Functional analysis of encapsulated hepatic progenitor cells.
A major challenge in developing therapies based on progenitor or stem cell populations (from sources other than bone marrow) involves developing a mode to deliver these cells in a manner that optimizes their viability, engraftment, proliferation, and differentiation. We have previously isolated a hepatic progenitor cell (HPC) population from adult liver tissue that differentiates into hepatic and biliary cell subtypes. We postulated that, using electrostatic encapsulation, we could reproducibly generate an ex vivo environment for the HPCs. We also theorized that this approach would foster cellular viability and function of the progenitor cell population. Using this encapsulation process, we consistently produced beads with uniform diameters between 200 and 700 microm. In vitro analysis of the encapsulated beads demonstrated extended periods of viability and function based on albumin production, urea metabolism, and glycogen storage. In conclusion, HPC encapsulation fosters the subsequent differentiation of HPCs into functional cells while maintaining their viability in long-term culture. These results demonstrate the efficacy of this method using somatic-derived progenitor cell populations and pave the way for clinical therapies.


Evaluation of an algorithmic approach to pediatric back pain.
Pediatric patients require a systematic approach to treating back pain that minimizes the number of diagnostic studies without missing specific diagnoses. This study reviews an algorithm for the evaluation of pediatric back pain and assesses critical factors in the history and physical examination that are predictive of specific diagnoses. Eighty-seven pediatric patients with thoracic and/or lumbar back pain were treated utilizing after this algorithm. If initial plain radiographs were positive, patients were considered to have a specific diagnosis. If negative, patients with constant pain, night pain, radicular pain, and/or an abnormal neurological examination obtained a follow-up magnetic resonance imaging. Patients with negative radiographs and intermittent pain were diagnosed with nonspecific back pain. Twenty-one (24%) of 87 patients had positive radiographs and were treated for their specific diagnoses. Nineteen (29%) of 66 patients with negative radiographs had constant pain, night pain, radicular pain, and/or an abnormal neurological examination. Ten of these 19 patients had a specific diagnosis determined by magnetic resonance imaging. Therefore, 31 (36%) of 87 patients had a specific diagnosis. Back pain of other 56 patients was of a nonspecific nature. No specific diagnoses were missed at latest follow-up. Specificity for determining a specific diagnosis was very high for radicular pain (100%), abnormal neurological examination (100%), and night pain (95%). Radicular pain and an abnormal neurological examination also had high positive predictive value (100%). Lumbar pain was the most sensitive (67%) and had the highest negative predictive value (75%). This algorithm seems to be an effective tool for diagnosing pediatric back pain, and this should help to reduce costs and patient/family anxiety and to avoid unnecessary radiation exposure.


Coronavirus Disease-2019 Pneumonia and Pulmonary Embolism: Presentation of Four Cases.
Since the beginning of the Coronavirus Disease-2019 (COVID-19) outbreak, elevated D-dimer levels as an acute-phase reactant have been reported in some patients. Additionally, the patients with pneumonia are at increased risk of developing thromboembolic events. Diagnosing acute pulmonary embolism and deep vein thrombosis can be challenging in SARS-CoV2-positive patients. Here, we report four patients with COVID-19 pneumonia to highlight the possibility of acute thromboembolism in these patients. The physicians should be aware of this complication and even consider prophylactic anticoagulant therapy in proper clinical settings. How to cite this article: Alikhani F, Aalinezhad M, Haji Rezaei M, Akbari P, Hashemi M. Coronavirus Disease-2019 Pneumonia and Pulmonary Embolism: Presentation of Four Cases. Indian J Crit Care Med 2020;24(9):873-876.


Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer.
To evaluate the capability of a novel sentinel lymph node (SLN) mapping algorithm to reduce the need for pelvic lymphadenectomy (PLND) in patients with low-grade (G1-2) endometrial cancer (LGEC). Patients with LGEC underwent evaluation according to a novel lymphatic assessment algorithm during hysterectomy with SLN biopsy at two academic gynecologic oncology programs. Side-specific PLND was only performed if ipsilateral SLN mapping failed and high-risk uterine features were identified on frozen section (FS). Side-specific and PLND rates were compared to theoretical PLND rates based on the NCCN EC SLN mapping algorithm. Since 11/2015, 113 LGEC patients have been managed according to the algorithm. SLN mapping was bilateral (81%), unilateral (12%), or neither (6%). Nine patients (8.0%) had LN metastases identified. Of the 21 patients requiring intraoperative FS due to failed SLN mapping, high-risk uterine features were identified in eight (38%). These patients underwent either bilateral (2) or unilateral (6) PLND. Side-specific and overall PLND rates were 5.3% and 7.1%, respectively. If all patients with failed mapping had undergone PLND according to the NCCN algorithm, side-specific and overall PLND rates would have been higher, 12.4% and 18.6%, respectively (P=0.01). All patients who failed to map and did not undergo side-specific PLND had low-risk uterine features on final pathology. Lymphatic assessment using SLN mapping followed by selective FS to determine need for PLND is feasible. When compared to the NCCN algorithm, this novel "Reflex Frozen Section" strategy eliminates PLND in patients at lowest risk for metastasis without compromising identification of metastatic nodal disease.


The human parasite fauna: towards an analysis and interpretation.
A breakdown of the human parasite fauna shows approximately 270 species, with almost equal numbers of nematodes, flukes and protozoa and smaller numbers of arthropods and tapeworms. More than 70% are 'adventitious' species for which man is an incidental host. Only 16% are 'core' species, dependent on man for their survival. For 26% man is the usual source of human infection, and for 51% the source is other mammals. A sequence is illustrated showing how parasites may arrive by the host-transfer or co-evolutionary pathways. Adventitious parasites have a narrower geographical range than core species. The richest representation of the major species is in the Aethiopian Zoogeographical Region and the poorest is in the Australasian. Some 14 pairs of closely related forms occur in the main fauna. Some implications of this analysis with respect to man's early history are discussed speculatively.


Differences in Reproductive Behavior between Spawning and Non-Spawning Zebrafish Pairs and the Effects of 17α-Ethinylestradiol (EE2).
Reproductive success manifested by spawning and fertilization, in most fish, depends partly on an appropriate courtship behavior by both sexes. The zebrafish reproductive behavior can be resolved in some of its constituent elements by a computerized vision system and described in unbiased quantitative terms. Pairs of adult male and female zebrafish were monitored with automatic video tracking at 16 Hz for 45 min in a tank with a spawning area in one corner. Subsequently, spawning, if any, was registered and the swimming behavior and mutual interactions of the two fish were quantified. Further, temporal and frequency distributions of average velocity and turning rate were produced. It is demonstrated that the courtship behavior in spawning pairs differs markedly from non-spawning pairs with differences in both male and female behavior. EE2 (17α-ethinylestradiol), a contraceptive hormone found in aquatic environments, has only a slight effect on these behavior differences between spawning and non-spawning pairs.


The epidemiology of HIV transmission: trends, structure and dynamics.
"This review summarizes dynamic processes in human immunodeficiency virus (HIV) transmission. A brief overview of current trends in the HIV epidemic is followed by a discussion of the basic components of HIV transmission. Several epidemiologic models are then described that seek to delineate how HIV transmission is structured by human relationships and the implications of those structural relationships for the evolving epidemic."


A new two-dimensional cadmium(II) coordination polymer based on the asymmetric dicarboxylic acid homophthalic acid: synthesis, structure and properties.
A new coordination polymer poly[[μ2-4,4'-bis(2-methylimidazol-1-yl)biphenyl-κ2N3:N3']bis[μ3-2-(2-carboxylatophenyl)acetato-κ5O,O':O',O'':O'']dicadmium(II)], [Cd(C9H6O4)(C20H18N4)0.5]n or [Cd(HMPH)(4,4'-BMIBP)0.5]n [H2HMPH is homophthalic acid and 4,4'-BMIBP is 4,4'-bis(2-methylimidazol-1-yl)biphenyl], (I), was synthesized by the solvothermal method and was structurally characterized by means of single-crystal X-ray diffraction, IR spectroscopy and elemental analysis. Coordination polymer (I) exhibits a two-dimensional layer based on one-dimensional [Cd(HMPH)]n chains. Remarkably, photocatalytic degradation experiments on methylene blue (MB) indicated that (I) exhibits an obvious degradation effect. Moreover, an investigation of the luminescence properties of (I) revealed that it could be considered as a potential highly selective luminescence sensor for nitrofurantoin (NFT).


