Randomized study of percutaneous endoscopic gastrostomy versus nasogastric tubes for enteral feeding in head and neck cancer patients treated with (chemo)radiation.
Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGT) for nutritional support of patients with head and neck cancer undergoing curative (chemo)radiotherapy without any good scientific basis. A randomized trial was conducted to compare PEG tubes and NGT in terms of nutritional outcomes, complications, patient satisfaction and cost. The study was closed early because of poor accrual, predominantly due to patients' reluctance to be randomized. There were 33 patients eligible for analysis. Nutritional support with both tubes was good. There were no significant differences in overall complication rates, chest infection rates or in patients' assessment of their overall quality of life. The cost of a PEG tube was 10 times that of an NGT. The duration of use of PEG tubes was significantly longer, a median 139 days compared with a median 66 days for NGT. We found no evidence to support the routine use of PEG tubes over NGT in this patient group.


Paratome: an online tool for systematic identification of antigen-binding regions in antibodies based on sequence or structure.
Antibodies are capable of specifically recognizing and binding antigens. Identification of the antigen-binding site, commonly dubbed paratope, is of high importance both for medical and biological applications. To date, the identification of antigen-binding regions (ABRs) relies on tools for the identification of complementarity-determining regions (CDRs). However, we have shown that up to 22% of the residues that actually bind the antigen fall outside the traditionally defined CDRs. The Paratome web server predicts the ABRs of an antibody, given its amino acid sequence or 3D structure. It is based on a set of consensus regions derived from a structural alignment of a non-redundant set of all known antibody-antigen complexes. Given a query sequence or structure, the server identifies the regions in the query antibody that correspond to the consensus ABRs. An independent set of antibody-antigen complexes was used to test the server and it was shown to correctly identify at least 94% of the antigen-binding residues. The Paratome web server is freely available at http://www.ofranlab.org/paratome/.


Calmodulin mutations affecting Gly114 impair binding to the NaV1.5 IQ-domain.
Missense variants in CALM genes encoding the Ca2+-binding protein calmodulin (CaM) cause severe cardiac arrhythmias. The disease mechanisms have been attributed to dysregulation of RyR2, for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and/or CaV1.2, for Long-QT Syndrome (LQTS). Recently, a novel CALM2 variant, G114R, was identified in a mother and two of her four children, all of whom died suddenly while asleep at a young age. The G114R variant impairs closure of CaV1.2 and RyR2, consistent with a CPVT and/or mild LQTS phenotype. However, the children carrying the CALM2 G114R variant displayed a phenotype commonly observed with variants in NaV1.5, i.e., Brugada Syndrome (BrS) or LQT3, where death while asleep is a common feature. We therefore hypothesized that the G114R variant specifically would interfere with NaV1.5 binding. Here, we demonstrate that CaM binding to the NaV1.5 IQ-domain is severely impaired for two CaM variants G114R and G114W. The impact was most severe at low and intermediate Ca2+ concentrations (up to 4 µM) resulting in more than a 50-fold reduction in NaV1.5 binding affinity, and a smaller 1.5 to 11-fold reduction at high Ca2+ concentrations (25-400 µM). In contrast, the arrhythmogenic CaM-N98S variant only induced a 1.5-fold reduction in NaV1.5 binding and only at 4 µM Ca2+. A non-arrhythmogenic I10T variant in CaM did not impair NaV1.5 IQ binding. These data suggest that the interaction between NaV1.5 and CaM is decreased with certain CaM variants, which may alter the cardiac sodium current, INa. Overall, these results suggest that the phenotypic spectrum of calmodulinopathies may likely expand to include BrS- and/or LQT3-like traits.


Diagnostic efficacy of color Doppler ultrasound in evaluation of cervical lymphadenopathy.
To evaluate the efficacy of color Doppler ultrasound (CDUS) in differentiating benign and malignant cervical lymph nodes by detecting differences in blood flow patterns. In this cross-sectional prospective study, 25 untreated patients with clinical evidence of cervical lymphadenopathy were evaluated. CDUS was performed for 80 cervical lymph nodes. The gray scale parameters of the lymph node and intranodal perfusion sites were the key CDUS features used to differentiate between reactive and metastatic lymph nodes. Histopathological confirmations were obtained and compared with the results of CDUS. Initially, 53 cervical lymph nodes were evaluated by clinical examination. Twenty-seven additional lymph nodes (53 + 27 = 80) were discovered by CDUS evaluation. Gray scale parameters for lymph nodes such as size of lymph node, shape of lymph node, and presence or absence of hilum revealed highly significant results (P < 0.0001). Color Doppler flow signals revealed that central/hilar flow was characteristic for benign nodes whereas peripheral/mixed flow was characteristic for malignant nodes, the findings were highly significant (P < 0.0001). Gray scale and color Doppler features are used to differentiate benign and malignant nodes. Within the limitations of this study, CDUS evaluation was found to be highly significant with a high sensitivity and specificity over clinical evaluation CDUS examination provides a prospect to reduce the need for biopsy/fine needle aspiration cytology in reactive nodes.


Further study of restored and un-restored teeth subjected to high temperatures.
Forensic dentistry has been shown to be of fundamental importance in medico-legal investigations aimed at identifying human remains involving high temperature incidents because dental remains and prosthetic devices are resistant to quite high thermal change. In this project we studied teeth containing class I and V amalgam and composite fillings and compared them to un-restored teeth when exposed to high temperatures. Twenty five un-restored teeth, 25 teeth with class I amalgam restorations, 25 teeth with class V amalgam restorations and 25 teeth with class I composite fillings were placed in a furnace and heated at a rate of 30 degrees C/min. The effects at the predetermined temperatures 200, 400, 600, 800, 1000 and 1100 degrees C were examined macroscopically and then observed microscopically by means of a stereomicroscope. Our observations showed that the class I amalgam restorations at the different temperature levels remained in place, maintaining their shape despite disintegration of the crowns, whilst the class I composite restorations remained in place but in an altered shape. Comparing restored with un-restored teeth we observed different responses in crown disintegration at the different temperature levels.


Modelling biological puncture: a mathematical framework for determining the energetics and scaling.
Biological puncture systems use a diversity of morphological tools (stingers, teeth, spines etc.) to penetrate target tissues for a variety of functions (prey capture, defence, reproduction). These systems are united by a set of underlying physical rules which dictate their mechanics. While previous studies have illustrated form-function relationships in individual systems, these underlying rules have not been formalized. We present a mathematical model for biological puncture events based on energy balance that allows for the derivation of analytical scaling relations between energy expenditure and shape, size and material response. The model identifies three necessary energy contributions during puncture: fracture creation, elastic deformation of the material and overcoming friction during penetration. The theoretical predictions are verified using finite-element analyses and experimental tests. Comparison between different scaling relationships leads to a ratio of released fracture energy and deformation energy contributions acting as a measure of puncture efficiency for a system that incorporates both tool shape and material response. The model represents a framework for exploring the diversity of biological puncture systems in a rigorous fashion and allows future work to examine how fundamental physical laws influence the evolution of these systems.


Effects of co-exposure to atrazine and ethanol on the oxidative damage of kidney and liver in Wistar rats.
Both ethanol (EtoH) and atrazine (ATZ) have hepatic and nephro-toxic effects in rats. In the present study, the toxicity of EtoH (5 g kg-1) on the kidney and liver in the absence or in the presence of different doses of ATZ (50, 100, 300 mg kg-1) was evaluated after 21 days in rats. Results showed that the mixture effects on catalase and superoxide dismutase activities were more severe in both tissues compared to EtoH alone, especially as the dose of ATZ was increased. Hepatic malondialdehyde level (an index of lipid peroxidation) was increased from 20.32% in the EtoH +50 mg kg-1 ATZ-treated rats to 34% in the EtoH +300 mg kg-1 ATZ-treated rats compared to the EtoH values. Renal malondialdehyde values remain as high as 81% in the EtoH-treated rats and the different combine exposure groups. Furthermore, as the dose of ATZ in the mixture was increased, serum uric acid level increased compared to the EtoH values. When the EtoH +300 mg kg-1 ATZ-animals were pretreated with curcumin (an antioxidant), the histopathological changes and peroxidative damages in both tissues were blocked. The exposure of EtoH-treated rats to ATZ enhanced renal and hepatic peroxidative damages in rats.


The timing of the involvement of the frontal eye fields and posterior parietal cortex in visual search.
The frontal eye fields (FEFs) and posterior parietal cortex (PPC) are important for target detection in conjunction visual search but the relative timings of their contribution have not been compared directly. We addressed this using temporally specific double pulse transcranial magnetic stimulation delivered at different times over FEFs and PPC during performance of a visual search task. Disruption of performance was earlier (0/40 ms) with FEF stimulation than with PPC stimulation (120/160 ms), revealing a clear and substantial temporal dissociation of the involvement of these two areas in conjunction visual search. We discuss these timings with reference to the respective roles of FEF and PPC in the modulation of extrastriate visual areas and selection of responses.


Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers.
Type 1 diabetes results from selective T-cell-mediated destruction of the insulin-producing beta-cells in the pancreas. In this process, islet epitope-specific CD8(+) T-cells play a pivotal role. Thus, monitoring of multiple islet-specific CD8(+) T-cells may prove to be valuable for measuring disease activity, progression, and intervention. Yet, conventional detection techniques (ELISPOT and HLA tetramers) require many cells and are relatively insensitive. Here, we used a combinatorial quantum dot major histocompatibility complex multimer technique to simultaneously monitor the presence of HLA-A2 restricted insulin B(10-18), prepro-insulin (PPI)(15-24), islet antigen (IA)-2(797-805), GAD65(114-123), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(265-273), and prepro islet amyloid polypeptide (ppIAPP)(5-13)-specific CD8(+) T-cells in recent-onset diabetic patients, their siblings, healthy control subjects, and islet cell transplantation recipients. Using this kit, islet autoreactive CD8(+) T-cells recognizing insulin B(10-18), IA-2(797-805), and IGRP(265-273) were shown to be frequently detectable in recent-onset diabetic patients but rarely in healthy control subjects; PPI(15-24) proved to be the most sensitive epitope. Applying the "Diab-Q-kit" to samples of islet cell transplantation recipients allowed detection of changes of autoreactive T-cell frequencies against multiple islet cell-derived epitopes that were associated with disease activity and correlated with clinical outcome. A kit was developed that allows simultaneous detection of CD8(+) T-cells reactive to multiple HLA-A2-restricted beta-cell epitopes requiring limited amounts of blood, without a need for in vitro culture, that is applicable on stored blood samples.


