The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells.
We have generated several stable cell lines expressing GFP-labeled centrin. This fusion protein becomes concentrated in the lumen of both centrioles, making them clearly visible in the living cell. Time-lapse fluorescence microscopy reveals that the centriole pair inherited after mitosis splits during or just after telophase. At this time the mother centriole remains near the cell center while the daughter migrates extensively throughout the cytoplasm. This differential behavior is not related to the presence of a nucleus because it is also observed in enucleated cells. The characteristic motions of the daughter centriole persist in the absence of microtubules (Mts). or actin, but are arrested when both Mts and actin filaments are disrupted. As the centrioles replicate at the G1/S transition the movements exhibited by the original daughter become progressively attenuated, and by the onset of mitosis its behavior is indistinguishable from that of the mother centriole. While both centrioles possess associated gamma-tubulin, and nucleate similar number of Mts in Mt repolymerization experiments. during G1 and S only the mother centriole is located at the focus of the Mt array. A model, based on differences in Mt anchoring and release by the mother and daughter centrioles, is proposed to explain these results.


Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid carcinoma.
DNA BER pathway is related with carcinogenesis. We hypothesized that functional polymorphisms of three BER genes, XRCC1, apurinic/apyrimidinic endonuclease (APE1), and ADPRT, confer risks for DTC and its progression. Five common nonsynonymous single nucleotide polymorphisms (Arg194Trp, Arg280His, and Arg399Gln for XRCC1; Asp148Glu for APE1; and Val762Ala for ADPRT) were genotyped in Chinese DTC cases and controls. The XRCC1-194Trp/Trp genotype showed a significantly increased risk for DTC (odds ratio, 1.85; 95% confidence interval, 1.11-3.07; P = 0.018). Subset analysis based on regional LN metastasis showed that the genetic effect came primarily from the subjects with LN metastasis (odds ratio, 4.54; 95% confidence interval, 2.11-9.79; P = 0.0001), but no significant association for subjects without LN metastasis. The other four single nucleotide polymorphisms did not show significant results. Haplotype analysis of XRCC1 polymorphisms yielded a significant result (P = 0.004), especially in the subjects with LN metastasis (P = 0.0002). Moreover, we found that XRCC1-194Trp and ADPRT-762Ala variants collectively contributed to an increased risk of the disease and LN metastasis, with the combined variant homozygotes exhibiting the highest 3.18-fold risk for DTC (P = 0.046) and 9.25-fold risk for DTC with LN metastasis (P = 0.004). The XRCC1 polymorphisms, especially the 194Trp allele, may have an effect on DTC development and progression. This variant can interact with ADPRT-762Ala variant to further substantially increase susceptibility to the disease and regional LN metastasis. Identifying these risk genetic markers could provide more insight into the DTC pathogenesis and may also provide information to develop better prevention and therapeutic strategies.


Minimally invasive transforaminal lumbar interbody fusion for the treatment of degenerative lumbar diseases.
Prospective cohort study. To determine whether minimally invasive transforaminal lumbar interbody fusion (TLIF) using the tubular retractor system reduces the approach-related morbidity inherent in conventional open surgery. Posterior lumbar fusion using the tubular retractor system has been reported and described well. Supporters have claimed that minimally invasive techniques reduce soft-tissue trauma, blood loss, postoperative pain, transfusion needs, and the length of hospital stay, as compared with reports describing the traditional open procedure. However, there are few studies of minimally invasive TLIF, especially studies that directly compared minimally invasive and open approaches in a single center. Between May 2005 and December 2006, a total of 62 patients underwent 1-level TLIF by 1 surgeon in 1 hospital. Of 62 patients, 32 underwent minimally invasive TLIF using the tubular retractor system, and the other 30 underwent the traditional open procedure. The operative duration, blood loss, complications, and recovery time were recorded. The clinical outcomes were evaluated by the Oswestry Disability Index and the Visual Analog Scale. The soft-tissue injury was assessed by measuring serum creatine kinase. Radiographic images were obtained before surgery and during follow-up. The minimally invasive group was found to have reduced blood loss, fewer transfusions, less postoperative back pain, lower serum creatine kinase on the third postoperative day, a shorter time to ambulation, and a briefer hospital stay. The Oswestry Disability Index and Visual Analog Scale scores were significantly lower in the minimally invasive group during follow-up. However, the open group had a shorter operative duration. The complications in the 2 groups were similar, but 2 cases of screw malposition occurred in the minimally invasive group. Minimally invasive TLIF as a management of 1-level degenerative lumbar diseases is superior to the traditional open procedure in terms of postoperative back pain, total blood loss, need for transfusion, time to ambulation, length of hospital stay, soft-tissue injury, and functional recovery. However, this procedure takes longer operative duration and requires close attention to the risk of technical complications. Longer-term studies involving a larger sample are needed to validate the long-term efficacy of minimally TLIF.


Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents.
A novel technique for the selective detection of ultrasound contrast agents, called pulse inversion Doppler, has been developed. In this technique, a conventional Doppler or color Doppler pulse sequence is modified by inverting every second transmit pulse. Either conventional or harmonic Doppler processing is then performed on the received echoes. In the resulting Doppler spectra, Doppler shifts from linear and nonlinear scattering are separated into two distinct regions that can be analyzed separately or combined to estimate the ratio of nonlinear to linear scattering from a region of tissue. The maximum Doppler shift that can be detected is 1/2 the normal Nyquist limit. This has the advantage over conventional harmonic Doppler that it can function over the entire bandwidth of the echo signal, thus achieving superior spatial resolution in the Doppler image. In vitro measurements comparing flowing agent and cellulose particles suggest that pulse inversion Doppler can provide 3 to 10 dB more agent to tissue contrast than harmonic imaging with similar pulses. Similar measurements suggest that broadband pulse inversion Doppler can provide up to 16 dB more contrast than broadband conventional Doppler. Nonlinear propagation effects limit the maximum contrast obtainable with both harmonic and pulse inversion Doppler techniques.


Challenges to nurses' efforts of retrieving, documenting, and communicating patient care information.
To examine information flow, a vital component of a patient's care and outcomes, in a sample of multiple hospital nursing units to uncover potential sources of error and opportunities for systematic improvement. This was a qualitative study of a sample of eight medical-surgical nursing units from four diverse hospitals in one US state. We conducted direct work observations of nursing staff's communication patterns for entire shifts (8 or 12 h) for a total of 200 h and gathered related documentation artifacts for analyses. Data were coded using qualitative content analysis procedures and then synthesized and organized thematically to characterize current practices. Three major themes emerged from the analyses, which represent serious vulnerabilities in the flow of patient care information during nurse hand-offs and to the entire interdisciplinary team across time and settings. The three themes are: (1) variation in nurse documentation and communication; (2) the absence of a centralized care overview in the patient's electronic health record, ie, easily accessible by the entire care team; and (3) rarity of interdisciplinary communication. The care information flow vulnerabilities are a catalyst for multiple types of serious and undetectable clinical errors. We have two major recommendations to address the gaps: (1) to standardize the format, content, and words used to document core information, such as the plan of care, and make this easily accessible to all team members; (2) to conduct extensive usability testing to ensure that tools in the electronic health record help the disconnected interdisciplinary team members to maintain a shared understanding of the patient's plan.


Effect of Laser Panretinal Photocoagulation Combined with Lucentis on Long-Term Visual Acuity of Patients with Retinal Arterial Macroaneurysm.
To analyze the efficacy of laser panretinal photocoagulation in combination with Lucentis treatment on patients with retinal arterial macroaneurysm and investigate more effective novel therapy options to treat retinal arterial macroaneurysm. This study was conducted in the Pediatric department of Chongqing Aier Hospital between October 2016 and October 2020, and a total of 62 inpatients were enrolled for the study. Patients were randomly organized into two groups, an 'observation group' with patients receiving combinational treatment of laser panretinal photocoagulation and Lucentis, and a 'control group' with patients treated by only laser panretinal photocoagulation, were allotted. Though a comparative statistical analysis, the clinical outcomes and adverse effects on both groups, including their best corrected visual acuity, central macular thickness, intraocular pressure, and required number of laser treatments before and after treatments, were investigated. Also prognosis associated factors for patient's visual function, were analyzed. The clinical efficacy of the combinational treatment of laser panretinal photocoagulation and Lucentis was better than single laser panretinal photocoagulation treatment, accompanied by decreased incidence of adverse reactions (P < .05). For a combinational treatment, the observation group showed improved best corrected visual acuity and reduced central macular thickness and intraocular pressure, including fewer laser treatments (P < .05). Also, a better prognostic quality of life score; (measured as physical function, mental state, visual function, and social activity ability of patients), was observed for a combinational treatment than that of laser panretinal photocoagulation treatment (P < .05). Laser panretinal photocoagulation combined with lucentis can deliver with reduced incidence of adverse effects compared to laser panretinal photocoagulation treatment and hence can more effectively contribute to retinal rehabilitation of patients with retinal arterial macroaneurysm.


