Acute Illness (SCAI) was formed in 2004 from the leading research groups using DMM in the study of acute inflammation. This society believes that it is important to offer guidelines for the design, development, and use of DMM in the setting of AIR research to avoid the "garbage in, garbage out" problem. Accordingly, SCAI identified a need for and carried out a critical appraisal of DMM as currently used in the setting of acute illness. The SCAI annual meeting in 2005, the Fourth International Conference on Complexity in Acute Illness (Cologne, Germany), was structured with the intent of developing a consensus statement on the methods and execution of DMM in AIR research. The conference was organized to include a series of interactive breakout sessions that included thought leaders from both the DMM and acute illness fields, the results of which were then presented in summary form to the entire group for discussion and consensus. The information in this article represents the concatenation of those presentations. The output from the Fourth International Conference on Complexity in Acute Illness involved consensus statements for the following topics: (1) the need for DMM; (2) a suggested approach for the process of establishing a modeling project; (3) the type of "wet" laboratory experiments and data needed to establish a modeling project; (4) general quality measures for data to be input to a modeling project; and (5) a descriptive list of several types of DMM to provide guidance in selection of a method for a project. We believe that the complexity of biological systems requires that DMM needs to be among the methods used to improve understanding and make progress with attempts to characterize and manipulate the AIR. We believe that this consensus statement will help guide the integration, rational implementation, and standardization of DMM into general biomedical research.


Correlations between Phytohormones and Drought Tolerance in Selected Brassica Crops: Chinese Cabbage, White Cabbage and Kale.
Drought is one of the major abiotic stresses affecting the productivity of Brassica crops. To understand the role of phytohormones in drought tolerance, we subjected Chinese cabbage (B. rapa ssp. pekinensis), white cabbage (B. oleracea var. capitata), and kale (B. oleracea var. acephala) to drought and examined the stress response on the physiological, biochemical and hormonal levels. The phytohormones abscisic acid (ABA), auxin indole-3-acetic acid (IAA), brassinosteroids (BRs), cytokinins (CKs), jasmonates (JAs), and salicylic acid (SA) were analyzed by ultra-high-performance liquid chromatography⁻tandem mass spectrometry (UHPLC-MS/MS). Based on the physiological and biochemical markers the Chinese cabbage exhibited the lowest tolerance, followed by the white cabbage, while the kale appeared to be the most tolerant to drought. The drought tolerance of the kale correlated with increased levels of SA, ABA, IAA, CKs iP(R) and cZ(R), and typhasterol (TY), a precursor of active BRs. In contrast, the drought sensitivity of the Chinese cabbage correlated with a significant increase in ABA, JAs and the active BRs castasterol (CS) and brassinolide (BL). The moderately tolerant white cabbage, positioned between the kale and Chinese cabbage, showed more similarity in terms of the phytohormone patterns with the kale. We concluded that the drought tolerance in Brassicaceae is mostly determined by the increased endogenous levels of IAA, CKs, ABA and SA and the decreased levels of active BRs.


HPV viral load determination during pregnancy as a possible cervical cancer risk.
Pregnancy may be a risk factor for cervical human papillomavirus (HPV) infection due to associated increased hormonal level and immunosuppression. Although a majority of such infections are transient, persistent infection may lead to premalignant/malignant cervical lesion. The viral burden is thought to be an indicator for persistence of the infection and malignant transformation. To assess pregnancy as a risk factor for cervical HPV infection, we compared HPV prevalence and viral load among 25 pregnant women to those of 24 non-pregnant and 28 cervical cancer cases. HPV DNA was detected in the cervical cells by PCR using MY09/MY11 primers. HPV positive cases were retested with a low stringency PCR method to ascertain the viral load. HPV prevalences of 68%, 25% and 89% were observed among pregnant women, non-pregnant women and in the cervical cancer cases, respectively. High viral load was frequently (40%) observed in cervical cancer patients. Median viral copy number/cell did not vary much between the non-pregnant and pregnant women. However, pregnant women had a predominantly moderate viral load whereas the low viral load was more frequent in non-pregnant women. High viral load was found to be associated with the presence of HPV 16 in the cervical cancer cases as compared to pregnant/non-pregnant HPV infected women.


Vaginal cuff dehiscence with bowel evisceration after robotic hysterectomy.
Vaginal cuff dehisence with bowel evisceration after hysterectomy is a very rare complication. However, the incidance of this complication appears to be increased with the widely used techniques of laparoscopic surgery especially with robotic hysterectomy. In this case report we aimed to evaluate the risk factors and treatment methods for this complication.


[Application of plasma prostate electrovaporization system in the treatment of rectal cicatricial stenosis].
To evaluate the feasibility, maneuver and efficacy of plasma prostate electrovaporization system in the treatment of rectal cicatricial stenosis. According to similar procedure of transurethral resection prostate(TURP), intrarectal cicatriclectomy was performed with plasma prostate electrovaporization system in 7 patients with rectal low cicatricial stenosis after rectal cancer treatment (5 patients with transabdominal low anterior resection,2 patients with 3-dimension precise radiotherapy) to remove obstruction and dilate enteric cavity. Seven patients underwent 12 operations, including one operation in 3 patients, two operations in 3 patients, 3 operations in one patient. Resected rectal cicatricial tissue ranged from 5 to 15 g. Mean operation time was 41 min (25 to 40). Operation successful rate was 100% without complications such as perforation, bleeding and infection. All the patients had smooth defecation. Plasma prostate electrovaporization system is an effective treatment for rectal cicatricial stenosis with tiny trauma.


Specific ethene surface activation on silver oxide covered Ag[111] from the interplay of STM experiment and theory.
High-resolution scanning tunneling microscopy (STM) images at 5 K, simultaneously resolving the molecular adsorbate and the honeycomb structure of the well-defined Ag[111]-p(4 x 4)+Ag(1.83)O substrate, assign the adsorption site for ethene on the silver oxide surface. Ethene molecules are exclusively adsorbed above a particular subset of Ag(delta)(+) sites in the hexagonal rings of the oxide. Extensive density functional theory (DFT) slab calculations confirm that this is the most stable site, with an adsorption energy of 0.4 eV (39 kJ mol(-1)). Adsorption is accompanied by a large deformation of the hexagonal oxide ring and a significant increase in the C-C bond length. STM image simulations provide qualitative agreement with the experimental images, and the molecular orientation is discussed with the help of simple molecular orbital arguments.