Specific aneusomies in Chinese hamster cells at different stages of neoplastic transformation, initiated by nitrosomethylurea.
Aneuploidy is ubiquitous in cancer, and its phenotypes are inevitably dominant and abnormal. In view of these facts we recently proposed that aneuploidy is sufficient for carcinogenesis generating cancer-specific aneusomies via a chain reaction of autocatalytic aneuploidizations. According to this hypothesis a carcinogen initiates carcinogenesis via a random aneuploidy. Aneuploidy then generates transformation stage-specific aneusomies and further random aneusomies autocatalytically, because it renders chromosome segregation and repair mechanisms error-prone. The hypothesis predicts that several specific aneusomies can cause the same cancers, because several chromosomes also cooperate in normal differentiation. Here we describe experiments on the Chinese hamster (CH) that confirm this hypothesis. (i) Random aneuploidy was detected before transformation in up to 90% of CH embryo cells treated with the carcinogen nitrosomethylurea (NMU). (ii) Several specific aneusomies were found in 70-100% of the aneuploid cells from colonies transformed with NMU in vitro and from tumors generated by NMU-transformed cells in syngeneic animals. Among the aneuploid in vitro transformed cells, 79% were trisomic for chromosome 3, and 59% were monosomic for chromosome 10, compared with 8% expected for random distribution of any aneusomy among the 12 CH chromosomes. Moreover, 52% shared both trisomy 3 and monosomy 10 compared with 0.6% expected for random distribution of any two aneusomies. Among the tumor cells, 65% were trisomic for chromosome 3, 51% were trisomic for chromosome 5, and 30% shared both trisomies. Aneuploid cells without these specific aneusomies may contain minor transformation-specific aneusomies or may be untransformed. (iii) Random aneusomies and structurally altered chromosomes increased with the generations of transformed cells to the point where their origins became unidentifiable in tumors. We conclude that specific aneusomies are necessary for carcinogenesis.


Genetic activity of the carcinogen N-nitrosodiethanolamine (NDELA) on unstable mutant alleles of the white locus in Drosophila melanogaster.
The genetic activities of the carcinogen N-nitrosodiethanolamine (NDELA) were assayed somatically and germinally on two stocks carrying unstable alleles of the white (w+) eye colour gene: one incorporating a TE (z TE w+; coded UZ), the other with a tandem duplication of part of the encoding w+ sequence (wi16). Treatment was applied topically on late embryonic and early larval stages over a wide dose range (0.01-2.0 M) and the general mutagenic levels actually achieved were measured in terms of the X-recessive mutations (lethals and visibles) recovered in Muller-5 tests on samples of the males scored for somatic sectoring. The carcinogen was germinally ineffective on the z TE w+ and wi16 loci even at the maximal tested dose (2.0 M), and was only weakly mutagenic with respect to the X-recessives (lethals + visibles) at massive doses (1.0-2.0 M). In contrast, it proved to be genetically effective somatically, inducing red eye sectors through regulatory effects involving the TE in the UZ stock and complete reversion to w+ in the case of wi16 at comparatively moderate doses (less than or equal to 0.26 M). The possible implications of the demonstration of the genetic activity of NDELA in the soma to the carcinogenic process, and to the wider problem of screening for environmental genotoxic compounds, are discussed.


Thermoresponsive micelles from Jeffamine-b-poly(L-glutamic acid) double hydrophilic block copolymers.
Double hydrophilic block copolymers (DHBC) consisting of a Jeffamine block, a statistical copolymer based on ethylene oxide and propylene oxide units possessing a lower critical solution temperature (LCST) of 30 degrees C in water, and poly(L-glutamic acid) as a pH-responsive block were synthesized by ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride using an amino-terminated Jeffamine macroinitiator, followed by hydrolysis. This DHBC proved thermoresponsive as evidenced by dynamic light scattering and small-angle neutron scattering experiments. Spherical micelles with a Jeffamine core and a poly(L-glutamic acid) corona were formed above the LCST of Jeffamine. The size of the core of such micelles decreased with increasing temperature, with complete core dehydration being achieved at 66 degrees C. Such behavior, commonly observed for thermosensitive homopolymers forming mesoglobules, is thus demonstrated here for a DHBC that self-assembles to generate thermoresponsive micelles of high colloidal stability.


Estimating a modified Grubb's exponent in healthy human brains with near infrared spectroscopy and transcranial Doppler.
The relationship between cerebral blood volume (CBV) and flow (CBF) has been widely studied. One of the most significant early studies was by Grubb et al (1974 Stroke 5 630-9), who conducted hypercapnia studies in primates with positron emission tomography (PET) and empirically found CBV = 0.8 CBF(0.38). The exponent used here has since been known as the Grubb's exponent. In this paper, we define a similar exponent known as the modified Grubb's exponent, G', which is based on CBV and cerebral blood flow velocity (CBFV) estimated by near infrared spectroscopy (NIRS) and transcranial Doppler respectively, i.e. G' = log(CBV/CBV(0))/log(CBFV/CBFV(0)), where CBV(0) and CBFV(0) are baseline values. The aim of this study was to estimate the nominal value of the modified Grubb's exponent in healthy human brains. We conducted hypercapnia and hypocapnia studies on 14 healthy adult subjects. The correlation coefficient between log(CBV/CBV(0)) and log(CBFV/CBFV(0)) is 0.71 (p < 0.0001). We found a modified Grubb's exponent of 0.13 (the 95% confidence bounds are 0.10 and 0.17) which is expectedly lower than the conventional Grubb's exponents estimated by other techniques. The modified Grubb's exponent is a simple measure to quantify the hemodynamics between local CBV and global CBFV in the brain and as such may provide insight on brain physiology. Both NIRS and transcranial Doppler techniques are non-invasive and portable, facilitating future studies in other population groups such as brain-injured patients.


Alteration in respiratory physiology in obesity for anesthesia-critical care physician.
Obesity is known to be a major risk factor of a whole range of cardiovascular, metabolic and respiratory disorders. The pattern of regional fat distribution plays an important role in the pre-disposition of obese subjects to respiratory complications. Obesity is responsible for important changes in respiratory function both during spontaneous breathing as well as during general anesthesia and mechanical ventilation. The most characteristic abnormalities consist of decreased functional residual capacity, reduced expiratory reserve volume, decreased compliance and increased resistance of the respiratory system. Breathing at low lung volume promotes airway closure in the dependent lung zones with consequent gas exchange abnormalities even though lung carbon monoxide-diffusing capacity is normal or increased. Weight loss can reduce many of the alterations in pulmonary function related to obesity.


Pathological features of paraganglioma in the lumbar spinal canal: A case report.
This study aims to investigate the pathological features of a patient with paraganglioma in the lumbar spinal canal. The patient was 36 years old male with electrical pain in the waist and buttock which occurred intermittently, and was not relieved under oral use of analgesics. Immunohistochemical staining was performed to diagnose the disease. The results revealed that the size of the tumor was 3.4 × 1.6 × 1.4 cm. The hematoxylin and eosin (H&E)-stained tumor cells mainly presented with an organ-like arrangement under low power microscope, showing prominent chrysanthemum-like, pseudo glandular or pseudo papillary arrangements. The surrounding area of the nest presented with sinusoids, and fibrosis and focal calcification could be observed in the interstitial space among the lesions. Immunohistochemistry results showed that the chief cells were positive for neuron-specific enolase (NSE), Syn and CgA, and Sertoli cells were positive for S-100. Paraganglioma is a very rare malignant tumor. This tumor should be distinguished from ependymoma, meningioma and hemangioblastoma, to avoid misdiagnosis, and missed diagnosis.


An anterior function for the Drosophila posterior determinant Pumilio.
Bicoid is a key determinant of anterior Drosophila development. We demonstrate that the prototypical Puf protein Pumilio temporally regulates bicoid (bcd) mRNA translation via evolutionarily conserved Nanos response elements (NRE) in its 3'UTR. Disruption of Pumilio-bcd mRNA interaction by either Pumilio or bcd NRE mutations caused delayed bcd mRNA deadenylation and stabilization, resulting in protracted Bicoid protein expression during embryogenesis. Phenotypically, embryos from transgenic mothers that harbor bcd NRE mutations exhibited dominant anterior patterning defects and we discovered similar head defects in embryos from pum(-) mothers. Hence, Pumilio is required for normal anterior development. Since bcd mRNA resides outside the posterior gradient of the canonical partner of Pumilio, Nanos, our data suggest that Pumilio can recruit different partners to specifically regulate distinct mRNAs.