LC-MS/MS study of the degradation processes of nitisinone and its by-products.
Nitisinone (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, NTBC) was the first synthetically produced triketone herbicide. However, its unsatisfactory herbicidal properties, negative impact on the natural environment and the high cost of synthesis have hindered its commercialization as a plant protection agent. Nevertheless, NTBC has become the medical treatment of choice for a rare hereditary metabolic disease -hepatorenal tyrosinemia. Literature review shows that most research on nitisinone focuses on its medical applications, while there are neither in-depth studies of its stability nor its degradation pathways. Therefore, the aim of our study was to employ liquid chromatography coupled with mass spectrometry (LC-MS/MS) to determine the stability of NTBC in different experimental conditions (pH of solution, temperature, time of incubation, ultraviolet radiation), identify its degradation products and determine the stability of the latter. Electrospray ionization (ESI) in the negative ion mode was used as an ionization method and the analytes were detected by multiple reaction monitoring. We show that nitisinone stability increases with increasing pH of the solution. At pH similar to that of gastric juice in the human stomach, two major products of NTBC degradation are formed: 2-amino-4-(trifluoromethyl)benzoic acid (ATFA) and 2-nitro-4-(trifluoromethyl)benzoic acid (NTFA), which show considerable stability under studied conditions. The results of these studies shed new light on the properties of NTBC, therefore contributing to better understanding of possible risks and benefits of its medical application.


Modeling of the thermal migration mechanisms of atomic oxygen in Ar, Kr, and Xe crystals.
Accommodation and migration of the ground-state (2s22p4 3P) oxygen atom in the ideal Ar, Kr, and Xe rare gas crystals are investigated using the classical model. The model accounts for anisotropy of interaction between guest and host atoms, spin-orbit coupling, and lattice relaxation. Interstitial and substitutional accommodations are found to be the only thermodynamically stable sites for trapping atomic oxygen. Mixing of electronic states coupled to lattice distortions justifies that its long-range thermal migration follows the adiabatic ground-state potential energy surface. Search for the migration paths reveals a common direct mechanism for interstitial diffusion. Substitutional atoms are activated by the point lattice defects, whereas the direct guest-host exchange meets a higher activation barrier. These three low-energy migration mechanisms provide plausible interpretation for multiple migration activation thresholds observed in Kr and Xe free-standing crystals, confirmed by reasonable agreement between calculated and measured activation energies. An important effect of interaction anisotropy and a minor role of spin-orbit coupling are emphasized.


Application of three focused cluster detection methods to study geographic variation in the incidence of multiple sclerosis in Manitoba, Canada.
Macroscopic geographic variation in the incidence and prevalence of MS is well-recognized. Microscopic geographic variation in the distribution of MS is also recognized, but less well-studied. Most studies have focused on prevalent cases of MS, although studies of variation in disease incidence are more relevant for developing etiologic hypotheses. We aimed to study geographic variation in the incidence of MS using three different methods. We used population-based administrative (health claims) data to identify 2,290 incident cases of MS in the province of Manitoba, Canada from 1990 to 2006. We applied three focused cluster-detection procedures, including the circular spatial scan statistic (CSS), flexible spatial scan statistic (FSS), and Bayesian disease mapping (BYM), to the dataset. The CSS and FSS methods identified 30 and 26 regions as potential clusters, respectively, although the regions identified differed slightly due to the non-circular shape of some regions in Manitoba. The BYM approach identified 37 regions as potential clusters, again with some differences as compared to the other two methods. Twelve regions were identified as potential clusters by all three methods. All methods identified the western part of the city of Winnipeg as a significant cluster. Using the BYM approach, the incidence of MS was highest among areas of higher socioeconomic status. Two methods CSS and FSS only capture geographical variations and are not able to control for confounders at the same time which may lead to mis-identification of clusters. However, the BYM method can simultaneously identify geographical variations and control for possible confounders.


Fine Sampling of the R→T Quaternary-Structure Transition of a Tetrameric Hemoglobin.
Although the end points of the functional transitions of tetrameric hemoglobins (Hbs) have been well characterized, atomic-resolution data on R-T intermediate states are extremely limited. Herein, the X-ray structures of two independent tetramers of the fully ligated carbomonoxy form of Trematomus newnesi hemoglobin (Hb1Tn) within the same crystal are described. These structures show peculiar features in the heme pocket, EF corner, and tertiary/quaternary structure. Distal histidine side chains have a propensity to swing out of the heme pocket and thus allow compression of the EF corner. In this rotameric state, the distal His group does not interact with the CO ligand, consistent with FTIR spectra recorded in solution. At the quaternary-structure level, one tetramer is an intermediate R-T state, whereas the other assumes a T-like structure. Altogether, the structures of these tetramers provide the best available atomic-level picture of the R→T transition of vertebrate Hbs.


PTSD diagnoses among Iraq and Afghanistan veterans: comparison of administrative data to chart review.
To guide budgetary and policy-level decisions, the U.S. Department of Veterans Affairs (VA) produces quarterly reports that count the number of Iraq and Afghanistan veterans with International Classification of Diseases, 9(th) Revision, Clinical Modification (ICD-9-CM) codes for posttraumatic stress disorder (PTSD; 309.81) in their electronic medical record administrative data. We explored the accuracy of VA administrative data (i.e., diagnostic codes used for billing purposes), by comparing it to chart review evidence of PTSD (i.e., medical progress notes and all other clinical documentation contained in the entire VA medical record). We reviewed VA electronic medical records for a nationwide sample of 1,000 Iraq and Afghanistan veterans with at least one ICD-9-CM code for PTSD in their VA administrative data. Among veterans sampled, 99.9% had 2 or more ICD-9-CM codes for PTSD. Reviewing all VA electronic medical record notes for these 1,000 veterans for the full course of their VA health care history revealed that PTSD was diagnosed by a mental health provider for 89.6%, refuted for 5.6%, and PTSD was never evaluated by a mental health provider for 4.8%. VA treatment notes for the 12 months preceding chart review showed that 661 veterans sampled received a VA PTSD diagnosis during that 12-month timeframe, and of these 555 were diagnosed by a mental health provider (83.9%). Thus, the presence of an ICD-9-CM code for PTSD approximated diagnoses by VA mental health providers across time points (89.6% for entire treatment history and 83.9% for 12 months prior to chart review). Administrative data offer large-scale means to track diagnoses and treatment utilization; however, their limitations are many, including the inability to detect false-negatives.


Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models.
The objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid peroxidation products depend on both the duration and severity of the exposure to hypoxia. Largest effects are observed with exposure to hypoxia at high altitude, but other factors, including ultraviolet light, exercise, exertion, and low intake of antioxidants, might contribute to the effect observed in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity.


Hydrogen bonding and pi-pi stacking in hexaaquairon(II) bis(4',7-dimethoxyisoflavone-3'-sulfonate) octahydrate.
In the structure of the title compound, [Fe(H2O)6](C17H13O7S)2.8H2O, 16 hydrogen bonds exist between the centrosymmetric [Fe(H2O)6]2+ cation, the isoflavone-3'-sulfonate anions and the coordinated and solvent water molecules. pi-pi stacking interactions between the isoflavone units, hydrogen bonding and electrostatic interactions result in a three-dimensional supramolecular structure.


The Effect of Diagnosis-Related Groups on the Shift of Medical Services From Inpatient to Outpatient Settings: A National Claims-Based Analysis.
The purpose of this study was to determine whether the introduction of diagnosis-related groups (DRGs) shifted the medical services from inpatient to outpatient settings. Using a difference-in-difference analysis, the changes in length of stay, outpatient visit days within 30 days before hospitalization, and outpatient visit days within 30 days after hospital discharge were evaluated. The length of stay was reduced after the DRG policy, consistent with previous studies. Outpatient visit days within 30 days before a hospital admission increased significantly after the policy change. In addition, outpatient visit days within 30 days after a hospital discharge increased in all the medical institutions excluding hospitals. The study findings are consistent with the expectation that providers respond to changes in the payment system to protect or enhance their economic interests. Health care providers in Korea responded to the DRG policy by reducing the intensity of inpatient treatment and transferring costs to outpatient settings.


Toxic effects of octylphenol on cultured rat and murine splenocytes.
Alkylphenol polyethoxylates and alkylphenols, such as 4-tertoctylphenol (OP), are environmental contaminants. Because these compounds are toxic to aquatic animals, we studied the effects of OP on splenocytes removed from male Fischer 344 rats or male Balb/c mice and cultured in vitro. Cell viability was assessed by trypan blue exclusion after 5 or 27 hr of culture. Culture with 0.08% ETOH (vehicle) or any dose of OP did not alter total cell number or the percentage of viable cells after 5 hr. Culture of cells with two different alkylphenol polyethoxylates for 5 hr resulted in the loss of all cells. The percentages of viable rat or mouse cells after 27 hr of culture were decreased significantly by 10(-12) M OP or greater concentrations. The actions of OP, dexamethasone (DEX), and 17 beta-estradiol on rat splenocytes were compared. Dexamethasone was more toxic than OP after 24 hr of culture; 17 beta-estradiol was not toxic. Dexamethasone and OP, but not 17 beta-estradiol, caused significant nuclear condensation after 3 hr of culture (acridine orange staining) or 4 hr of culture (propidium iodide staining). The toxicity of 10(-6) M OP, but not that of 10(-6) M DEX, was eliminated when mouse splenocytes were cultured in Ca2+ -free medium. Significantly more mouse splenocytes containing free 3'-OH DNA ends were detected by activated cell sorter analyses when the cells had been incubated for 4 hr with 10(-4) or 10(-6) M OP or 10(-6) M DEX. The results of these studies demonstrate that OP is toxic to cultured rat and mouse splenocytes and suggest that this toxic effect is exerted, at least partially, through Ca2+-dependent apoptosis.


Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.
There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations.


Ultra-broadband Nonlinear Saturable Absorption for Two-dimensional Bi2TexSe3-x Nanosheets.
We report the ultra-broadband nonlinear optical (NLO) response of Bi2TexSe3-x nanosheets produced by a facile solvothermal method. Our result show that the extracted basic optical nonlinearity parameters of Bi2TexSe3-x nanosheets, αNL, Imχ((3)), and FOM reach ~10(4) cm/GW, ~10(-8) esu and ~10(-13) esu cm, respectively, which are several orders of magnitude larger than those of bulk dielectrics. We further observed the excitation intensity dependence of the NLO absorption coefficient and the NLO response sensitivity. The mechanisms of those phenomena were proposed based on physical model. The wavelength dependence of the NLO response of Bi2TexSe3-x nanosheets was investigated, and we determined that the Bi2TexSe3-x nanosheets possess an ultra-broadband nonlinear saturable absorption property covering a range from the visible to the near-infrared band, with the NLO absorption insensitive to the excitation wavelength. This work provide fundamental and systematic insight into the NLO response of Bi2TexSe3-x nanosheets and support their application in photonic devices in the future.


[Thrombolysis during cardiopulmonary resuscitation].
Between 40 and 90 cardiopulmonary resuscitations are performed per 100,000 inhabitants each year in western industrialised nations. In 50-70% of these patients, either fulminant pulmonary embolism or acute myocardial infarction is the underlying cause of cardiac arrest. Based on this fact, thrombolysis may represent a new and effective causal therapeutic strategy in patients suffering from cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. In the past, thrombolysis was contraindicated during cardiopulmonary resuscitation due to great fears of severe bleeding complications (resuscitation-mediated or lysis-induced intracerebral bleeding). For a long time, only clinical case reports or small clinical case series were reported in the literature, however, recently, the first clinical studies focusing on the safety and efficacy of thrombolytic therapy during out-of-hospital cardiopulmonary resuscitation have been published. Besides a specific therapeutic causal effect on pulmonary artery emboli and coronary artery thrombosis, experimental data strongly indicate that thrombolysis might also have an impact on cerebral microcirculatory reperfusion during and after cardiopulmonary resuscitation. This effect might be responsible for the exceptionally good neurological outcome observed in patients treated with thrombolytic agents during cardiopulmonary resuscitation and might be a result of the proven imbalance of the endogenous coagulation system in patients suffering from cardiac arrest. This coagulation imbalance is thought to be responsible for postresuscitation cerebral microcirculatory reperfusion disorders in patients after cardiac arrest and cardiopulmonary resuscitation. In summary, recent clinical and experimental data focusing on thrombolysis during cardiopulmonary resuscitation strongly indicate, that thrombolysis may represent a new and relatively safe therapeutic option during resuscitation after cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. If the results of an international randomised, controlled clinical multicentre trial presently underway confirm the previous clinical findings, thrombolysis during cardiopulmonary resuscitation could become an important part of future cardiopulmonary resuscitation algorithms.


Parental cancer: catalyst for positive growth and change.
Cancer is a disease that affects the entire family, with each member having unique psychological needs. To date, there has been limited research into the effect of parental cancer on adult children. Furthermore, existing research has largely overlooked the possibility of positive psychological growth in the adult offspring of cancer patients. To investigate the perceived benefits arising from parental cancer, 11 interviews were undertaken with adults whose parents had been diagnosed with cancer, to discuss their experiences of their parent's illness, and their evaluation of both the positive and negative changes that had arisen. All participants were able to identify positive outcomes in direct response to their parent's cancer. Frequently suggested changes included improved relationships with their sick parent, an increased emphasis on family, revised life priorities, and personal development. The implications of these findings, their link to posttraumatic growth theory, and avenues for future research are discussed.


Biomechanical evaluation of the anterior drawer test: the contribution of the lateral ankle ligaments.
The contributions of the lateral ankle ligaments to resisting anterior-posterior displacement of the talus were evaluated in eight unembalmed cadaveric ankles. While holding the distal tibia fixed, loads of 150 N were applied to the talus in the anterior and posterior directions in the neutral, dorsiflexed, and plantarflexed positions using an hydraulic test system. Tests were performed on the intact specimens then after sequential sectioning of the lateral ligaments of the ankle. Under strictly anteroposterior loading and without an axial (weight-bearing) load applied, no single ligament could be isolated as having a dominant stabilizing function.


Emerging Role of Oxidative Stress on EGFR and OGG1-BER Cross-Regulation: Implications in Thyroid Physiopathology.
Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, the molecular mechanisms concerning the role of oxidative stress remain elusive. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyperactivation of mitogen-activated protein kinase (MAPK) and PI3K/Akt, which mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationships between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K/Akt and MAPK/ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a human non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the results obtained by gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/PTC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells). Gene expression data also delineated that MUTYH gene could play a physiological role in crosstalk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall, our data on OGG1 protein expression suggest that it was physiologically regulated in response to oxidative modulation of ErbB, and that these might be dysregulated in the signaling pathway involving AKT in the progression of thyroid malignancies with RET/PTC rearrangements.


FADD is required for multiple signaling events downstream of the receptor Fas.
To identify essential components of the Fas-induced apoptotic signaling pathway, Jurkat T lymphocytes were chemically mutagenized and selected for clones that were resistant to Fas-induced apoptosis. We obtained five cell lines that contain mutations in the adaptor FADD. All five cell lines did not express FADD by immunoblot analysis and were completely resistant to Fas-induced death. Complementation of the FADD mutant cell lines with wild-type FADD restored Fas-mediated apoptosis. Fas activation of caspase-2, caspase-3, caspase-7, and caspase-8 and the proteolytic cleavage of substrates such as BID, protein kinase Cdelta, and poly(ADP-ribose) polymerase were completely defective in the FADD mutant cell lines. In addition, Fas activation of the stress kinases p38 and c-Jun NH2 kinase and the generation of ceramide in response to Fas ligation were blocked in the FADD mutant cell lines. These data indicate that FADD is essential for multiple signaling events downstream of Fas.


Basing drug scheduling decisions on scientific ranking of harmfulness: false promise from false premises.
In recent years a number of studies have attempted to rank drugs by a single measure of harmfulness as the basis for decisions about scheduling and classification. These efforts are fundamentally flawed, both conceptually and methodologically. The effort to provide a single measure masks the variety of non-comparable dimensions that are relevant, the fact that benefits are ignored for most, but not all, drugs and that the harms of a drug are not invariant to the policy regime chosen. Methodologically, the most prominent recent effort ignores drug interactions and mixes aggregate and individual harms inappropriately. Instead we suggest that multiple dimensions of harm need to be displayed to inform human judgments of what drugs should be scheduled. Harm is not usefully reducible to a single dimension, and even perfect rankings would not constitute a 'sufficient statistic' for determining scheduling decisions.


Soy Food Intake Associated with Obesity and Hypertension in Children and Adolescents in Guangzhou, Southern China.
The associations between soy food intake and cardio-metabolic risk factors in children remain unclear due to limited evidence. We aim to explore soy food intake and its association with the risks of obesity and hypertension in Chinese children and adolescents. A total of 10,536 children and adolescents aged 7-18 years (5125 boys and 5411 girls) were enrolled in a cross-sectional study in Guangzhou City, southern China. Data on demographic characteristics and dietary consumption were collected using self-reported questionnaires, and anthropometric characteristics were measured. Obesity, abdominal obesity, and hypertension were defined using Chinese criteria for children and adolescents. A multiple logistic regression model was applied to estimate the association between soy food intake and obesity and hypertension. Roughly 39.5% of the participants consumed soy food more than three times per week. The mean amounts of liquid and solid soy food intake were 0.35 ± 0.54 cups/day and 0.46 ± 0.63 servings/day, respectively. The adjusted odds ratios (OR) of hypertension among those with high liquid soy food intake and a high frequency of all soy food intake (more than three times/week) were 0.79 (95% confidence interval (CI), 0.67-0.94), and 0.83 (95% CI, 0.70-0.97) compared to those with no intake. Additionally, the adjusted OR of obesity among those with high solid soy food intake and a high frequency of all soy food intake were 1.34 (95% CI, 1.09-1.63) and 1.30 (95% CI, 1.07-1.58), respectively. In conclusion, 39.5% of southern Chinese children and adolescents had high soy food intake (more than three times/week), which was significantly associated with a lower prevalence of hypertension and a greater prevalence of obesity.


Multichannel audio monitor for detecting electrical signals.
The multichannel audio monitor (MUCAM) permits the simultaneous auditory monitoring of concurrent trains of electrical signals generated by as many as eight different sources. The basic working principle of this device is the modulation of the amplitude of a given pure tone by the incoming signals of each input channel. The MUCAM thus converts a complex, multichannel, temporal signal sequence into a musical melody suitable for instant, subliminal pattern analysis by the human ear. Neurophysiological experiments requiring multi-electrode recordings have provided one useful application of the MUCAM.