The locus of visual search's interference on visual working memory.
Visual attention and visual working memory (VWM) are interacting systems. Most research has been directed toward how a retained VWM load can influence visual search behavior. However, the relationship between the two is bidirectional. When performing a visual search while maintaining a VWM load, decreases in change detection accuracy are often seen. Woodman and Luck (2010) argued that this interference was due to the onset of the search display leading to disruption. The current work attempts to identify the exact component of visual search that leads to interference with VWM. Potentially interference could be due to an attentional component of the task or a procedural artifact of the dual-task paradigm. Over five experiments, different attentional tasks were completed in the retention period of a difficult change detection task. Memory interference was measured as accuracy decrements in these conditions compared to trials where no attentional task was completed. Over the five experiments, one factor was highlighted as a sufficient cause for interference: the addition of nontarget items in the attentional task. Procedural artifacts were ruled out as potential sources of interference including: response bindings, eye movements, nontarget variance, spatial shifts of attention, perceptual load, and the time it took to complete the attentional task. It is proposed that interference arises from the attentional selective process of choosing the target item out of the nontargets. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell.
Cervical cancer is often associated with eosinophil (EOS) infiltration, but the source and the role of EOS are still largely unknown. Our previous work has established that thymic stromal lymphopoietin (TSLP) can stimulate the growth of cervical cancer cell in an autocrine manner. Here, we report that EOS infiltration of the lesion site increased gradually with the progression of cervical cancer. The increase in TSLP secretion in HeLa and SiHa cells induced by hypoxia led to a high level of chemokine CCL17 production by HeLa and SiHa cells, and recruited more EOS to the cancer lesion. In addition, TSLP derived from HeLa and SiHa cells promoted proliferation, up-regulated the levels of anti-inflammatory cytokines (IL-10, IL-4, IL-5 and IL-13), and decreased the expression of CD80 and CD86 of EOS. Such educated EOS significantly promoted proliferation and restricted the apoptosis of cervical cancer cells, which was associated with the up-regulation of Ki-67, PCNA and Bcl-2, and the down-regulation of Fas and FasL in HeLa and SiHa cells. These results suggest that a high level of TSLP in cancer lesions mediated by hypoxia is an important regulator of the progression of cervical cancer by recruiting and licensing tumor-associated EOS to promote the growth of the cervical cancer cell itself. This provides a scientific basis on which potential therapeutic strategies could be targeted to cervical cancer, especially for patients with massive infiltrations of EOS.


When to return to play after an ankle sprain.
An ankle sprain may not seem like a big deal, but returning to play without proper rehabilitation will increase your chances of injuring your ankle again-maybe even more seriously. Taking the time to fully recover will actually put you back in the game faster. The checklist on the other side of this page will take the guesswork out of knowing when you are ready to return to play safely.


Understanding the critical components of a successful cleanroom and barrier isolator project.
The critical components of clean-room and barrier isolator systems are described. Cleanroom and barrier isolator systems have four basic parts: the physical structure, the internal environment, the interaction technology, and the monitoring system. To create an aseptic environment, pharmacists must understand each of these components and be able to provide vendors with clear specifications. Among the decisions pharmacists must make are what materials should be used in construction, how many filters to use and where these should be placed, how to best reduce the contamination challenge to the area, and the best means of monitoring the room's air cleanliness. Evaluation of each component should be made on the basis of durability, functionality, and cost. Pharmacists must also have a set of criteria to help them choose a vendor. They must know their state's requirements and ensure that whatever system is built for their organization will meet all regulations. Cleanroom and barrier isolator systems must adhere to Federal Standard 209E, which defines standard classes of air cleanliness that are based on specific concentrations and sizes of airborne particles. Having an understanding of the basic components of cleanroom and barrier isolator systems will help pharmacists define their needs and describe them to vendors.


Double Inferior Vena Cava and its Implications During Endovascular and Surgical Interventions: A Word of Caution.
Double inferior vena cava (DIVC) is present in 0.2%-3.0% of the general population. Its presence can be detected by computed tomographic angiography or magnetic resonance imaging. Identifying the presence of DIVC is important to define its relationship with the renal vein, its size when IVC filters are planned, the location of the left renal vein in relationship to the aorta, and for planning of IVC filter placement in the setting of deep vein thrombosis and pulmonary embolism. Finally, this entity should not be mistaken for lymphadenopathy and its course should be well understood before abdominal and pelvic/retroperitoneal surgical interventions.


c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression in Japanese breast cancers: their relationship to the histology and other disease parameters.
We studied c-erbB-2 and c-erbA-1 (ear-1) gene amplification, and c-erbB-2 protein expression in 123 primary Japanese breast cancers. c-erbB-2 amplification was found in 19 of the 123 tumors (15%), and c-erbA-1 was coamplified in 7 of the 19. The presence or absence of c-erbB-2 amplification correlated with the grade of cellular atypism (P = 0.008), or that of mitotic index (P = 0.002), but not with the histologic types. The tumor size (P = 0.04) and the lymph node status (P = 0.06) were associated, but the patients' age, the TNM stage, or the presence or absence of estrogen or progesterone receptors was not associated, with c-erbB-2 amplification. There were no differences in the histologic type, cellular atypism, mitotic index, and other disease parameters between tumors with c-erbB-2 amplification only and those with coamplification of c-erbB-2 and c-erbA-1. Paraffin sections from all 19 tumors with c-erbB-2 amplification, and those from only one of 104 tumors without the amplification were positively stained with polyclonal anti-c-erbB-2 protein antibody. Since the correlation between the amplification and the protein expression was excellent, such immunohistochemical studies may be substituted for the time-consuming DNA studies using Southern blotting.


Safety constraints in an artificial pancreatic beta cell: an implementation of model predictive control with insulin on board.
Type 1 diabetes mellitus (T1DM) is characterized by the destruction of pancreatic beta cells, resulting in the inability to produce sufficient insulin to maintain normoglycemia. As a result, people with T1DM depend on exogenous insulin that is given either by multiple daily injections or by an insulin pump to control their blood glucose. A challenging task is to design the next step in T1DM therapy: a fully automated insulin delivery system consisting of an artificial pancreatic beta cell that shall provide both safe and effective therapy. The core of such a system is a control algorithm that calculates the insulin dose based on automated glucose measurements. A model predictive control (MPC) algorithm was designed to control glycemia by controlling exogenous insulin delivery. The MPC algorithm contained a dynamic safety constraint, insulin on board (IOB), which incorporated the clinical values of correction factor and insulin-to-carbohydrate ratio along with estimated insulin action decay curves as part of the optimal control solution. The results emphasized the ability of the IOB constraint to significantly improve the glucose/insulin control trajectories in the presence of aggressive control actions. The simulation results indicated that 50% of the simulations conducted without the IOB constraint resulted in hypoglycemic events, compared to 10% of the simulations that included the IOB constraint. Achieving both efficacy and safety in an artificial pancreatic beta cell calls for an IOB safety constraint that is able to override aggressive control moves (large insulin doses), thereby minimizing the risk of hypoglycemia.


Analysis of finite element models for head injury investigation: reconstruction of four real-world impacts.
Previous studies have shown that both excessive linear and rotational accelerations are the cause of head injuries. Although the head injury criterion has been beneficial as an indicator of head injury risk, it only considers linear acceleration, so there is a need to consider both types of motion in future safety standards. Advanced models of the head/brain complex have recently been developed to gain a better understanding of head injury biomechanics. While these models have been verified against laboratory experimental data, there is a lack of suitable real-world data available for validation. Hence, using two computer models of the head/brain, the objective of the current study was to reconstruct four real-world crashes with known head injury outcomes in a full-vehicle crash laboratory, simulate head/brain responses using kinematics obtained during these reconstructions, and to compare the results predicted by the models against the actual injuries sustained by the occupant. Cases where the occupant sustained no head injuries (AIS 0) and head injuries of severity AIS 4, AIS 5, and multiple head injuries were selected. Data collected from a 9-accelerometer skull were input into the Wayne State University Head Injury Model (WSUHIM) and the NHTSA Simulated Injury Monitor (SIMon). The results demonstrated that both models were able to predict varying injury severities consistent with the difference in AIS injury levels in the real-world cases. The WSUHIM predicted a slightly higher injury threshold than the SIMon, probably due to the finer mesh and different software used for the simulations, and could also determine regions of the brain which had been injured. With further validation, finite element models can be used to establish an injury criterion for each type of brain injury in the future.