An Acute Care Sepsis Response System Targeting Improved Antibiotic Administration.
Pediatric sepsis quality improvement in emergency departments has been well described and associated with improved survival. Acute care (non-ICU inpatient) units differ in important ways, and optimal approaches to improving sepsis processes and outcomes in this setting are not yet known. Our objective was to increase the proportion of acute care sepsis cases in our health system with initial antibiotic order-to-administration time ≤60 minutes by 20% from a baseline of 43% to 52% by December 2020. Employing the Model for Improvement with broad stakeholder engagement, we developed and implemented interventions aimed at effective intervention for sepsis cases on acute care units. We analyzed process and outcome metrics over time using statistical process control charts. We used descriptive statistics to explore differences in antibiotic order-to-administration time and inform ongoing improvement. We cared for 187 patients with sepsis over the course of our initiative. The proportion within our goal antibiotic order-to-administration time rose from 43% to 64% with evidence of special cause variation after our interventions. Of all patients, 66% experienced ICU transfer and 4% died. We successfully decreased antibiotic order-to-administration time. We also introduced a novel model for sepsis response systems that integrates interventions designed for the complexities of acute care settings. We demonstrated impactful local improvements in the acute care setting where quality improvement reports and success have previously been limited.


Surgical Anatomy of the Uncinate Process and Transverse Foramen Determined by Computed Tomography.
Study Design Computed tomography-based cohort study. Objective Although there are publications concerning the relationship between the vertebral artery and uncinate process, there is no practical guide detailing the dimensions of this region to use during decompression of the intervertebral foramen. The purpose of this study is to determine the anatomic parameters that can be used as a guide for thorough decompression of the intervertebral foramen. Methods Fifty-one patients with three-dimensional computed tomography scans of the cervical spine from 2003 to 2012 were included. On axial views, we measured the distance from the midline to the medial and lateral cortices of the pedicle bilaterally from C3 to C7. On coronal reconstructed views, we measured the minimum height of the uncinate process from the cranial cortex of the pedicle adjacent to the posterior cortex of vertebral body and the maximal height of the uncinate process from the cranial cortex of the pedicle at the midportion of the vertebral body bilaterally from C3 to C7. Results The mean distances from midline to the medial and lateral cortices of the pedicle were 10.1 ± 1.3 mm and 13.9 ± 1.5 mm, respectively. The mean minimum height of the uncinate process from the cranial cortex of the pedicle was 4.6 ± 1.6 mm and the mean maximal height was 6.1 ± 1.7 mm. Conclusions Our results suggest that in most cases, one can thoroughly decompress the intervertebral foramen by removing the uncinate out to 13 mm laterally from the midline and 4 mm above the pedicle without violating the transverse foramen.


Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system.
Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1-/- ) results in impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1oe ) leads to abnormally high bone mass. Similarly, loss-of-function mutations in COL13A1 in humans produce muscle weakness, decreased motor synapse function and mild dysmorphic skeletal features. Here, analysis of the exogenous overexpression of collagen XIII in various muscles revealed highly increased transcript and protein levels, especially in the diaphragm. Unexpectedly, the main location of exogenous collagen XIII in the muscle was extrasynaptic, in fibroblast-like cells, while some motor synapses were devoid of collagen XIII, possibly due to a dominant negative effect. Concomitantly, phenotypical changes in the NMJs of the Col13a1oe mice partly resembled those previously observed in Col13a1-/- mice. Namely, the overall increase in collagen XIII expression in the muscle produced both pre- and postsynaptic abnormalities at the NMJ, especially in the diaphragm. We discovered delayed and compromised acetylcholine receptor (AChR) clustering, axonal neurofilament aggregation, patchy acetylcholine vesicle (AChV) accumulation, disrupted adhesion of the nerve and muscle, Schwann cell invagination and altered evoked synaptic function. Furthermore, the patterns of the nerve trunks and AChR clusters in the diaphragm were broader in the adult muscles, and already prenatally in the Col13a1oe mice, suggesting collagen XIII involvement in the development of the neuromuscular system. Overall, these results confirm the role of collagen XIII at the neuromuscular synapses and highlight the importance of its correct expression and localization for motor synapse formation and function.


Chain-length and mode-delocalization dependent amide-I anharmonicity in peptide oligomers.
The diagonal anharmonicities of the amide-I mode in the alanine oligomers are examined in the normal-mode basis by ab initio calculations. The selected oligomers range from dimer to heptamer, in either the α-helical or β-sheet conformations. It is found that the anharmonicity varies from mode to mode within the same oligomer. For a given amide-I mode, the anharmonicity is closely related to the delocalization extent of the mode: the less it delocalizes, the larger the anharmonicity it has. Thus, the single-mode potential energy distribution (PED(max)) can be used as an indicator of the magnitude of the anharmonicity. It is found that as the peptide chain length increases, the averaged diagonal anharmonicity generally decreases; however, the sum of the averaged diagonal and off-diagonal anharmonicities within a peptide roughly remains a constant for all the oligomers examined, indicating the excitonic characteristics of the amide-I modes. Excitonic coupling tends to decrease the diagonal anharmonicities in a coupled system with multiple chromophores, which explains the observed behavior of the anharmonicities. The excitonic nature of the amide-I band in peptide oligomers is thus verified by the anharmonic computations. Isotopic substitution effect on the anharmonicities and mode localizations of the amide-I modes in peptides is also discussed.


Transport Pathways in the Neotropical Sponge Aplysina.
Strands of cells distinct from the rest of the tissue were found running lengthwise through the endosome of four species of the sponge Aplysina. Although the strands were more highly pigmented than the adjacent tissue and could be removed intact with forceps, ultra-structural studies revealed no obvious barrier separating the cells in the strands from the rest of the tissue. The strands consist of stretches of elongate cells tightly aligned along densely bundled collagen fibrils, and areas of other elongate cells that possess numerous filopodia. When sponges were fed fluorescent latex beads in situ, beads were taken up and transported specifically into the strands; eventually they were found at the tip of the sponge and further down the stalk, away from the site of feeding. Beads injected into endosomal strands were also transported upwards in the strands to the tip of the sponge. Video microscopy of cells in strands that had been exposed along a portion of their length showed no bulk movement of cells; but individual cells were seen moving in both directions along the strands at 0.025-0.04 {mu}m.s-1. The endosomal cell strands are suggestive of a primitive nutrient transport pathway in sponges.


Early Hearing Detection and Intervention-Pediatric Audiology Links to Services EHDI-PALS: Building a National Facility Database.
To create a searchable web-based national audiology facility directory using a standardized survey, so parents and providers could identify which facilities had capacity to provide appropriate services based on child's age. An Early Hearing Detection and Intervention-Pediatric Audiology Links to Services expert panel was convened to create a survey to collect audiology facility information. Professional practice documents were reviewed, a survey was designed to collect pertinent test protocols of each audiology facility, and a standard of care template was created to cross-check survey answers. Audiology facility information across the United States was collected and compiled into a directory structured and displayed in an interactive website, ehdipals.org. Since November 7, 2012, to May 21, 2016, over 1000 facilities have completed the survey and become listed in the Early Hearing Detection and Intervention-Pediatric Audiology Links to Services directory. The site has registered 10,759 unique visitors, 151,981 page views, and 9134 unique searches from consumers. User feedback has been positive overall. A searchable, web-based facility directory has proven useful to consumers as a tool to help them differentiate whether a facility was set up to test newborns versus young children. Use of a preprogrammed standard of practice template to cross-check survey answers was also shown to be a practical aid.


[In vitro model system of transepithelial migration of neutrophil by Helicobacter pylori].
Migration of neutrophil across the intestinal epithelium is a structural hallmark of active intestinal diseases. One of the characteristic histologic features of Helicobacter pylori (H. pylori) infection is neutrophil infiltration of the gastric mucosa. This study was aimed to establish an in vitro model system of transepithelial migration of neutrophil by H. pylori. Caco-2 cells were grown on polycarbonate membrane. Confluence and integrity were assessed by measuring the transepithelial electrical resistance (TER) and paracellular permeability of macromolecular marker. IL-8 mRNA expression was assessed after H. pylori infection by quantitative RT-PCR. Isolated neutrophils and H. pylori were applied to the basolateral and apical compartment in separate. Also neutrophil transmigration was assessed by light and electron microscopy. Paracellular leakage of 3[H]-mannitol was negligible over TER 166 Omega x cm2. IL-8 mRNA expression increased after H. pylori infection. Neutrophil transmigration was increased by adding of N-formyl-methionyl-leucyl-phenylalanine or H. pylori. This in vitro model system could be applied to the study of pathogenesis of H. pylori infection. A further study of quantification of transmigrated neutrophils is demanded to reach a confirmation.


Nurses' and therapists experiences with occupational musculoskeletal injuries.
Occupational musculoskeletal injuries are costly to the health care industry. It is estimated that 12% of nurses leave the profession annually because of back injuries. With the use of grounded theory methodology, 15 nursing personnel and physical therapists were interviewed about their perceptions of occupational musculoskeletal injuries. Analysis of the data identified major themes, including feelings of fear and frustration; chronic issue and part of the job; love of the profession and concerns about continuing in the profession; increased risk of injury; compliant with treatment; negative impact on quality of life; negative feelings about the occupational health department; and educational needs. A theory began to emerge in which health care workers accepted occupational injuries as part of the job and took no action or initiated only minor interventions to prevent work-related injuries. The study indicates a need for education and better communication.


Clinical outcomes of synchronous head and neck and esophageal cancer.
To investigate clinical outcomes of synchronous head and neck and esophageal cancer (SHNEC). We retrospectively reviewed 27 SHNEC patients treated with curative intent at a single institution. The treatment modality for individual cases was usually determined on a case by case basis. The median follow-up duration for the surviving patients was 28.2 months. The most common site of head and neck cancer was hypopharyngeal carcinoma (n = 21, 77.7%). The lower esophagus was the most common location of esophageal carcinoma (n = 16, 59.3%). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 57.5% and 39.6%. Major pattern of failure was locoregional recurrence in the study patients. Esophageal cancer stage, the Eastern Cooperative Oncology Group (ECOG) performance status, and pretreatment weight loss were significant prognostic factors for OS in univariate analysis. Treatment-related death was observed in two patients, and one patient developed a grade 4 late treatment-related complication. Although the survival outcome for SHNEC is poor, long-term survival might be achievable with aggressive treatment with stage I-II esophageal cancer and good performance.


