Phase behavior of a binary symmetric mixture in slitlike pores with opposing walls: application of density functional approach.
We study adsorption of a symmetric binary Lennard-Jones mixture, which exhibits partial mixing in a bulk phase, in slitlike pores formed by the walls having antisymmetric properties with respect to the components. The calculations are carried out by means of a density functional approach. We show that under suitable conditions the pore filling may occur as a sequence of two first-order transitions. The capillary condensation may lead to an "antisymmetric" liquidlike film, the symmetry of which follows the symmetry of the adsorbing potential, or to a "demixed" film, the symmetry of which is only weakly associated with the symmetry of the adsorption potential. The additional first-order antisymmetric-demixed film transition begins at the triple point temperature and ends at the critical end point temperature.


[Clinical research progress of selective laser trabeculoplasty].
Selective Laser Trabeculoplasty (SLT) is an effective laser treatment modality for controlling intraocular pressure (IOP) in open-angle glaucoma (OAG). Compared to other laser techniques targeting the trabecular meshwork, SLT has demonstrated favorable efficacy and safety. This article aims to summarize the application and advancements of SLT in Chinese OAG patients, focusing on its effectiveness in reducing IOP and postoperative adverse reactions that may influence OAG. By examining SLT from these perspectives, we aim to provide insights for the standardized promotion of SLT and enhancement of clinical glaucoma management in China.


[gamma-heavy chain production as an epiphenomenon in non-Hodgkin's lymphoma].
A 46-year-old woman was found to have localized lymphoplasmocytic lymphoma (low-malignancy non-Hodgkin lymphoma). Repeated recurrences required various chemotherapy courses with different drugs. Gamma heavy chains in serum and urine, as well as in blast cells in bone marrow, were first found 3 years later as part of a follow-up examination. When the lymphoplasmocytic lymphoma subsequently changed into a highly malignant disseminated large-cell lymphoma, the monoclonal gamma heavy chain-producing components no longer occurred. During continuing treatment and presumably selection of different cell clones the now terminal chemotherapy-resistant lymphoma again produced biclonal IgG heavy chains. The gamma heavy chain production added little to the histomorphological characterization of the underlying lymphoma, as well as its treatment and prognosis.


Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.
Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website.


Simultaneous pancreas kidney transplantation: initial experience of the Emory University transplant service.
The successful replacement of islet tissue by pancreas transplantation appears to be beneficial in the early course of those uremic diabetic recipients who receive a simultaneous renal transplant. The long-term advantages of SKP transplantation remain to be determined, however, current improvement in patient and graft survival following SPK and the difficulties thus far reported in islet cell transplantation have renewed clinical interests in SPK, PAK and PA transplantation. In our experience, pancreas transplantation has been a challenging technical, immunological and physiological endeavor which was well received by our patients despite the initial problems and complications we and they encountered. Notwithstanding extensive preparation, our team experienced a "learning curve" and we present many of the lessons we learned. This knowledge has aided our transplant team in the successful management and avoidance of these complications and other inherent problems associated with SKP transplantation in subsequent patients.


Role of lipoproteins and prolactin in luteal function in the ferret.
This study investigated luteal function in vitro during early pregnancy and pseudopregnancy in the ferret. Corpora lutea taken from animals on Day 13 following the ovulatory stimulus (mating or gonadotropin treatment) were dissociated with collagenase and incubated with ovine prolactin (Prl), ovine luteinizing hormone (LH), total lipoprotein fraction from canine serum, canine high-density lipoproteins (HDL), canine low-density lipoproteins (LDL) or combinations of Prl, LH, HDL, and LDL. Total lipoproteins produced statistically definable increases in progesterone accumulation in incubation media at 5 microliter (approx. 50 micrograms protein) through 25 microliter (250 micrograms protein) of the total lipoprotein solution. LDL in doses of 1 or more microgram protein stimulated progesterone accumulation in 2-h incubations and a similar stimulation was observed in the presence of 60 or more micrograms HDL. Prl, LH or the combination of Prl and LH had no apparent stimulatory influence on progesterone accumulation in vitro. Prl in combination with LDL further stimulated progesterone output by luteal cells in short-term incubation relative to LDL alone. Prl and LH together with LDL produced an increase in stimulation over LDL alone, but, for the most part, this augmentation did not exceed that recorded in the presence of the combination of Prl and LDL. No interactions between HDL and luteotropic hormones were present. The results indicate that lipoproteins increase progesterone output from ferret luteal cells, presumably by providing substrate for steroid hormone synthesis. No direct role for LH in ferret luteal function emerged from these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between joint kinetic factors and the walk-run gait transition speed during human locomotion.
The primary purpose of this project was to examine whether lower extremity joint kinetic factors are related to the walk-run gait transition during human locomotion. Following determination of the preferred transition speed (PTS), each of the 16 subjects walked down a 25-m runway, and over a floor-mounted force platform at five speeds (70, 80, 90, 100, and 110% of the PTS), and ran over the force platform at three speeds (80, 100, and 120% of the PTS) while being videotaped (240 Hz) from the right sagittal plane. Two-dimensional kinematic data were synchronized with ground reaction force data (960 Hz). After smoothing, ankle and knee joint moments and powers were calculated using standard inverse dynamics calculations. The maximum dorsiflexor moment was the only variable tested that increased as walking speed increased and then decreased when gait changed to a run at the PTS, meeting the criteria set to indicate that this variable influences the walk-run gait transition during human locomotion. This supports previous research suggesting that an important factor in changing gaits at the PTS is the prevention of undue stress in the dorsiflexor muscles.


Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.
Downregulation in the astroglial glutamate transporter EAAT2 in amyotrophic lateral sclerosis (ALS) patients and mutant SOD1 mouse models of ALS is believed to contribute to the death of motor neurons by excitotoxicity. We previously reported that caspase-3 cleaves EAAT2 at a unique cleavage consensus site located in its c-terminus domain, a proteolytic cleavage that also occurs in vivo in the mutant SOD1 mouse model of ALS and leads to accumulation of a sumoylated EAAT2 C-terminus fragment (CTE-SUMO1) beginning around onset of disease. CTE-SUMO1 accumulates in PML nuclear bodies of astrocytes and causes them to alter their mature phenotypes and secrete factors toxic to motor neurons. Here, we report that mutating the caspase-3 consensus site in the EAAT2 sequence with an aspartate to asparagine mutation (D504N), thereby inhibiting caspase-3 cleavage of EAAT2, confers protection to the SOD1-G93A mouse. EAAT2-D504N knock-in mutant mice were generated and crossed with SOD1-G93A mice to assess the in vivo pathogenic relevance for ALS symptoms of EAAT2 cleavage. The mutation did not affect normal EAAT2 function nor non-ALS mice. In agreement with the timing of CTE-SUMO1 accumulation, while onset of disease was not affected, the mutation caused an extension in progression time, a delay in the development of hindlimb and forelimb muscle weakness, and a significant increase in the lifespan of SOD1-G93A mice.


Financial services employees' experience of peer-led and clinician-led critical incident stress debriefing following armed robberies.
This study investigates financial services employees' experience of critical incident stress debriefing (CISD) and their views about peers and clinicians as facilitators. Semi-structured interview accounts of four participants who had experienced both peer-led and clinician-led CISD were analyzed using grounded theory. A core category, ambivalence, permeated each interview and divided into two poles: pathologizing and normalizing. The most frequently occurring sub-category was a dislike of professionalism. Participants preferred the peer debriefer who was perceived to have more personal involvement and with whom they felt more empowered and understood. The findings suggest that the status of the debriefer as 'peer' or 'clinician' may be a crucial variable in the effectiveness of CISD and should be considered when reviewing the outcome literature.