Identification of two Mycobacterium tuberculosis H37Rv ORFs involved in resistance to killing by human macrophages.
The ability of Mycobacterium tuberculosis to survive and replicate in macrophages is crucial for the mycobacterium's ability to infect the host and cause tuberculosis. To identify Mycobacterium tuberculosis genes involved in survival in macrophages, a library of non-pathogenic Mycobacterium smegmatis bacteria, each carrying an individual integrated cosmid containing M. tuberculosis H37Rv genomic DNA, was passed through THP-1 human macrophages three times. Two of the clones recovered from this enrichment process, sur2 and sur3, exhibited significantly increased survival relative to wild-type bacteria. In coinfection experiments, the ratio of sur2 colonies to wild-type colonies was 1:1 at 0 hours but increased to 20:1 at 24 hours post phagocytosis. The ratio of sur3 colonies to wild-type colonies was 1:1 at 0 hours and 5:1 at 24 hours. The M. tuberculosis ORFs responsible for increased survival were shown to be Rv0365c for the sur2 clone and Rv2235 for the sur3 clone. These ORFs encode proteins with as-of-yet unknown functions. We identified two M. tuberculosis ORFs which may be involved in the ability of tubercle bacilli to survive in macrophages.


Intestinal hemorrhage caused by Meckel's diverticulum with ectopic gastric mucosa on polypoid lesion: a case report.
Meckel's diverticulum may sometimes present as an intraluminal polypoid mass causing small bowel obstruction; however, gastrointestinal bleeding due to Meckel's diverticulum with a polypoid lesion is rare. A 14-year-old girl presented with tarry stool and syncope in our hospital. Laboratory examination showed iron-deficiency anemia with a low hemoglobin level of 5.8 g/dl. The bleeding site was detected by neither upper gastrointestinal endoscopy nor colonoscopy. Transanal double-balloon enteroscopy showed a diverticulum with an ulceration at a site approximately 50 cm from the ileocecal valve and a polypoid lesion inside of the diverticulum. Histopathological examination of a polypoid lesion revealed an ectopic gastric mucosa of the fundic type. Furthermore, technetium-99m pertechnetate scintigraphy showed a hot spot in her lower right abdomen. On the basis of these findings, she was diagnosed as having hemorrhagic Meckel's diverticulum. Single-incision laparoscopy-assisted segmental bowel resection of the ileum was performed. The patient recovered well, and she was discharged from the hospital on postoperative day 7. She was doing well 6 months later without evidence of reoccurrence. In this report, we describe a case of Meckel's diverticulum with a polypoid lesion; hemorrhage may have occurred owing to the ulceration of the ileal mucosa with which the polypoid lesion directly came in contact. We consider this case to be of interest to gain insight into the site and mechanism of ulceration associated with Meckel's diverticulum.


[Mechanisms and regulation of the programmed cell death].
The programmed cell death usually is identified with apoptosis, though a scheduled sequence of events can be observed also in autophagy, mitotic catastrophe and, under certain circumstances, in necrosis. Apoptosis begins with activation of the initiator caspases (cysteine proteases) in the signaling complexes: the apoptosome (on the intrinsic or mitochondrial pathway) or the degradosome (on the extrinsic or death receptor pathway). The proteolytic cascade then leads, through activation of downstream caspases and DNases, to digestion of cell components. Mitochondria play a central role in apoptosis by releasing cytochrome c--the essential component of the apoptosome, Smac/Diablo and OmiI/HtrA2--that bind the caspase inhibitors (IAPs), and endonuclease G and AIF--that are responsible for DNA degradation. Those factors get out of mitochondrium through the Bax and Bak protein-containing channels. The process is fast and complete, probably due to mechanoenzyme--driven remodeling of the organellum structure as well as to phospholipid peroxidation and proteolysis in the inner membrane. The release of the mitochondrial factors can be stimulated by protein p53, histone H1.2 and poly(ADP-ribose) that are sent from the nucleus in consequence of a cyto- and genotoxic stress, under the control of cAbl kinase.


Online, cross-disciplinary team science training for health and medical professionals: Evaluation of COALESCE (teamscience.net).
The National Academies of Sciences (NAS) emphasize the need for interdisciplinary team science (TS) training, but few training resources are available. COALESCE, an open-access tool developed with National Institutes of Health support and located at teamscience.net, is considered a gold standard resource but has not previously been evaluated. COALESCE launched four learning modules in 2011. The Science of TS (SciTS) module, an interactive encyclopedia, introduces foundational concepts. Three scenario-based modules simulate TS challenges in behavioral, clinical, and basic biomedical sciences. This study examined user characteristics, usage patterns, and effects of completing the four modules on TS knowledge, attitudes, and skills. Repeated measures ANOVA tested for pre-post changes in performance and compared learning by users with biomedical versus other disciplinary backgrounds. From 2011 through 2017, the site attracted 16,280 new users who engaged in 6461 sessions that lasted more than 1 min. The modal registrant identified as working in a biomedical field (47%), in an academic institution (72%), and expressed greater interest in the practice than the SciTS (67%). Those completing pre- and post-tests (n = 989) showed significant improvement in knowledge, attitudes, and skills after taking all scenario-based modules (p < 0.005); knowledge and attitudes were unchanged after the SciTS encyclopedia. Biomedical and other health professionals improved comparably. Evaluation of the TS training tool at teamscience.net indicates broad dissemination and positive TS-related outcomes. Site upgrades implemented between 2018 and 2020, including adding five new modules, are expected to increase the robustness and accessibility of the COALESCE training resource.


Osteoclast clearance from periodontal tissues during orthodontic tooth movement.
The presence of osteoclasts at locations of alveolar bone remodeling is antecedent to orthodontic tooth movement. Cell recruitment and clearance are the mechanisms by which osteoclast populations are regulated. Research in other tissues has revealed that many cells die after their functional lives are past by a process called apoptosis, or programmed cell death. The purpose of this study was to examine the role of apoptosis in osteoclast clearance at orthodontically treated sites as a function of time and location. Orthodontic appliances were placed on 96 rats of the Sprague-Dawley strain. The rats were assigned to either treatment or sham (control) groups and killed 1, 3, 5, and 7 days after appliance placement. Tissue samples were prepared for histochemical evaluation and quantification of morphologic features. Tartrate-resistant acid phosphatase (TRAP) and ApopTag (TdT-mediated dUTP-biotin nick 3' end labeling) stains were used to identify osteoclasts and committed preosteoclasts and to discriminate between apoptotic and nonapoptotic nuclei. Pyknotic nuclei and apoptotic bodies were also counted as a morphologic assessment of apoptosis. The percentages of TRAP/ApopTag-positive nuclei were measured in 4 different periodontal regions. There was a highly significant difference in the overall percentage of TRAP/ApopTag-positive nuclei between the control and the treatment groups at 3, 5, and 7 days (P <.001). Morphologic criteria were also statistically different at days 5 and 7 (P <.05). These data strongly suggested that osteoclasts recruited for orthodontic tooth movement are, at least in part, cleared by apoptosis.


Radiocaesium activities in wheat in Croatia.
Results of systematic, long-term measurements of 137Cs activities in wheat are summarized. 137Cs fallout activity affected wheat activity the coefficient of correlation being 0.91. A model used by UNSCEAR was used to describe 137Cs transfer from fallout deposition to wheat. The transfer coefficient was calculated to be 6.1 x 10(-3) Bq yr kg-1/(Bq m-2). The dose incurred by wheat consumption was estimated for the Croatian population, the annual collective equivalent dose being approximately 550 man Sv for the 1965-1992 period. After the Chernobyl nuclear accident the 134Cs: 137Cs activity ratio in wheat was approximately 0.5, and did not differ from that for other environmental samples.