[European normative recommendations for medical gas pipeline systems].
Several recent decisions have been made in order to increase the security of medical gases delivery in French hospitals. These different changes affect: 1) the hospital itself with the creation of working groups in charge of both monitoring and maintenance of gases networks; 2) the pharmaceutical regulation with promotion of several gases to the status of drugs or need of CE marking for the whole gas network. European rules onset required to give up French former norms (NF) to the profit of "NF EN" rules. Nevertheless, the new norm NF EN 737-3 which concerns medical gases distribution systems does not affect principal clauses of the previous NF S 90-155. It introduces new elements allowing to deploy two types of medical gases networks: the double pressure level used in France and the single pressure level used in the rest of Europe. This new norm, which attempts to harmonize alarm control systems in both types of networks, suffers from important limitations describing the double pressure level systems. Lastly, the final checking proposed by this new norm is very different from the previous one, and is likely to be problematic for the final users within the hospital.


Species differences in pulmonary N-oxidation of chlorpromazine and imipramine.
Our previous studies have demonstrated that chlorpromazine (CPZ) and imipramine (IMP) are metabolized appreciably via N-oxidation catalyzed by pulmonary microsomal flavin monooxygenase in the rat but not in the rabbit. The present work deals with the species differences in N-oxidase of pulmonary microsomes from male cat, dog, goat, guinea pig, hamster, mouse, pig, rabbit and rat. Although CPZ-N-oxidizing activities were generally higher than IMP-N-oxidizing activities, the CPZ-/IMP-oxidizing activity ratios were not constant among the species tested. Little or no activity was detected in the guinea pig and rabbit lung. The following ranking was assigned: mouse less than hamster less than pig less than rat less than dog less than cat less than guinea pig less than goat less than rabbit for CPZ, and pig less than rat less than mouse less than dog less than hamster less than cat less than guinea pig less than goat less than rabbit for IMP. Nitrosobenzene, a known inhibitor of N-oxidase reductase, inhibited rather than increasing the N-oxidation of both substrates. Therefore, it is unlikely that the marked species differences in pulmonary N-oxidase activities are due to differences in N-oxide reductase. Optimum pH for CPZ-N-oxidase was relatively broad over a range of 7.4-8.5 for rat and 8-9.5 for other species. The pH optima for IMP-N-oxidase ranged from 8.5 to 9.5. n-Octylamine accelerated CPZ-N-oxidation in most species. IMP-N-oxidation was affected to a lesser extent by this primary amine. DPEA (2,4-dichloro-6-phenyl- phenoxyethylamine ) also stimulated the CPZ-N-oxidation in rat, pig and cat but inhibited IMP-N-oxidation in these species.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstructive surgery for congenitally malformed mitral valve.
The study aims were to evaluate early and mid-term survival and freedom from reoperation in patients with isolated mitral valve (MV) congenital malformation (MVCM) or in association with other cardiac defects, and to identify predictors for poor early and late outcome. Between January 1990 and February 2001, 58 children with MVCM underwent MV-conserving surgery; patients were allocated to group I (n = 21) with isolated MVCM, and group II (n = 37) with MVCM and associated congenital heart defects (ACHD). MV stenosis was identified in 10 (48%) group I patients, and 11 (30%) group II patients (p = NS); MV insufficiency was present in 11 (52%) patients in group I, and in 26 (70%) of group II (p = NS). The most frequently found MVCM were annular dilatation (n = 13) cases and elongated chordae (n = 14). Hammock MV was found in nine patients (15%). Six (10%) hospital deaths occurred. Mortality was 5% (n = 1) in group I, and 13% (n = 5) in group II (p = 0.4). Mean repair techniques per patient was 2.05+/-0.4 and 2.3+/-0.3 in groups I and II respectively (p = 0.009). Mechanical ventilation time was 2.1+/-1 and 2.8+/-0.7 days in groups I and II (p = 0.003). The incidence of postoperative mitral regurgitation grade > or =1 was significantly higher in group II (p = 0.008). At five-year follow up, actuarial survival was 91.5% in group I and 86% in group II (p = 0.037). Actuarial reoperation-free survival was 85% in group I and 73% in group II (p = 0.01). Multivariate analysis showed age >12 months (p = 0.033), hammock MV (p = 0.0088) and ACHD (p = 0.0048) were strong predictors for poor event-free survival. MV repair for MVCM provides acceptable early and mid-term outcome in terms of mortality and freedom from reoperation. ACHD significantly reduce early and late postoperative survival and freedom from reoperation.


Investigation of the Spectroscopic Information on Functional Groups Related to Carbohydrates in Different Morphological Fractions of Corn Stover and Their Relationship to Nutrient Supply and Biodegradation Characteristics.
The objectives of this study were to investigate (1) nutritive values and biodegradation characteristics and (2) mid-IR spectroscopic features within the regions associated with carbohydrate functional groups (including cellulosic component (CELC), structural carbohydrate (STCHO), and total carbohydrate (CHO)) in different morphological fractions of corn stover. Furthermore, correlation and regression analyses were also applied to determine the relationship between nutritional values and spectroscopic parameters. The results showed that different morphological sections of corn stover had different nutrient supplies, in situ biodegradation characteristics, and spectral structural features within carbohydrate regions. The stem rind and ear husk were both high in fibrous content, which led to the lowest effective degradabilities (ED) among these stalk fractions. The ED values of NDF were ranked ear husk > stem pith > leaf blade > leaf sheath > whole plant > stem rind. Intensities of peak height and area within carbohydrate regions were relatively more stable compared with spectral ratio profiles. Significant difference was found only in peak area intensity of CELC, which was at the highest level for stem rind, followed by stem pith, leaf sheath, whole plant, leaf blade, and ear husk. Correlation results showed that changes in some carbohydrate spectral ratios were highly associated with carbohydrate chemical profiles and in situ rumen degradation kinetics. Among the various carbohydrate molecular spectral parameters that were tested in multiple regression analysis, CHO height ratios, and area ratios of CELC:CHO and CELC:STCHO as well as CELC area were mostly sensitive to nutrient supply and biodegradation characteristics in different morphological fractions of corn stover.


[Schizophrenic patients in ambulatory treatment of a psychiatric hospital and in general practice of established psychiatrists].
Two large samples of schizophrenic patients treated in a psychiatric hospital outpatient clinic (n = 108) and by psychiatrists in office practice (n = 265) are compared in regard to socio-demographic and illness characteristics, pharmacological treatment, tardive dyskinesia rate and psychopathological status--also with respect to results on an outcome-scale. For the outpatient clinic patients changes in hospitalization rates and duration of stay, together with predictors of psychosocial outcome dimensions are reported. The strongest differences between the samples are found in a more complicated course of illness for the outpatient clinic patients, which is interpreted as indication for a higher vulnerability. Against expectation, socio-demographic variables showed no significant differences.


Prostate surgery expenses, 1991.
During 1991, average total charges for a radical prostatectomy among MetLife group health policy holders and dependents averaged $18,140; comparable charges for a transurethral resection of the prostate (TURP) were $7,970. The Pacific area reported the highest average total charges for both procedures--charges 25 percent above the U.S. average for both surgeries. Among the 14 states with 10 or more radical prostatectomies reported to MetLife, California led with total charges of $24,850 (37 percent above the U.S. average) and Minnesota reported the lowest average total charges ($12,480, 31 percent lower than the norm). In the 32 states with 10 or more TURPs during 1991, the charges ranged from the highest in Massachusetts ($11,250, 41 percent above average) to the lowest in Washington ($5,170,35 percent below the United States). Just over two-thirds of the total charges for each surgical procedure was due to the hospital portion of the bill. Physician charges were more than twice as high for a radical prostatectomy than for a TURP, e.g., $5,730 versus $2,630. Hospital stays averaged 7.5 days for a radical prostatectomy and 4.3 days for a TURP. The stays were longest in New Jersey for both procedures.


High survival in out-of-hospital cardiopulmonary resuscitation--7 years' incidence according to the Utstein template in a small town in Northern Norway.
Core data according to the Utstein template was compiled from all out-of-hospital resuscitations in the city of Bodø, Northern Norway, over 7 years (1992-98). Out of a population of 34,500, 149 resuscitations were attempted. A cardiac aetiology was present in 123 patients and their median age was 72.1 years. Eighteen of the 96 patients having suffered a witnessed arrest of cardiac origin were alive after 1 year (18.8%). Fifteen had the best cerebral performance score (scale 1-5) and three had a score of 2. Survival among all resuscitated patients (149) was 18.8% also, giving a number of 62 attempted resuscitations and 11.2 survivors per 100,000 inhabitants per year, respectively. Thirty-three per cent of witnessed cardiac arrests with ventricular fibrillation or ventricular tachycardia survived to discharge, but only 7% with asystole. When the arrest was witnessed, median response time was 5 minutes, and was 3 minutes for the survivors. To our knowledge, this is the highest survival of out-of-hospital arrests in Scandinavia reported so far, and is chiefly explained by short turnout distances.