Troponin I chimera analysis of the cardiac myofilament tension response to protein kinase A.
Viral-mediated gene transfer of troponin I (TnI) isoforms and chimeras into adult rat cardiac myocytes was used to investigate the role TnI domains play in the myofilament tension response to protein kinase A (PKA). In myocytes expressing endogenous cardiac TnI (cTnI), PKA phosphorylated TnI and myosin-binding protein C and decreased the Ca2+ sensitivity of myofilament tension. In marked contrast, PKA did not influence Ca2+-activated tension in myocytes expressing the slow skeletal isoform of TnI or a chimera (N-slow/card-C TnI), which lack the unique phosphorylatable amino terminal extension found in cTnI. PKA-mediated phosphorylation of a second TnI chimera, N-card/slow-C TnI, which has the amino terminal region of cTnI, caused a decrease in the Ca2+ sensitivity of tension comparable in magnitude to control myocytes. Based on these results, we propose the amino terminal region shared by cTnI and N-card/slow-C TnI plays a central role in determining the magnitude of the PKA-mediated shift in myofilament Ca2+ sensitivity, independent of the isoform-specific functional domains previously defined within the carboxyl terminal backbone of TnI. Interestingly, exposure of permeabilized myocytes to acidic pH after PKA-mediated phosphorylation of cTnI resulted in an additive decrease in myofilament Ca2+ sensitivity. The isoform-specific, pH-sensitive region within TnI lies in the carboxyl terminus of TnI, and the additive response provides further evidence for the presence of a separate domain that directly transduces the PKA phosphorylation signal.


Endoplasmic reticulum-associated degradation of cytochrome P450 CYP3A4 in Saccharomyces cerevisiae: further characterization of cellular participants and structural determinants.
The monotopic, endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) undergo variable proteolytic turnover. CYP3A4, the dominant human liver drug-metabolizing enzyme, is degraded via a ubiquitin (Ub)-dependent 26S proteasomal pathway after heterologous expression in Saccharomyces cerevisiae. This turnover involves the Ub-conjugating enzyme Ubc7p and the 19S proteasomal subunit Hrd2p but is independent of Hrd1p/Hrd3p, a major Ub-ligase (E3) involved in ER protein degradation. We now show that CYP3A4 ERAD also involves the Ubc7p-ER anchor Cue1p, because CYP3A4 is significantly stabilized at the stationary growth phase in Cue1p-deficient yeast. To determine whether the other major Ub-ligase Doa10p or Rsp5p involved in ER protein degradation functions in CYP3A4 ERAD, wild type and Doa10p- or Rsp5p-deficient yeast strains were also similarly examined. No appreciable CYP3A4 stabilization was detected in either Doa10p- or Rsp5p-deficient yeast, thereby excluding these E3s and revealing that CYP3A4 ERAD involves a novel or yet to be identified E3. Similar studies also revealed that the Cdc48p-Ufd1p-Hrd4p complex, responsible for the translocation of polyubiquitinated ER proteins was critical for CYP3A4 ERAD. We previously reported that grafting of the C-terminal (CT) CYP3A4 heptapeptide onto the CYP2B1 C terminus switched its proteolytic susceptibility from predominantly vacuolar to proteasomal degradation. To determine the relevance of this CT heptapeptide to CYP3A4 ERAD, CYP3A4 degradation after CT heptapeptide-deletion (CYP3A4DeltaCT) was similarly examined in yeast. These findings revealed that CYP3A4DeltaCT was also degraded by Ubc7p-26S proteasomal pathway, thereby indicating that this CT heptapeptide is not critical for CYP3A4 proteasomal degradation. Thus, unlike CYP2B1, CYP3A4 harbors additional/multiple structural degrons for its recruitment into the Ubproteasomal pathway.


Model-based deep learning framework for accelerated optical projection tomography.
In this work, we propose a model-based deep learning reconstruction algorithm for optical projection tomography (ToMoDL), to greatly reduce acquisition and reconstruction times. The proposed method iterates over a data consistency step and an image domain artefact removal step achieved by a convolutional neural network. A preprocessing stage is also included to avoid potential misalignments between the sample center of rotation and the detector. The algorithm is trained using a database of wild-type zebrafish (Danio rerio) at different stages of development to minimise the mean square error for a fixed number of iterations. Using a cross-validation scheme, we compare the results to other reconstruction methods, such as filtered backprojection, compressed sensing and a direct deep learning method where the pseudo-inverse solution is corrected by a U-Net. The proposed method performs equally well or better than the alternatives. For a highly reduced number of projections, only the U-Net method provides images comparable to those obtained with ToMoDL. However, ToMoDL has a much better performance if the amount of data available for training is limited, given that the number of network trainable parameters is smaller.


Red meat allergy induced by tick bites: A Norwegian case report.
Food allergies, especially delayed hypersensitivity reactions, are often challenging for both patients and clinicians. Here, we report the case of a 64-year-old man who had allergic reactions six hours after eating a meal containing red meat. He reported that he had several tick bites in months before the reaction. High serum specific IgE levels of alpha-gal confirmed the diagnosis of alpha-gal allergic reaction with delayed onset after red meat ingestion caused by tick bite.


Solving constraint satisfaction and optimization problems by a neuro-fuzzy approach.
The solution of constrained satisfaction and constrained optimization problems using a Hopfield model requires determination of the values of a certain number of coefficients linked to the surrounding conditions of the problem. It is quite difficult to determine these values, mainly because a heuristic search is necessary. This is not only time-consuming but may lead to solutions that are far from optimal, or even nonvalid ones. So far, there have been no works in literature offering a general method for the search for coefficents with will guarantee optimal or close to optimal solutions. This paper proposes a fuzzy approach which allows automatic determination of Hopfield coefficients.


Membrane Binding of Antimicrobial Peptides Is Modulated by Lipid Charge Modification.
Peptide interactions with lipid bilayers play a key role in a range of biological processes and depend on electrostatic interactions between charged amino acids and lipid headgroups. Antimicrobial peptides (AMPs) initiate the killing of bacteria by binding to and destabilizing their membranes. The multiple peptide resistance factor (MprF) provides a defense mechanism for bacteria against a broad range of AMPs. MprF reduces the negative charge of bacterial membranes through enzymatic conversion of the anionic lipid phosphatidyl glycerol (PG) to either zwitterionic alanyl-phosphatidyl glycerol (Ala-PG) or cationic lysyl-phosphatidyl glycerol (Lys-PG). The resulting change in the membrane charge is suggested to reduce the binding of AMPs to membranes, thus impeding downstream AMP activity. Using coarse-grained molecular dynamics to investigate the effects of these modified lipids on AMP binding to model membranes, we show that AMPs have substantially reduced affinity for model membranes containing Ala-PG or Lys-PG. More than 5000 simulations in total are used to define the relationship between lipid bilayer composition, peptide sequence (using five different membrane-active peptides), and peptide binding to membranes. The degree of interaction of a peptide with a membrane correlates with the membrane surface charge density. Free energy profile (potential of mean force) calculations reveal that the lipid modifications due to MprF alter the energy barrier to peptide helix penetration of the bilayer. These results will offer a guide to the design of novel peptides, which addresses the issue of resistance via MprF-mediated membrane modification.


A tensorial approach to access cognitive workload related to mental arithmetic from EEG functional connectivity estimates.
The association of functional connectivity patterns with particular cognitive tasks has long been a topic of interest in neuroscience, e.g., studies of functional connectivity have demonstrated its potential use for decoding various brain states. However, the high-dimensionality of the pairwise functional connectivity limits its usefulness in some real-time applications. In the present study, the methodology of tensor subspace analysis (TSA) is used to reduce the initial high-dimensionality of the pairwise coupling in the original functional connectivity network to a space of condensed descriptive power, which would significantly decrease the computational cost and facilitate the differentiation of brain states. We assess the feasibility of the proposed method on EEG recordings when the subject was performing mental arithmetic task which differ only in the difficulty level (easy: 1-digit addition v.s. 3-digit additions). Two different cortical connective networks were detected, and by comparing the functional connectivity networks in different work states, it was found that the task-difficulty is best reflected in the connectivity structure of sub-graphs extending over parietooccipital sites. Incorporating this data-driven information within original TSA methodology, we succeeded in predicting the difficulty level from connectivity patterns in an efficient way that can be implemented so as to work in real-time.


Sexual Assault Among College Students Attending a Historically Black College/University.
Sexual assault constitutes a significant public health problem on college campuses including historically Black colleges and universities (HBCU). Recent research suggests that sexual assault is increasing on college campuses. However, there are few studies examining the prevalence and risk factors for sexual assault at HBCUs. To address this gap, the current study examined the prevalence, correlates, and outcomes of sexual assault at an HBCU. Participants in the study were 264 undergraduate students from an HBCU in the mid-Atlantic region. The majority of participants were female (71%), African American (91%), and seniors (41%). After providing informed consent, participants completed a Climate Assessment survey administered by the university's Office of Diversity. Findings revealed that since starting college about 20% of students experienced sexual contact without consent. Of those sexually assaulted, 20% reported they were incapacitated or under the influence of alcohol (15%) at the time of the assault. About 17% of those assaulted experienced a physical injury and/or poor mental health outcomes (e.g., anxiety, depression, flashbacks). Participants reported not disclosing information of their assault due to embarrassment, afraid of retaliation from the perpetrator, believing it was a private matter. Close friends were more likely to be told about sexual assault. The study supports the need to address sexual assault on HBCU campuses through strong prevention and intervention programs and to address barriers to reporting.