Obesity: assessment and management in primary care.
Obesity is a complex, multifactorial condition in which excess body fat may put a person at health risk. National data indicate that the prevalence of obesity in the United States is increasing in children and adults. Reversing these trends requires changes in individual behavior and the elimination of societal barriers to healthy lifestyle choices. Basic treatment of overweight and obese patients requires a comprehensive approach involving diet and nutrition, regular physical activity, and behavioral change, with an emphasis on long-term weight management rather than short-term extreme weight reduction. Physicians and other health professionals have an important role in promoting preventive measures and encouraging positive lifestyle behaviors, as well as identifying and treating obesity-related comorbidities. Health professionals also have a role in counseling patients about safe and effective weight loss and weight maintenance programs. Recent evidence-based guidelines from the National Heart, Lung, and Blood Institute, as well as recommendations from the American Academy of Pediatrics, American Association of Clinical Endocrinologists/American College of Endocrinology, American Obesity Association, U.S. Clinical Preventive Services Task Force, Institute of Medicine, and World Health Organization can be consulted for information and guidance on the identification and management of overweight and obese patients.


The effect of isocaloric, energy-restrictive, KETOgenic diet on metabolism, inflammation, nutrition deficiencies and oxidative stress in women with overweight and obesity (KETO-MINOX): Study protocol.
Obesity is considered one of the biggest health problems of the 21st century, becoming a worldwide epidemic, leading to the development of many diseases and increasing the risk of premature death. The first step in reducing body weight is a calorie-restricted diet. To date, there are many different diet types available, including the ketogenic diet (KD) which is recently gaining a lot of attention. However, all the physiological consequences of KD in the human body are not fully understood. Therefore, this study aims to evaluate the effectiveness of an eight-week, isocaloric, energy-restricted, KD as a weight management solution in women with overweight and obesity compared to a standard, balanced diet with the same calorie content. The primary outcome is to evaluate the effects of a KD on body weight and composition. The secondary outcomes are to evaluate the effect of KD-related weight loss on inflammation, oxidative stress, nutritional status, profiles of metabolites in breath, which informs about the metabolic changes in the body, obesity and diabetes-associated parameters, including a lipid profile, status of adipokines and hormones. Notably, in this trial, the long-term effects and efficiency of the KD will be studied. In summary, the proposed study will fill the gap in knowledge about the effects of KD on inflammation, obesity-associated parameters, nutritional deficiencies, oxidative stress and metabolism in a single study. ClinicalTrail.gov registration number: NCT05652972.


Caregiver's burden in pulmonary arterial hypertension: a clinical review.
Caregiver's burden is a multidimensional phenomenon affecting care-givers physically, emotionally and socially. It is critical to examine the burden of caregivers, because of the complex responsibility they have with their partners. There are relatively few studies that have examined factors linked with psychological burden amongst caregivers of pulmonary arterial hypertension (PAH) patients. Hence, it is pertinent to develop a good understanding of these factors and develop appropriate management strategies, modified to assist PAH caregivers.


A comparative study of recombinant mouse and human apurinic/apyrimidinic endonuclease.
Mammalian apurinic/apyrimidinic endonuclease (APE1) initiates the repair of abasic sites (AP-sites), which are highly toxic, mutagenic, and implicated in carcinogenesis. Also, reducing the activity of APE1 protein in cancer cells and tumors sensitizes mammalian tumor cells to a variety of laboratory and clinical chemotherapeutic agents. In general, mouse models are used in studies of basic mechanisms of carcinogenesis, as well as pre-clinical studies before transitioning into humans. Human APE1 (hAPE1) has previously been cloned, expressed, and extensively characterized. However, the knowledge regarding the characterization of mouse APE1 (mAPE1) is very limited. Here we have expressed and purified full-length hAPE1 and mAPE1 in and from E. coli to near homogeneity. mAPE1 showed comparable fast reaction kinetics to its human counterpart. Steady-state enzyme kinetics showed an apparent K(m) of 91 nM and k(cat) of 4.2 s(-1) of mAPE1 for the THF cleavage reaction. For hAPE1 apparent K(m) and k(cat) were 82 nM and 3.2 s(-1), respectively, under similar reaction conditions. However, k(cat)/K(m) were in similar range for both APE1s. The optimum pH was in the range of 7.5-8 for both APE1s and had an optimal activity at 50-100 mM KCl, and they showed Mg(2+) dependence and abrogation of activity at high salt. Circular dichroism spectroscopy revealed that increasing the Mg(2+) concentration altered the ratio of "turns" to "β-strands" for both proteins, and this change may be associated with the conformational changes required to achieve an active state. Overall, compared to hAPE1, mAPE1 has higher K(m) and k(cat) values. However, overall results from this study suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. Thus, the conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology. This includes the development and validation of effective APE1 inhibitors as chemosensitizers in clinical studies.


A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C.
Dilated cardiomyopathy is characterized by ventricular dilation with systolic dysfunction of cardiac muscle. Recent genetic studies have revealed that mutations in genes for cytoskeleton proteins distributed in the Z-disc and/or intercalated discs of the cardiac muscle are major predictors of cardiomyopathy. However, as mutations in these genes can account for only a part of the patient population, there should be another disease-causing gene(s) for cardiomyopathy. Cypher/ZASP appears to be an ideal candidate for the cardiomyopathy causative gene, because Cypher/ZASP encodes a Z-disc associated protein, and recent studies have demonstrated that Cypher/ZASP knock-out mice develop cardiomyopathy. In this study, we searched for sequence variations in Cypher/ZASP in 96 unrelated Japanese patients with dilated cardiomyopathy. A D626N mutation located within the third LIM domain was identified in a familial case but not found in the unrelated controls. A family study of the patient showed that all affected siblings tested had the same mutation. Clinical information of the affected family members suggested that the mutation was associated with late onset cardiomyopathy. To reveal the biochemical changes due to the mutation, we performed a yeast two-hybrid assay and a pull-down assay. It was demonstrated by both assays that the D626N mutation of Cypher/ZASP increased the affinity of the LIM domain for protein kinase C, suggesting a novel biochemical mechanism of the pathogenesis of dilated cardiomyopathy.


P-Glycoprotein and Androgen Receptor Expression Reveals Independence of Canine Prostate Cancer from Androgen Hormone Stimulation.
Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.


Matrix Metalloproteinases in Helicobacter pylori-Associated Gastritis and Gastric Cancer.
Gastric cancer is one of the leading causes of the cancer-related mortality worldwide. The etiology of this disease is complex and involves genetic predisposition and environmental factors, including Helicobacter pylori. Infection of the stomach with H. pylori leads to gastritis and gastric atrophy, which can progress stepwise to gastric cancer. Matrix metalloproteinases (MMPs) actively participate in the pathology development. The further progression of gastric cancer seems to be less dependent on bacteria but of intra-tumor cell dynamics. Bioinformatics data confirmed an important role of the extracellular matrix constituents and specific MMPs in stomach carcinoma invasion and metastasis, and revised their potential as predictors of the disease outcome. In this review, we describe, in detail, the impact of MMPs in H. pylori-associated gastritis and gastric cancer.