The Transtheoretical model's processes of change in the heart of a physical activity intervention: A series of n-of-1.
The objectives were a) to test whether a Processes of Change (POC)-personalized Transtheoretical model (TTM)-based intervention could increase physical activity (PA) among inactive adults, and b) to examine whether the intervention increased the level of TTM theoretical constructs. The following hypotheses were formulated: 1) PA levels will be significantly higher during and after the intervention in comparison to baseline measures; 2) the level of targeted POCs will increase during the intervention; 3) non targeted POCs will stay stable, and 4) self-efficacy and decisional balance levels will increase during the intervention. A series of N-of-1 with A (1 to 2-week)-B(10-week)-A'(2-week) design were conducted with 12 inactive adults. Behavioral counselors used behavior change techniques to target TTM constructs and supervise PA. Interventions were individualized based on the 5 POCs with the lowest pre-intervention level. Device-based and subjective PA along with TTM measures were collected weekly online. PA data were analyzed with piecewise linear models. A visual analysis was run to examine the TTM constructs. Device, self-reported and TTM data were available for five, seven and five participants, respectively. A significant self-reported PA increase for six participants was found during the phase B and A2. A significant device-measured PA increase was observed in two participants during the study. A substantial increase of targeted POC from baseline for all participants with available data was observed. This study provides the first evidence of behavioral and psychological effects of a POC-personalized TTM-based intervention in inactive adults.


Identifying Protein-Protein Interactions by Proximity Biotinylation with AirID and splitAirID.
Proteins frequently function in high-order complexes. Defining protein-protein interactions is essential to acquiring a full understanding of their activity and regulation. Proximity biotinylation has emerged as a highly specific approach to capture transient and stable interactions in living cells or organisms. Proximity biotinylation exploits promiscuous biotinylating enzymes fused to a bait protein, resulting in the biotinylation of adjacent endogenous proteins. Biotinylated interactors are purified under very strict conditions and identified by mass spectrometry to obtain a high-confidence list of candidate binding partners. AirID is a recently described biotin ligase specifically engineered for proximity labeling. This protocol details proximity biotinylation by AirID, using protein complexes that form during a type I interferon response as an example. It covers the construction and validation of AirID fusion proteins and the enrichment and identification of biotinylated interactors. We describe a variation on the protocol using splitAirID. In this case, AirID is split into two inactive fragments and ligase activity is only restored upon dimerization of the bait proteins. This permits selective detection of proteins that interact with homo- or heterodimeric forms of the bait. The protocol considers design strategies, optimization, and the properties of different biotin ligases to identify optimal conditions for each experimental question. We also discuss common pitfalls and how to troubleshoot them. These approaches allow proximity biotinylation to be a powerful tool for defining protein interactomes. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Construction and functional validation of AirID fusion proteins Alternate Protocol: Construction and functional validation of splitAirID fusion proteins Support Protocol: Western blot for biotinylated proteins Basic Protocol 2: Biotinylation, enrichment, and identification of protein interactors.


Evaluation of the health hazard of clove cigarettes. Council on Scientific Affairs.
Resolution 43 (1987 Annual Meeting), adopted by the House of Delegates, resolved that the American Medical Association study the dangers associated with clove cigarettes, that policy recommendations regarding regulation of clove and other tobacco additives be developed, and that this information be made available to physicians and the public. Clove cigarettes are tobacco products. They therefore possess all the hazards associated with smoking all-tobacco cigarettes. In addition, inhaling clove cigarette smoke has been associated with severe lung injury in a few susceptible individuals with prodromal respiratory infection. Some individuals with normal respiratory tracts have apparently suffered aspiration pneumonitis as the result of a diminished gag reflex induced by a local anesthetic action of eugenol (the active component of cloves), which is volatilized into the smoke. The American Medical Association has an existing policy vigorously opposing the use of any tobacco product; no exemption from this policy is made for clove-containing cigarettes.


Transition to Targeted Therapies Improved the Prognosis and Increased the Utilization of Medical Treatments among Patients with Synchronous Metastatic Renal Cell Cancer.
Since the introduction of targeted therapies (TTs) for metastatic renal cell cancer (mRCC) in 2005, a limited amount of epidemiological data on efficacy of modern drug therapies for synchronous mRCC has been published. We present a comprehensive nationwide cohort including all cases of primarily metastasized renal cell cancer among adults diagnosed between 2005 and 2010, based on data from the Finnish Cancer Registry and patient records from treating hospitals. Applied treatment protocols and survival outcomes were analyzed. A total of 977 patients were included in the analysis; 499 patients were diagnosed between 2005 and 2007 and 478 patients were diagnosed between 2008 and 2010. The median overall survival (OS) was 8.80 months (95% confidence interval (CI): 7.60-10.02). The median OS of the patients diagnosed at the latter era was significantly better (11.1; 95% CI: 8.8-13.4 vs. 7.0; 95% CI: 5.7-8.3 months, p ≤ 0.001). A total number of 524 (53.8%) patients received drug therapy. Altogether, TTs including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTORi), and vascular endothelial growth factor inhibitor covered 331 (63.2%) of first-line treatments, whereas interferon and its combinations with chemotherapy were used for 186 (35.5%) patients. The median OS rates for TT and interferon as first-line therapy groups were 19.9 (16.9-22.8) and 14.9 (12.3-17.4) months, respectively. The OS for patients who did not receive drug therapy after cytoreductive nephrectomy was dismal. We found that the OS estimate of mRCC patients in Finland has improved since the introduction of tyrosine kinase inhibitors. However, the prognosis remains poor for frail, elderly patients with an impaired performance status.


Machine Learning Approaches to Identify Nicknames from A Statewide Health Information Exchange.
Patient matching is essential to minimize fragmentation of patient data. Existing patient matching efforts often do not account for nickname use. We sought to develop decision models that could identify true nicknames using features representing the phonetical and structural similarity of nickname pairs. We identified potential male and female name pairs from the Indiana Network for Patient Care (INPC), and developed a series of features that represented their phonetical and structural similarities. Next, we used the XGBoost classifier and hyperparameter tuning to build decision models to identify nicknames using these feature sets and a manually reviewed gold standard. Decision models reported high precision/positive predictive value and accuracy scores for both male and female name pairs despite the low number of true nickname matches in the datasets under study. Ours is one of the first efforts to identify patient nicknames using machine learning approaches.


Inhibitor-Directed Spin Labelling-A High Precision and Minimally Invasive Technique to Study the Conformation of Proteins in Solution.
Pulsed electron-electron double resonance spectroscopy (known as PELDOR or DEER) has recently become a very popular tool in structural biology. The technique can be used to accurately measure distance distributions within macromolecules or macromolecular complexes, and has become a standard method to validate structural models and to study the conformational flexibility of macromolecules. It can be applied in solution, in lipid environments or even in cells. Because most biological macromolecules are diamagnetic, they are normally invisible for PELDOR spectroscopy. To render a particular target molecule accessible for PELDOR, it can be engineered to contain only one or two surface-exposed cysteine residues, which can be efficiently spin-labelled using thiol-reactive nitroxide compounds. This method has been coined "site-directed spin labelling" (SDSL) and is normally straight-forward. But, SDSL can be very challenging for proteins with many native cysteines, or even a single functionally or structurally important cysteine residue. For such cases, alternative spin labelling techniques are needed. Here we describe the concept of "inhibitor-directed spin labelling" (IDSL) as an approach to spin label suitable cysteine-rich proteins in a site-directed and highly specific manner by employing bespoke spin-labelled inhibitors. Advantages and disadvantages of IDSL are discussed.


Circulating levels of adiponectin, leptin, fetuin-A and retinol-binding protein in patients with tuberculosis: markers of metabolism and inflammation.
Wasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4). The plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals (=no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation (=active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA). In the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P=0.0033 and P=0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP. Our data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines.


A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine-needle aspiration cytology.
Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low-grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56-year-old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin-laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions.


1-Methyl-amino-3-(2,4,6-trimethyl-phen-yl)propan-2-ol.
The methyl-amino-propyl chain in the title compound, C(13)H(21)NO, adopts an extended zigzag conformation and the N atom shows a trigonal coordination. The N atom acts as hydrogen-bond acceptor to the hy-droxy group of an adjacent mol-ecule, generating a helical chain running along the b axis. The amino H atom is not involved in hydrogen bonding.


Hearing Results Following Type 1 Tympanoplasty in Elderly Patients.
The outcomes of type 1 tympanoplasty in elderly patients remain controversial. Therefore, more studies are needed to clarify the prognosis of elderly patients after tympanoplasty. The purpose of this study was to evaluate the clinical outcomes of type 1 tympanoplasty in elderly patients. We retrospectively analyzed data from 116 patients who underwent type 1 tympanoplasty due to chronic otitis media. Seventy-one of the 116 patients were elderly individuals aged 65 years or older (study group). Forty-five patients were younger than 65 years (control group). Due to cochlear intolerance by aging in the study group, we used dexamethasone soaked gelfoam packing in the middle ear and intraoperative dexamethasone injection. To compare the outcomes between groups, we determined the mean hearing levels by averaging the hearing thresholds. The differences in the air-bone gaps before and after tympanoplasty were compared between groups. In the study group, 54 patients had an underlying disease (76%). Hypertension was the most common underlying disease. The postoperative air conduction (AC) and bone conduction (BC) improved in both the study group and the control group. In the control group, postoperative air-bone gap (ABG) was significantly higher than preoperative ABG. Although the postoperative ABG improved in the study group, the improvement was insignificant. Although significant improvement of ABG was not achieved, postoperative AC and BC were improved. Intraoperative dexamethasone injection and dexamethasone soaked gelfoam packing in the middle ear was effective to prevent deterioration of BC after operation.


The plurality of Chinese and American medical moralities: toward an interpretive cross-cultural bioethics.
Since the late 1970s, American appraisals of Chinese medical ethics and Chinese responses to American bioethics range from frank criticism to warm appreciation, from refutation to acceptance. Yet in the United States as well as in China, American bioethics and Chinese medical ethics have been seen, respectively, as individualistic and communitarian. In this widely-accepted general comparison, the great variation in the two medical moralities, especially the diversity of Chinese experiences, has been unfortunately minimized, if not totally ignored. Neither American bioethics nor Chinese medical ethics is a field with only one dominant way of thinking. Medical moralities in America and China -- traditional and modern -- have always been plural and diverse. For example, American and Chinese cultures and medical moralities both exhibit individualistic and communitarian traditions. For this reason, bioethics in general and cross-cultural bioethics in particular must be fundamentally interpretive. Interpretive cross-cultural bioethics appreciates the plurality of medical morality within any culture. It can serve as a vital means of social and cultural criticism through engaged interpretations.