Direct analysis of 15N-label in amino and amide groups of glutamine and asparagine.
A novel method for on-line determination of the amount and position of 15N-labeling in complex mixtures of amino acids is presented. Underivatized amino acids were analyzed by ion-pair chromatography in combination with mass spectrometry. This enables the direct determination of the 15N label distribution. The fragmentation pathways of the nitrogen moieties of glutamine (Gln) and asparagine (Asn) were studied in detail using all mono 15N isotopomers, which led to a method for differentiating between 15N-amide and 15N-amino labeling. The fragmentation involving the amino and amide groups of Gln led to distinct ion structures. The equivalent fragmentation pattern was not observed for Asn. Instead, the amide group of Asn was eliminated as HNCO in a secondary process. The developed analytical method was evaluated by analysis of a range of standard mixtures taking into account different levels of 15N abundance and distribution between the amino and amide groups. The detection limit (3 SD) for the presence of a 15N label was 0.7 and 1.0% for Gln and Asn, respectively. The determination of the positional labeling follows a nonlinear function. A representative example at 30% 15N was used as a benchmark resulting in average relative standard deviations of 2.7 and 15% for Gln and Asn, respectively. The corresponding expectation windows for the positional labeling were found to be 2 and 12%, respectively.


Clinical manifestations and diagnostic methods in pulmonary angiosarcoma: protocol for a scoping review.
Angiosarcoma involving the lung can represent either primary or metastatic malignancy. Due to the rarity of this condition, knowledge surrounding the natural history and clinical presentation is scarce. The aim of this scoping review is to summarize the existing literature on pulmonary angiosarcoma, particularly as it pertains to the clinical presentation and ancillary tests used for diagnosis in addition to histopathology. We will conduct a systematic search using Ovid MEDLINE and EMBASE electronic databases. Two investigators will independently screen identified titles and abstracts to select articles reporting on pulmonary angiosarcoma. The data will be summarized in a narrative fashion and organized according to aspects of epidemiology, risk factors, clinical presentation, diagnostic methods, and treatment. Scoping reviews are increasingly used to synthesize the evidence on a particular topic, to identify gaps in the literature, and to determine if future systematic reviews are feasible. In order to improve the care of patients with angiosarcoma, earlier recognition and diagnosis is required. This review will be valuable for highlighting the range of clinical presentations and the role of imaging and other diagnostic tools in the diagnosis of metastatic and primary pulmonary angiosarcoma. PROSPERO registration: CRD42017059052.


Expression of the HOX-2.3 homeobox gene in human lymphocytes and lymphoid tissues.
Homeobox proteins are sequence-specific DNA-binding proteins initially implicated in the control of gene expression in developing tissues; however, there is increasing evidence that these proteins are important in gene regulation in adult tissues. A cDNA for the homeobox gene HOX-2.3 was isolated from an adult human B-lymphocyte cDNA library. Northern blot analysis showed expression of a 1.1 and a 1.6 kb messenger RNA (mRNA) in a human B-cell line. RNase protection assays demonstrated variable expression in both human B- and T-cell lines. Virally transformed and nontransformed lymphocyte cell lines expressed HOX-2.3 transcripts. Essentially no transcripts were found in unactivated normal B and T lymphocytes; however, B-cell activation with Staphylococcus aureus Cowan strain I and phorbol myristate acetate (PMA) or T-cell activation with phytohemagglutinin and PMA were accompanied by a rapid induction of HOX-2.3 expression even in the presence of the protein synthesis inhibitor, cycloheximide. In situ hybridization was performed to examine HOX-2.3 expression in lymphoid tissues. HOX-2.3 mRNA was detected in the thymic cortex from an 8-year-old child, in the germinal centers in adult tonsil, and in a limited number of hematopoietic cells from the bone marrow. These findings suggest the involvement of HOX-2.3 in regulating gene transcription not only in developing tissues but in hematopoietic and lymphoid tissues as well.


Development of a Geant4-based independent patient dose validation system with an elaborate multileaf collimator simulation model.
Despite the improvements in the dose calculation models of the commercial treatment planning systems (TPS), their ability to accurately predict patient dose is still limited. One of the limitations is caused by the simplified model of the multileaf collimator (MLC). The aim of this study was to develop a Monte Carlo (MC) method-based independent patient dose validation system with an elaborate MLC model for more accurate dose evaluation. Varian Clinac 2300 IX was simulated using Geant4 toolkits, after which MC commissioning with measurements was performed to validate the simulation model. A DICOM-RT interface was developed to obtain the beam delivery conditions including the hundreds of MLC motions. Finally, the TPS dose distributions were compared with the MC dose distributions for water phantom cases and a patient case. Our results show that the TPS overestimated the absolute abutting leakage dose in the closed MLC field, with about 20% more of the maximum dose than that of the MC calculation. For water phantom cases, the dose distributions inside the target region were almost identical with the dose difference of less than 2%, while the dose near the edge of the target shows difference about 10% between Geant4 and TPS due to geometrical differences in MLC model. For the patient analysis, the Geant4 and TPS doses of all organs were matched well within 1.4% of the prescribed dose. However, for organs located in areas with high ratio of leaf pairs with distances less than 10 mm leaf pair (LP(<10mm) ), the maximum dose of TPS was overestimated by about 3% of the prescribed dose. These dose comparison results demonstrate that our system for calculating the patient dose is quite accurate. Furthermore, if the MLC sequences in treatment plan have a large ratio of LP(short) , more than 3% dose difference in normal tissue could be seen.


Spin splitting and reemergence of charge compensation in monolayer WTe2 by 3d transition-metal adsorption.
The semimetallic WTe2 has sparked intense interest owing to the non-saturating magnetoresistance, pressure-driven superconductivity and possession of type-II Weyl fermions. The unexpected and fascinating quantum properties are thought to be closely related to its delicate Fermi surface and a special electron-hole-pocket structure. However, in the single-layer limit, the electron-hole-pocket structure is missing owing to the lack of interlayer interaction. Herewith, we demonstrate that 3d transition-metal adsorption is an effective method to modify the electronic properties of monolayer WTe2 by density functional theory. Spin-splitting and spin-degenerate bands are realized in Ti-, V-, Cr-, Mn-, Fe-, and Co- and Sc-, Ni-, Cu-, and Zn-adsorbed systems, respectively. Especially, the reemergence of the electron-hole pockets appears in the Ni-adsorbed system. The calculated results are robust against inclusion of spin-orbit coupling and Coulomb interaction.


Familial ectodermal dysplasia: a peers' agony.
Ectodermal dysplasias include a various group of inherited disorders which share primary defect in the development of two or more tissues of embryonic ectodermal origin. Though there are many subtypes, ectodermal dysplasias are mainly hidrotic ectodermal dysplasia and hypohidrotic ectodermal dysplasia, among which the most common variety is X linked hypohidrotic ectodermal dysplasia. We report a rare case of X linked hypohidrotic ectodermal dysplasia occurring in a family with various skin, hair and oral abnormalities.