Impact of a health maintenance organization hospitalist system in academic pediatrics.
Hospitalist systems decrease length of stay (LOS) and cost for hospitalized adults. Whether hospitalist systems decrease LOS and cost for hospitalized children has not been conclusively established. We wanted to determine whether a health maintenance organization's (HMO's) implementation of a pediatric hospitalist system affected LOS, costs, mortality, readmission rate, follow-up rate, and parents' ratings of care. Interrupted time-series study of general pediatric patients admitted to a freestanding pediatric teaching hospital from 1993 to 1998. The intervention group consisted of all patients admitted to a staff model not-for-profit HMO that began using hospitalists in October 1996. Patients in other HMOs and traditional insurance groups were studied for comparison. The main outcomes were mean LOS and inflation-adjusted costs. Other outcomes included parents' ratings of care and mortality, readmission, and follow-up rates. Immediately after the introduction of the hospitalist system, mean LOS for staff model not-for-profit HMO fell 12% (0.3 days), and mean cost of hospitalization decreased 16% ($217) compared with prehospitalist levels. Parental ratings of care, initially somewhat low, improved substantially. Seven-day follow-up rates, mortality, and readmission rates did not change. Comparison groups experienced no concurrent improvements in LOS, cost, parental ratings, mortality, or readmission rates. A pediatric hospitalist system within a staff-model HMO significantly improved LOS, cost, and parental ratings of care without affecting rates of posthospitalization follow-up. Additional studies are needed both to measure broader aspects of quality and to assess the impact of such a program on patients being cared for through other types of delivery and insurance systems.


Initial outcomes from universal newborn hearing screening in Avon.
The Avon Area Health Authority was a first-phase site for introduction of universal newborn screening in the UK. The aims of this study were: to review the programme's results to date; to assess the impact screening would have on other services (e.g. the cochlear implant programme); and to assess the longer term outcome for children identified by the screening programme. All children identified by the Avon universal newborn hearing screening programme between April 2002 and July 2006. Fifty-four children with a bilateral hearing impairment of worse than 40 dBHL were identified from a screened population of approximately 44 000. Nine of these children were put forward for cochlear implantation, and seven had been implanted at the time of writing. Thirteen of these children were identified with possible auditory neuropathy or dys-synchrony. All the newborn hearing screening programme criteria assessed were met. The screening programme was effective. Some areas may need review in order to optimise patient care.


20 unusual presentations of accommodative esotropia.
This paper will discuss several unusual presentations of accommodative esotropia. A total of 20 patients with unusual case histories who presented with accommodative esotropia were studied retrospectively. These patients were separated into 3 categories. The first contained children who had their onset of accommodative esotropia after a traumatic event such as head trauma or ocular trauma. The second involved infants between 3 and 5 months of age who presented with accommodative esotropia. The third showed the onset of accommodative esotropia associated with diabetic ketoacidosis. (There were no other metabolic disorders associated with accommodative esotropia.) All patients resolved their esotropia with glasses initially but 2 did require surgery several years after the onset of the esotropia. Children under 5 months of age with intermittent esotropia and/or significant amounts of hyperopia should have the diagnosis of accommodative esotropia considered as the etiology of their esotropia. Children with the onset of esotropia associated with trauma who have significant amounts of hyperopia should also have accommodative esotropia considered as an etiology of their crossing.


Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.
We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.


Epidemiologic investigations on brain tumors in the GDR: possibilities and limits.
Animal experiments and recent industrial medicine investigations suggest that chemical carcinogens in the environment could be responsible for some types of human brain tumors. Confirmation demands data on the epidemiology of human tumors of a precision which has been unavailable. Prerequisites for valid epidemiologic studies are presented and the current situation in the GDR is critically evaluated in that context. The conditions for such studies are met fully only in early childhood. Based on files of the National Cancer Registry of the GDR, 1960-1979, 55 children with histopathologically confirmed tumors of the central nervous system prior to the end of the first year of life have been identified. The overall frequency was 1.1 per 100,000 births. Males were affected more than twice as often as females. Incidence for the years 1970-1979 was significantly higher than for 1960-1969. Possible explanations are critically explored and it is concluded that further epidemiologic studies of brain tumor etiology in early life must also consider children with onset of tumor symptoms during the first year of life but in whom histological confirmation was secured thereafter.


Fibroblast growth factors in the management of spinal cord injury.
Spinal cord injury (SCI) possesses a significant health and economic burden worldwide. Traumatic SCI is a devastating condition that evolves through two successive stages. Throughout each of these stages, disturbances in ionic homeostasis, local oedema, ischaemia, focal haemorrhage, free radicals stress and inflammatory response were observed. Although there are no fully restorative cures available for SCI patients, various molecular, cellular and rehabilitative therapies, such as limiting local inflammation, preventing secondary cell death and enhancing the plasticity of local circuits in the spinal cord, were described. Current preclinical studies have showed that fibroblast growth factors (FGFs) alone or combination therapies utilizing cell transplantation and biomaterial scaffolds are proven effective for treating SCI in animal models. More importantly, some studies further demonstrated a paucity of clinical transfer usage to promote functional recovery of numerous patients with SCI. In this review, we focus on the therapeutic capacity and pitfalls of the FGF family and its clinical application for treating SCI, including the signalling component of the FGF pathway and the role in the central nervous system, the pathophysiology of SCI and the targets for FGF treatment. We also discuss the challenges and potential for the clinical translation of FGF-based approaches into treatments for SCI.


Synergistic inhibition of lysophosphatidic acid signaling by charged and uncharged local anesthetics.
We investigated the mechanism of benzocaine (permanently uncharged) and QX314 (permanently charged) inhibition of lysophosphatidic acid (LPA) signaling. To determine their site of action, we studied effects of these drugs, alone and in combination, on LPA-induced Ca2+-dependent Cl currents (I(Cl(Ca))) in Xenopus oocytes. After 10 min exposure to benzocaine, QX314 (10(-6)-10(-2) M), or both, we measured effects on I(Cl(Ca)) induced by LPA (with and without protein kinase [PKC] activation/inhibition) and on I(Cl(Ca)) induced by the intracellular injection of IP3 and GTPgammaS. LPA application to oocytes resulted in I(Cl(Ca)) (50% effective concentration approximately 10(-8) M). Both anesthetics inhibited LPA signaling concentration-dependently (50% inhibitory concentration [IC50] benzocaine 0.9 mM, QX314 0.66 mM). The combination acted synergistically (IC50 benzocaine 0.097 mM/QX314 0.048 mM). Intracellular signaling pathways were not affected. This study shows that benzocaine and QX314 inhibit LPA signaling and act synergistically, which is most easily explained by the existence of two different binding sites. Lack of inhibition of IP3 or GTPgammaS-induced I(Cl(Ca)) identifies the receptor as a target. Activation of PKC can be excluded as a potential mechanism. Lysophosphatidic acid may play a role in wound healing, and its signaling is inhibited by local anesthetics. We identified the membrane receptor as the local anesthetic site of action and showed that charged (QX314) and uncharged (benzocaine) local anesthetics inhibit lysophosphatidic acid signaling synergistically, which can be explained by the presence of different binding sites.


Variables associated with circuit life span in critically ill patients undergoing continuous renal replacement therapy: a prospective observational study.
One of the greatest problems in performing continuous renal replacement therapy (CRRT) is premature coagulation of the circuit. The aim of the current study was to monitor the circuit function prospectively and analyze patient-related variables that may affect circuit life. Critically ill patients admitted to the intensive care unit of a tertiary hospital between August 2010 and August 2011 receiving continuous veno-venous hemofiltration (CVVH) with systemic heparin anticoagulation were prospectively studied. Variables including body temperature, blood pH value, ionized calcium level, activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, and heparin dose were collected and analyzed for their association with circuit life span. Fifty-four patients treated by CVVH were included, with 255 filters. The filter life was 29.7 ± 13.4 hours (mean ± standard deviation [SD]). Circuits with longer survival time appeared to have lower body temperature (37.80 ± 1.14 vs. 36.36 ± 1.09; p< 0.05), lower levels of serum ionized calcium (0.80 vs. 1.29; p< 0.05), and to be more acidic (7.233 vs. 7.377; p< 0.05). Cox regression showed that pH value and ionized calcium levels were significantly associated with circuit life. Other variables of hematocrit, albumin levels, platelet count, aPTT, PT, or dose of heparin were not significantly associated with circuit life.


[Process approach experience of university trust].
This job has the scope to make to comprise the importance of the quality system applied to a complex organization describing the phases that have characterized the definition and the improvement of one organizational-managerial procedure for the prevention and the treatment of a problem of great importance in the within of the care process (ulcer pressure), demonstrating as the personnel involvement is one of change strategy used .