Stability analysis of associative memory network composed of stochastic neurons and dynamic synapses.
We investigate the dynamical properties of an associative memory network consisting of stochastic neurons and dynamic synapses that show short-term depression and facilitation. In the stochastic neuron model used in this study, the efficacy of the synaptic transmission changes according to the short-term depression or facilitation mechanism. We derive a macroscopic mean field model that captures the overall dynamical properties of the stochastic model. We analyze the stability and bifurcation structure of the mean field model, and show the dependence of the memory retrieval performance on the noise intensity and parameters that determine the properties of the dynamic synapses, i.e., time constants for depressing and facilitating processes. The associative memory network exhibits a variety of dynamical states, including the memory and pseudo-memory states, as well as oscillatory states among memory patterns. This study provides comprehensive insight into the dynamical properties of the associative memory network with dynamic synapses.


Mineralization of regenerated cellulose hydrogels induced by human bone marrow stromal cells.
The proliferation of cultured human bone marrow stromal cells (HBMSC) on regenerated cellulose hydrogels was assessed. Regenerated cellulose hydrogels showed good rates of HBMSC proliferation, the cells exhibiting a flattened morphology, and after 22 days in culture, the cells had homogeneously colonized the surface of the materials. Moreover, since the early days in culture, between the surface of the materials and attached cells a continuous granulated hydroxyapatite layer was formed. It has been previously demonstrated in vitro, but without cells, that these materials did not mineralize. Hence, it seems that HBMSC promoted the mineralization of the surface.


Novel approaches in anti-angiogenic treatment targeting endothelial F-actin: a new anti-angiogenic strategy?
As a functional blood supply is crucial for growth of solid tumors, the development of anticancer agents to inhibit the formation of new tumor blood vessels is an area of extensive research. Endothelial cell motility driven by the dynamics of the cytoskeleton is a key feature of angiogenesis. Agents that preferentially target endothelial tubulin are well established, and inhibition of the endothelial actin dynamics appears to be another promising anti-angiogenic strategy. Remodeling of the actin cytoskeleton is regulated by several pathways involving a large number of signaling proteins. Therefore, therapeutic strategies for the modulation of actin dynamics include agents that target the actin cytoskeleton directly, as well as inhibitors of actin binding proteins and regulators in upstream pathways. This review provides an overview of the regulation of the actin cytoskeleton and proteins that could potentially be targeted by therapeutic agents. In addition, an outline of promising agents, which includes recombinant proteins, endogenous effectors and treatment regimes that exert anti-angiogenic effects partly mediated by affecting endothelial actin dynamics is provided.


The executive control correlate of loneliness in healthy older people.
Perceived loneliness has implications in both cognitive and affective domains. High loneliness is considered to be a major risk factor for major depressive disorder. Loneliness is also associated with impaired executive control functioning (ECF) including multiple cognitive subdomains, such as working memory, planning, response inhibition, and attention control. However, little knowledge exists as to whether perceived loneliness is associated with impaired functioning of specific ECF components. The relationship between perceived loneliness and the latent dimensions capturing multiple measures across different ECF paradigms has not been established. In this study, we first investigated the latent dimensions of ECF processes across a comprehensive range of paradigms using exploratory factor analysis. We then examined the association of perceived loneliness and the resulted ECF components in older adults while simultaneously controlling for other demographic and affective measures. Four components emerged from the factor analysis: social cognition and processing speed, planning and working memory, selective, divided attention and inhibition control, and sustained attention and motor inhibition. We observed that the second ECF component, planning and working memory, was a significant predictor of perceived loneliness even after controlling for depressive characteristics measured by the Geriatric Depression Scale. Our findings have potential clinical significance in the older population, by showing that planning and working memory functions may predict perceived loneliness, which is also associated with higher risk for major depression. Thus, older individuals who have lower planning and working memory functions may be specifically targeted for possible early prevention of chronic loneliness and depression.


PDM-SHD NFDM transmission with envelope-detection feedback polarization tracking and optical injection locking.
Nonlinear frequency division multiplexing (NFDM) systems, especially the eigenvalue communications have the potential to overcome the nonlinear Shannon capacity limit. However, the baud rate of eigenvalue communications is typically restricted to a few GBaud, making it challenging to mitigate laser frequency impairments such as the phase noise and frequency offset (FO) using digital signal processing (DSP) algorithms in intradyne detections (IDs). Therefore, we introduce the polarization division multiplexing-self-homodyne detection (PDM-SHD) into the NFDM link, which could overcome the impact of phase noise and FO by transmitting a pilot carrier originating from the transmitter laser to the receiver through the orthogonal polarization state of signal. To separate the signal from the carrier at the receiver, a carrier to signal power ratio (CSPR) unrestricted adaptive polarization controlling strategy is proposed and implemented by exploiting the optical intensity fluctuation of the light in a particular polarization rather than its direct optical power as the feedback. Optical injection locking (OIL) is used subsequently to amplify optical power of pilot carrier and mitigate the impact of signal-signal beat interference (SSBI). Additionally, the effects of cross-polarization modulation (XPolM) and modulation instability (MI) in long haul transmission are explored and inhibited. The results show that the tolerable FO range is about 3.5 GHz, which is 17 times larger than the ID one. When 16-amplitude phase shift keying (APSK) or 64-APSK constellations are used, identical Q-factor performance can be obtained by using distributed feedback (DFB, ∼10 MHz) laser, external cavity laser (ECL, ∼100kHz), or fiber laser (FL, ∼100 Hz), respectively, which demonstrates that our proposed PDM-SHD eigenvalue communication structure is insensitive to the laser linewidth. Under the impact of cycle slip, the Q-factor difference of 16-APSK signal between the ECL-ID system and ECL-SHD system can be up to 8.73 dB after 1500 km transmission.


Visualization of laser-induced breakdown spectroscopy data of mouse organs based on the feature extraction method.
At present, there is no comprehensive and systematic research on laser-induced breakdown spectroscopy (LIBS) data visualization. In particular, the LIBS spectra of biological samples have large noise and weak signals, which seriously affect the feature visualization. Here, three commonly used sample visualization methods were compared, and a new method was applied for tissue sample visualization. We used the LIBS mapping technique to obtain LIBS spectra of different organ slice samples from mice. LIBS spectral distribution was visualized after extracting the region of interest. The three spectral visualization methods are compared, and the performance of visualization algorithms is quantitatively analyzed. The potential of heat-diffusion for the affinity-based transition embedding (PHATE) method highlights the details of the LIBS spectral distribution while maintaining the overall structure of the data. The correlation coefficient between dimensionality reduction data and raw data is 0.97, and the average distance between samples of different categories is 0.64, which are superior to those of traditional principal component analysis (PCA), multidimensional scaling (MDS), and t-distributed stochastic neighbor embedding (t-SNE). The results show that the PHATE method can serve as a very promising LIBS spectral visualization tool.


Evaluation of fox-chasing enclosures as sites of potential introduction and establishment of Echinococcus multilocularis.
Following detection of Echinococcus multilocularis in red foxes (Vulpes vulpes) illegally imported into South Carolina (USA) for release in fox-chasing enclosures, a survey for E. multilocularis was conducted in four enclosures in Georgia (USA) and six enclosures in South Carolina. Survey methods included examination of potential small mammal intermediate hosts (n = 390) for E. multilocularis larvae, examination of fox and coyote (Canis latrans) scats (n = 59) for taeniid eggs, and examination of one possible canine definitive hosts for adult E. multilocularis. All intermediate and definitive hosts examined were negative for E. multilocularis and taeniid eggs were not recovered from fox and coyote fecal samples. Thus, E. multilocularis may not yet be established in fox-chasing enclosures in Georgia and South Carolina. Despite the failure to demonstrate E. multilocularis in the fox-chasing enclosures surveyed, translocation of wild canids from known enzootic regions should be discouraged because E. multilocularis is known to be ecologically adaptable and because contact with potentially infected definitive hosts during translocation is a public health risk.


Payment reform to support lasting practice reform in primary care.
Establishing and sustaining patient-centered medical homes will require new investments in primary care. The Payment Reform Task Force of the Patient-Centered Primary Care Collaborative consensus statement recommends a blend of different payment strategies for the majority of patients in a practice along with risk adjustment. It also recommends shifting focus to value, ensuring that the working environment for primary care is improved, optimizing administrative practicality and relying on pilots with systematic evaluation and review to evolve the best strategy.


Reconstruction of edge density profiles on Large Helical Device using ultrashort-pulse reflectometry.
Reflectometry has been expected to be one of the key diagnostics to measure density profiles. We have applied an ultrashort-pulse reflectometry (USPR) system to Large Helical Device in the National Institute for Fusion Science. Wide frequency band system is required to obtain wide density profile since an incident wave is reflected at the density layer corresponding to its cutoff frequency. The reflectometry utilizes an impulse with less than 30 ps pulse width as a source. Since the bandwidth of an impulse has an inverse relation to the pulse width, we can cover the frequency range of micro- to millimeter waves (18-40 GHz) with a single source. The density profiles can be reconstructed by collecting time-of-flight (TOF) signals for each frequency component of an impulse reflected from the corresponding cutoff layer. We utilize the signal record analysis (SRA) method to reconstruct the density profiles from the TOF signal. The effectiveness of the SRA method for the profile reconstruction is confirmed by a simulation study of the USPR using a finite-difference time domain method.