Customized Stromal Lenticule Implantation for Keratoconus.
To investigate the potential benefit of keratoconus surgery using customized corneal stromal donor lenticules obtained from myopic small incision lenticule extraction (SMILE) surgery by femtosecond laser. In this prospective, consecutive, non-comparative series of cases, 22 lenticules were obtained from 22 myopic patients who had SMILE with a lenticule central thickness of greater than 110 µm. The lenticules were implanted in 22 eyes with advanced keratoconus. The lenticules were customized for the purpose of the implantation with either a simple necklace or necklace-with-ring shape (compound form) depending on the corneal thickness and corneal topography configuration of the implanted keratoconic eyes. The lenticules were implanted into a 9.5-mm corneal lamellar pocket created by the femtosecond laser. Changes in densitometry, thickness, confocal microscopy, corrected distance visual acuity (CDVA), and endothelial cell density were investigated. Intrastromal lenticule implantation was successfully performed in all cases without any complication. Corneal thickness showed a mean enhancement of 100.4 µm at the thinnest point. On biomicroscopy, all corneas were clear at 1 year postoperatively and there was a significant improvement in corneal densitometry during the entire follow-up period. Confocal biomicroscopy showed collagen reactivation without any inflammatory features caused by the implanted fresh lenticules. CDVA improved from 0.70 to 0.49 logMAR (P = .001) and keratometry decreased from 54.68 ± 2.77 to 51.95 ± 2.21 diopters (P = .006). Customized SMILE lenticule implantation by femtosecond laser proved to be feasible, resulting in an improvement in vision, topography, and refraction in the implanted eyes. [J Refract Surg. 2020;36(12):786-794.].


Coccygectomy: an effective treatment option for chronic coccydynia: retrospective results in 41 consecutive patients.
Between 1993 and 2008, 41 patients underwent total coccygectomy for coccydynia which had failed to respond to six months of conservative management. Of these, 40 patients were available for clinical review and 39 completed a questionnaire giving their evaluation of the effect of the operation. Excellent or good results were obtained in 33 of the 41 patients, comprising 18 of the 21 patients with coccydynia due to trauma, five of the eight patients with symptoms following childbirth and ten of 12 idiopathic onset. In eight patients the results were moderate or poor, although none described worse pain after the operation. The only post-operative complication was superficial wound infection which occurred in five patients and which settled fully with antibiotic treatment. One patient required re-operation for excision of the distal cornua of the sacrum. Total coccygectomy offered satisfactory relief of pain in the majority of patients regardless of the cause of their symptoms.


The influence of specific antibodies and complement on the motility and the viability of Entamoeba histolytica trophozoites.
The distribution of peroxidase-labeled normal or specific rabbit immunoglobulin (Ig) in Entamoeba histolytica trophozoites was studied by transmission electron microscopy. Small amounts of normal Ig became attached to the cell surface but did not redistribute. Internalized specific Ig was firmly bound to the inner membranes of phagocytosis vacuoles, while aggregates of normal Ig were dispersed over the vacuolar lumen. The distribution of fluorescein isothiocyanate-labeled Ig in living amebae was correlated with the cell motility at different times. Immobilization coincided with the cellular metabolic processing of internalized material. Remobilization occurred when the Ig was degraded and antibodies again bound to the reappearing surface antigens. E. histolytica activated complement by the classical pathway. Fresh guinea pig serum alone did not produce lysis which, however, did occur when it was added together with normal rabbit Ig. Normal rabbit Ig may constitute a complement-fixing substrate and activate complement by the classical pathway. Immobilization of the amebae by cytochalasin B (10 micrograms/ml) increased the susceptibility to cytolytic effects of specific antibodies or complement, or both. Pharmacological inhibition of cell motility might augment the immunological defence of the host against amebic infection.


Extrasynaptic Neurotransmission Mediated by Exocytosis and Diffusive Release of Transmitter Substances.
This review article deals with the mechanisms of extrasynaptic release of transmitter substances, namely the release from the soma, axon and dendrites in the absence of postsynaptic counterparts. Extrasynaptic release occurs by exocytosis or diffusion. Spillover from the synaptic cleft also contributes to extrasynaptic neurotransmission. Here, we first describe two well-known examples of exocytosis from the neuronal soma, which may release copious amounts of transmitter for up to hundreds of seconds after electrical stimulation. The mechanisms for somatic exocytosis of the low molecular weight transmitter serotonin, and the peptides oxytocin and vasopressin have been studied in detail. Serotonin release from leech neurons and oxytocin and vasopressin from rodent neurons have a common multi-step mechanism, which is completely different from that for exocytosis from presynaptic endings. Most transmitters and peptides released extrasynaptically seem to follow this same mechanism. Extrasynaptic exocytosis may occur onto glial cells, which act as intermediaries for long-term and long-distance transmission. The second part of this review article focuses on the release upon synthesis of the representative diffusible molecules nitric oxide (NO) and endocannabinoids. Diffusible molecules are synthesized "on demand" from postsynaptic terminals in response to electrical activity and intracellular calcium elevations. Their effects include the retrograde modulation of presynaptic electrical activity and transmitter release. Extrasynaptic neurotransmission is well exemplified in the retina. Light-evoked extrasynaptic communication sets the gain for visual responses and integrates the activity of neurons, glia and blood vessels. Understanding how extrasynaptic communication changes the function of hard-wired circuits has become fundamental to understand the function of the nervous system.


Distance canonical correlation analysis with application to an imaging-genetic study.
Distance correlation is a measure that can detect both linear and nonlinear associations. However, applying distance correlation to imaging genetic studies often needs multiple testing correction due to the large number of multiple inferences. As a result, the sensitivity of its detection may be low. We propose a new model, distance canonical correlation analysis (DCCA), which overcomes this problem by searching a combination of features with the highest distance correlation. This is achieved by constructing a distance kernel function followed by solving a subsequent optimization problem. The ability to detect both linear and nonlinear associations makes DCCA suitable for analyzing complex multimodal and imaging-genetic associations. When applied to a brain imaging-genetic study from the Philadelphia Neurodevelopmental Cohort (PNC), DCCA detected several mental disorder-related gene pathways and brain networks. Experiments on brain connectivity found that the default mode network had strong nonlinear connections with other brain networks. When applied to the study of age effects, DCCA revealed that the connections of brain networks were relatively weak in younger groups but became stronger at older age stages. It indicates that adolescence is a vital stage for brain development. DCCA thus reveals a number of interesting findings and demonstrates a powerful new approach for analyzing multimodal brain imaging data.


Fertility rates in men with normal semen characteristics: spermatozoal testing by induction of the acrosome reaction and Wright-Giemsa staining for subtle abnormal forms.
Little is known about the fertility potential of semen from men who fulfill the accepted criteria of normal semen quality. We examined retrospectively the fertility rates of semen donors with normal semen quality. Donor performance was evaluated in women who had no known infertility factors or had only ovulatory dysfunction corrected by clomiphene. Cycles of therapeutic donor insemination were monitored for ovulation, and pregnancy outcome was followed up. Pregnancy resulted from therapeutic donor insemination with 21 donors and did not result in pregnancy with five (the range of the percentage of cycles in which pregnancy occurred was zero to 31). The comparison of donor semen analysis characteristics with pregnancy rates indicated that the total number of motile spermatozoa per ejaculate correlated with pregnancy rate (P = .04). Cox proportional hazard regression analysis showed that when the value for percentage of abnormal forms was combined with the total number of motile spermatozoa, a significant negative association was found between abnormal forms and conception (P = .04). Experiments comparing semen from high-fertility donors (top quartile of pregnancy rate) and low-fertility donors (lowest quartile) demonstrated a greater proportion of spermatozoa with inducible acrosome reactions in the high-fertility group (P less than .05). A Wright-Giemsa stain used to detect subtle abnormal forms in spermatozoa did not discriminate between the groups. These data suggest that differences in fertility potential exist among donors, even though all may exceed the accepted criteria for normal semen quality. Differences in the ability of spermatozoa to capacitate or undergo the acrosome reaction may be a mechanism for diminished fertility in donors with normal semen characteristics.