Quality of life and symptoms after surgery for gastroesophageal cancer: a pilot study.
Oncologic outcomes of gastroesophageal surgery may be similar, but little is known about the impact on patients' postoperative symptom experience and quality of life (QOL). The purpose of this pilot study was to describe overall QOL and symptom experience of individuals who underwent either total gastrectomy with Roux-en-Y esophagojejunostomy or esophagogastrectomy for adenocarcinoma of the gastroesophageal junction. The Gastroenterology Quality of Life Index (GQLI) and the Life After Gastric Surgery (LAGS), developed by the investigators for measuring symptom frequency, were used to measure variables of interest. The sample (n = 27) had a relatively high QOL, but experienced difficulties with eating patterns, physical functioning, socialization, and happiness. There were significant differences between the two procedures related to QOL and symptom frequency in that individuals who had the total gastrectomy fared somewhat better. Further, patients who had esophagogastrectomy had greater symptom frequency and significantly poorer QOL. Although initially compelling, these data warrant further investigation into the QOL and symptom impact in a more diverse population of patients with cancer of the stomach or esophagus. These results, however, suggest several areas where nursing interventions could help these patients.


Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls.
Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce. Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS. Patients included 59 obese girls with PCOS aged 12-18 yr. Intervention was a 1-yr lifestyle intervention based on nutrition education, exercise training, and behavior therapy. Menses cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG were evaluated. In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of -3.9 kg/m(2)) improved most CRF and decreased their IMT (by a mean of -0.01 cm). Testosterone concentrations decreased (by a mean of -0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (-42%) and oligoamenorrhea (-19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = -0.35; P = 0.048). A linear regression model with changes in IMT as dependent variable demonstrated a significant association with changes in blood pressure and weight status but not with changes in testosterone. Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.


Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.
Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential (AP) and the transient outward potassium current (Ito ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and Ito current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2nd day and moderate rejection at the 4th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration (APD) of cardiomyocytes in the allogeneic group was significantly prolonged (APD90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2nd day, P=0.0016; APD90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4th day, P=0.0064). The current density of Ito was significantly decreased at the 4th day after cardiac transplantation. The APD of cardiomyocytes was significantly prolonged during acute cardiac rejection in rats, which might be partly attributed to decreased current densities of Ito .


Pharmacokinetics of laetispicine and its brain distribution in rats.
Laetispicine, which is a novel amide alkaloid isolated from the stem of Piper laetispicum, has been proven to possess antidepressant and antinociceptive effects. This study examined the pharmacokinetic characteristics of laetispicine in plasma and brain distribution in rats by a simple sensitive HPLC-UV method. The separation was performed on a reverse-phase ODS column (250 mm x 4.6 mm, i.d., 5 microm) with a mobile phase composed of acetonitrile-water (75:25, v/v) as the mobile phase at a flow rate of 1.0 ml/min with UV detection at 259 nm. The calibration curve of laetispicine in rat plasma showed excellent linear behavior between 0.005-5.0 microg/ml (r2 = 0.9992), and between 0.02-0.5 microg/ml (r2 = 0.9952) in rat brain samples. The lower limit of quantification (LLOQ) was found to be 0.005 microg/ml in rat plasma and 0.02 microg/ml in rat brain samples. This HPLC assay was a precise and reliable method for the analysis of laetispicine in pharmacokinetic studies. Laetispicine was rapidly and extensively transported across the blood-brain barrier (BBB) and distributed into different brain regions.


Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic review of causes and mechanisms.
Loss of benefit of a previously effective treatment regimen, also known as tolerance, can be an important barrier to the successful preventive treatment of migraine. We undertook a systematic review of the literature to identify the prevalence and possible mechanisms of drug tolerance in migraine prophylaxis. Results demonstrate that the frequency of tolerance to prophylactic migraine treatment is unknown, but available data support an estimate that it occurs in 1-8% of patients receiving prophylaxis. Four broad types of tolerance were identified that are likely to be relevant to migraine prophylaxis. These are pharmacokinetic, pharmacodynamic, behavioral, and cross tolerance. The mechanisms that underlie these types of tolerance determine whether their effects can be overcome or minimized. For example, certain forms of tolerance may be affected by manipulation of environmental cues associated with drug administration, by the order in which drugs are used, and by the concomitant use of other medications. Many medications used for migraine prophylaxis exert their effects through the endogenous opioid system. The implications of this finding are explored, particularly the parallels between medication overuse headache and tolerance to migraine prophylaxis. Given the many ways in which tolerance to migraine medications may develop, in some ways it is not surprising that migraine-preventive drugs stop working; it is more surprising that in many cases they do not.


[Improvement of quantitative method on anti-HBs].
Through detecting the standard preparation with series of concentration to indirectly calculate the anti-HBs concentration of the serum samples, a suitable anti-HBs quantitative method for our laboratory was found after comparing the two kinds of methods. Detecting the anti-HBs standard preparation with series of concentration by RIA method, standard curvilinear equations were obtained by the means of fitting the detected result and the corresponding concentration by log-log model and exponential curve model respectively. Then the fitting efficiency of two curves was compared. By calculating the concentrations of the reference using two standard curvilinear equations, we can compare the accuracy of two quantitative methods. The error mean square of the exponential curve model is low as 1.2971 and the determinate coefficient is close to 1 with the value of 0.9904. The average concentrations (n=6) of the detected reference calculated by two curvilinear equation with the actual concentration of 30.0 mIU/mL are (32.28 +/- 1.06) and (31.91 +/- 1.06) mIU/ mL respectively. The concentration calculated by exponential curve model is only 6.37% higher than the actual concentration. Fitting by exponential curve model is more practical to estimate the actual concentration of the serum samples those will be detected. It can be used as an optimal quantitative method to detect anti-HBs concentration.


Studies of sick building syndrome. IV. Mycotoxicosis.
There has been increasing public attention to the potential health risks of mold exposure, particularly in wet buildings. A variety of molds has been isolated from both damaged homes and businesses, including agents that secrete toxigenic materials. One area that is attracting particular notice is the relative toxigenic potential of mycotoxins. Although exposure to molds can produce significant mucosal irritation, there are very few data to suggest long-term ill effects. More importantly, there is no evidence in humans that mold exposure leads to nonmucosal pathology. In fact, many of the data on toxigenic molds are derived from animal toxicity studies, and these are based primarily, on ingestion. Although every attempt should be made to improve the quality of indoor air, including avoidance of molds, the human illnesses attributed to fungal exposure are, with the exception of invasive infections and mold allergy, relatively rare. In this review we discuss selected aspects of the microbiology of mycotoxin-producing molds and their potential role in human immunopathology with respect to wet building environments.


Acute lymphoid leukemia following polycythemia vera.
The tendency to evolve into acute leukemia is a well-known characteristic of polycythemia vera (PV), which is shared with the remaining chronic myeloproliferative disorders and increases after the administration of cytotoxic agents. Acute transformation is usually of myeloid phenotype, whereas acute lymphoid leukemia (ALL) following PV is seldom observed. A 63-year-old woman is described who developed ALL at 6 years from the initial diagnosis of PV, for which she had received radioactive phosphorus and hydroxyurea. The ALL was of B-cell type, corresponding to the L-3 subtype of the FAB classification. Despite the administration of combination chemotherapy the patient died shortly after the diagnosis of acute leukemia. The present case adds to seven previously described patients with the above association, all of whom had received cytotoxic therapy for PV. Median interval from PV to ALL diagnosis was 10 years, and there was a predominance of the B-cell phenotype. The prognosis was poor since all but one of the patients had a short survival after ALL diagnosis. The possible etiological and pathogenetic link between PV and the subsequent ALL is discussed.


[Tuberculosis in Poland 2000--at the turn of the century].
The aim of this paper was to evaluate incidence, prevalence and mortality from TB in Poland in 2000 and to examine trends of TB incidence. Individual date on tuberculosis cases reported to National TB Register and data of prevalence and mortality from TB were analysed. The paper presents the epidemiological situation of TB in Poland in 2000. The year of 2000 was the seventh consecutive year of decline at TB incidence after previous years (1991-1993) of increase. In 2000 there were 11,477 newly registered TB cases, of which 1428 were relapses. The incidence was 29.7 per 100,000 population, /26.0 were the new cases and 3.7 relapses/. Relapses represented 12.4% of all registered cases. The incidence in 2000 was 5.7% lower than in 1999, but the rate of decline was smaller than in previous year--8.4%. Among the total number of newly registered cases there were 6518 cases--16.9 per 100,000--bacteriologically confirmed, of which 3.713 cases were sputum smear positive. The proportion of bacteriologically confirmed cases was 56.8% and of sputum smear positive--33.9% which is rather low, but similar to previous years. In view of sufficient network of laboratory services this low proportion of bacteriological confirmation of diagnosis may indicate low quality of bacteriological examinations. In 95.5% of cases the diagnosis was respiratory tuberculosis. Low proportion--4.5%--of extrarespiratory tuberculosis, which have continued for many years, may indicate inadequacies in diagnosis and registration of this form of disease. The incidence of tuberculosis increases with age, from 1.4 in children up to 62.4 among 65 and older. The proportion of cases in the age group 20-44 years is still high (34.7%). The incidence in men (40.9) is two times higher than in women (19.1), and in rural population higher than in urban--30.5 and 29.2 respectively. The prevalence of tuberculosis at the end of 2000 was 38.5 (14,895 cases), of which 55.4% were bacteriologically confirmed cases (8252 cases). In the latter group there were 232 cases bacteriologically positive for longer than one year, and 369 cases resistant to at least 1 drug. The proportion of resistant cases (3.9%) is similar to previous years and does not seem to influence the overall effectiveness of chemotherapy. There were 1.022 (1.024) deaths due to tuberculosis 995 (985)--respiratory tuberculosis and 27 (39) extrarespiratory tuberculosis) reported in 1999 i.e. (2.6) per 100,000. Almost 43% of all deaths were in patients 65 year of age and older. Since many years the TB mortality is the order of 0.3% of total mortality. In recent years incidence of TB in Poland decreased. The incidence of tuberculosis in Poland was about 2 times higher than the average for E.U. countries, but lower than in other Eastern European countries. The distance between Poland and countries with lowest incidence in Europe is estimated at 25-30 years. Tuberculosis has been and will remain a major public health problem in Poland for many decades.