Mapping the details of contact effect of modulated Au-octanedithiol-Au break junction by force-conductance cross-correlation.
We have measured the force and conductance of Au-octanedithiol-Au junctions using a modified conducting atomic force microscopy break junction technique with sawtooth modulations. Force-conductance two-dimensional cross-correlation histogram (FC-2DCCH) analysis for the single-molecule plateaus is demonstrated. Interestingly, four strong correlated regions appear in FC-2DCCHs consistently when modulations with different amplitudes are applied, in sharp contrast to the results under no modulation. These regions reflect the conductance and force changes during the transition of two molecule/electrode contact configurations. As the modulation amplitude increases, intermediate transition states of the contact configurations are discerned and further confirmed by comparing individual traces. This study unravels the relation between force and conductance hidden in the data of a modulated single-molecule break junction system and provides a fresh understanding of electron transport properties at molecule/electrode interfaces.


The Uncharted Link Between Desogestrel and Hypercalcemia.
This report presents a unique case of hypercalcemia with an elusive etiology. A 37-year-old Caucasian female with a history of gonadotropin-secreting pituitary microadenoma and recurrent nephrolithiasis was found to have hypercalcemia, hypercalciuria, elevated 1,25-dihydroxyvitamin D levels, and low parathyroid hormone levels. Extensive investigations were conducted to identify the cause, including ruling out sarcoidosis and other granulomatous disorders. Imaging and diagnostic testing revealed normal results. The patient's condition considerably improved after the cessation of an oral contraceptive pill containing desogestrel. This surprising association raises the possibility that the use of desogestrel could result in hypercalcemia as one of the side effects. To ensure proper care and avoid consequences linked to severe hypercalcemia, a high index of suspicion is needed to detect the underlying cause of hypercalcemia, even in the absence of usual indications.


Cryptosporidium dose response studies: variation between isolates.
The infectivity of three different isolates of the waterborne protozoan parasite Cryptosporidium parvum has been tested in human feeding studies. These three isolates (Iowa, TAMU, and UCP) have different ID50s, indicating substantial variation in their infectivity for humans. This finding is of great importance for quantitative risk assessment as it provides strong evidence for heterogeneity in infectivity among isolates of the same species.


Rare and Common Variants Conferring Risk of Tooth Agenesis.
We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.


Induction of quinone reductase by withanolides.
Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.


Rufibacter roseolus sp. nov. and Rufibacter aurantiacus sp. nov., isolated from desert soil.
Two novel bacterial strains, designated as SYSU D00344T and SYSU D00433T, were isolated from soil of Gurbantunggut Desert in Xinjiang, north-west PR China. Cells of both strains were Gram-stain-negative, aerobic, short-rod-shaped, catalase-positive and non-motile. Oxidase activities of SYSU D00344T and SYSU D00433T were negative and positive, respectively. Optimal growth occurred at 30 °C, with 0-0.5 % (w/v) NaCl and at pH 7.0. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that they represented members of the genus Rufibacter and were closely related to Rufibacter hautae NBS58-1T. The results of phylogenomic analysis indicated that the two strains formed two independent and robust branches distinct from all reference type strains. The analyses of average nucleotide identity (ANI), digital DNA-DNA hybridisation (dDDH) values and 16S rRNA gene similarities between the two strains and their relatives further demonstrated that SYSU D00344T and SYSU D00433T represented two different novel genospecies. The polar lipids consisted of phosphatidylethanolamine, one unidentified glycolipid, two unidentified aminophospholipids, and two or four unidentified lipids. MK-7 was the only respiratory quinone. The major fatty acids (>10 %) for both strains were identified as iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), as well as summed feature 4 (anteiso-C17 : 1B and/or iso-C17 : 1I) for SYSU D00344T and C16 : 1ω5c for SYSU D00433T. On the basis of the phylogenetic, phenotypic, chemotaxonomic and genotypic characteristics, we propose Rufibacter roseolus sp. nov. and Rufibacter aurantiacus sp. nov. as two novel species in the genus Rufibacter. The type strains are SYSU D00344T (=CGMCC 1.8625T=MCCC 1K04971T=KCTC 82274T) and SYSU D00433T (=CGMCC 1.8617T=MCCC 1K04982T=KCTC 82277T), respectively.


HOXA9 transcriptionally regulates the EPHB4 receptor to modulate trophoblast migration and invasion.
Functional placenta formation is crucially dependent on extravillous trophoblast migration and invasion. EPHB4 has been identified to play a negative but important role in regulating trophoblast biological function, whereas the upstream regulation mechanism remains unknown. As reported, there is a transcriptional stimulation of EPHB4 expression consequent to HOXA9 activation in endothelial cells (ECs). Therefore, this study is conducted to investigate the role of HOXA9 and its relationship with EPHB4 in trophoblast cells. Both mRNA and protein expression levels of HOXA9 and EPHB4 were measured in preeclamptic placenta (n = 15) and normal placenta (n = 15). Next, the expression and location of HOXA9 and EPHB4 in first-trimester villi were shown via immunohistochemistry. Trophoblast cell line HTR-8/SVneo was used to explore the effect of HOXA9 on EPHB4 expression and trophoblast bioactivity by gain- and loss-of function studies. In addition, chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to clarify the regulation mechanism of HOXA9 on EPHB4 expression in HTR-8/SVneo. HOXA9 and EPHB4 expression were increased in preeclamptic placenta compared with normal placenta. HOXA9 could promote EPHB4 expression and impaired HTR-8/SVneo cells migration and invasion. ChIP and luciferase assays revealed that HOXA9 could directly bind to EPHB4 promoter and promoted its transcription. HOXA9 transcriptionally regulated EPHB4 expression to modulate trophoblasts migration and invasion, which may suggest a contribution of HOXA9-EPHB4 in the poor placentation in the pathogenesis of preeclampsia.


Impact of 13-valent pneumococal conjugate polysaccharide vaccination in exacerbations rate of COPD patients with moderate to severe obstruction.
One of the major microorganisms described as the cause of exacerbations of chronic obstructive pulmonary disease (COPD) is Streptococcus pneumoniae. The aim of this study is to evaluate the impact of 13-valent pneumococcal conjugate polysaccharide vaccine (PCV13) on COPD patients with regard to the development of exacerbations and the possible differential effect according to the patient's phenotype. Prospective observational study of patients with COPD and FEV1 ≤ 65% and 18-month follow-up. Main variables: vaccination status with PCV13, phenotype "exacerbator" or "non-exacerbator", number of exacerbations, hospitalization and deaths. A descriptive statistical analysis was performed according to the nature of the variable and an inferential analysis with CI95%, bivariate contrasts, and multivariate analysis. Significance level 5%. The statistical packages EPIDAT 3.0 and SPSS version 21.0 were used. 121 patients were included. Twenty-four percent were labeled as phenotype exacerbator. 36% were vaccinated with PCV13. During follow-up, 68% of patients had at least one exacerbation and 27% required hospitalization. We observed similarity (p> 0.05) in the number of exacerbations and deaths; however, the percentage of hospitalization in the vaccinated was 18%, compared to 32% in the non-vaccinated group. In the multivariate adjustment (controlling for the phenotype), an adjusted OR of 2.77 risk of hospitalization was observed in the non-vaccinated group (p = 0.044). Non-vaccination with PCV13 almost triples the risk of hospitalization in patients with COPD.


Insulin-like growth factors in the fed and fasted states.
The effect of GH administration (5 mg twice daily for 5 days) on the serum concentration of insulin-like growth factors I and II (IGF I and IGF II) was compared in GH-deficient subjects during a period of fasting and a period of normal food intake. Before treatment with GH, the mean concentration of IGF I was 35.2 +/- 7.5 ng/ml. After 5 days of GH treatment in the fed state, IGF I increased nearly 10-fold to 317.4 +/- 55.9 ng/ml (P less than 0.001 vs. pretreatment value). During fasting, identical treatment of the group resulted in only a modest increase of IGF I to 81 +/- 23 ng/ml (P less than 0.001 vs. fed state response). The serum concentration of IGF II before therapy was reduced to only 174 +/- 37 ng/ml. With GH given in the fed state, IGF II increased to 793 +/- 171 ng/ml. These data suggest that IGF II, like IGF I, is GH dependent and, hence, a somatomedin. GH therapy in the fasted state increased IGF II to 437 +/- 70 ng/ml (P = 0.05 vs. fed state response). In a second study, six normal subjects were fasted for 72 h. The integrated serum IGF I concentration (24 samples/subject) decreased 42% by the third day of fasting; IGF II decreased 27% during the same period. The data from both studies are consistent with the conclusion that the metabolic milieu of fasting inhibits IGF secretion in man. IGF I appears to be affected more than IGF II.


Klebsiella antibodies in ankylosing spondylitis and Proteus antibodies in rheumatoid arthritis.
Antibodies to Klebsiella, but not to other bacteria, have been shown to be present in patients with active ankylosing spondylitis (AS) by seven different techniques. Antibodies to Proteus, but not to E. coli or Klebsiella, have been shown to be present in patients with active rheumatoid arthritis (RA) by three different techniques. It is suggested AS and RA are forms of reactive arthritis, to Klebsiella and Proteus respectively, probably mediated by cross-reactivity to HLA antigens.


Tolerability profile of bevacizumab in metastatic colorectal cancer: about a Medical Department experience.
Colorectal cancer is one of the most common cancers worldwide, and associated with high mortality rates in our country. The prognosis of patients diagnosed with metastatic colorectal cancer (mCRC) has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. Bevacizumab is well suited for use in combination with first or second line chemotherapy in the treatment of mCRC because its side effects are predictable and appear not to add to the incidence or severity of the side effects of chemotherapy. The aim of our small study is to explore the tolerability profile of bevacizumab used in daily clinical practice in patients with metastatic colorectal cancer (mCRC) in our department.