[Clonidine compared to midazolam for intravenous premedication for ambulatory procedures. A controlled double blind study in ASA 1 patients].
Midazolam is frequently used for premedication in day-case surgical patients whereas clonidine is rarely administered for this indication. However, clonidine has several useful effects that make the drug an interesting alternative to conventional premedicants. Thus, in this randomised, double-blind, and controlled study the anxiolytic effect of midazolam was compared to that of clonidine. Furthermore, effects on postoperative complaints and minor complications, and readiness for discharge were investigated. 100 ASA-1 patients undergoing wisdom teeth extraction on a day-case basis were included into the analysis. A further 50 patients who received no premedication served as a control group. General anaesthesia was standardised (propofol-fentanyl-isoflurane in N2O/O2). The anxiolytic effect of the premedication was assessed using the Erlanger anxiety- and tension scale (EAS). The test was applied before and after intravenous premedication with 1.5 micrograms/kg clonidine or 50 micrograms/kg midazolam and repeated once postoperatively. During recovery the incidence and severity of pain, nausea and vomiting, and shivering were recorded. The readiness for discharge was assessed using standardised discharge criteria. The recording of data was completed by a telephone interview on the day after surgery. The demographic data of the groups did not differ. In the two treatment groups there was a time-dependent decrease of anxiety and tension. However, postoperatively there was no difference between the levels of anxiety and inner tension between the premedicated patients and the untreated control group. Furthermore there was no difference in the incidence and severity of any postoperative complications. Time until the patients were ready for discharge did not differ between the three groups. The effects of an intravenous premedication with 1.5 micrograms/kg clonidine or 50 micrograms/kg midazolam, respectively in young ASA-1 patients undergoing minor surgical procedures on a day-case basis are restricted to decrease of anxiety and inner tension before surgery. No beneficial effects were found during the postoperative period compared with untreated control patients.


Chromosomal evolution of rDNA and H3 histone genes in representative Romaleidae grasshoppers from northeast Brazil.
Grasshoppers from the Romaleidae family are well distributed in the Neotropical Region and represent a diversified and multicolored group in which the karyotype is conserved. Few studies have been conducted to understand the evolutionary dynamics of multigene families. Here, we report the chromosomal locations of the 18S and 5S rDNA and H3 histone multigene families in four grasshopper species from the Romaleidae family, revealed by fluorescent in situ hybridization (FISH). The 5S rDNA gene was located in one or two chromosome pairs, depending on the species, and was found in a basal distribution pattern. Its chromosomal location was highly conserved among these species. The 18S rDNA was located in a single medium-sized chromosomal pair in all species analyzed. Its chromosomal location was near the centromere in the proximal or pericentromeric regions. The location of the H3 histone gene was highly conserved, with slight chromosomal location differences among some species. To our knowledge, this is the first report of a megameric chromosome carrying both the chromosomal markers 18S rDNA and the H3 histone genes, thereby expanding our understanding of such chromosomes. The 5S and 18S rDNA genes and the H3 histone genes showed a conservative pattern in the species that we analyzed. A basal distribution pattern for 5S rDNA was observed with a location on the fourth chromosomal pair, and it was identified as the possible ancestral bearer. The 18S rDNA and H3 histone genes were restricted to a single pair of chromosomes, representing an ancestral pattern. Our results reinforce the known taxonomic relationships between Chromacris and Xestotrachelus, which are two close genera.


Risk factors and neurodegenerative mechanisms in stroke related dementia.
Considerable evidence indicates that systemic vascular diseases are associated with neurodegenerative processes preceding cognitive decline and dementia. Conditions such as hypertension, diabetes, atrial fibrillation, ischemic heart disease, dyslipidaemia and obesity have propensity to induce strokes, which increase risk of dementia up to five-fold in the elderly. The link between vascular diseases and clinical Alzheimer's disease (AD) also exists but pathological confirmation has often been lacking. However, more than 30% of stroke survivors will develop dementia within two years. Transient ischaemic attacks and silent infarcts may unmask neurodegenerative processes characterized by primary pathologies such as those found in AD. Cerebral infarction and neurodegenerative pathologies are additive and accelerate dementia. Medial temporal atrophy is a strong predictor of dementia and also appears a feature in demented stroke survivors with minimal AD pathology. The atrophy is attributed to selective smaller cell volumes in the hippocampus and likely frontal lobe that may reflect loss of neuronal arborization and connectivity. Therapeutic strategies that maintain or restore functional morphology in surviving neurons could prevent further cognitive decline in post stroke and ageing related dementias.


Low-Bandwidth and Compute-Bound RGB-D Planar Semantic SLAM.
Visual simultaneous location and mapping (SLAM) using RGB-D cameras has been a necessary capability for intelligent mobile robots. However, when using point-cloud map representations as most RGB-D SLAM systems do, limitations in onboard compute resources, and especially communication bandwidth can significantly limit the quantity of data processed and shared. This article proposes techniques that help address these challenges by mapping point clouds to parametric models in order to reduce computation and bandwidth load on agents. This contribution is coupled with a convolutional neural network (CNN) that extracts semantic information. Semantics provide guidance in object modeling which can reduce the geometric complexity of the environment. Pairing a parametric model with a semantic label allows agents to share the knowledge of the world with much less complexity, opening a door for multi-agent systems to perform complex tasking, and human-robot cooperation. This article takes the first step towards a generalized parametric model by limiting the geometric primitives to a planar surface and providing semantic labels when appropriate. Two novel compression algorithms for depth data and a method to independently fit planes to RGB-D data are provided, so that plane data can be used for real-time odometry estimation and mapping. Additionally, we extend maps with semantic information predicted from sparse geometries (planes) by a CNN. In experiments, the advantages of our approach in terms of computational and bandwidth resources savings are demonstrated and compared with other state-of-the-art SLAM systems.


Adding sweet potato vines improve the quality of rice straw silage.
Rice straw and sweet potato vines are the main by-products of agricultural crops, and their disposal creates problems for the environment in the south of China. In order to establish an easy method for making rice straw silage successfully, experiments were conduct to evaluate fermentation quality and nutritive value of rice straw silages ensiled with or without sweet potato vine. Paddy rice straw (PR) and upland rice straw (UP) were ensiled alone or with sweet potato vines (SP) by a ratio of 1:1 (fresh matter basis), over 3 years. Compared with rice straw silages ensiled alone, the mixed-material silages (PR + SP, UR + SP) showed higher fermentation quality with lower propionic acid content and NH3 -N ratio of total N, and higher (P < 0.05) concentrations of lactic acid and acetic acid, resulting in decrease (P < 0.05) of dry matter loss and higher (P < 0.05) in vitro ruminal dry matter digestion. When the fermentation quality, chemical composition and in vitro rumen fermentation characteristics were considered, ensiling would be an effective way of utilization of rice straw and sweet potato vines in the regions where rice and sweet potato are harvested at same season, and the sweet potato vines have the potential to improve rice straw fermentation quality with low water soluble carbohydrate content in south of China.


Time-to-contact and multiscale entropy identify differences in postural control in adolescent idiopathic scoliosis.
Previous reports on changes in postural control in adolescent idiopathic scoliosis (AIS) compared to healthy controls have been inconsistent. This may suggest center of pressure (COP) sway parameters are not sufficient for determining the ability to maintain quiet upright stance indicating more complex measures may be needed to examine postural control in AIS. The purpose of this investigation was to compare postural control between AIS of different severity levels and healthy controls using time-to-contact (TtC), the complexity index of multiscale entropy (C(r)), and COP sway parameters. Thirty-six AIS patients were classified as pre-bracing or pre-operative and compared to 10 healthy control subjects. Overall, the AIS patients showed significantly greater COP sway in mediolateral direction, but deficits with respect to the anteroposterior direction were only systematically identified with the time-to-contact and entropy measures. The multiscale entropy (C(r)) results indicate that those with AIS utilize a different control strategy from healthy controls in the mediolateral direction that is more constrained, less complex and less adaptable. AIS severity further reduced this adaptability in the anteroposterior direction. These results indicate it is necessary to examine both planes of motion when investigating postural control in AIS. Additionally, the application of the measures used to assess the nature of the postural control changes in AIS should also be considered.


Early expression of interleukin-2 mRNA by peripheral blood mononuclear cells isolated from nickel-allergic subjects and subsequently exposed to nickel in vitro.
The aim pf the present study was to characterize the time course of the synthesis of mRNA encoding interleukin-2 (IL-2) by peripheral blood mononuclear cells (PBMCs) isolated from nickel-allergic women and subsequently exposed to nickel sulphate in vitro. The level of this mRNA (determined by employing real-time polymerase chain reaction [PCR]) and of the corresponding protein (quantitated using an enzyme-linked immunosorbent assay [ELISA]) were significantly increased after only 10 and 24 h of incubation, respectively. The increased level of mRNA coding for IL-2 supports the hypothesis that this process is a key part of the response to nickel stimulation of PBMCs of hypersensitive subjects.


Analysis of tar compounds and quantification of naphthalene from thermal treatment of household biowaste.
Household biowaste represent the organic fraction of municipal solid waste and are an underutilized resource. Although previous studies have performed pyrolysis of organic waste, the vast majority has been on specific presorted feedstock or conventional lignocellulosic streams. Therefore, there is a lack of pyrolysis applications on representative food waste as retrieved from households and this can be attributed primarily to their high water content and their degradability. But via the intermediate step of drying, long-term storage and thermal treatment have become possible. In the framework of this study, household biowaste were pyrolyzed for the production of carbonaceous materials with a main focus on the analysis of produced tar compounds. Tars can be corrosive or cause clogging and disrupt the operation of pyrolysis and gasification plants. Their analysis has faced several difficulties due to inconsistency in the methodologies that have been applied by various groups. The tar protocol has provided a solid framework for consistent analysis of tars but until now has been solely used for the case of gasification. This study aimed to apply the tar protocol for pyrolysis and to enhance the detectability of the method for a wider range of tars by means of elemental analysis, attenuated total reflectance (ATR) and gas chromatography-mass spectrometry (GC-MS). GC- MS was performed by means of a specific column for PAHs identification and calibration methods were developed for the proper quantification of naphthalene which is the dominant tar compound. The results of the analysis showed that naphthalene concentration increased from torrefaction to carbonization but then decreased significantly for high temperature pyrolysis at 860 °C.