Morphological and functional changes in the rat heart after X irradiation: strain differences.
The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change. In spite of the marked strain differences observed in cardiac output and rubidium extraction, blood perfusion per gram of ventricular muscle was apparently not modified in both strains of rat after irradiation. These findings indicated that the correlation between morphological effects after irradiation and the functional expression of damage is highly complex.


Characteristics of interruptions during medication administration: An integrative review of direct observational studies.
To synthesise and summarise data gathered by direct observation of the characteristics of interruptions in the context of nursing medication administration (MA) in hospital settings. Interruptions are prevalent during the MA process performed by nurses in hospital settings and have been found to be associated with an increase in frequency and severity of nursing MA errors. In addition, interruptions decrease task efficiency, leading to longer MA completion times. Integrative review. The electronic databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, PsycARTICLES and Google Scholar were searched using the terms "interruptions" AND "medication administration" AND "direct observation." Nine articles met the inclusion criteria. Interruptions are likely to occur at least once during nursing MA processes in hospital settings. This finding applies to medication administered to one patient, termed a medication pass, and medication administered to multiple patients, termed a medication round. Interruptions are most commonly caused by another nurse or staff member or are self-initiated, and last approximately 1 min in length. A raised awareness among staff of the most common sources of interruptions may encourage changes that lead to a decrease in the occurrence of interruptions. In addition, nurse leaders can apply an understanding of the common characteristics of interruptions to guide research, policies and educational methods aimed at interruption management strategies. The findings from this review can be used to guide the identification and development of targeted interventions and strategies that would have the most substantial impact to reduce and manage interruptions during MA. Interruption management strategies have the potential to lead to a decrease in medication errors and an increase in task efficiency.


Comparative genomic analysis of the human and nematode Caenorhabditis elegans uncovers potential reproductive genes and disease associations in humans.
Reproduction is an important biological process. However, studies of human reproduction at the molecular level are limited due to the difficulty of performing in vivo studies. Hence, a mechanistic understanding of human reproduction remains still poor. Thus, it is important to use an alternative model organism for mechanistic studies of human reproduction. In this study, we used the nematode Caenorhabditis elegans as a model for studying human reproduction and identified 61 human and 535 worm reproductive genes through a combination of comparative genomic and Gene Ontology (GO) analyses. Interestingly, in terms of sex specificity, the number of male-specific genes was greater than the number of female-specific genes. Gene enrichment analysis identified biologically significant processes such as protein localization to cajal bodies/telomeres/nuclear bodies/chromosomes, helicase activity, pyrimidine biosynthesis, and determination of adult lifespan. Regarding the analysis of human reproductive diseases among the identified genes, 10 and 12 genes were identified in the human- and C. elegans-based analyses, respectively. In addition, RNA interference knockdown of a newly identified F52H2.6/DHCR24 gene increased brood size and ovulation/egg-laying rate in C. elegans. Therefore, gene identification, disease associations, and a proof-of-concept experiment using C. elegans will not only provide insights into mechanistic study of human reproduction, but also demonstrate the utility in studying human reproduction.


Radiation efficiency of damped plates.
The radiation efficiency of damped plates is discussed in this letter. Below the critical frequency of a plate, numerical results show that the radiation efficiency is much influenced by damping. Some modifications of the classical formulas given by Cremer for an infinite plate and Leppington for a finite rectangular plate are proposed to include the influence of the damping on the radiation efficiency.


A novel radiation-shielding undergarment using tungsten functional paper for patients with permanent prostate brachytherapy.
Tungsten functional paper (TFP) is a paper-based radiation-shielding material, which is lead-free and easy to cut. We developed a radiation protection undergarment using TFP for prostate cancer patients treated with permanent 125I seed implantation (PSI). The aim of this study was to evaluate the shielding ability of the undergarment with respect to household contacts and members of the public. Between October 2016 and April 2017, a total of 10 prostate cancer patients treated with PSI were enrolled in this prospective study. The external radiation exposure from each patient 1 day after PSI was measured with and without the undergarment. Measurements were performed using a survey meter at 100 cm from the surface of the patient's body. The exposure rates were measured from five directions: anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior. The measured radiation exposure rates without the undergarment, expressed as mean ± standard deviation, from the anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior directions were 1.28 ± 0.43 μSv/h, 0.70 ± 0.34 μSv/h, 0.21 ± 0.062 μSv/h, 0.65 ± 0.33 μSv/h and 1.24 ± 0.41 μSv/h, respectively. The undergarment was found to have (mean ± standard deviation) shielding abilities of 88.7 ± 5.8%, 44.0 ± 42.1%, 50.6 ± 15.9%, 72.9 ± 27.0% and 90.4 ± 10.7% from the anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior directions, respectively. In conclusion, this shielding undergarment is a useful device that has the potential to reduce radiation exposure for the general public and the patient's family.


The impact of social support and stress on academic burnout among medical students in online learning: The mediating role of resilience.
As the COVID-19 pandemic continues, online learning and long-term isolation from social and clinical settings has exacerbated mental health problems and symptoms of academic burnout among medical students. However, few studies have discussed symptoms of academic burnout as a result of reduced social support, and increased stress among medical students during the process of online learning. To fill this gap, this study investigated the influencing factors and mechanism of academic burnout in medical students' online learning process. Both the positive inhibition effect of positive factors such as social support, and the negative aggravation effect of negative factors such as stress were explored, while the mediating and protecting role of resilience is also discussed. We collected survey data from a total of 817 medical students from a medical school in China who participated in online learning during the fall 2021 semester. An online questionnaire was sent to the students in January, 2022. Items adapted from the DASS Scale developed by Lovibond and Lovibond were used to measure medical students' stress levels. The perceived social support of medical students was assessed by the Gregory MSPSS. Resilience was evaluated by the 10-Item Connor-Davidson Resilience Scale (CD-RISC). Items from the Maslach Burnout Inventory-Student Survey (MBI-SS) were used to calculate students' academic burnout. Descriptive analysis, correlation analysis, hierarchical linear regression analysis and structural equation modeling were used to analyze the collected data. The results identified that in the context of online learning there was a positive correlation between medical students' stress and academic burnout, and their resilience played a partial mediating role. However, social support did not directly affect academic burnout, but inhibited the prevalence of academic burnout through resilience. In addition, stress was negatively related to resilience, while social support was positively related to resilience. Resilience was found to be negatively related to medical students' academic burnout in online learning. The results of this study can provide a reference for the future development of appropriate educational strategies and coping measures to ameliorate the academic burnout of medical students.


Orbital Rosai-Dorfman disease with subperiosteal bone involvement mimicking eosinophilic granuloma.
The presentation of RDD as an anterior subperiosteal orbital mass with bone involvement has, to the authors' knowledge, not been previously reported. We describe a case of Rosai-Dorfman disease (RDD) presenting as an anterior superolateral subperiosteal orbital mass with erosion of overlying bone mimicking eosinophilic granuloma. It was debulked using endoscopic-guided curettage and the patient was given both local and systemic corticosteroids. Careful histological analysis revealed the diagnosis of RDD and the patient remains asymptomatic and recurrence free at 16 months follow-up. Involvement of the pituitary gland, a recognized yet unusual finding in this condition was also noted. RDD should be considered in the differential diagnosis of a soft tissue mass of the superolateral orbit.