DGAT1, DGAT2 and PDAT expression in seeds and other tissues of epoxy and hydroxy fatty acid accumulating plants.
Triacylglycerol (TAG) is the main storage lipid in plants. Acyl-CoA: diacylglycerol acyltransferase (DGAT1 and DGAT2) and phospholipid: diacylglycerol acyltransferase (PDAT) can catalyze TAG synthesis. It is unclear how these three independent genes are regulated in developing seeds, and particularly if they have specific functions in the high accumulation of unusual fatty acids in seed oil. The expression patterns of DGAT1, DGAT2 and a PDAT in relation to the accumulation of oil and epoxy and hydroxy fatty acids in developing seeds of the plant species Vernonia galamensis, Euphorbia lagascae, Stokesia laevis and castor that accumulate high levels of these fatty acids in comparison with soybean and Arabidopsis were investigated. The expression patterns of DGAT1, DGAT2 and the PDAT are consistent with all three enzymes playing a role in the high epoxy or hydroxy fatty acid accumulation in developing seeds of these plants. PDAT and DGAT2 transcript levels are present at much higher levels in developing seeds of epoxy and hydroxy fatty acid accumulating plants than in soybeans or Arabidopsis. Moreover, PDAT, DGAT1 and DGAT2 are found to be expressed in many different plant tissues, suggesting that these enzymes may have other roles in addition to seed oil accumulation. DGAT1 appears to be a major enzyme for seed oil accumulation at least in Arabidopsis and soybeans. For the epoxy and hydroxy fatty acid accumulating plants, DGAT2 and PDAT also show expression patterns consistent with a role in the selective accumulation of these unusual fatty acids in seed oil.


Tissue-specific genotype-phenotype correlations among USH2A-related disorders in the RUSH2A study.
We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.


Iron dysregulation in movement disorders.
Iron is an essential element necessary for energy production, DNA and neurotransmitter synthesis, myelination and phospholipid metabolism. Neurodegeneration with brain iron accumulation (NBIA) involves several genetic disorders, two of which, aceruloplasminemia and neuroferritinopathy, are caused by mutations in genes directly involved in iron metabolic pathway, and others, such as pantothenate-kinase 2, phospholipase-A2 and fatty acid 2-hydroxylase associated neurodegeneration, are caused by mutations in genes coding for proteins involved in phospholipid metabolism. Phospholipids are major constituents of myelin and iron accumulation has been linked to myelin derangements. Another group of NBIAs is caused by mutations in lysosomal enzymes or transporters such as ATP13A2, mucolipin-1 and possibly also β-galactosidase and α-fucosidase. Increased cellular iron uptake in these diseases may be caused by impaired recycling of iron which normally involves lysosomes. Abnormal iron utilization by mitochondria, as has been proposed in Friedreich's ataxia, is another possible mechanism of iron accumulation. Other, more common degenerative movement disorders, such as Parkinson's disease, Huntington's disease, multiple system atrophy and progressive supranuclear palsy also exhibit increased brain iron content. Finally, brain iron deficiency has been implicated in restless legs syndrome. This review provides an update on recent findings related to genetics, pathogenic mechanisms, diagnosis, and treatment of movement disorders associated with dysregulation of brain iron. We also propose a new classification of NBIAs.


[A simple-irrigating system for endoscopic sinus surgery].
The most troublesome problem during endoscopic surgery is fouling of the endoscope lens (tip) with blood. Irrigating systems are available on the market but they are relatively very expensive. We present our own simple irrigating system, very effective and inexpensive. The system consists of: polyethylene catheter No 6, sterile intravenous line with interposed stopcock, 500 ml saline solution, endoscope. The catheter is fixed to the endoscope with sterile sticks and connected to the bottle of saline solution with intravenous line. During the operation the irrigant solution flow is controlled with interposed stopcock. A simple irrigating system allows cleaning of blood from the endoscope obviating the need for frequent removal of the endoscope from the nose. This allows more rapid and safer endoscopic surgery. It is very simple and cheap.


Darker deals? Male dark tetrad preferences for female sex worker services.
The present study explored links between male Dark Tetrad personality traits (psychopathy, Machiavellianism, narcissism, sadism) and preferences for using outdoor and indoor female sex worker services. We also investigated the mediating effects of perceiving sex workers as deviant and as victims. Heterosexual males (N = 347) were recruited to take part in an online survey investigating personality and attitudes towards female sex workers. Path analyses revealed that psychopathy and sadism positively predicted preferences for outdoor but not indoor female sex services. Sex worker choice mediated positive links between narcissism and outdoor female sex worker preferences. Compared to indoor, outdoor sex services are associated with increased aggression and violence. Our findings highlight the importance of considering narcissism and particularly psychopathy and sadism when investigating individual male preferences for outdoor sex services that are being offered by particularly vulnerable women.


Current-induced instability of domain walls in cylindrical nanowires.
We study the current-driven domain wall (DW) motion in cylindrical nanowires using micromagnetic simulations by implementing the Landau-Lifshitz-Gilbert equation with nonlocal spin-transfer torque in a finite difference micromagnetic package. We find that in the presence of DW, Gaussian wave packets (spin waves) will be generated when the charge current is suddenly applied to the system. This effect is excluded when using the local spin-transfer torque. The existence of spin waves emission indicates that transverse domain walls can not move arbitrarily fast in cylindrical nanowires although they are free from the Walker limit. We establish an upper velocity limit for DW motion by analyzing the stability of Gaussian wave packets using the local spin-transfer torque. Micromagnetic simulations show that the stable region obtained by using nonlocal spin-transfer torque is smaller than that by using its local counterpart. This limitation is essential for multiple DWs since the instability of Gaussian wave packets will break the structure of multiple DWs.


Association of Reperfusion After Thrombolysis With Clinical Outcome Across the 4.5- to 9-Hours and Wake-up Stroke Time Window: A Meta-Analysis of the EXTEND and EPITHET Randomized Clinical Trials.
Intravenous alteplase reduces disability after ischemic stroke in patients 4.5 to 9 hours after onset and with wake-up onset stroke selected using perfusion imaging mismatch. However, whether the benefit is consistent across the 4.5- to 6-hours, 6- to 9-hours, and wake-up stroke epochs is uncertain. To examine the association of reperfusion with reduced disability, including by onset-to-randomization time strata in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) randomized clinical trials. Individual patient meta-analysis of randomized clinical trials performed from August 2001 to June 2018 with 3-month follow-up. Patients had acute ischemic stroke with 4.5-to 9-hours poststroke onset or with wake-up stroke were randomized to alteplase or placebo after perfusion mismatch imaging. Analysis began July 2019 and ended May 2020. Reperfusion was defined as more than 90% reduction in time to maximum of more than 6 seconds' lesion volume at 24- to 72-hour follow-up. Ordinal logistic regression adjusted for baseline age and National Institutes of Health Stroke Scale score was used to analyze functional improvement in day 90 modified Rankin Scale score overall, including a reperfusion × time-to-randomization multiplicative interaction term, and in the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata. Symptomatic hemorrhage was defined as large parenchymal hematoma with a National Institutes of Health Stroke Scale score increase of 4 points or more. Reperfusion was assessable in 270 of 295 patients (92%), 68 of 133 (51%) in the alteplase group, and 38 of 137 (28%) in the placebo reperfused group (P < .001). The median (interquartile range) age was 76 (66-81) years in the reperfusion group vs 74 (64.5-81.0) years in the group with no reperfusion. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (7-15) in the reperfusion group vs 12 (8.0-17.5) in the no reperfusion group. Overall, reperfusion was associated with improved functional outcome (common odds ratio, 7.7; 95% CI, 4.6-12.8; P < .001). Reperfusion was associated with significantly improved functional outcome in each of the 4.5- to 6-hours, 6- to 9-hours, and wake-up time strata, with no evidence of association between time to randomization and beneficial effect of reperfusion (P = .63). Symptomatic hemorrhage, assessed in all 294 patients, occurred in 3 of 51 (5.9%) in the 4.5- to 6-hours group, 2 of 28 (7.1%) in the 6- to 9-hours group, and 4 of 73 (5.5%) in the wake-up stroke in patients treated with alteplase (Fisher P = .91). Strong benefits of reperfusion in all time strata without differential risk in symptomatic hemorrhage support the consistent treatment effect of alteplase in perfusion mismatch-selected patients throughout the 4.5- to 9-hours and wake-up stroke time window.