[Survival of the poliomyelitis virus in environmental objects].
The guanidine-dependent variant of poliovirus type I was shown to survive in soil and on tomato plants for 60 and 25 days, and in the roots, stems, leaves for 15, 20, and 8 days, respectively. Extrapolation of the significance of these results indicates that the decline of concentration of the indicator virus in the soil and on the vegetables and its increase and decline in the root system, stems, leaves, and in tomatoes is of exponential nature.


The Le(a) antigen and neonatal hyperbilirubinemia in Taiwan.
Neonatal jaundice is known to be more severe in Taiwanese infants than in Caucasian infants. Although ABO fetomaternal incompatibility and glucose-6-phosphate dehydrogenase deficiency have been shown to play a role in the etiology of neonatal jaundice in some Taiwanese infants, the etiology in the majority of cases is unknown. In this study we found that in Taiwanese newborn infants, the red cell Le(a) antigen appeared later in infants who were jaundiced (peak serum bilirubin levels of > 12 mg/dl during the first week of life) than in infants who were not. However, the Leb antigen, and hence the transferase encoded by the Se and Se(w) genes, did not appear to be similarly involved in the etiology of physiological jaundice. Thus it would appear that the Le gene-specified transferase is less active or has a delayed function, in jaundiced infants. The relationship between the Le gene-specified transferase and bilirubin has yet to be established.


Inventing a herbal tradition: The complex roots of the current popularity of Epilobium angustifolium in Eastern Europe.
Currently various scientific and popular sources provide a wide spectrum of ethnopharmacological information on many plants, yet the sources of that information, as well as the information itself, are often not clear, potentially resulting in the erroneous use of plants among lay people or even in official medicine. Our field studies in seven countries on the Eastern edge of Europe have revealed an unusual increase in the medicinal use of Epilobium angustifolium L., especially in Estonia, where the majority of uses were specifically related to "men's problems". THE AIM OF THE CURRENT WORK IS: to understand the recent and sudden increase in the interest in the use of E. angustifolium in Estonia; to evaluate the extent of documented traditional use of E. angustifolium among sources of knowledge considered traditional; to track different sources describing (or attributed as describing) the benefits of E. angustifolium; and to detect direct and indirect influences of the written sources on the currently documented local uses of E. angustifolium on the Eastern edge of Europe. In this study we used a variety of methods: semi-structured interviews with 599 people in 7 countries, historical data analysis and historical ethnopharmacological source analysis. We researched historical and archival sources, and academic and popular literature published on the medicinal use of E. angustifolium in the regions of our field sites as well as internationally, paying close attention to the literature that might have directly or indirectly contributed to the popularity of E. angustifolium at different times in history. Our results show that the sudden and recent popularity in the medical use of E. angustifolium in Estonia has been caused by local popular authors with academic medical backgrounds, relying simultaneously on "western" and Russian sources. While Russian sources have propagated (partially unpublished) results from the 1930s, "western" sources are scientific insights derived from the popularization of other Epilobium species by Austrian herbalist Maria Treben. The information Treben disseminated could have been originated from a previous peak in popularity of E. angustifolium in USA in the second half of the 19th century, caused in turn by misinterpretation of ancient herbals. The traditional uses of E. angustifolium were related to wounds and skin diseases, fever, pain (headache, sore throat, childbirth), and abdominal-related problems (constipation, stomach ache) and intestinal bleeding. Few more uses were based on the similarity principle. The main theme, however, is the fragmentation of use and its lack of consistency apart from wounds and skin diseases. Historical ethnobotanical investigations could help to avoid creating repeating waves of popularity of plants that have already been tried for certain diseases and later abandoned as not fully effective. There is, of course, a chance that E. angustifolium could also finally be proven to be clinically safe and cost-effective for treating benign prostatic hyperplasia, but this has not yet happened despite recent intensive research. Documented traditional use would suggest investigating the dermatological, intestinal anti-hemorrhagic and pain inhibiting properties of this plant, if any.


Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor α.
Although estrogens are known to have a deleterious effect on the venous thrombosis risk and a preventive action on the development of arterial atheroma, their effect on platelet function in vivo remains unclear. Here, we demonstrate that a chronic high physiologic level of estradiol (E2) in mice leads to a marked decrease in platelet responsiveness ex vivo and in vivo compared with ovariectomized controls. E2 treatment led to increased bleeding time and a resistance to thromboembolism. Hematopoietic chimera mice harboring a selective deletion of estrogen receptors (ERs) α or β were used to demonstrate that the effects of E2 were exclusively because of hematopoietic ERα. Within ERα the activation function-1 domain was not required for resistance to thromboembolism, as was previously shown for atheroprotection. This domain is mandatory for E2-mediated reproductive function and suggests that this role is controlled independently. Differential proteomics indicated that E2 treatment modulated the expression of platelet proteins including β1 tubulin and a few other proteins that may impact platelet production and activation. Overall, these data demonstrate a previously unrecognized role for E2 in regulating the platelet proteome and platelet function, and point to new potential antithrombotic and vasculoprotective therapeutic strategies.


The effect of day and night shifts on oxidative stress and anxiety symptoms of the nurses.
Oxidative stress is believed to have a role in the development of chronic diseases. It is also known that long-term night and shift work in nurses might be associated with many health-related problems like fatigue, sleep problems, anxiety and difficulties in maintaining regular lifestyles. In this study, we aimed to evaluate the changes of oxidative stress parameters and anxiety indexes of the nurses on day and night shifts. One hundred and twenty nurses in ordinary service and intensive care unit (ICU) were enrolled to the study. Subjects were divided into 2 groups; group 1 (n = 60) consisted of nurses working in a day shift and group 2 (n = 60) as working in the night shift. Further, both groups were divided in to 2 groups again; group la and 2a (both n = 30) who working in the ICU, group 1b and 2b (both n = 30) in the ordinary service. Just before and the end of the shifts, blood samples were obtained to measure total antioxidant status (TAS) and total oxidant status (TOS). Oxidative stress index (OSI) was calculated. Anxiety index were determined at the end of the shift using State-Trait Anxiety Inventory index. Oxidative stress parameters were increased in all nurses at the end of the day and night shifts (p < 0.05). However, both in service and ICU nurses TAS, TOS, and OSI levels were not significantly different at the beginning and the end of the shifts (p > 0.05). Anxiety indexes of each ordinary service and ICU nurses were found to be similar (p > 0.05). Ordinary service and ICU nurses' oxidative stress parameters and anxiety indexes were not different and all nurses suffer the similar effects of the shifts both in day and night.


Assessing dose-response relationships by cumulative exposures in epidemiological studies.
If the occurrence of disease monotonically increases with the degree of exposure in an epidemiologic study, a dose-response (or exposure-response) relationship is indicated and facilitates the interpretation that the exposure has a causal role. It is not uncommon, however, that there is some effect in terms of an overall increased relative risk but no clear dose-response relationship. Models presented here show that cumulative exposure, as involving the duration of exposure, is not an adequate parameter when more recent exposure or the intensity of the exposure plays the greater role for the disease outcome. In lack of a dose-response pattern by cumulative exposure, the interpretation of an overall increased risk might well be that there is no definite effect. The proper consideration should be, however, that the measure of exposure could be inadequate, suggesting a need for further analyses and evaluations of the material studied.


[The effect of recombinant interleukin 1beta on cytochrome P-450 dependent monooxygenases in rat liver and kidney].
Effects of a single administration of the human recombinant interleukin 1beta (rIL-1beta, betaleukin) on the cytochrome P-450 dependent monooxygenase activity in rat liver and kidney were evaluated in intact rats and on the background of cytochrome P-450 inductors. It was found that betaleukin suppressed the CYP1A1/2-dependent ethoxyresorufin-o-deethylase activity in both liver and kidney, as well as the CYP2C-dependent dibenzylfluorescein-debenzylase and CYP2E1-dependent nitrophenol-hydroxylase activity in liver, but induced CYP3A-dependent N-demethylation of erythromycin in liver and kidney. Betaleukin also inhibited the beta-naphthoflavone-induced monooxygenase activity in liver, while only insignificantly acted upon the induced monooxygenases in kidney. Betaleukin decreased the pyridine-induced CYP2E1-dependent monooxygenation in liver and CYP1A1/2-dependent monooxygenation in kidney. Therefore, the character and direction of the influence of rIL-1beta on cytochrome P450 belonging to various subfamilies are variable and tissue-specific.


Harnessing the Electric Spark of Life to Cure Skin Wounds.
Significance: Skin wounds cause great distress and are a huge economic burden, particularly with an increasingly aging population that heals poorly. There is an urgent need for better therapies that improve repair. Intracellular signaling pathways that regulate wound repair are activated by growth factors, hormones, and cytokines released at the wound. In addition, endogenous electric fields (EFs) are generated by epithelia in response to injury and are an important cue that coordinates cell behavior at wounds. Electrical stimulation (ES), therefore, holds the potential to be effective therapeutically in treating wounds. Recent Advances: ES of wounds is an old idea based on observations of the natural occurrence of EF at wound sites. However, it is now receiving increasing attention, because (1) the underpinning mechanisms are being clarified; (2) devices that measure skin wound currents are in place; and (3) medical devices that apply EF to poorly healing wounds are in clinical use with promising results. Critical Issues: Several signaling proteins transduce the EF influence to cells. However, a bigger picture of the EF-proteome is needed in order to understand this complex process and target it in a controlled manner. Future Directions: Dissecting the signaling pathways driving electrical wound healing will allow further identification of key molecular switches that control the cellular response to EFs. These findings herald the development of a new concept, the use of hydrogel electrodes impregnated with small molecules that target signaling pathways to explore the potential of dual electric-pharmacological therapies to repair wounds.