Genetic Characterization of Influenza A Viruses in Japanese Swine in 2015 to 2019.
To assess the current status of influenza A viruses of swine (IAVs-S) throughout Japan and to investigate how these viruses persisted and evolve on pig farms, we genetically characterized IAVs-S isolated during 2015 to 2019. Nasal swab samples collected through active surveillance and lung tissue samples collected for diagnosis yielded 424 IAVs-S, comprising 78 H1N1, 331 H1N2, and 15 H3N2 viruses, from farms in 21 sampled prefectures in Japan. Phylogenetic analyses of surface genes revealed that the 1A.1 classical swine H1 lineage has evolved uniquely since the late 1970s among pig populations in Japan. During 2015 to 2019, A(H1N1)pdm09 viruses repeatedly became introduced into farms and reassorted with endemic H1N2 and H3N2 IAVs-S. H3N2 IAVs-S isolated during 2015 to 2019 formed a clade that originated from 1999-2000 human seasonal influenza viruses; this situation differs from previous reports, in which H3N2 IAVs-S derived from human seasonal influenza viruses were transmitted sporadically from humans to swine but then disappeared without becoming established within the pig population. At farms where IAVs-S were frequently isolated for at least 3 years, multiple introductions of IAVs-S with phylogenetically distinct hemagglutinin (HA) genes occurred. In addition, at one farm, IAVs-S derived from a single introduction persisted for at least 3 years and carried no mutations at the deduced antigenic sites of the hemagglutinin protein, except for one at the antigenic site (Sa). Our results extend our understanding regarding the status of IAVs-S currently circulating in Japan and how they genetically evolve at the farm level.IMPORTANCE Understanding the current status of influenza A viruses of swine (IAVs-S) and their evolution at the farm level is important for controlling these pathogens. Efforts to monitor IAVs-S during 2015 to 2019 yielded H1N1, H1N2, and H3N2 viruses. H1 genes in Japanese swine formed a unique clade in the classical swine H1 lineage of 1A.1, and H3 genes originating from 1999-2000 human seasonal influenza viruses appear to have become established among Japanese swine. A(H1N1)pdm09-derived H1 genes became introduced repeatedly and reassorted with endemic IAVs-S, resulting in various combinations of surface and internal genes among pig populations in Japan. At the farm level, multiple introductions of IAVs-S with phylogenetically distinct HA sequences occurred, or IAVs-S derived from a single introduction have persisted for at least 3 years with only a single mutation at the antigenic site of the HA protein. Continued monitoring of IAVs-S is necessary to update and maximize control strategies.


Time to Blood Culture Positivity by Pathogen and Primary Service.
Initiation and continuation of empirical antimicrobial agents for a 48-72-hour observation period is routine practice in the diagnosis and treatment of infants and children with concern for bacteremia. We examined blood cultures at a freestanding pediatric hospital over a 6-year period to determine the time to positivity. Data were extracted for all patients who were hospitalized and had blood cultures drawn between January 2013 and December 2018. Time to positivity was calculated on the basis of date and time culture was collected compared with date and time growth was first reported. Over a 6-year period, 89 663 blood cultures were obtained, of which 6184 had positive results. After exclusions, a total of 2121 positive blood culture results remained, including 1454 (69%) pathogens and 667 contaminants (31%). For all positive blood culture results, the number and percentage positive at 24, 36, and 48 hours were 1441 of 2121 (68%), 1845 of 2121 (87%) and 1970 of 2121 (93%), respectively. One hundred twenty-five (66 pathogens, 59 contaminants) of the 89 663 cultures (0.14%) yielded positive results between 36 and 48 hours, indicating that 719 patients would need to be treated for 48 hours rather than 36 hours to prevent 1 case of antibiotic termination before positive result. Median times to positive result by pathogen and service line are presented. This study reveals that ≤36 hours may be a sufficient period of observation for infants and children started on empirical antimicrobial agents for concern for bacteremia. These findings highlight opportunities for antimicrobial stewardship to limit antimicrobial .


Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands.
Epidemiological studies have shown a positive association of colon cancer with hyperlipidemia. Furthermore, signaling generated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma ligands, suggested to be candidate tumor preventive agents, has been shown to lower serum triglyceride levels. In the present study, we assessed hyperlipidemia in Apc-deficient mice, model animals for human familial adenomatous polyposis, and examined the effects of pioglitazone and bezafibrate, respectively, PPARgamma and PPARalpha agonists, on both hyperlipidemia and intestinal polyposis. Serum lipid levels in Apc(1309) mice and Min mice from 6 to 15 weeks of age were measured. Although serum levels of triglyceride and cholesterol were low in both Apc(1309) and wild-type mice at 6 weeks, triglycerides were elevated 10-fold in Apc(1309) mice by the age of 12 weeks but not in their wild-type counterparts. Cholesterol was also increased significantly, and marked centrilobular-restricted steatosis was observed in the livers of aged Apc(1309) mice. Similar findings were observed for Min mice at 15 weeks of age. Moreover, lipoprotein lipase mRNA levels in the liver and small intestine of Apc(1309) and Min mice were demonstrated to be lower than those in wild-type mice. Treatment of Apc(1309) mice with 100 and 200 ppm pioglitazone or bezafibrate for 6 weeks from 6 weeks of age caused dose-dependent reduction in serum triglycerides and cholesterol, along with reduction in the numbers of intestinal polyps to 67% of the control value. The present study clearly demonstrated a hyperlipidemic state in Apc gene-deficient mice and a potential of PPARalpha and PPARgamma ligands to suppress both hyperlipidemia and polyp formation. Hyperlipidemia in these mice may thus be associated with their intestinal lesion development.


Real-time observation of multi-mode vibronic coherence in pentafluoropyridine.
The ultrafast dynamics of pentafluoropyridine in the 1 1B2 (ππ*) electronic state excited at λpump = 255 nm is investigated by femtosecond time-resolved time-of-flight mass spectrometry and photoelectron imaging spectroscopy. A pronounced, long-lived, and complex periodic modulation of the transient ion yield signal with contributions by four distinct frequency components, 72 cm-1, 144 cm-1, 251 cm-1, and 281 cm-1, is observed for up to 9 ps. The recorded photoelectron images display a spectral band from the excited 1 1B2 (ππ*) state only in the oscillation maxima; the signal is strongly reduced in the oscillation minima. Supported by electronic structure calculations at the RI-SCS-CC2 and XMCQDPT2 levels of theory, the oscillating components of the signal are identified as frequencies of b1 symmetry coupling modes in a vibronic coherence of the 1 1B2 (ππ*) and 1 1A2 (πσ*) electronic states. The optical excitation initiates regular and periodic wavepacket motion along those out-of-plane modes. In the distorted molecular structure, the initially excited state acquires substantial πσ* character that modulates the transition dipole moment for ionization and results in the observed oscillations.


High-resolution magnetic resonance imaging of the upper eyelid: correlation with the position of the skin crease in the upper eyelid.
The position and appearance of the upper eyelid crease is one of the challenges in eyelid surgery. The aim of this study was to compare the clinical appearance of the upper eyelid crease with its anatomy, including the position of the levator, the septum, and the orbital fat as determined by Magnetic Resonance Imaging (MRI). Oculoplastic examination was performed in normal volunteers of the same age with different appearances of the upper eyelid. MRI (Intera 1.5 T, Philips, the Netherlands) was carried out with both head and surface coils in all volunteers. Subjects were asked to keep their eyes closed during the whole procedure, thus reducing artefacts due to eyeball movements. The protocol lasted 8 minutes and included a multiplanar scout to obtain T1-weighted 3D-images. Thin sagittal T2 sequences were obtained along the plane of the optic nerve and focused on both orbits, allowing a precise analysis of the orbital content and eyelid anatomy. Six volunteers were included in this prospective study, three of Caucasian origin and three of North African, Central African and Asian origin, respectively. We distinguished two appearances of the crease: in some cases, the superior eyelid sulcus was convex, while in other cases it was concave. The superior eyelid fold was either high or low. Two Caucasian subjects had a deep, concave superior eyelid sulcus with a high crease. This crease appearance was correlated with a short concave appearance of the septum, which pulled back the pre-aponeurotic fat. The non-Caucasian volunteers all had a convex superior eyelid sulcus. The orbital septum insertion was low on the levator aponeurosis, and the orbital fat pad drooped onto the levator muscle, accounting for the convexity of the upper eyelid sulcus. A skin fold was formed by redundant skin over the crease. MRI provides excellent images and allows a good analysis of the upper eyelid components. It permits a detailed analysis of the architecture for a better understanding of its appearance and of the crease position, although further investigation with a larger number of volunteers is required.


Dual role for p75(NTR) signaling in survival and cell death: can intracellular mediators provide an explanation?
Several recent reports support a dual role of p75(NTR) in cell death, as well as survival, depending on the physiological or developmental stage of the cells. Coexpression of the TrkA receptor with p75(NTR) further enhances the complexity of nerve growth factor (NGF) signaling. Recent identification of serine/threonine kinases that interact with the p75(NTR) provides an explanation for the lack of an apparent kinase domain needed for signaling. In this report, we review the possible roles of the intracellular proteins that directly interact with the p75(NTR), atypical protein kinase C (PKC) binding protein, p62 and second messengers in the functional antagonism exhibited by TrkA and p75(NTR) with an emphasis on the nuclear factor-kappa B activation pathway.


Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea.
To determine the efficacy of intravenous (IV) Fentanyl in dyspnoeic patients with advanced cancer. Dyspnoeic patients with advanced cancer satisfying the selection criteria received (IV) Fentanyl and were evaluated for response 24 hours post-administration in a prospective observational study. Altogether 36 patients were enrolled into the study. However, data from only 16 patients could be analysed as 20 patients had died or were too sick to self-report scores. Seven out of 16 patients responded to IV Fentanyl although the result was not statistically significant (non-responders versus responders: 56.3% vs 43.8%, p = 0.33). The strongest correlations for variables predictive of responder status were the absence of anxiety and lung metastases. This exploratory study shows that IV Fentanyl can alleviate dyspnea in some patients but is an example of the difficulties conducting dyspnea research. Future studies would benefit from novel developments in the areas of measuring dyspnea in dying patients and statistical analysis of small sample sizes.


Hepatitis C virus infections in oral and injectable drug users.
To assess the frequency of hepatitis C virus antibodies (anti HCV) and exposure to hepatitis B virus in injectable and oral drug users in Auckland. Sera from 110 injectable drug users and 154 oral drug users were tested for anti HCV as well as hepatitis B and D virus markers. Liver function tests were also performed. 73% of injectable drug using persons and 4% of oral drug using persons were positive for anti HCV. Over half of persons with a positive anti HCV result had an abnormal elevation of the liver enzyme alanine aminotransferase (ALT). Total HBV exposure was similar in both injectable drug user and oral drug user groups at approximately 30%, with little difference between ethnic groups. There were no positive results for hepatitis D virus infection. Injectable drug users who are anti HCV positive may represent a potential source of HCV infection in the community. An upgraded educational programme, perhaps in conjunction with the needle/syringe exchange programme, may be required to ensure drug users are aware of the risks of HCV infection to both themselves and the community.


Odor discrimination and odor quality perception in rats with disruption of connections between the olfactory epithelium and olfactory bulbs.
Rats were trained using olfactometry and operant conditioning to discriminate among homologous fatty acids, homologous aldehydes, and a series of unrelated odors. Their memory for the positive and negative assignment of each odor (tested under extinction) was assessed before and after they had received selective lesions of the olfactory bulbs or injection of the olfactory epithelial toxin 3-methyl indole (3-MI). Response accuracy on the memory test provided a measure of the extent to which treatments altered the remembered perceptual quality of the odors. The degree of deafferentation of the bulb by treatment with 3-MI was assessed using anterograde transport of horseradish peroxidase applied to the olfactory epithelium. Rats treated with 3-MI had a detectable reaction product only in varying numbers of glomeruli on the lateral and, in some cases, posterior medial walls of the olfactory bulb. Bulbar lesions destroyed the dorsal and dorsomedial bulbar areas that have been identified in optical and electrophysiological studies as showing responses to fatty acids. Rats with bulbar lesions had good to near perfect retention on their post-treatment memory test on all odor pairs, as did 3-MI-treated rats that still had substantial input to glomeruli on the lateral or posterior medial wall of the bulb. 3-MI-treated rats with substantially fewer afferent connections had severe retention deficits, particularly for the aldehyde and fatty acid odors, but this loss was secondary to deficits in the ability to discriminate among these odors. The results indicate that input to bulbar areas that are activated by a series of homologous odors may not be essential for odor discrimination and that deafferentation of the majority of bulbar glomeruli may be primarily without effect on odor quality perception as assessed by the memory test. These outcomes point to a much higher degree of redundancy within the olfactory bulb than that envisioned by current combinatorial or odotopic hypotheses of odor quality coding or, alternatively, to mechanisms of odor coding used in the awake behaving animal that have not yet been elucidated.


Effect of hydrogen acceptors on D-xylose fermentation by anaerobic culture of immobilized Pachysolen tannophilus cells.
The effect of hydrogen acceptors on the kinetic parameters of D-xylose fermentation under anaerobic conditions was studied in a transient culture of immobilized Pachysolen tannophilus cells. Addition of oxygen to a steady-state culture resulted in a rapid increase (up to fivefold) in the rates of ethanol production and D-xylose uptake, but the rate of xylitol production was unaffected. Furthermore, the molar ethanol yield increased from 0.97 to 1.43 in the presence of oxygen. The moles of ethanol produced per moles of oxygen utilized were considerably greater than would be predicted from the stoichiometry of D-xylose fermentation, which suggests that the organism required oxygen for other functions in addition to its role as a hydrogen acceptor in D-xylose metabolism. When the artificial hydrogen acceptors acetone, acetaldehyde, and acetoin were added to the culture, the rate of ethanol production increased while the xylitol production rate decreased but the rate of xylose uptake was unaffected. The molar ethanol yields increased from 1.03 to 1.63, 1.43, and 1.24 upon addition of acetaldehyde, acetone, and acetoin, respectively, at the expense of the molar xylitol yields. The hydrogen acceptors sodium acetate, methylene blue, benzyl viologen, phenazine methosulfate, indigo carmine, and tetrazolium chloride had no effect on ethanol production.


Use of alternative therapies among Mexican Americans in the Texas Rio Grande Valley.
Alternative therapies have gained increasing recognition and usage in North America during the past decade. In a descriptive study with a convenience sample of 213 Mexican Americans, three research questions were asked: (1) What specific kinds of alternative therapies do Mexicans in the Rio Grande Valley use? (2) What percentage of the sample group uses alternative therapies? and (3) Do the users of alternative therapies self-report these visits to their established, conventional, primary health care provider? Findings showed that 44% of respondents had used an alternative practitioner one or more times during the previous year. The most commonly sought therapies were herbal medicine, spiritual healing and prayer, massage, relaxation techniques, chiropractic, and visits to a curandero (Mexican folk healer). The majority (66%) never report visits to alternative practitioners to their established primary health provider.


Cerebral Arteriovenous Malformation Deep Draining Veins Not Observed on Preoperative Angiography Identified on Postoperative Angiography.
Postoperative digital subtraction angiography (DSA) is the gold standard for establishing a cure of an arteriovenous malformation (AVM) after treatment. The incidence of residual AVM identified on postoperative DSA ranges from 1.8 to 11%. Although this is important for finalizing the treatment of AVMs, postoperative DSA rarely shows new findings that were not previously identified on preoperative imaging. We present a unique case where we identified residual AVM nidus on immediate postoperative DSA that drained into two deep veins that were not evident on preoperative DSA and increased the AVM grade from Spetzler-Martin grade II to III. To our knowledge, this finding has not been previously reported in the literature. We resected the residual AVM nidus identified on postoperative DSA, leading to an angiographic cure. The patient demonstrated a postoperative right-sided supplementary motor area syndrome that resolved over time with therapy. She made a complete functional recovery by her one-month follow-up appointment.


Who pays for work-related traumatic injuries? Payer distribution in washington state by ethnicity, injury severity, and year (1998-2008).
Acute work-related trauma is a leading cause of death and disability for U.S. workers but it is difficult to obtain information about injured workers not covered by workers' compensation (WC). This study aimed to: (1) describe trends in expected payer and linkage to WC claims, (2) compare characteristics of injured workers who did and did not have a linked WC claim, and (3) describe variation in expected payer and linkage to WC claims by ethnicity and injury severity. Data for injuries occurring from 1998 through 2008 were obtained from the Washington State Trauma Registry and linked to WC claims. We found that 27% of work-related traumatic injuries did not have WC listed as a payer, while 37% did not link to a WC claim. Among those with WC listed as a payer, the odds of having a linked WC claim were 57% lower for workers with other non-WC insurance compared with the otherwise uninsured. Latinos were more likely to have a linked WC claim compared with non-Latinos, but there was no significant difference after partially controlling for WC-covered employment and other insurance. This study demonstrated the importance of considering differential access to other insurance coverage and adaptation by health care settings to financial pressures when assessing trends in occupational injury incidence and reporting, especially when using WC as a proxy for work-relatedness. The addition of occupation, industry, and work status to trauma registries and hospital discharge databases would improve surveillance, research, policy and prevention efforts.