Significance of genome-wide association studies in molecular anthropology.
The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.


Experience with immediate and delayed mandibular reconstruction.
The functional disability and cosmetic deformity after jaw and neck dissection can be very severe due to soft tissue and mandibular loss. Reconstruction of the mandible alone without soft tissue coverage can be complicated with prosthetic exposure, infection and, finally, rejection. We attempted to reconstruct the mandible at the time of tumor resection in a group of patients, using titanium mesh with marrow, rib, scapular spine, and clavicle. We used myocutaneous flaps in order to obtain intraoral coverage of the mandibular grafts. In a second group of patients, delayed reconstruction of the jaw was performed 6 months to 2 years after tumor resection. Titanium mesh prostheses were used for reconstruction of the mandible in conjunction with myocutaneous flaps for soft tissue augmentation. Osteomyocutaneous flaps were also used. The results and complications in 54 patients are presented.


[Sport accidents in Haute-Savoie: Results from the EPAC 2004-2013 survey].
Regular physical activity and sport have many health benefits but they can also result in injury, which can be quite severe. Data recorded from 2004 to 2013 in an Haute-Savoie emergency department for the home and leisure injuries survey (EPAC) were analyzed in order to describe the characteristics of sport related injuries in an area particularly attractive for winter and air sports. A total of 43,505 sport related injuries were recorded: team sports (30%), winter sports (25%) and cycling (23%) accounted for the most accidents. Men were more at risk than women (sex ratio = 2.3), and the age group 10-14 years were mostly injured (21% of all injuries). Overall, falls were the most frequent mechanism of injury. Climbing, winter sports and air sports led to the most hospitalizations. The risk of hospitalization following a sport related injury was higher in men, when age increased and when the place of residence was located outside Haute-Savoie. Complementary surveys are necessary to estimate the impact on injury incidence of the use of protective equipment (helmet, gloves), the level of sporting proficiency, level of supervision, or whether or not the victim was a member of a sport club.


[A case of acute renal failure and liver dysfunction induced by carbamazepine(CBZ)].
A 56-year-old female with symptomatic epilepsy was admitted to our hospital because of acute renal failure(ARF) and liver dysfunction(LD) after receiving CBZ for two months. She had suffered a drug eruption caused by phenobarbital and valproate six months previously. Renal and liver biopsies presented acute interstitial nephritis and active chronic hepatitis, respectively. Drug-induced lymphocyte stimulating test showed CBZ positivity. Steroid therapy resulted in recovery from ARF and LD. CBZ sometimes causes ARF or LD, but rarely induces both simultaneously, especially in adults. Pathological evidence of two lesions other than from autopsy seems to be the first step in this case. Cross reaction with other antiepileptic agents was also of interest, suggesting that one member of the cytochrome P450 subfamily, CYP3A, participated in the mechanism.


Erythropoietin secretion in patients with chronic renal failure after pure oxygen breathing.
The present study aimed to assess the relationship between erythropoietin (EPO) secretion and hyperoxemia in uremic patients. In 19 patients with chronic renal failure (10 were hemodialyzed and 9 were not dialyzed) and in 13 healthy subjects plasma erythropoietin levels were assessed during 6 h of air breathing and a second time during 2 h of pure oxygen breathing and during 4 h after discontinued oxygen breathing. Under basal conditions, uremic patients showed higher plasma erythropoietin levels (39.85 +/- 5.86 mU/ml in hemodialyzed and 29.05 +/- 4.94 mU/ml in nondialyzed patients) as compared with healthy controls (21.04 +/- 1.77 mU/ml). Pure oxygen breathing was followed by a significant decline of plasma EPO levels both in patients with chronic renal failure and in the control group. However, this decline was significantly less marked and of longer duration in chronic renal failure patients than in healthy controls.


[Return to work after cardiac valvular surgery. Retrospective study of a series of 105 patients].
This was a retrospective study realised by a mailed questionnaire of the medical and socio-professional conditions of return to work in patients with valvular heart disease aged 20 to 59 and operated in the cardiac surgery department of Rennes University Hospital in 1998. The results concern 105 patients of whom 78 were working before surgery and 27 were unemployed, and 53 were professionally active after surgery. The average age was 48 +/- 9 years and the male/female ratio was 2.38. After surgery, 78.4% of patients were NYHA Stages I or II, compared with 38.1% before surgery. Three main surgical procedures were carried out, sometimes in association: aortic valve replacement (71.4%), mitral valve replacement (21%) and mitral valvuloplasty (11.4%). Valve replacement was with a mechanical prosthesis in 83% of cases, a bioprosthesis in 11% of cases and a homograft in 6% of cases. Return to work (67.9%) after an average of 5.3 +/- 3.9 months was correlated with the following factors: age: 50 years old patients or more, were less likely to return to work (p < 0.02); postoperative NYHA stage: patients in stages III and IV were less likely to return to work (p < 0.03); the time off work before surgery: the longer the time (threshold > 6 months) the less likely the patients are to return to work (p < 0.03). Return to work was preferred to non-return (p < 0.03). This study shows the difficulties of professional rehabilitation of patients despite a satisfactory general condition. This is partially explained by the difficult economic context which favorises invalidity but also by the lack of information concerning the role of works doctors in the return to work. The realisation of a liaison file with permission of the person concerned between the general practitioner, the cardiologist and a medico-social security doctor and works doctor should remedy the difficulties in communication and sustain a policy of return to work.


Hepatitis C virus-polymerase chain reaction minipool testing: 3 years in the largest Swiss blood transfusion service.
Hepatitis C virus-polymerase chain reaction (HCV-PCR) minipool testing can improve the safety of labile blood products owing to a reduction in the diagnostic preseroconversion window period. In Switzerland, HCV-PCR minipool testing for the release of labile blood components became mandatory in September 1999. In the largest Swiss blood transfusion centre, HCV-PCR minipool testing began in January 1999. This report analyses the performance of the test during a 3-year period: 1 January 1999 to 31 December 2001. EDTA-blood was collected in either standard tubes or plasma preparation (PPT) tubes from 10 blood transfusion services in Switzerland and then sent to the Blood Transfusion Service SRC Berne. Up to 48 donor samples were pooled overnight using Tecan Genesis RSP 200/8 pipettors. Viral RNA was extracted by using the Qiagen QIAamp 96 viral RNA BioRobot kit on a BioRobot 9604. For PCR amplification and detection of HCV or internal control (IC) sequences, the Roche Cobas Amplicor v2.0 test kit was used. Data management, pool resolution and identification of positive samples were performed using the PMS Software from Tecan. In the 3-year period from 1 January 1999 to 31 December 2001, 839056 blood donor samples were tested in minipools of up to 48 samples. Thirty-five HCV-PCR-positive donations were identified. Thirty-four samples had antibodies against HCV and were therefore also detected by screening for antibody to HCV (anti-HCV). In October 2001, one seronegative (but PCR-positive) donor was detected. HCV-PCR minipool testing was successfully introduced in the largest Swiss blood transfusion service. It was shown that the release of HCV-PCR minipool results can be accomplished concurrently with the results of serological analysis. The challenge with a seronegative, but PCR-positive, donor demonstrates that the minipool testing strategy adds additional safety to blood products.