Circadian system controlling release of sperm in the insect testes.
Release of mature sperm from the testis into seminal ducts of the gypsy moth exhibits a circadian rhythm. The rhythm of sperm release was shown to persist in vitro, in isolated complexes of testis and seminal ducts cultured in light-dark cycles or in constant darkness. The phase of the rhythm was also reset in vitro by exposure to shifted light-dark cycles. Therefore, the testis-seminal ducts complex from the gypsy moth is photosensitive and contains a circadian pacemaker, which controls the rhythm of sperm movement. This finding extends the range of structures in multicellular organisms that are known to contain circadian oscillators and provides a new model system in which circadian mechanisms may be studied.


Comparison of restriction enzyme analysis and pulsed-field gradient gel electrophoresis as typing systems for Candida albicans.
Candida species are an important cause of infection in immunocompromised hosts and the leading cause of nosocomial fungal infections. Study of the epidemiology of Candida infection has been difficult because of lack of a reliable typing system. We describe a typing system utilizing contour-clamped homogeneous electric fields (CHEF), which is a modified version of pulsed-field gradient gel electrophoresis, and compared it with restriction enzyme analysis (REA) of genomic DNA. The study was done with 35 Candida albicans clinical isolates from separate patients. CHEF and REA were performed on each isolate, and the patterns were compared. The REA procedure revealed 17 strain types while the CHEF procedure was able to distinguish 23 strain types of C. albicans. The CHEF technique yields unique patterns of chromosomal bands that can be used to distinguish clinical isolates and demonstrates greater sensitivity than REA.


Engineering cancer cell membranes with endogenously upregulated HSP70 as a reinforced antigenic repertoire for the construction of material-free prophylactic cancer vaccines.
Immune cells distinguish cancer cells mainly relying on their membrane-membrane communication. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. We exploit cancer cell membranes as the whole cancer antigen repertoire and reinforce its immunogenicity by cellular engineering to modulate the cytomembrane's immune-associated functions. This study reports a vaccine platform based on radiation-engineered cancer cells, of which the membrane HSP70 protein as the immune chaperon/traitor is endogenously upregulated. The resulting positive influences are shown to cover immunogenic steps occurring in antigen-presenting cells, including the uptake and the cross-presentation of the cancer antigens, thus amplifying cancer-specific immunogenicity. Membrane vaccines offer chances to introduce desired metal ions through membrane-metal complexation. Using Mn2+ ion as the costimulatory interferon genes agonist, immune activity is enhanced to further boost adaptive cancer immunogenicity. Results have evidenced that this artificially engineered membrane vaccine with favorable bio-safety could considerably reduce tumorigenicity and inhibit tumor growth. This study provides a universally applicable and facilely available cancer vaccine platform by artificial engineering of cancer cells to inherit and amplify the natural merits of cancer cell membranes. STATEMENT OF SIGNIFICANCE: The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. Cancer cell membrane presents superior advantages as the whole cancer antigen repertoire, including the reported and the unidentified antigens, but its immunogenicity is far from satisfactory. Cellular engineering approaches offer chances to endogenously modulate the immune-associated functions of cell membranes. Such a reinforced vaccine based on the engineered cancer cell membranes matches better the natural immune recognition pathway than the conventional vaccines.


Behavior of the vestibular nerve following labyrinthectomy.
Transtympanic labyrinthectomy was performed on 24 cats, and after survival times of one month to three years, the temporal bones were prepared for light microscopic study. The operated ears showed mean neuronal losses of 12% in six months, 24% in 1 year, 35% in 2 years, and 53% in 3 years. These was no evidence of regeneration of vestibular nerve fibers nor of formation of traumatic neuromata. The temporal bones of two human subjects who had undergone transtympanic labyrinthectomy are also presented; one shows atrophy of the vestibular nerves while the other exhibits proliferation of nerve fibers not resembling a neuroma. It is concluded that the afferent vestibular nerves undergo slow but progressive atrophy following labyrinthectomy and that they have no potential for the creation of amputation neuromata. The evidence suggests that excision of the vestibular nerves may have no therapeutic advantage over labyrinthectomy in the treatment of intractable vertigo.


SDR® vs traditional composite in class II restorations in primary molars.
This study aims to compare the clinical characteristics of a new flowable resin-based composite with those of a traditional composite when applied to deciduous molars for class II restorations. Twentyeight children between 6-12 years of age, with paired minimal Class II cavities present on their primary molars, were chosen. The paired cavities were restored with either a microhybrid composite or a new flowable resin-based composite. The composites were assigned to cavities in either the right or left side of the mouth, using random allocation tables. Each pair of restorations were clinically assessed at sixmonth intervals following the United States Public Health Service criteria. The prevalence of carious lesions was higher in maxillar molars (53.6%) compared to the mandibular molars (46.4%). At 24 months, Charlie or Delta scores in the paired groups were not seen in any patient, thus demonstrating a clinical success. The statistical analysis using Pearson's chi-squared test did not reveal significant p-values for any parameter except the proximal contact showing significant p-values for this parameter. SDR appears to be the material of choice for the restoration of deciduous teeth due to its clinical features shown at 24 months as well as its ease and speed of application.


Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood--report of the German Multicentre Allergy Study (MAS 90).
Controversial data have emerged regarding the question whether cat exposure in childhood favours or decreases the risk of sensitization and allergic airway disease. In a prospective birth-cohort study, we assessed the association between longitudinal cat allergen exposure, sensitization (immunoglobulin E, IgE), IgG antibody (ab) levels to cat and the development of asthma in children up to the age of 10 years. Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 10 years were available for 750 children. Assessments included yearly measurements of specific serum IgE to cat and at age 6 and 18 months, 3, 4 and 10 years measurement of cat allergen Fel d 1 in house dust samples. Additionally, Fel d 1-specific IgG ab were determined in 378 serum samples of 207 children. Endotoxin exposure in mattress dust was measured in a subgroup of 153 children at age 10 years. From age 4 years on, International Study of Asthma and Allergy in Childhood (ISAAC) questionnaires were completed yearly in order to assess the prevalence of wheeze and asthma. Serum IgG-levels to cat showed a large variation, however, intraindividually values showed rather constant concentration over a longer time period. The IgG levels at school-age correlated with cat allergen exposure during the first 2 years of life. Specific IgE to cat was clearly associated with wheeze ever, current wheeze and bronchial hyperresponsiveness (BHR), this was also observed for children with specific IgE ab to cat (>0.35 kU/l) plus IgG levels above 125 U/ml. A large percentage of very highly exposed children showed high IgG but no IgE responses to cat, however, not all highly exposed children were found to be protected from sensitization. Children with IgG but without IgE ab to cat showed the lowest prevalence of wheeze ever and current wheeze despite high cat allergen exposure, however, this trend did not achieve significance. While homes of cat owners showed higher Fel d 1 concentrations than homes without cats, homes of cat owners were not found to have higher endotoxin levels in carpet dust samples than homes without cats. We could confirm that high cat allergen exposure in a cohort with lower community prevalence of cats is associated with higher serum IgG and IgE levels to cat in schoolchildren. Sensitization to cat allergen (IgE) is a risk factor for childhood asthma. While exposure to cat allergen during infancy is associated with sensitization (IgE), only in the very highly exposed children the likelihood of sensitization (IgE) is decreased and high IgG levels to cat without IgE were associated with low risk of wheeze. However, cat-specific IgG ab levels did not protect children with IgE-mediated sensitization from wheeze.


Emergency surgical management of acute aortic dissection: role of transesophageal echocardiography.
The accuracy of transesophageal echocardiography in the diagnosis and surgical management of acute aortic dissection was determined in 54 patients who underwent surgery for acute aortic dissection. Results of the investigations were compared to the surgical assessment. From April 1993 to November 1997, we operated 54 patients (44 male and 10 female) for acute aortic dissection. Mean age was 60 +/- 9 years. At surgery, a De Bakey type I aortic dissection was diagnosed in 30 patients, type II in 23 and type III retrograde in 1. Operating procedures were: replacement of ascending aorta (24 cases), replacement of ascending aorta and aortic arch (17 cases), replacement of ascending aorta and aortic valve replacement (2 cases), Bentall procedure (6 cases) and end-to-end anastomosis of the ascending aorta (4 cases). Initial diagnosis, performed in emergency wards, was done on a clinical basis in 6 patients, on CT scan in 19, on transthoracic echocardiography in 14, and on TEE basis in 12. Three patients underwent angiography before our evaluation. As per our protocol, all patients underwent confirmation of the diagnosis by TEE. Seven patients needed additional instrumental investigations, 2 with CT scan and 5 with angiography. TEE confirmed the diagnosis of aortic dissection in all cases but one. Moreover, it described the site of the intimal tear, the extension of the dissecting process and accessory findings, such as pericardial effusion, aortic incompetence and left ventricular function. The interval between patient presentation and skin incision was a maximum of 70 minutes. At surgery, diagnosis of De Bakey classification was confirmed in 98% of cases; in 90.7% of cases exact location of the entry site was confirmed. In one case, an entry site in the arch diagnosed by TEE but not recognized at surgery, was observed at necropsy. Intraoperatively, we routinely used TEE to monitor retrograde systemic perfusion and correct implant of the vascular prosthesis. One case of malperfusion of the thoracic aorta through the false lumen was observed and managed. In one case we diagnosed acute obstruction of the prosthesis by bleeding in the wrapped aorta, which required reoperation. Assessment of ventricular function was obtained in all patients: in two cases, observation of low right ventricular function led us to perform aortocoronary by-pass to the right coronary artery. In conclusion, the high level of correspondence between TEE diagnosis and surgical anatomy prompted us to perform transesophageal echocardiography as the primary and often sole diagnostic procedure in acute aortic dissection. TEE, in experienced hands, has proven to be a highly reliable, safe and low-cost diagnostic tool. It can be performed at the patient's bedside within just a few minutes of the suspected diagnosis, thereby lowering the mortality rate of the natural history. Again, it can also be used in the operating theatre as an "on-line examination" as well as for assessment of correct surgical repair. Other diagnostic procedures do not yield more information and can cause dangerous delays in intervention.