Distance delivery of nutrition education.
Questions often arise about the quality of an educational experience in a distance format. Debate exists as to whether the relatively new format of on-line education can offer an equivalent learning experience for students, and the perception remains that virtual learning is impersonal. We examined students' experience in an introductory undergraduate nutrition course that had been remodelled as an asynchronous, active-learning, student-centred model. The investigation used the framework of instructional message design, a concept based on cognitive science principles, to highlight themes in student survey and focus group data. Results indicate that a motivating and accessible quality educational experience is possible in an on-line format through a student-centred model. Such a model provides a means to offer education to a diverse and larger audience. Further investigation is needed to determine faculty professional development needs and cost-effective ways to expand the model. Such a model provides alternatives to expand delivery to encourage interest in the field, and to provide continuing education for allied professionals and the general public.


Family theory and family therapy models: comparative review with implications for nursing practice.
Although theories of the family and theories of family therapy have different origins and purposes, both provide the basis for a family focused nursing approach. Family theory is a practice theory with a focus on health while family therapy is a practice theory with a focus on pathology. Thus, the contributions of each are different. For nurses to adapt and apply the principles of the two theories correctly, they first must understand whether application of a basic theory with a focus on health or a practice theory with a focus on pathology is appropriate in the particular nursing situation. For example, if a husband is hospitalized, recovering from a myocardial infarction, a family focused nursing approach is mandatory in providing optimal nursing care. Assessment of the family situation will provide clues for the functional or dysfunctional state of the family and the appropriateness of utilizing family theory or family therapy principles. If the current state of family relationships is optimal, application of family theory principles than can be applied to guide health promotion on a family level is appropriate. Organizational and dynamic aspects of the family promoting the husband's recovery can be accentuated, supported, and emphasized in the nursing care. However, if the current state of family relationships is pathological, application of family therapy principles is appropriate. Here the goal of the nursing care is restoration of functional organizational patterns and interactive processes between family members.


Monte Carlo modeling of polarized light propagation: Stokes vs. Jones. Part I.
This bipartite comparative study aims at inspecting the similarities and differences between the Jones and Stokes-Mueller formalisms when modeling polarized light propagation with numerical simulations of the Monte Carlo type. In this first part, we review the theoretical concepts that concern light propagation and detection with both pure and partially/totally unpolarized states. The latter case involving fluctuations, or "depolarizing effects," is of special interest here: Jones and Stokes-Mueller are equally apt to model such effects and are expected to yield identical results. In a second, ensuing paper, empirical evidence is provided by means of numerical experiments, using both formalisms.


[Dentogenic infections-part I: the significance of bacterial isolation of dentogenic infections under routineous conditions].
The microflora of odontogenic infections is typically polymicrobial with increased resistance rates against various antibiotics. The purpose of the present study was to analyze bacterial spectra and resistance in odontogenic infections under routineous conditions.Microbiological samples were collected and transported under routineous conditions in a prospective study of 19 patients. All Bacterial spectra and resistance rates were compared with the results of a former prospective evaluation.There were 11 men, 5 woman and 3 children (age range of 2-86 years). A total of only 38 bacterial strains were analyzed. The ratio between aerobes and anaerobes was nearly 1:1. The resistance rates were nearly the same for Penicillin G, but a 2-fold increased resistance for clindamycin against aerobes and a more than 10-fold increased resistance against anaerobes was noted.Prospective studies under standardized conditions are necessary to isolate strict anaerobes and to detect changes in antibiotic efficiency.


Documenting changes in the delivery of substance abuse services: the Status of the "100 best treatment centers for alcoholism and drug abuse" of 1988.
This study explores the impact of managed care on the substance abuse service system by reviewing the current status of the programs that were among the elite service providers in 1988. A survey was conducted assessing the status of the one hundred centers touted as the 100 best treatment centers for alcoholism and drug abuse (Sunshine& Wright, 1988). Findings include the following: Almost a third of these centers (31%) are no longer providing services, the majority of the programs who reported data continue to provide services primarily at a residential level of care (92%); however occupancy rates have dropped, the number of annual inpatient admissions have risen, and the length of treatment episodes has significantly decreased. In 1988, almost all (97.5%) facilities adhered to the 28-day treatment regiment, as evidenced by average treatment episodes of 26 days or longer. However, in 2001, the majority of programs (57.5%) reported treatment episodes of 25 days or less. While these facilities represent a fraction of the number of facilities that provide substance abuse services, they do exemplify elite programs that should be insulated from economic troubles, and help to document the changes that have occurred in the delivery system. Awareness of these changes is important for every social worker that advocates for substance abuse services.


Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.
Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040) in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se.


Duchenne muscular dystrophy: Drug development and regulatory considerations.
Duchenne muscular dystrophy (DMD) is one of the most commonly recognized dystrophinopathies. There are no approved therapeutic options available for this disease but recent discoveries have led to hope that effective therapies might be forthcoming. With funding from patient advocacy groups, private investors, and governmental bodies such as the Food and Drug Administration Office of Orphan Product Development (FDA/OOPD), gene modification and other molecular therapies are being actively investigated. However, since DMD patients are few in number and disease manifestations vary considerably in early and late stages of disease, obtaining the data needed for full evaluation of putative therapies may prove challenging. Should ambulation remain the focus of Phase 2/3 studies or should consideration be given to the primary causes of late-stage morbidity and mortality, e.g., cardiac and respiratory dysfunction related to reduced or absent dystrophin production? It seems reasonable to argue that clinical trials planned for DMD should consider the entire population.


Cyclosporin maintenance therapy for severe atopic dermatitis.
Twelve patients with chronic severe atopic dermatitis were treated with cyclosporin A (CsA) in a dose of 5.0 mg/kg/day. All patients except one showed a good therapeutic response. After week six, the CsA dose was reduced until an increased activity of atopic dermatitis was noticed (minimal effective dose). The minimal effective dose fluctuated with the severity of the atopic dermatitis. The mean minimal effective dose was approximately 4.0 mg/kg/day. Maintenance therapy with CsA for atopic dermatitis seems to be effective but may be hampered by side effects in the same way as CsA therapy is hampered by side effects in the treatment of psoriasis.


The microstructure and micromechanics of the tendon-bone insertion.
The exceptional mechanical properties of the load-bearing connection of tendon to bone rely on an intricate interplay of its biomolecular composition, microstructure and micromechanics. Here we identify that the Achilles tendon-bone insertion is characterized by an interface region of ∼500 μm with a distinct fibre organization and biomolecular composition. Within this region, we identify a heterogeneous mechanical response by micromechanical testing coupled with multiscale confocal microscopy. This leads to localized strains that can be larger than the remotely applied strain. The subset of fibres that sustain the majority of loading in the interface area changes with the angle of force application. Proteomic analysis detects enrichment of 22 proteins in the interfacial region that are predominantly involved in cartilage and skeletal development as well as proteoglycan metabolism. The presented mechanisms mark a guideline for further biomimetic strategies to rationally design hard-soft interfaces.


Analysis of transfer genes and gene products within the traB-traC region of the Escherichia coli fertility factor, F.
A series of plasmids that carry overlapping segments of F DNA encoding the genes in the traB-traC interval was constructed, and a restriction enzyme map of the region was derived. Plasmids carrying deletions that had been introduced at an HpaI site within this interval were also isolated. The ability of these plasmids to complement transfer of F lac plasmids carrying mutations in traB, traV, and traW, and traC was analyzed. The protein products of the plasmids were labeled in UV-irradiated cells and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. These analyses showed that the product of traV is a polypeptide that migrates with an apparent molecular weight of 21,000. It was not detected when [35S]methionine was used to label plasmid products, but was readily detected in 14C-amino acid labeling experiments. A 21,500-dalton product appeared to stem from the region assigned to traP. A 9,000-dalton product was found to stem from a locus, named traR, that is located between traV and traC. No traW activity could be detected from the region of tra DNA examined. Our data also indicated that traC is located in a more promoter-proximal position than suggested on earlier maps. The plasmids constructed are expected to be useful in studies designed to identify the specific functions of the traB, -P, -V, -R, and -C products.