Fulminant legionellosis in two patients treated with infliximab for Crohn's disease: case series and literature review.
Two cases of fulminant pulmonary legionellosis, complicated by prolonged intensive care unit stays and acute respiratory distress syndrome, and who were recently treated with infliximab for Crohn's disease, are described. A review of the literature revealed three additional cases in patients with inflammatory bowel disease, and a total of 22 cases of Legionella pneumophila pneumonia in the context of treatment with antitumour necrosis (TNF)-alpha medications. The median age of the patients was 49 years, and men and women were affected equally. The case fatality rate was 14% (three of 22). Early recognition and treatment of this anti-TNF-alpha-related complication would likely result in reduced mortality and morbidity. Physicians prescribing anti-TNF-alpha drugs should be aware of this association.


Follow-Up of Persistent Tracheal Stenosis After Surgery for a Double Aortic Arch.
Persistent respiratory symptoms often occur after surgical repair of double aortic arch (DAA). Most often, symptoms are relatively mild and tend to be self-limited and improve with growth. Multidetector computed tomography (MDCT) imaging can be used to obtain needed anatomic information regarding the potential for extrinsic airway compression and is minimally invasive, safe, and readily available after surgery. We herein report the cases of two patients with persistent airway symptoms after surgical therapy for a double aortic arch. One of the patients eventually required aortopexy in order to achieve complete relief from recurrent symptoms of airway compression. In the other case, wheezing persisted following surgical division of the vascular ring, but it resolved over time without further intervention. In both cases, serial follow-up imaging with computed tomography scans was informative and helped guide management decisions.


How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation.
The specificity of T cells is that each T cell has only one T cell receptor (TCR). A T cell clone represents a collection of T cells with the same TCR sequence. Thus, the number of different T cell clones in an organism reflects the number of different T cell receptors (TCRs) that arise from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution, are important factors in immune functions. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. We describe the heterogeneous steady-state population of naive T cells (those that have not yet been antigenically triggered) by using a mean-field model of a regulated birth-death-immigration process. After accounting for random sampling, we investigate how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or "clone counts"). By using reasonable physiological parameter values and fitting predicted clone counts to experimentally sampled clone abundances, we show that realistic levels of heterogeneity in immigration rates cause very little change to predicted clone-counts, but that modest heterogeneity in proliferation rates can generate the observed clone abundances. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed.


Lipid and Fatty Acid composition of chloroplast envelope membranes from species with differing net photosynthesis.
Lipid and fatty acid compositions were determined for chloroplast envelope membranes isolated from spinach (Spinacia oleracea L.), sunflower (Helianthus annuus L.), and maize (Zea mays L.) leaves. The lipid composition was similar in sunflower, spinach, and undifferentiated maize chloroplast envelope membranes and different in maize mesophyll chloroplast envelope membranes. The predominant lipid constituents in all envelope membranes were monogalactosyldiglyceride (27 to 46%), digalactosyldiglyceride (18 to 33%), and phosphatidylcholine (7 to 30%). The fatty acid composition was also similar in sunflower and spinach chloroplast envelope membranes in comparison to those from maize. The major acyl fatty acids of the chloroplast envelope membrane were palmitic (C(16:0), 41 and 36%) and linolenic (C(18:3), 29 and 40%) acids for spinach and sunflower; palmitic (77%) and stearic (C(18:0), 12%) acids for young maize; and palmitic (61%), stearic (14%), and linolenic (13%) acids for mature maize. The differences in lipid and acyl fatty acid compositions among these plants which vary in their rates of net photosynthesis were largely quantitative rather than qualitative.


Prenatal diagnosis of fatal infantile olivopontocerebellar hypoplasia syndrome.
We report the first case of prenatal diagnosis of fatal infantile olivopontocerebellar hypoplasia syndrome, OMIM 225753. Ultrasound findings noted at 28 weeks' gestation included polyhydramnios, a small stomach bubble, a small but morphologically normal cerebellum, dilatation of the fourth ventricle, and long periods of normal fetal movement punctuated by sudden bursts of violent seizure-like activity of the fetal extremities. At birth, the child was noted to be hypertonic, myoclonic, hyper-reflexic, demonstrated poor gastrointestinal motility, and had severe apneic episodes. Magnetic resonance imaging (MRI) demonstrated marked hypoplasia or atrophy of the cerebellum, pons and medulla, mild atrophy of the cerebral cortex, and mild ex vacuo venticulomegaly of the fourth, third and lateral ventricles. This child died from respiratory insufficiency at 14 days of age. The parents of this child had previously lost a child with similar clinical and anatomical findings. Prenatal sonographers should be aware of the existence of this rare syndrome and should look carefully at the size of the cerebellum in cases of polyhydramnios or when in utero 'seizure-like' activity is seen. The importance of establishing this diagnosis lies in the fact that it appears to have a very poor postnatal prognosis and is likely to be inherited as an autosomal recessive disease.


Expansion of clinical pharmacy services through staff development.
A program that trains and uses staff pharmacists for clinical services is described. A position was created that is filled by staff pharmacists on six-week rotations. All full-time pharmacists may participate; they work under the direction and supervision of clinical pharmacists. Basic responsibilities in the rotation include responding to drug information requests, assisting with drug-use evaluation and adverse drug experience programs, assisting with research, writing and editing for newsletters, participating in staff development programs, and reviewing and clarifying drug orders for the skilled-nursing facility. About 60% of eligible pharmacists have participated in this program. The pharmacists have gained new practice skills, greater opportunity for career enhancement, and improved attitudes toward work and colleagues, and the department has been able to provide more clinical services. The focus of the rotation is now being changed from performing clinical tasks to assuming more responsibility for patient outcomes related to drug therapy. A rotating clinical position has enabled staff pharmacists to gain additional nondispensing skills and contribute to the development and maintenance of clinical services.


Time since immigration and health services utilization of Korean-American older adults living in Los Angeles County.
The aim of this study was to characterize ambulatory healthcare utilization of older Korean Americans and its association with length of time since immigration. It was hypothesized that older Korean Americans who were recent immigrants would use outpatient physician visits less often than early immigrants. The data are from the 2000 Korean-American Health Survey, which assessed the health status and medical needs of Korean Americans living in Los Angeles County. The dependent variable was the number of visits to a physician for check-up or consultation. Multivariate regression modeling was used to assess the influence of length of time since immigration on the dependent variable controlling for predisposing, enabling, and need variables for a sample of 208 Koreans Americans aged 65 and older. Results indicated that high school education in Korea and health insurance status were significant predictors of number of visits to a physician during the previous year (P<.05). The main variable of interest, the number of years living in the United States, approached significance at P=.09. It was concluded that enabling variables such as education and health insurance significantly influenced use of healthcare services in the older Korean-American population. The lack of studies regarding older minority populations and their access to healthcare further highlight theneed not only to characterize the access of these often-vulnerable populations, but also to generate interest for further studies.


Rethinking Opsins.
Opsins, the protein moieties of animal visual photo-pigments, have emerged as moonlighting proteins with diverse, light-dependent and -independent physiological functions. This raises the need to revise some basic assumptions concerning opsin expression, structure, classification, and evolution.


Multiple antigen immunostaining procedures.
Detection of multiple antigens in the same tissue section can be done by combining a range of immunohisto/cytochemical techniques based either on light microscopic chromogenic precipitates or fluorochrome labeling. Light microscopic techniques preferred for this purpose use combinations of immunogold silver staining (black precipitate), immunoperoxidase, immunoalkaline phosphatase and immunogalactosidase methods using chromogens of different colors. Fluorochrome labels favored for these combinations include AMCA (blue), FITC (green), rhodamine (orange-red) and Cy5 (far red), their matching synthetic members from the Alexa series, or quantum dots. Antibodies directly labeled or those from noncross-reacting animal species (e.g., mouse, rabbit, goat, guinea pig etc.) can be applied simultaneously. When the antigens of interest are in separate cells or cell compartments (e.g., in cell membrane, cytoplasm or nucleus), and only cross-reacting antibodies are available, there have also been ways of avoiding unwanted cross-talk. These include the exploitation of the shielding effect of chromogens; inactivation of immuno-sequences of the first staining by using either acidic elution, formaldehyde fixation or microwave heating; combining unlabeled and hapten-labeled antibodies; or using labeled monovalent F(ab) secondary antibodies. In this chapter we briefly discuss the principle of multiple antigen immunolabeling and provide useful protocols for its performance.