"I kind of gave up on it after a while, became too hard, closed my eyes, didn't want to know about it"-adults with type 1 diabetes mellitus describe defeat in the context of low social support.
Type 1 diabetes mellitus (T1DM) is a lifelong condition that requires diligent self-management to avoid complications. Living with T1DM is a considerable challenge and the inability to follow a prescribed regimen is often termed non-compliance. However, this fails to acknowledge that for some people the barriers to glycaemic control may be insurmountable. This qualitative study explores the structural determinants, social context and lived experience of T1DM with 17 adults to understand influences on patterns of self-care, engagement with and trust in health-care services, and health outcomes. Their stories tell us that strong social support is vital to disease adaptation and ongoing management. When social support is absent, the story is one of struggling with intensive diabetes management alone and difficulty controlling blood glucose levels. When confronted with suboptimal glycaemic control, participants isolated from social support developed combative relationships with health-care providers and disengaged from health care. Their subsequent slide to chronic comorbid illness is steep and this study reveals the heartache and loss experienced when difficult life circumstances and low levels of social support have led to irreparable kidney damage. Patterns of poor glycaemic control viewed in the health-care encounter without an understanding of the context or life circumstances in which they are occurring can lead to an inability to engage with health-care services. Disengagement from services and the absence of specialist care further isolates people, leaving them managing their diabetes alone with limited success.


Learning the rules of collective cell migration using deep attention networks.
Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the 'rules' behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that is intuitive to the researcher. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors-epithelial, endothelial, and metastatic breast cancer cells-and show how the results complement traditional biophysical approaches. In particular, we present attention maps indicating the relative influence of neighboring cells to the learned turning decisions of a 'focal cell'-the primary cell of interest in a collective setting. Colloquially, we refer to this learned relative influence as 'attention', as it serves as a proxy for the physical parameters modifying the focal cell's future motion as a function of each neighbor cell. These attention networks reveal distinct patterns of influence and attention unique to each model tissue. Endothelial cells exhibit tightly focused attention on their immediate forward-most neighbors, while cells in more expansile epithelial tissues are more broadly influenced by neighbors in a relatively large forward sector. Attention maps of ensembles of more mesenchymal, metastatic cells reveal completely symmetric attention patterns, indicating the lack of any particular coordination or direction of interest. Moreover, we show how attention networks are capable of detecting and learning how these rules change based on biophysical context, such as location within the tissue and cellular crowding. That these results require only cellular trajectories and no modeling assumptions highlights the potential of attention networks for providing further biological insights into complex cellular systems.


Submodality and columnar organization of the second somatic sensory area in cats.
Electrophysiological responses of 519 single and 405 multiple neurons located in the distal forelimb zone of the second somatic sensory cortex (SII) of 11 intact cats were characterized according to their submodality and receptive field properties. In 4 of these animals, 46 single and 134 multiple neuronal responses were studied after transection of the dorsal columns contralateral to the cortical recording sites. Receptive field positions overlapped considerably in SII during orthogonal electrode penetrations, but were shifted during tangential penetrations. Analysis of the receptive field positions for neurons encountered in tangential penetrations indicated that receptive fields rarely overlapped when the neurons were separated by more than 750 microns. Using a variety of hand-held stimuli, neuronal responses were assessed according to several criteria including: velocity, adaptation, following rate, spontaneous activity, and whether the response was elicited by stimulating hairs, skin, claws, or deep tissue. Based on these parameters, it was possible to discern several types of neuronal responses in SII. Among these, over 60% of the neurons in our sample responded best to movement of hairs. A smaller number of neurons responded as though they received inputs from Pacinian receptors or rapidly adapting receptors in the glabrous skin. In about 20% of the single neuron sample, it was not possible to identify a selective adequate stimulus, however, these cells responded to somatic stimuli, such as taps. Approximately 5% of the neurons could not be driven with somatic sensory stimuli. Following dorsal column lesions, some neurons in SII still responded to cutaneous stimulation, primarily hair movement. Most SII neurons were more difficult to drive, the responses were more sluggish and receptive fields were less well-defined. A greater proportion of single neuron responses (greater than 60%) could not be activated by any type of somatic sensory stimulus. These results indicate that the dorsal columns provide a potent, but not exclusive, source of afferent input to SII.


The accuracy of C-reactive protein in the diagnosis of acute appendicitis compared with that of clinical diagnosis.
Acute appendicitis is one of the most common surgical emergencies. Its diagnosis is usually made depending on presenting history, clinical evaluation and laboratory tests. It has been estimated that the accuracy of the clinical diagnosis of acute appendicitis is lying between 76% and 92% (1). Negative appendectomies are one of the burdens facing not only the general surgeon but also the patient himself and the society as a whole, since appendectomy, as any other operation, results in socio-economic impacts in form of lost working days and declined productivity. To determine the accuracy of c-reactive protein (CRP) in the diagnosis of acute appendicitis in comparison with the accuracy of clinical diagnosis. This is a prospective study of all appendectomized patients during a one-year period in King Hussein Hospital in Amman/Jordan. A total of 98 patients were included in this study. The diagnosis of acute appendicitis was histopathologically confirmed in 89 patients (91%), while 9 normal appendixes (9%) were removed. The readings of CRP were ranging between 0 and 11.7 mg/l (mean 5.6 mg/l) in patients with normal appendixes, and between 6-93.4 mg/l (mean 36.2 mg/l) in patients with acute appendicitis. Normal CRP readings were found in 4 patients with acute appendicitis, and of the 9 cases with normal appendectomy, CRP level was elevated in only one patient, so the CRP levels were true (positively or negatively) in 93 patients and it was false positive in one patient (11%) and false negative in 4 patients (4%). On the other hand, the clinical diagnosis was correct in 89 cases (91%) and false in 9 cases (9%), the difference is statistically significant (p value = 0.009). We conclude that CRP is very helpful in the diagnosis of acute appendicitis, but it doesn't replace the clinical skills of general surgeons.


Stepped care model of pain management and quality of pain care in long-term opioid therapy.
Successful organizational improvement processes depend on application of reliable metrics to establish targets and to monitor progress. This study examined the utility of the Pain Care Quality (PCQ) extraction tool in evaluating implementation of the Stepped Care Model for Pain Management at one Veterans Health Administration (VHA) healthcare system over 4 yr and in a non-VHA Federally qualified health center (FQHC) over 2 yr. Two hundred progress notes per year from VHA and 150 notes per year from FQHC primary care prescribers of long-term opioid therapy (>90 consecutive days) were randomly sampled. Each note was coded for the presence or absence of key dimensions of PCQ (i.e., pain assessment, treatment plans, pain reassessment/outcomes, patient education). General estimating equations controlling for provider and facility were used to examine changes in PCQ items over time. Improvements in the VHA were noted in pain reassessment and patient education, with trends in positive directions for all dimensions. Results suggest that the PCQ extraction tool is feasible and may be responsive to efforts to promote organizational improvements in pain care. Future research is indicated to improve the reliability of the PCQ extraction tool and enhance its usability.


Family history of Alzheimer's disease and hippocampal structure in healthy people.
Structural brain changes appear years before the onset of Alzheimer's disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimer's disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated the influence of APOE-4 genotype and family history risks on cortical thickness in medial temporal lobe subregions among volunteers without cognitive impairment. High-resolution magnetic resonance imaging (MRI) and a cortical unfolding method were performed on 26 subjects (APOE-4 carriers: N=13; noncarriers: N=13) with at least one first-degree relative with Alzheimer's disease and 25 subjects (APOE-4 carriers: N=12; noncarriers: N=13) without this risk factor. All subjects (mean age: 62.3 years [SD=10.7]; range=38-86 years) were cognitively healthy. Family history of Alzheimer's disease and APOE-4 status were associated with a thinner cortex in the entorhinal region, subiculum, and adjacent medial temporal lobe subfields. Although these associations were additive, family history of Alzheimer's disease explained a greater proportion of the unique variance in cortical thickness than APOE-4 carrier status. APOE-4 carrier status and family history of Alzheimer's disease are independently associated with and contribute additively to hippocampal cortical thinning.


Low Protein Intake Is Associated with Frailty in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies.
(1) Background: Several factors have been suggested to be associated with the physiopathology of frailty in older adults, and nutrition (especially protein intake) has been attributed fundamental importance in this context. The objective of this study was to conduct a systematic review and meta-analysis to investigate the relationship between protein intake and frailty status in older adults. (2) Methods: A search of scientific studies was conducted in the main databases (Medline, Scopus, Cochrane library), and in the reference lists of selected articles. The search terms included synonyms and Medical Subject Headings and involved the use of Boolean operators which allowed the combination of words and search terms. Observational studies-cross-sectional and longitudinal-that met the eligibility criteria were included in the review. Article selection and data extraction were performed by two independent reviewers. Meta-analyses with random effects were performed. Publication bias was measured using the Strengthening the Reporting of Observational Studies in Epidemiology instrument. (3) Results: In the final sample, 10 articles, seven cross-sectional and three longitudinal, were included in the present study. Overall, studies investigated a total of 50,284 older adults from three different continents between 2006 and 2018. Four cross-sectional studies were included in the meta-analyses. The results demonstrated that a high protein intake was negatively associated with frailty status in older adults (odds ratio: 0.67, confidence interval = 0.56 to 0.82, p = 0.0001). (4) Conclusions: Our findings suggest that a high consumption of dietary protein is inversely associated with frailty in older adults.