Progress in photocatalytic CO2 reduction based on single-atom catalysts.
Reduced CO2 emissions, conversion, and reuse are critical steps toward carbon peaking and carbon neutrality. Converting CO2 into high-value carbon-containing compounds or fuels may effectively address the energy shortage and environmental issues, which is consistent with the notion of sustainable development. Photocatalytic CO2 reduction processes have become one of the research focuses, where single-atom catalysts have demonstrated significant benefits owing to their excellent percentage of atom utilization. However, among the crucial challenges confronting contemporary research is the production of efficient, low-cost, and durable photocatalysts. In this paper, we offer a comprehensive overview of the study growth on single-atom catalysts for photocatalytic CO2 reduction reactions, describe several techniques for preparing single-atom catalysts, and discuss the advantages and disadvantages of single-atom catalysts and present the study findings of three single-atom photocatalysts with TiO2, g-C3N4 and MOFs materials as carriers based on the interaction between single atoms and carriers, and finally provide an outlook on the innovation of photocatalytic CO2 reduction reactions.


Ligand-Free RuCl3-Catalyzed Alkylation of Methylazaarenes with Alcohols.
RuCl3 efficiently catalyzes the alkylation of methylquinolines, methylpyridines, 2-methyl-benzooxazoles, and 2-methyl-quinoxalines with alkyl- or aryl-alcohols as alkylating agents. This synthetically useful and atom economical transformation does not require additional ligands. The mechanistic study indicated the alkylation reaction underwent a stepwise transfer hydrogenation, aldol condensation, and hydrogenation reaction pathway.


Extranodal soft tissue metastasis as an independent prognostic factor in gastric cancer patients aged under 70 years after curative gastrectomy.
Accumulating evidence confirms the potential prognostic value of extranodal soft tissue metastasis (ESTM) in patients with solid cancers. The aim of this study was to elucidate the potential relationship between ESTM and lymph node (LN) metastasis, demonstrate clinicopathological predictive prognostic factors for ESTM and LN metastasis, and identify the prognostic value of ESTM for gastric cancer (GC) patients aged under 70 years. A total of 580 GC patients who underwent the curative resection between 2003 and 2011 were included to identify if ESTM is essential to improve the accuracy of prognostic evaluation of the GC patients postoperatively. Overall survival rates were tested by Kaplan-Meier analysis. Univariate and multivariate analyses were applied to clarify the independent prognostic factors. Logistic regression analysis was adopted to clarify the risk factors for evaluating the presence of ESTM and LN metastasis. After cut-point survival analysis, the GC patients were divided into three subgroups based on the number of ESTM and then incorporated into the pTNM stage of gastric carcinoma to identify the possibility and necessity of incorporating ESTM into staging. ESTM was associated with advanced pT, pN and pTNM categories, large tumour size and the presence of signet-ring cell (SRC) variants. Survival analyses revealed that ESTM was associated with the OS and was an independent prognostic predictor in this GC patient cohort. Logistic regression analysis proved that ESTM and pT stage are significantly correlated with LN metastasis. Additionally, the ESTM was incorporated into the eighth edition of the pTNM classification and the prognostic evaluation of pTNME classification were calculated directly, and the results indicated that ESTM can reduce the stage migration. ESTM is a significant independent predictor of survival in GC patients. To achieve R0 surgery, lymph nodes, soft tissues, fascia and adipose tissue should be resected en bloc at the same time as lymph node dissection. ESTM should be incorporated into pTNM staging according to the number retrieved from postoperative samples.


America's affordable housing crisis: a contract unfulfilled.
For many poor Americans, having a decent home and suitable living environment remains a dream. This lack of adequate housing is not only a burden for many of the poor, but it is harmful to the larger society as well, because of the adverse effects of inadequate housing on public health. Not only is the failure to provide adequate housing shortsighted from a policy perspective, but it is also a failure to live up to societal obligations. There is a societal obligation to meet the housing needs of everyone, including the most disadvantaged. Housing assistance must become a federally-funded entitlement.


Long-range Stripe Nanodomains in Epitaxial (110) BiFeO3 Thin Films on (100) NdGaO3 Substrate.
Here, we report the observation of ferroelectric and ferroelastic nanodomains in (110)-oriented BiFeO3 (BFO) thin films epitaxially grown on low symmetric (100) NdGaO3 (NGO) substrate. We observed long range ordering of ferroelectric 109° stripe nanodomains separated by periodic vertical domain walls in as-grown 130 nm thick BFO films. The effect of La0.67Sr0.33CoO3 (LSCO) conducting interlayer on domain configurations in BFO/NGO film was also observed with relatively short range-ordering of stripe domains due to the modified electrostatic boundary conditions in BFO/LSCO/NGO film. Additional studies on B-site doping of Nb ions in BFO films showed change in the domain structures due to doping induced change in lattice anisotropy while maintaining the stripe domain morphology with 109° domain wall. This long-range array of ferroelectric and ferroelastic domains can be useful for optoelectronic devices and ferroelastic templates for strain coupled artificial magnetoelectric heterostructures.


Glutaredoxin 1 Downregulation in the Substantia Nigra Leads to Dopaminergic Degeneration in Mice.
Parkinson's disease (PD) is characterized by a severe loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Perturbation of protein thiol redox homeostasis has been shown to play a role in the dysregulation of cell death and cell survival signaling pathways in these neurons. Glutaredoxin 1 (Grx1) is a thiol/disulfide oxidoreductase that catalyzes the deglutathionylation of proteins and is important for regulation of cellular protein thiol redox homeostasis. We evaluated if the downregulation of Grx1 could lead to dopaminergic degeneration and PD-relevant motor deficits in mice. Grx1 was downregulated unilaterally through viral vector-mediated transduction of short hairpin RNA against Grx1 into the SNpc. Behavioral assessment was performed through rotarod and elevated body swing test. Stereological analysis of tyrosine hydroxylase-positive and Nissl-positive neurons was carried out to evaluate neurodegeneration. Downregulation of Grx1 resulted in contralateral bias of elevated body swing and reduced latency to fall off, accelerating rotarod. This was accompanied by a loss of tyrosine hydroxylase-positive neurons in the SNpc and their DA projections in the striatum. Furthermore, there was a loss Nissl-positive neurons in the SNpc, indicating cell death. This was selective to the SNpc neurons because DA neurons in the ventral tegmental area were unaffected akin to that seen in human PD. Furthermore, Grx1 mRNA expression was substantially decreased in the SNpc from PD patients. Our study indicates that Grx1 is critical for the survival of SNpc DA neurons and that it is downregulated in human PD. © 2020 International Parkinson and Movement Disorder Society.