Non-Mendelian development defects: animal models and implications for research into human disease.
The major groups of malformations in man are polygenic in origin but this review deals only with defects due to non-Mendelian factors. Animal models that help in identifying the causes and in understanding the numerous and often subtle mechanisms of human malformations are of particular value. Many chemicals, physical agents, and nutritional deficiencies affect experimental species but few are teratogenic for domestic animals and even fewer for man. The known fetopathic viruses of animals and man cross the placenta to cause chronic, nonlethal fetal damage without harm to the mother. Ionizing radiations are teratogenic for all species and hyperthermia for many, but the role of the latter in human development is uncertain. The identification of more animal species with spontaneous or induced defects comparable to those found in man and of additional causative teratogens will increase the resources available for research into the causes and mechanisms of abnormal development in man. No animal species is ideal in teratological research but each has its virtues. This report comments on the present status of research in teratology and the trends that might profitably be followed in the future.


Epidemiologic insights into pediatric kidney stone disease.
The epidemiology of pediatric kidney stone has not yet been as rigorously defined as that of adult kidney stone disease. Herein, we review our recent epidemiologic works characterizing pediatric stone disease using the Kids' Inpatient Database (KID). Specifically we investigated the age and gender distribution of pediatric kidney stone disease, changes in disease prevalence over time, and medical comorbidities associated with this disorder. We identified patients by International Classification of Disease 9th Edition (ICD-9) codes for renal and ureteral calculi as the primary diagnosis. Medical comorbidities were identified using specific comorbidity software. Statistical comparisons between children with and without stone disease were performed. In the first decade of life, stone disease was more prevalent among males than females; however, in the second decade of life females were more commonly affected. Of note, there was a significant increase in treated stone disease across both genders between 1997 and 2003. We also found that the risk of kidney stone diagnosis in children younger than 6 years of age was significantly associated with hypertension and diabetes mellitus. The gender distribution among pediatric stone formers varies significantly by age, although overall females have a greater prevalence than males. There is also a strong association of stone disease and both diabetes and hypertension, although this was only observed in children less than 6 years of age. Taken all together, these findings suggest that urolithiasis in the young child is a complex systemic disease process.


Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor.
Activation of the Galphas-coupled EP2 receptor for prostaglandin E2 (PGE(2)) promotes cell survival in several models of tissue damage. To advance understanding of EP2 functions, we designed experiments to develop allosteric potentiators of this key prostaglandin receptor. Screens of 292,000 compounds identified 93 that at 20 microM (i) potentiated the cAMP response to a low concentration of PGE(2) by > 50%; (ii) had no effect on EP4 or beta2 adrenergic receptors, the cAMP assay itself, or the parent cell line; and (iii) increased the potency of PGE(2) on EP2 receptors at least 3-fold. In aqueous solution, the active compounds are largely present as nanoparticles that appear to serve as active reservoirs for bioactive monomer. From 94 compounds synthesized or purchased, based on the modification of one hit compound, the most active increased the potency of PGE(2) on EP2 receptors 4- to 5-fold at 10 to 20 microM and showed substantial neuroprotection in an excitotoxicity model. These small molecules represent previously undescribed allosteric modulators of a PGE(2) receptor. Our results strongly reinforce the notion that activation of EP2 receptors by endogenous PGE(2) released in a cell-injury setting is neuroprotective.


Domain V of m-calpain shows the potential to form an oblique-orientated alpha-helix, which may modulate the enzyme's activity via interactions with anionic lipid.
The activity of m-calpain, a heterodimeric, Ca2+-dependent cysteine protease appears to be modulated by membrane interactions involving oblique-orientated alpha-helix formation by a segment, GTAMRILGGVI, in the protein's smaller subunit. Here, graphical and hydrophobic moment-based analyses predicted that this segment may form an alpha-helix with strong structural resemblance to the influenza virus peptide, HA2, a known oblique-orientated alpha-helix former. Fourier transform infrared spectroscopy showed that a peptide homologue of the GTAMRILGGVI segment, VP1, adopted low levels of alpha-helical structure ( approximately 20%) in the presence of zwitterionic lipid and induced a minor decrease (3 degrees C) in the gel to liquid-crystalline phase transition temperature, TC, of the hydrocarbon chains of zwitterionic membranes, suggesting interaction with the lipid headgroup region. In contrast, VP1 adopted high levels of alpha-helical structure (65%) in the presence of anionic lipid, induced a large increase (10 degrees C) in the TC of anionic membranes, and showed high levels of anionic lipid monolayer penetration (DeltaSP = 5.5 mN.m-1), suggesting deep levels of membrane penetration. VP1 showed strong haemolytic ability (LD50 = 1.45 mm), but in the presence of ionic agents, this ability, and that of VP1 to penetrate anionic lipid monolayers, was greatly reduced. In combination, our results suggest that m-calpain domain V may penetrate membranes via the adoption of an oblique-orientated alpha-helix and electrostatic interactions. We speculate that these interactions may involve snorkelling by an arginine residue located in the polar face of this alpha-helix.


Connecting narrative with mental health learning through discussion and analysis of selected contemporary films.
In a recently completed qualitative study of nursing leaders' views of requirements for practice, seven aspects of recovery practice were revealed as central for graduates to learn. It is challenging to provide an in-depth understanding of recovery in a nursing curriculum because there are so many competing content areas and, as a result, time is constrained. However, because it is so vital to understand, educators would benefit from developing and sharing teaching strategies that explore recovery deeply, memorably, and engagingly, in order to encourage theory to be put into practice. Recent research into narrative pedagogy suggests that better use of stories, especially those that have strong emotional pull, such as well-made films and memoirs, may offer solutions to creative educators. Stories can have transformative potential, because once heard and heeded, the person can never go back to exactly how they were before. Recovery learned in this way becomes a threshold concept for the mental health curriculum. This paper outlines an engaging and time-efficient teaching strategy to develop these skills, drawing on the concept of narrative pedagogy.


Claudication symptom experience in men and women: Is there a difference?
Previous research has shown that differences exist between men and women in clinicians' perception of some cardiovascular symptoms, such as angina associated with coronary heart disease. However, a gap exists in literature about the potential gender differences in the experience of claudication symptoms related to peripheral arterial disease (PAD). The specific aim of this study was to determine whether differences exist between men and women with PAD in their experience of claudication. A qualitative analysis of a parent study in which men and women with PAD described their claudication symptoms was used to address the objective. In the parent study, open-ended, tape-recorded interviews were conducted with 38 patients (24 men, 14 women) ages 44 to 83 years (mean 65) from 2 United States medical centers during 1996 to 1997 to report patient experience of PAD. In the present study, a content-analysis approach was used to examine these interviews and explore whether different patterns were present in the way men and women describe their claudication symptoms. Four major themes were identified in how patients described their claudication symptoms: (1) symptom descriptions; (2) pathophysiology descriptions; (3) response descriptions; and (4) understanding of disease process. Overall, no striking gender differences in the claudication symptom experience of this subject group were evident. However, some subtle gender differences were identified. Regardless of gender, it is important for clinicians to remember that many different types of claudication symptom descriptions exist. The subtle gender differences in claudication descriptions reported during the interviews could be investigated through further interview sessions with questions developed specifically to elicit information about the claudication experience and possible gender differences in these descriptions. Assessment and care management should expand to include symptom experience beyond classic claudication.