Vagovagal reflex motility patterns of the rat esophagus.
Esophageal reflex motility and its neural correlates were investigated in 94 urethan-anesthetized adult male albino rats. When distended by means of a stationary balloon, the cervical and thoracic esophageal portion responded with a single pressure wave (type I response), whereas the diaphragmatic (intercrural) segment exhibited rhythmic contractions (type II response). Balloon deflation resulted in an off response aboral to the balloon. Bilateral cervical vagotomy or systemic D-tubocurarine abolished all types of reflex responses. Both type I and type II responses were associated with multiunit discharges in the central subnucleus of the solitary tract complex (NTSC) and the compact formation of the nucleus ambiguus (AMBC). Type I discharges, consisting of single bursts, and type II discharges, consisting of rhythmic 0.6-Hz bursts, preceded intraesophageal pressure waves in a fixed phase relationship, persisted after contralateral vagotomy, and were eliminated by ipsilateral vagotomy. During neuromuscular paralysis, peak intraburst discharge rates were reduced in both the NTSC and AMBC, with a concomitant decrease in rhythmicity. It is concluded that bolusevoked peristalsis of the rat esophagus is 1) segmentally organized; 2) effected by a bilateral uncrossed reflex arc consisting of vagal viscerosensory, NTSC premotor, and AMBC motoneurons innervating the striated muscle tunic and 3) strongly facilitated by reafferent feedback.


Stroma AReactive Invasion Front Areas (SARIFA) proves prognostic relevance in gastric carcinoma and is based on a tumor-adipocyte interaction indicating an altered immune response.
Recently, we presented Stroma AReactive Invasion Front Areas (SARIFA) as a new histomorphologic negative prognostic biomarker in gastric cancer. It is defined as direct contact between tumor cells and fat cells. The aim of this study was to further elucidate the underlying genomic, transcriptional, and immunological mechanisms of the SARIFA phenomenon. To address these questions, SARIFA was classified on H&E-stained tissue sections of three cohorts: an external cohort (n = 489, prognostic validation), the TCGA-STAD cohort (n = 194, genomic and transcriptomic analysis), and a local cohort (n = 60, digital spatial profiling (whole transcriptome) and double RNA in situ hybridization/immunostaining of cytokines). SARIFA status proved to be an independent negative prognostic factor for overall survival in an external cohort of gastric carcinomas. In TCGA-STAD cohort, SARIFA is not driven by distinct genomic alterations, whereas the gene expression analyses showed an upregulation of FABP4 in SARIFA-positive tumors. In addition, the transcriptional regulations of white adipocyte differentiation, triglyceride metabolism, and catabolism were upregulated in pathway analyses. In the DSP analysis of SARIFA-positive tumors, FABP4 and the transcriptional regulation of white adipocyte differentiation were upregulated in macrophages. Additionally, a significantly lower expression of the cytokines IL6 and TNFα was observed at the invasion front. SARIFA proves to be a strong negative prognostic biomarker in advanced gastric cancer, implicating an interaction of tumor cells with tumor-promoting adipocytes with crucial changes in tumor cell metabolism. SARIFA is not driven by tumor genetics but is very likely driven by an altered immune response as a causative mechanism.


Recurrence of childhood multiple tic in late adult life.
In contrast to the lifelong persistence of symptoms characteristic of Gilles de la Tourette's syndrome, multiple tic of childhood is considered to be a self-limited disorder that remits by early adulthood. We describe four patients who had a history of multiple tic of childhood, complete absence of tics throughout most of their adult lives, and recurrence of tics in late adult life. All four had multiple tics that began before the age of 9 years and included both motor and vocal tics that changed in location and severity over time. None of the patients exhibited coprolalia. All tics subsided before the age of 20 years, only to recur after the age of 60 years, once again including both motor and vocal tics that changed in location and severity slowly over time. The one patient who was severely bothered by the recurrence of motor and vocal tics responded well to haloperidol. Although they do not fit into any accepted diagnostic category for multiple tic, these patients suggest that multiple tic of childhood can recur in adult life. This suggests that Gilles de la Tourette's syndrome may be a continuum for chronic multiple tic of childhood to full-blown classic Gilles de la Tourette's syndrome.


Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs.
Determining the mechanism of gene function is greatly enhanced using conditional mutagenesis. However, generating engineered conditional alleles is inefficient and has only been widely used in mice. Importantly, multiplex conditional mutagenesis requires extensive breeding. Here we demonstrate a system for one-generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We describe five distinct zebrafish U6 promoters for sgRNA expression and demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin receptor a and b, resulting in defects in pigmentation and glucose homeostasis. Furthermore, we demonstrate temporal and tissue-specific mutagenesis using transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts insulin receptor a and b, causing fasting hypoglycemia and postprandial hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye leads to impaired damage-induced photoreceptor regeneration. Our findings suggest that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible but rapid and straightforward.


Forensic and homeland security applications of modern portable Raman spectroscopy.
Modern detection and identification of chemical and biological hazards within the forensic and homeland security contexts may well require conducting the analysis in field while adapting a non-contact approach to the hazard. Technological achievements on both surface and resonance enhancement Raman scattering re-developed Raman spectroscopy to become the most adaptable spectroscopy technique for stand-off and non-contact analysis of hazards. On the other hand, spatially offset Raman spectroscopy proved to be very valuable for non-invasive chemical analysis of hazards concealed within non-transparent containers and packaging.


"I have to do it in secrecy": Provider Perspectives on HIV Service Delivery and Quality of Care for Key Populations in Zambia.
Key populations (KPs) experience suboptimal outcomes along the HIV care and prevention continua, but there is limited study of the challenges service providers encounter delivering HIV services to KPs, particularly in settings like Zambia, where provision of these services remains legally ambiguous. Seventy-seven providers completed in-depth interviews exploring constraints to HIV service delivery for KPs and recommendations for improving access and care quality. Thematic analysis identified salient challenges and opportunities to service delivery and quality of care for KPs, spanning interpersonal, institutional, and structural domains. Limited provider training in KP-specific needs was perceived to influence KP disclosure patterns in clinical settings, impeding service quality. The criminalization of KP sexual and drug use behaviors, coupled with perceived institutional and legal ambiguities to providing HIV services to KPs, cultivated unwelcoming service delivery environments for KPs. Findings elucidate opportunities for improving HIV service delivery/quality, from decentralized care to expanded legal protections for KPs and service providers.


Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study.
To predict the occurrence of inactive disease in JIA in the first 2 years of disease. An inception cohort of 152 treatment-naïve JIA patients with disease duration <6 months was analysed. Potential predictors were baseline clinical variables, joint US, gut microbiota composition and a panel of inflammation-related compounds in blood plasma. Various algorithms were employed to predict inactive disease according to Wallace criteria at 6-month intervals in the first 2 years. Performance of the models was evaluated using the split-cohort technique. The cohort was analysed in its entirety, and separate models were developed for oligoarticular patients, polyarticular RF negative patients and ANA positive patients. All models analysing the cohort as a whole showed poor performance in test data [area under the curve (AUC): <0.65]. The subgroup models performed better. Inactive disease was predicted by lower baseline juvenile arthritis DAS (JADAS)-71 and lower relative abundance of the operational taxonomic unit Mogibacteriaceae for oligoarticular patients (AUC in test data: 0.69); shorter duration of morning stiffness, higher haemoglobin and lower CXCL-9 levels at baseline for polyarticular RF negative patients (AUC in test data: 0.69); and shorter duration of morning stiffness and higher baseline haemoglobin for ANA positive patients (AUC in test data: 0.72). Inactive disease could not be predicted with satisfactory accuracy in the whole cohort, likely due to disease heterogeneity. Interesting predictors were found in more homogeneous subgroups. These need to be validated in future studies.


Successful emergency medical service training with virtual field trips using video during the COVID-19 pandemic: the Official Development Assistance Project in Uzbekistan.
The coronavirus disease 2019 pandemic saw many restrictions on the provision of emergency medical service (EMS) training through actual field trips (AFTs), requiring a search for alternatives. This study aimed to assess trainees' reactions to virtual field trips (VFTs) and determine the characteristics of instructional design for successful VFTs using edited videos and expert interviews. This study evaluated Uzbekistan trainees' reactions to the VFT of EMS training using questionnaires in three categories: satisfaction, relevance, and engagement. Factors of satisfaction and dissatisfaction were identified through open-ended questions. A total of 286 trainees responded to the survey during 15 educational sessions conducted from 2020 to 2022. The trainees' responses to the VFT were positive. Overall mean scores were 4.65±0.49, 4.63±0.50, and 4.63±0.50 out of 5 points for satisfaction, relevance, and engagement, respectively. The trainees reported that the most interesting and helpful videos concerned the introduction of an EMS training curriculum and the observation of training facilities, such as the simulation centers of educational institutes. The leading causes of satisfaction were (1) authenticity of the VFTs, (2) easy-to-understand content, and (3) relevance to the job. The trainees suggested that Uzbek or Russian voice-overs would be better than subtitles in the video clip for focusing on VFT. In situations where AFTs are not available, VFTs using edited videos and expert interviews are a good alternative to EMS education. Based on these results, it is possible that AFTs could be replaced by VFTs using qualified videos with designed instructions as a distance learning method under specific conditions.