A large prospective European cohort study of patients treated with strontium ranelate and followed up over 3 years.
Strontium ranelate has been available as an osteoporosis treatment in Europe since 2004. This article describes a large European observational survey of the use of strontium ranelate in clinical daily practice. A retrospective observational registry included 32,446 women consulting for postmenopausal osteoporosis in seven countries. Within the registry, 12,046 women were receiving strontium ranelate and were followed up over 3 years. The baseline characteristics of the follow-up cohort were similar to those of the whole registry cohort (age, 68.9 ± 10.3 years; body mass index, 25.6 ± 4.3 kg/m(2); lumbar spine T-score, -2.57 ± 0.85 SD; femoral neck T-score, -2.11 ± 0.86 SD). At baseline, 77 % of patients had at least one risk factor for osteoporosis, and 46 % had a previous history of osteoporotic fracture. Mean duration of follow-up was 32.0 ± 9.7 months, and treatment duration was 25.2 ± 13.7 months (24,956 patient-years of treatment). Persistence with strontium ranelate was 80 % at 1 year, 68 % at 2 years, and 64 % at 32 months; most patients (about 80 %) reported rarely omitting a dose. At least one emergent adverse event was reported in 2,674 (22 %) patients, most frequently gastrointestinal side effects. The crude incidence of venous thromboembolic events was 2.1/1,000 patient-years. No cases of hypersensitivity reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS), Steven-Johnson syndrome, or toxic epidermal necrolysis, were reported. During follow-up, a fracture occurred in 890 patients (7 %); 429 of the fractures were nonvertebral fractures. Our observational survey over 32 months indicated good rates of adherence with strontium ranelate and confirmed its good safety profile in the management of postmenopausal osteoporosis.


Glucocorticoids down-regulate lipopolysaccharide-induced de novo production of neurotensin mRNA in the rat hypothalamic, paraventricular, corticotrophin-releasing hormone neurons.
Intraperitoneal injection of the endotoxin lipopolysaccharide (LPS) produces inflammation accompanied by activation of the immune system and the secretion of cytokines. Cytokines stimulate the hypothalamo-pituitary-adrenal (HPA) axis to release the anti-inflammatory corticosterone which controls its own production by acting on the HPA axis. Upstream in the HPA axis are neuroendocrine corticotrophin-releasing hormone (CRH) neurons located in the paraventricular nucleus (PVN), whose multipeptidergic phenotype changes during inflammation: while CRH mRNA is up-regulated in these conditions, neurotensin (NT) mRNA expression is induced de novo. The negative feedback control of glucocorticoids on CRH production is well documented; however, their action on NT production in the PVN of the hypothalamus is poorly documented. The aim of this study was to determine if glucocorticoids modulate the de novo production of NT during inflammation. Using quantitative in situ hybridization histochemistry, we examined whether the absence (adrenalectomy) or excess (corticosterone implants) of glucocorticoids modulate de novo production of NT mRNA in the PVN during inflammation induced by LPS treatment. A relatively low dose of LPS (50 microg/kg) that is not efficient to induce NT mRNA production in the PVN becomes efficient after adrenalectomy. Moreover, corticosterone excess reduces LPS-induced production of NT mRNA in the PVN. Glucocorticoids exert a negative control on NT mRNA production in the PVN of the hypothalamus, and this effect requires that NT mRNA production be triggered, such as during inflammation.


Role of definitive chemoradiotherapy using docetaxel and 5-fluorouracil in patients with unresectable locally advanced esophageal squamous cell carcinoma: a phase II study.
Definitive chemoradiotherapy (CRT) with docetaxel (DOC) and 5-fluorouracil (5-FU) is a unique regimen for esophageal cancer. In this prospective phase II study, antitumor effect and safety of CRT using DOC and 5-FU for inoperable locally advanced esophageal cancer were evaluated. DOC 7.5 mg/m2 was infused on days 1, 8, 22, and 29. 5-FU 250 mg/m2 /day was infused continuously on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-45. Radiotherapy was given to 66 Gy in 33 fractions. Eleven patients with thoracic and five with cervical esophageal cancer were eligible. All patients had esophageal squamous cell carcinoma (ESCC). The response rate was 94%, with complete response in five patients (31%) and partial response in 10 (63%). Hematologic toxicity was mild; only one patient (6%) had Grade 1 leukopenia. Nonhematologic Grade 3 or higher adverse events were esophagitis (31%), anorexia (6%), and esophago-bronchial fistula (6%). No treatment-related deaths occurred. The median time to progression was 20 months and overall 3-year and 5-year survival were 44% and 31%, respectively. Definitive CRT using DOC and 5-FU could be performed safely, and it demonstrated a favorable antitumor effect for ESCC. This regimen might be indicated in patients in whom it is desirable to avoid myelosuppression and progression of renal impairment.


Forced unfolding of coiled-coils in fibrinogen by single-molecule AFM.
Fibrinogen is a blood plasma protein that, after activation by thrombin, assembles into fibrin fibers that form the elastic network of blood clots. We used atomic force microscopy to study the forced unfolding of engineered linear oligomers of fibrinogen, and we show that forced extension of the oligomers produces sawtooth patterns with a peak-to-peak length consistent with the independent unfolding of the coiled-coils in a cooperative two-state manner. In contrast with force plateaus seen for myosin coiled-coils that suggested rapid refolding of myosin, Monte Carlo simulations of fibrinogen unfolding confirm that fibrinogen refolding is negligible on experimental timescales. The distinct behavior of fibrinogen seems to be due to its topologically complex coiled-coils and an interaction between fibrinogen's alphaC-domains and its central region.


Aspiration lung injury.
Aspiration lung injury is caused by a failure of the normal protective mechanisms that prevent aspiration of gastric contents. Prevention measures are focused on preserving these protective mechanisms. There are three components to the lung injury. The first component is mechanical obstruction to airways from particles in the aspirate. Treatment is aggressive pulmonary toilet to restore airway patency. The second component, seen beginning in the first several hours, is a chemical injury to the airways, leading initially to bronchorrhea, airway constriction, and edema. Later, there is a marked increase in the risk of bacteria due to altered lung defenses. Treatment is supportive care. The third component is lung injury due to the inflammatory response. This process can evolve to an adult respiratory distress syndrome pattern. With modulation of lung inflammation (currently being developed), morbidity and mortality rates will decrease.


[Errors for delivery medications through gastrostomy devices: study of 109 children].
Gastrostomy is frequently used in clinical practice for drug administration. However modalities of drug administration via a gastrostomy device have been poorly studied and remain uncodified. To assess the mode of administration of drugs as well as errors associated with the use of a gastrostomy devices for drug delivery in children. Mode of administration of drugs was studied in 109 children (mean age 8.4+/-5.5 years, 72% neurologically impaired, 41% institutionalized children). A questionnaire was filled in by parents and/or caregivers. Errors of administration were classified as follows: galenic, due to preparation, physico-chemical interaction, lack of flushing the tube. Factors influencing the occurrence of errors were studied: living at home or in an institution, underlying disease, number of drugs administered via gastrostomy device. Errors were frequently observed: galenic (47%), due to preparation (42%), physico-chemical interaction (51%), lack of flushing (10%). Errors occurred more frequently in institutionalized children compared to children living at home (78 versus 25%, P<0.0005). Galenic errors were more frequent in neurologically impaired children (57 versus 30%, P<0.005). Many medications are administrated via gastrostomy tube in children. Errors are frequently observed and potentially dangerous.


[The functional role of the retino-tecto-thalamo-cortical system in rats].
After bilateral lesion of the posterior lateral thalamic nucleus in rats, studies been made of motor-feeding reflexes to light stimuli. Using spatial preference technique, it was shown that lesion of this nucleus (representing a part of the retino-tecto-thalamo-cortical system) disturbs differentiation of spatially uncoupled visual stimuli. These data confirm the idea on telencephalization of ancient retino-tectal part of the visual system in evolution and indicate that this part is involved into the analysis of spatial relationships.


DNA Replication in Engineered Escherichia coli Genomes with Extra Replication Origins.
The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects.


Infrared-to-Visible Light Conversion in Er(3+) -Yb(3+) :Lu3 Ga5 O12 Nanogarnets.
Er(3+) -Yb(3+) co-doped Lu3 Ga5 O12 nanogarnets were prepared and characterized; their structural and luminescence properties were determined as a function of the Yb(3+) concentration. The morphology of the nanogarnets was studied by HRTEM. Under 488 nm excitation, the nanogarnets emit green, red, and near-infrared light. The decay curves for the ((4) S3/2 , (2) H11/2 ) and (4) F9/2 levels of the Er(3+) ions exhibit a non-exponential nature under resonant laser excitation and their effective lifetimes are found to decrease with an increase in the Yb(3+) concentration from 1.0 to 10.0 mol %. The non-exponential decay curves are well fitted to the Inokuti-Hirayama model for S=8, indicating that the mechanism of interaction for energy transfer between the optically active ions is of dipole-quadrupole type. Upon 976 nm laser excitation, an intense green upconverted emission is clearly observed by the naked eyes. A significant enhancement of the red-to-green intensity ratio of Er(3+) ions was observed with an increase in Yb(3+) concentration. The power dependence and the dynamics of the upconverted emission confirm the existence of two-photon upconversion processes for the green and red emissions.