Qualitative Exploration of the Continuation of a Journal Club Experience by DPT Graduates in Their First Year of Practice.
To explore the experience of doctorate of physical therapy (DPT) graduates participating in a journal club (JC) during their first year of practice after completing a JC intervention in the last didactic semester of their entry-level program. n=7 DPTs participating in a JC during the first year of practice. A qualitative approach including semi-structured interviews and guided by a conceptual model for first-year PT practice was used. Interviews were transcribed verbatim and thematic data analysis was conducted. Six themes were identified: 1) sense of community, 2) maintaining accountability, 3) variety of perspectives, 4) informed clinical practice, 5) facilitated professional role adoption, and 6) challenges. Participants also provided recommendations for other recent graduates interested in beginning a JC. Exposure to a JC experience during the didactic phase of PT education may encourage graduates to embrace this professional behavior. Timing and meaningfulness of the JC intervention may be important factors to consider during implementation. New graduate participation in a JC may provide important support during the first year of practice. Most importantly, participation in a JC with an established community, such as fellow DPT graduates, may increase the salience and impact of this experience.


Distributed Fractional-Order Intelligent Adaptive Fault-Tolerant Formation-Containment Control of Two-Layer Networked Unmanned Airships for Safe Observation of a Smart City.
This article investigates a distributed fractional-order fault-tolerant formation-containment control (FOFTFCC) scheme for networked unmanned airships (UAs) to achieve safe observation of a smart city. In the proposed control method, an interval type-2 fuzzy neural network (IT2FNN) is first developed for each UA to approximate the unknown term associated with the loss-of-effectiveness faults in the distributed error dynamics, and then a disturbance observer (DO) is proposed to compensate for the approximation error and bias fault encountered by each UA, such that the composite learning strategy composed of the IT2FNN and the DO is obtained for each UA. Moreover, fractional-order (FO) calculus is incorporated into the control scheme to provide an extra degree of freedom for the parameter adjustments. The salient feature of the proposed control scheme is that the composite learning algorithm and FO calculus are integrated to achieve a satisfactory fault-tolerant formation-containment control performance even when a portion of leader/follower UAs is subjected to the actuator faults in a distributed communication network. Furthermore, it is shown by Lyapunov stability analysis that all leader UAs can track the virtual leader UA with time-varying offset vectors, and all follower UAs can converge into the convex hull spanned by the leader UAs. Finally, comparative hardware-in-the-loop (HIL) experimental results are presented to show the effectiveness and superiority of the proposed method.


Faculty members' provision of instructional accommodations to students with LD.
The existing research on the instructional accommodation process of college students with learning disabilities focuses on attitudes and theoretical models without delineating actual practices. To date, the discussion of facilitating factors and barriers to this process has been broad and lacking specificity. Surveys were mailed to 485 faculty members at the University of Massachusetts, Amherst, who received an instructional accommodation form from the office of Learning Disabilities Support Services in the fall of 1995. The survey focused on faculty members' reported degree of ease or difficulty in implementing instructional accommodations, their perceptions regarding adequacy of support, and their own beliefs and understandings concerning the need for and benefit of providing instructional accommodations. The results indicate that beliefs about the helpfulness of and need for instructional accommodations were associated with the provision of the accommodations. Also, a perception of support from the University influenced the ease of providing instructional accommodations. A significant difference was found between the behavior of tenure-track faculty and non-tenure-track faculty.


[A survey of virtual reality research: From technology to psychology].
A technology of virtual reality enables us to immerse ourselves into 3D synthesized environments. In this paper, I review recent researches on virtual reality focusing on (a) the terminology used in this research area, (b) technological approaches to setting up different components of virtual reality autonomy, interaction, and presence, (c) objective measures and subjective ratings of a viewer's sense of presence in virtual environments, (d) present applications of virtual reality in different fields and their relation to pictorial communication. This review concludes that intermodality conflict and measurement of sense of presence are the crucial perceptual and cognitive topics in virtual reality research.


Novel Contributors and Mechanisms of Cellular Senescence in Hypertension-Associated Premature Vascular Aging.
Hypertension has been described as a condition of premature vascular aging, relative to actual chronological age. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in hypertension. Nonetheless, the precise mechanisms that underlie the aged phenotype of arteries from hypertensive patients and animals remain elusive. Cellular senescence is an age-related physiologic process in which cells undergo irreversible growth arrest. Although controlled senescence negatively regulates cell proliferation and promotes tissue regeneration, uncontrolled senescence can contribute to disease pathogenesis by presenting the senescence-associated secretory phenotype, in which molecules such as proinflammatory cytokines, matrix metalloproteases, and reactive oxygen species are released into tissue microenvironments. This review will address and critically evaluate the current literature on the role of cellular senescence in hypertension, with particular emphasis on cells types that mediate and modulate vascular function and structure.


Dorsal penile nerve block vs topical placebo for circumcision in low-birth-weight neonates.
To investigate the efficacy and safety of dorsal penile nerve block (DPNB) and eutectic mixture of lidocaine (EMLA) for palliation of pain associated with circumcision in low-birth-weight infants. Randomized, blinded, controlled trial. Intensive care nursery (step down unit) at Georgetown University Medical Center, Washington, DC. Fifty neonates with weights of 1600 to 2500 g at the time of circumcision who were discharged from the hospital between May 1994 and June 1995 were randomly assigned to the DPNB, EMLA, or control group. Twenty-five infants who were otherwise eligible were excluded because of parental refusal of consent to participate. Infants in the DPNB and EMLA groups received anesthesia with subcutaneous injection of 1% lidocaine hydrochloride or topical EMLA, respectively. The control group received sham anesthesia with topical placebo (acid mantle cream). Changes in physiologic variables (heart rate, blood pressure, oxygen saturation, and respiratory rate) and behavioral score 20 minutes before, during, and 5 and 20 minutes after circumcision between DPNB and control groups. Surgical complications and adverse effects were also monitored. Fifty infants were enrolled in the study: 19 randomized to the DPNB group, 19 to the control group, and 12 to the EMLA group. Enrollment into the EMLA group was suspended early because of redness and blistering of the foreskin in 2 infants, and this entire group was excluded from further analysis. The clinical course was similar in all groups of infants. All circumcisions were performed without complication or technical difficulty. Statistically significant differences were noted in heart rate, respiratory rate, and behavioral score when comparing the DPNB group with controls during and after circumcision. Dorsal penile nerve block is safe and effective in controlling pain associated with circumcision in low-birth-weight infants.


Tumor Imaging With 68Ga-DOTA-FAPI-04 PET/CT: Comparison With 18F-FDG PET/CT in 22 Different Cancer Types.
Cancer-associated fibroblasts, which are densely found in tumor tissue, express high levels of fibroblast activation protein (FAP), and FAP inhibitors (FAPIs) labeled with radionuclides can be used in the diagnosis and treatment of cancer. In this study, the role of 68Ga-DOTA-FAPI-04 PET/CT in imaging of primary, metastatic, and recurrent cancers was investigated. A total of 42 patients (16 females, 26 males; mean age, 58.5 years; range, 31-84 years) with 22 different types of malignant diseases were included in the study. 68Ga-DOTA-FAPI-04 PET/CT imaging was performed 1 to 7 days after 18F-FDG PET/CT. Pathological uptake levels in primary tumoral lesions, lymph nodes, skeletal system, liver, peritoneal surfaces, and other body parts were compared between 2 PET/CTs. In addition, physiological uptake levels of 18F-FDG and 68Ga-FAPI were defined measuring the liver, thoracic aorta, gluteal muscle activities, and uterus activity in female patients. Of the 42 patients in the study group, 33 patients were included for staging, 8 patients for restaging, and 1 patient for evaluation of treatment response. 68Ga-DOTA-FAPI-04 PET/CT showed intense uptake in 94.2% of primary tumoral lesions. In patients with multiple myeloma, 18F-FDG uptake in the bone marrow was significantly higher than 68Ga-FAPI uptake, whereas in gastric signet ring cell tumors, 68Ga-FAPI uptake was found to be significantly higher than 18F-FDG uptake. It was observed that 68Ga-DOTA-FAPI-04 PET/CT detected bone, liver, and peritoneum metastases with higher sensitivity and accuracy compared 18F-FDG PET/CT. The preliminary findings of this study showed that 68Ga-DOTA-FAPI-04 PET/CT can contribute to the diagnostic process in solid tumors. Especially in malignancies with mild uptake on 18F-FDG PET/CT, it stands out in diagnosis, staging, and restaging. It is also predicted that FAPI molecules can be used for radionuclide therapy in patients with metastatic disease and unresponsive to other treatments showing intense uptake on 68Ga-DOTA-FAPI-04 PET/CT.


Demystifying hospital charges for hospital readmissions in 2017 in the United States for psychosis (DRG = 885).
Existing research on hospital charges is primarily focused on hospital admissions, but not on hospital readmissions. Our research fills this gap. We utilize the 2017 Hospital Readmissions database from the Agency for Healthcare Research and Quality (AHRQ) to empirically study factors that impact hospital charges for hospital readmissions. We focus on psychosis (DRG = 885) which has 609,360 records in 2017 in the AHRQ database. We employ regression analyses using patient demographics, inpatient care variables, and hospital characteristics to explain variance in hospital charges. Results show that inpatient care (diagnoses, procedures, length of stay), hospital ownership, and younger patients result in higher hospital charges.