Eye- and mouth-opening movements replacing head and hand responses in a microswitch program for an adolescent with deteriorating motor condition.
This study assessed the possibility of replacing head and hand responses (no longer feasible) with minimal movements within the microswitch-based program of an adolescent with deteriorating motor condition and multiple disabilities. The new movements, i.e., eye- and mouth-opening, were introduced individually and then combined through the simultaneous availability of the related microswitches. Data showed the participant acquired the new movements (responses) successfully and retained them at a 2-mo. postintervention check. Mood improvements, i.e., increases in indices of happiness, also occurred through the program. The conclusion was that a person with deteriorating motor conditions may be able to revitalize a microswitch-based occupational program and retain a constructive engagement if new, feasible responses are identified.


Structures of bacterial biosynthetic arginine decarboxylases.
Biosynthetic arginine decarboxylase (ADC; also known as SpeA) plays an important role in the biosynthesis of polyamines from arginine in bacteria and plants. SpeA is a pyridoxal-5'-phosphate (PLP)-dependent enzyme and shares weak sequence homology with several other PLP-dependent decarboxylases. Here, the crystal structure of PLP-bound SpeA from Campylobacter jejuni is reported at 3.0 Å resolution and that of Escherichia coli SpeA in complex with a sulfate ion is reported at 3.1 Å resolution. The structure of the SpeA monomer contains two large domains, an N-terminal TIM-barrel domain followed by a β-sandwich domain, as well as two smaller helical domains. The TIM-barrel and β-sandwich domains share structural homology with several other PLP-dependent decarboxylases, even though the sequence conservation among these enzymes is less than 25%. A similar tetramer is observed for both C. jejuni and E. coli SpeA, composed of two dimers of tightly associated monomers. The active site of SpeA is located at the interface of this dimer and is formed by residues from the TIM-barrel domain of one monomer and a highly conserved loop in the β-sandwich domain of the other monomer. The PLP cofactor is recognized by hydrogen-bonding, π-stacking and van der Waals interactions.


Role of calmodulin in blastocyst formation in the mouse.
Preimplantation mouse embryos were recovered by flushing the oviducts on Day 3 at 09:30-10:00 h, 15:30-16:00 h and 21:30-22:00 h: When placed in culture for 48 h, 79% of the 4-8 cell embryos recovered at 09:30-10:00 h developed into blastocysts, but a large number of these embryos failed to form blastocysts when exposed to trifluoperazine, a calmodulin antagonist, at 0.5 or 0.6 microM in culture. About 45% of the embryos recovered at 15:30-16:00 h were compacted and blastocyst formation was again markedly depressed in the presence of the drug. Advanced compacted embryos recovered at 21:30-22:00 h showed normal development into blastocysts in the presence of 0.6 microM-trifluoperazine. Trifluoperazine sulphoxide (the inactive form of trifluoperazine) at 0.6 or 1.2 microM concentration had no effect on blastocyst formation of uncompacted embryos recovered at 09:30-10:00 h. These embryos and those recovered at 21:30-22:00 h and developed into blastocysts in the presence of trifluoperazine were transferred to Day-4 pseudopregnant mice and healthy young were born. When exposed to calcium-free medium or medium containing trifluoperazine all compacted embryos recovered at 18:30 h became decompacted; development to the blastocyst stage was normal in medium alone but reduced when trifluoperazine was added. Compacted embryos recovered at 23:00 h showed 100% decompaction in the calcium-free medium but completely failed to decompact in the presence of 0.6 microM-trifluoperazine. We suggest that extracellular calcium is essential for the continuance of compaction, while intracellular calcium is required only during the initial phase of this process.


Span of management: concept analysis.
This paper is a report of a concept analysis of span of management. Span of management is an important structural variable in evaluating the contributions of nursing managers to healthcare systems. Span of management is typically measured as a ratio. A wide variety of operational definitions have been applied and these differences have not been reconciled. A search of CINAHL, PsychINFO and Business Source Premier was completed in 2007 using the terms span of management, span of control, organizational structure, hierarchy, supervisory ratio and work group size. Key publications (1975-2007) and seminal works were included. Review methods. Morse's concept analysis approach was used to determine the pragmatic utility of the concept. A critical appraisal of the literature assessed the use of the concept across disciplines, identified inconsistencies within the concept, and uncovered assumptions and conceptual gaps. At the organizational level, span represents supervisory capability. At the level of the manager, span may reflect reporting structure, closeness of contact, or scope of the role. At the work group level, span quantifies work group size. At the employee level, span represents employee support. These measures are influenced by units of measurement and by context. A systematic understanding of span of management concepts, measures and determinants will assist nurse executives in selecting parameters to quantify the allocation of managerial resources. Researchers can incorporate these parameters in comparisons across studies and in advancing the science of nursing management.


Topochemical Synthesis of Single-Crystalline Hydrogen-Bonded Cross-Linked Organic Frameworks and Their Guest-Induced Elastic Expansion.
Covalently linked single-crystalline porous organic materials are highly desired for structure-property analysis; however, periodically polymerizing organic entities into high dimensional networks is challenging. Here, we report a series of topologically divergent single-crystalline hydrogen-bonded cross-linked organic frameworks (HCOFs) with visible guest-induced elastic expansions, which mutually integrate high structural order and high flexibility into one framework. These HCOFs are synthesized by photo-cross-linking molecular crystals with alkyldithiols of different chain lengths. Their detailed structural information was revealed by single-crystal X-ray analysis and experimental investigations of HCOFs and their corresponding single-crystalline analogues. Upon guest adsorption, HCOF-2 crystals composed of a 3D self-entangled polymer network undergo anisotropic expansion to more than twice their original size, while the 2D-bilayer HCOF-3 crystals exhibit visible, layered sorption bands and form delaminated sheets along the plane of its 2D layers. The dynamic expansion of HCOF networks creates guest-induced porosity with over 473% greater volume than their permanent voids, as calculated from their record-breaking aqueous iodine adsorption capacities. Temperature-gated DMSO sorption investigations illustrated that the flexible nature of cross-linkers in HCOFs provides positive entropy from the coexistence of multiple conformations to allow for elastic expansion and contraction of the frameworks.


Suppression of tumor necrosis factor production by alcohol in lipopolysaccharide-stimulated culture.
Many studies have shown that alcohol consumption is associated with alteration in immune responses and increased incidence of infection in the host. Tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation, and plays a very important role in host's defenses against infection and tumor. We propose that one of the mechanisms of alcohol-mediated immunosuppression may be due to a defect in the synthesis and release of the TNF. To determine this, we studied the direct effect of alcohol on lipopolysaccharide (LPS)-induced TNF production by whole blood and total mononuclear cell from normal subjects. Aliquots of blood samples (1 ml) or ficoll-hypaque separated total mononuclear cells (1 x 10(6)/ml) were cultured with different concentrations of either ethanol or acetaldehyde in the presence or absence of LPS for 4 hr at 37 degrees C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF-sensitive WEHI 164 subclone 13 cell line. LPS at 10 micrograms/ml produced a maximal level of TNF compared with lower (1 micrograms/ml) or higher concentration (50 micrograms/ml) of LPS. Kinetics studies showed that an incubation time of 4 hr with LPS produced a maximum level of TNF production by blood. Alcohol, as low as 0.1% concentration, produced significant suppression of LPS-induced TNF production by whole blood, whereas alcohol at 0.2 and 0.3% concentrations were required to produce a significant suppression of TNF production by separated mononuclear cells. Anti-TNF-alpha antibodies significantly neutralized the LPS-induced TNF that suggests that blood monocytes may be the primary source of TNF production.(ABSTRACT TRUNCATED AT 250 WORDS)


Optically realizable localized wave solutions of the homogeneous scalar wave equation.
One of the most frequently discussed problems in construction of localized wave (LW) solutions of the homogeneous scalar wave equation has been their energy content--the LW's generally have infinite energy content and special methods have to be used to obtain physically realizable wave fields. So far the problem has mainly been addressed as a pure mathematical one and the proposed LW's can hardly be implemented in optics. In this paper we propose an approach for constructing physically realizable LW's that have a transparent interpretation in terms of optical setups. It will be shown that such LW's can be derived as finite aperture approximations of fundamental LW's, the focus wave modes.


Quantitation of mucin mRNA in respiratory and intestinal epithelial cells.
Mucin glycoproteins (mucins) are the major macromolecular constituents of mucus gels in mammalian respiratory, gastrointestinal, and reproductive tracts. Disorders of mucin glycosylation, which may result from either abnormal post-translational processing or differences in mucin protein gene expression, have been indicated in several diseases. Quantitation of mucin gene expression has been hindered by two features of human mucin genes: variable numbers of tandemly repeating nucleotides per mRNA molecule and polydisperse mRNA transcripts. We report here a method to quantitate mucin mRNA levels in epithelial cells and have evaluated three mucin genes, MUC1, MUC2, and MUC5, which are expressed in respiratory epithelium. The method uses the 3' non-tandem repeat mucin cDNA sequences, as they were shown to have a single-size transcript when amplified by the polymerase chain reaction, consistent with a one-to-one relationship with the mRNA molecule. The 3' non-tandem repeat cDNA sequences were cloned and transcribed in vitro to prepare complementary RNA (cRNA) standards. By comparison to a cRNA standard curve, mucin gene expression was evaluated in colon adenocarcinoma, pancreatic adenocarcinoma, and transformed respiratory epithelial cells and in nasal polyp tissue by slot blot analysis. CFPAC-1, a pancreatic adenocarcinoma cell line, expressed the highest MUC1 transcript levels. Colon adenocarcinoma cell lines varied in MUC2 expression levels, and one colon adenocarcinoma cell line, HT-29, had higher levels of MUC5 than MUC2. Nasal polyp tissue expressed more MUC5 mRNA than MUC1 or MUC2 mRNA. This mucin mRNA slot blot method provides a quantitative method for investigating the regulation of mucin gene expression in health and disease.