[Quality of life and health promotion in students of professional education institutions].
Evaluation of quality of life in adolescents attending professional education institutions revealed significant difference between their socio-medical characteristics and those of pupils in schools providing general education. The main risk factors in the two groups are identified. It is shown that social conditions, mode of teaching, and life style may contribute to the deterioration of health status and functional abilities of adolescents. The data obtained can be used in the elaboration of health protection programs for students of professional education institutions.


p21-activated protein kinase gamma-PAK is activated by ionizing radiation and other DNA-damaging agents. Similarities and differences to alpha-PAK.
The p21-activated protein kinase gamma-PAK is activated 2-5-fold in response to ionizing radiation (IR) in 3T3-L1 fibroblasts and U937 leukemia cells. gamma-PAK is activated in a dose- and time-dependent manner. Doses from 1 to 100 Gy result in significant stimulation of activity at 30 min, whereas maximal stimulation is observed at 120 min after irradiation. UV (80 J/m(2)) and the DNA-damaging drugs cytosine beta-D-arabinofuranoside (AraC) and cis-platinum(II)diammine dichloride (cisplatin) also induce gamma-PAK activation. The activation of gamma-PAK in response to IR or AraC is dependent on tyrosine kinase and phosphoinositide 3-kinase activity, as demonstrated by use of the inhibitors genistein and wortmannin; in contrast activation of gamma-PAK by cisplatin and UV is not affected significantly by these inhibitors, suggesting that gamma-PAK can be activated by more than one pathway in response to different types of DNA damage. In contrast to gamma-PAK, alpha-PAK and JNK are activated only by cisplatin and UV in 3T3-L1 cells, suggesting differential regulation of the protein kinases. This is the first time that members of the Ste20/PAK family of protein kinases have been shown to be involved in the cellular response to IR and other DNA-damaging agents.


A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.
Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO.


Proprioceptive Stabilizer™ training of the abdominal wall muscles in healthy subjects: a quasi-experimental study.
The present quasi-experimental study aimed to assess the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) thickness in healthy subjects with the proprioceptive Stabilizer™ training in abdominal wall muscles. A sample of 41 healthy participants (age: 31.9 ± 4.5 y; height: 1.7 ± 0.1 m; weight: 68.3 ± 13.1 kg; body mass index, BMI: 22.9 ± 2.7 kg/m2) were recruited to participate in this study. Ultrasound images of the EO, IO, TrA, rectus anterior (RA) and interrecti distance (IRD) were measured and analyzed by the ImageJ software. Measurements were made at rest and during the abdominal drawing-maneuver (ADIM) developed by the patients with the Stabilizer™ located in the low back holding 40 mmHg for 10 seconds with a visual stimulus provided by a circular pressure marker. Ultrasound measurements for the abdominal wall muscles showed statistically significant differences (Π < .05) for a thickness decrease of the EO, IO and a thickness increase of TrA. A proprioceptive Stabilizer™ training produced a thickness increase in TrA muscle and a thickness decrease in EO and IO muscles in healthy subjects. These findings suggest that a proprioceptive Stabilizer™ training could be useful in individuals with low back pain and lumbopelvic pain.


Marine Polyphenol Phlorotannins as a Natural Sleep Aid for Treatment of Insomnia: A Review of Sedative-Hypnotic Effects and Mechanism of Action.
Insomnia is a common sleep disorder. Natural sleep aids are gaining worldwide popularity as alternatives to prescription drugs for improving sleep. Recently, numerous studies have investigated the sedative-hypnotic effects of the polyphenols of terrestrial plants. The hypnotic effects of marine polyphenols have also been studied in recent years. Phlorotannins are marine polyphenols that are found only in brown algae. Phlorotannins exert sedative-hypnotic effects via the gamma-aminobutyric acid type A-benzodiazepine receptor. In addition, the brown seaweed Ecklonia cava supplement containing phlorotannins has been approved by the Ministry of Food and Drug Safety as a health-functional ingredient that helps improve sleep quality. Currently, it is meaningful to deal with the sedative-hypnotic effects of phlorotannins as natural sleep aids. The current review comprehensively presents the sedative-hypnotic effects in animal models and human clinical trials as well as their mechanism of action, extraction, purification, and safety.


Resuscitating the tracheostomy patient in the ED.
Emergency physicians must be masters of the airway. The patient with tracheostomy can present with complications, and because of anatomy, airway and resuscitation measures can present several unique challenges. Understanding tracheostomy basics, features, and complications will assist in the emergency medicine management of these patients. The aim of this review is to provide an overview of the basics and features of the tracheostomy, along with an approach to managing tracheostomy complications. This review provides background on the reasons for tracheostomy placement, basics of tracheostomy, and tracheostomy tube features. Emergency physicians will be faced with complications from these airway devices, including tracheostomy obstruction, decannulation or tube dislodgement, stenosis, tracheoinnominate fistula, and tracheoesophageal fistula. Critical patients should be evaluated in the resuscitation bay, and consultation with ENT should be completed while the patient is in the department. This review provides several algorithms for management of complications. Understanding these complications and an approach to airway management during cardiac arrest resuscitation is essential to optimizing patient care. Tracheostomy patients can present unique challenges for emergency physicians. Knowledge of the basics and features of tracheostomy tubes can assist physicians in managing life-threatening complications including tube obstruction, decannulation, bleeding, stenosis, and fistula.


Furosemide's one little hydrogen atom: NMR crystallography structure verification of powdered molecular organics.
The potential of NMR crystallography to verify molecular crystal structures deposited in structural databases is evaluated, with two structures of the pharmaceutical furosemide serving as examples. While the structures differ in the placement of one H atom, using this approach, we verify one of the structures in the Cambridge Structural Database using quantitative tools, while establishing that the other structure does not meet the verification criteria.


Evolutionary classification of ammonium, nitrate, and peptide transporters in land plants.
Nitrogen uptake, reallocation within the plant, and between subcellular compartments involves ammonium, nitrate and peptide transporters. Ammonium transporters are separated into two distinct families (AMT1 and AMT2), each comprised of five members on average in angiosperms. Nitrate transporters also form two discrete families (NRT1 and NRT2), with angiosperms having four NRT2s, on average. NRT1s share an evolutionary history with peptide transporters (PTRs). The NRT1/PTR family in land plants usually has more than 50 members and contains also members with distinct activities, such as glucosinolate and abscisic acid transport. Phylogenetic reconstructions of each family across 20 land plant species with available genome sequences were supplemented with subcellular localization and transmembrane topology predictions. This revealed that both AMT families diverged prior to the separation of bryophytes and vascular plants forming two distinct clans, designated as supergroups, each. Ten supergroups were identified for the NRT1/PTR family. It is apparent that nitrate and peptide transport within the NRT1/PTR family is polyphyletic, that is, nitrate and/or peptide transport likely evolved multiple times within land plants. The NRT2 family separated into two distinct clans early in vascular plant evolution. Subsequent duplications occurring prior to the eudicot/monocot separation led to the existence of two AMT1, six AMT2, 31 NRT1/PTR, and two NRT2 clans, designated as groups. Phylogenetic separation of groups suggests functional divergence within the angiosperms for each family. Distinct groups within the NRT1/PTR family appear to separate peptide and nitrate transport activities as well as other activities contained within the family, for example nitrite transport. Conversely, distinct activities, such as abscisic acid and glucosinolate transport, appear to have recently evolved from nitrate transporters.


[Implicaciones psiquiátricas y neurológicas en la literatura shakespeariana. Breve análisis].
William Shakespeare (1564-1616) is with no doubt one of the most prolific literary artists of all times; in addition to being an eminent playwright, his works reflect arguments that express medical knowledge, allude to concise descriptions that are relevant to medical practice of that time, and even to current medicine. He wrote between 35 and 38 plays, six lyric works and 154 sonnets (approximately) where finding little more than 700 references to medicine of those days is possible. For this reason, different scholars have analyzed the medical concepts within the Shakespearean literature; some agree that these may be the result of studies of his own, while others suggest that Shakespeare repeated the medical knowledge of some "men of wisdom" of his time. It should be mentioned that the author's contemporary London society lived in an overpopulated, nauseating, sexually promiscuous city that was plagued by pests and waste and continually besieged by epidemics whose treatments many times caused greater evil than benefit (for example, lead-based make-up). Some biographers credit syphilis, alcohol, and depression as the source of Shakespeare's creative production. Despite the myriad of authors who have analyzed the insinuations about medicine in Shakespeare's dramatic accounts, Sigmund Freud (1856-1939) is perhaps the most important; throughout his career he carried out a substantial analysis of the English playwright's works owing to his passion for literature and for this author.


Correlation of plasmid type and disease caused by Coxiella burnetii.
The obligate intracellular bacterium Coxiella burnetii is the etiological agent of acute Q-fever and chronic endocarditis in humans and of several zoonotic infections. The DNA from a variety of these disease isolates was compared for homology to the plasmid QpH1, found in the Nine Mile strain. Three patterns of homology were found in these isolates, i.e., one pattern identical to that of QpH1, one common to several endocarditis isolates and goat abortion isolates, and one common to the remaining group of endocarditis isolates. Plasmid DNA from the endocarditis-abortion isolate group, designated QpRS, was mapped by restriction enzyme analysis and compared with QpH1. These data show that QpRS was 2 to 3 kilobase pairs larger, contained DNA not found in QpH1, but was not generated from QpH1 by a single insertional event. Isolation of plasmid DNA from the second endocarditis group of isolates was not successful and may indicate that the plasmid has integrated into the chromosome. This analysis provides the first clear evidence that differences exist between C. burnetii isolates which cause various diseases, indicating that different C. burnetii strains may have unique virulence characteristics.