Social work roles and activities regarding psychiatric medication: results of a national survey.
This article reports the findings of a 2001 national survey of social workers regarding their everyday practice roles and activities regarding psychiatric medication. The results of this quantitative study indicate variability in the types of roles carried out by social workers with regard to psychiatric medication, but that perceptions of competence and appropriateness in these roles tended to be positively associated with frequency of roles performed. Using content analysis of two open-ended questions, the authors present themes for respondents' keys to success and desired changes in working with clients and colleagues around psychiatric medication. The results suggest that achieving greater role breadth and competence with regard to psychiatric medications may be best achieved by increasing social workers' knowledge about psychiatric medication, increasing their use of specific intervention skills, and increasing the frequency of professional contact between clinicians and prescribing physicians.


[Endothelin and nitric oxide in newborn kidney].
The review addresses two of vasoactive substances: endothelin and nitric oxide and describes how each of them effects the functions of endothelial cells of kidneys in newborn.


Triage of Intermediate-Care Patients in Pediatric Hospitals.
Hospitalized children have a wide range of acuity and risk of decompensation. The objective of this study was to determine where pediatric patients are triaged when they present to pediatric hospitals needing intense monitoring and nursing care, but do not require invasive monitoring or technology. We completed a telephone survey of pediatric hospitals in the United States with at least 2 non-neonatal pediatric wards and at least 50 acute inpatient beds. The survey consisted of a brief scripted portrayal of 6 hypothetical patients who may be admitted to a hospital's general floor, ICU, or an intermediate care unit (IMCU). The scenarios included severe asthma, bronchiolitis, croup, diabetic ketoacidosis, and patients dependent on home ventilation via noninvasive interface or tracheostomy. The hospital bed coordinator or emergency department charge nurse was asked where each hypothetical patient would be admitted in their hospital. A total192 hospitals met inclusion criteria and 164 hospitals (85%) responded. For all of the scenarios, most of the institutions triaged them to the PICU. Twenty-eight (17%) of the responding institutions triaged at least 1 of the patient scenarios to an IMCU. The presence of an IMCU decreased triage to the ICU for all scenarios when comparing hospitals with and without an IMCU (P < .001). Inpatient triage practices among pediatric hospitals vary widely for patients who require intense nursing or frequent monitoring due to specific acute illnesses or respiratory technologies. Institutions that have an IMCU available are less likely to send these patients to the ICU.


The indication for aseptic revision TKA does not influence 1-year outcomes: an analysis of 178 full TKA revisions from a prospective institutional registry.
Outcomes following revision total knee arthroplasty (TKA) may depend on the indication for revision surgery. We compared pain, patient-reported outcome measures (PROMs), and patient satisfaction among different indications for an aseptic TKA revision. This was a retrospective study of prospective data from an institutional registry of 178 primary TKAs revised between 2012 and 2020. Patients were grouped by the main reason for their revision: loosening, malposition, instability, or stiffness. Pain during mobilization and at rest (NRS 0-10), physical function (KOOS-PS and KSS), and quality of life (EQ-5D) were surveyed preoperatively and at 2 months and 1 year postoperatively. Patient satisfaction was evaluated through questions related to knee function and their willingness to undergo the same surgery again at 1-year follow-up. Pain and PROMs improved in all groups and did not differ statistically significantly between the 4 groups at 1-year follow-up, but equivalence for pain was not confirmed between groups. Overall, pain during mobilization improved by 2.4 (95% CI 1.9-3.0) at 1-year follow-up, which was both clinically and statistically significant. Improvements were seen within 2 months of surgery, with no further improvements seen 1 year postoperatively. Approximately 2/3 of patients reported that their knee function had improved and would undergo the same surgery again, at 1-year follow-up. Statistically significant and clinically relevant improvements in pain and PROMs were seen in all 4 revision groups 1 year after revision TKA. These results may assist clinicians and patients during preoperative counselling.


The natural history of cholelithiasis: the National Cooperative Gallstone Study.
The National Cooperative Gallstone Study, a double-masked, placebo-controlled, therapeutic trial of chenodiol (chenodeoxycholic acid), provided an opportunity to study the natural history of cholelithiasis in patients who choose nonsurgical management. The major component of the study comprised 916 patients, 305 of whom were randomly assigned to receive a placebo for 24 months. Among these 305 patients, the probability of having biliary tract pain during the 24 months of prospective evaluation was significantly increased if the patient had had a history of biliary tract pain in the 12 months before entry into the study (69% versus 31%). Thirty-eight percent of patients had stone growth (greater than 0.5 cm3), and 18% had a spontaneous decrease in stone volume. Despite the high incidence of biliary tract pain, nonelective cholecystectomy was required in only 4% of patients during the 24 months.


Designing Special Nonmetallic Superalkalis Based on a Cage-like Adamanzane Complexant.
In this study, to examine the possibility of using cage-like complexants to design nonmetallic superalkalis, a series of X@36adz (X = H, B, C, N, O, F, and Si) complexes have been constructed and investigated by embedding nonmetallic atoms into the 36adamanzane (36adz) complexant. Although X atoms possess very high ionization energies, these resulting X@36adz complexes possess low adiabatic ionization energies (AIEs) of 0.78-5.28 eV. In particular, the adiabatic ionization energies (AIEs) of X@36adz (X = H, B, C, N, and Si) are even lower than the ionization energy (3.89 eV) of Cs atoms, and thus, can be classified as novel nonmetallic superalkalis. Moreover, due to the existence of diffuse excess electrons in B@36adz, this complex not only possesses pretty low AIE of 2.16 eV but also exhibits a remarkably large first hyperpolarizability (β 0) of 1.35 × 106 au, indicating that it can also be considered as a new kind of nonlinear optical molecule. As a result, this study provides an effective approach to achieve new metal-free species with an excellent reducing capability by utilizing the cage-like organic complexants as building blocks.


An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response.
Oxygen deprivation (hypoxia) results in reprogrammed gene expression patterns that induce multifaceted cellular responses. Here we identify a regulated interaction between the serine/threonine kinase HIPK2 and the ubiquitin E3 ligase Siah2 as a mechanism controlling the hypoxic response. Under normoxic conditions, several mechanisms ensure HIPK2 stability: only a fraction of HIPK2 is found in association with Siah2, whereas HIPK2-mediated phosphorylation of this E3 ligase at positions 26, 28 and 68 weakens mutual binding and destabilizes its phosphorylated interaction partner. Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase. Accordingly, hypoxia-induced HIPK2 elimination is markedly reduced in Siah2-deficient cells. As HIPK2 has an important role as a negative regulator of gene expression, its elimination from promoter-associated repressor complexes allows the induction of a substantial fraction of hypoxia-induced genes.


Comparison of the new polyethersulfone high-flux membrane DIAPES HF800 with conventional high-flux membranes during on-line haemodiafiltration.
Current modalities of renal replacement therapy allow only a limited removal of larger, possibly toxic molecules, which accumulate in uraemia. Recently, a haemodiafilter has been made available with the new, high-flux, polyethersulfone-based membrane DIAPES HF800. We performed a study to compare DIAPES HF800 with two conventional high-flux membranes in on-line haemodiafiltration (HDF), with respect to the removal properties for the two marker proteins, beta(2)-microglobulin (beta(2)m, 11.8 kDa) and albumin (66.5 kDa). In a prospective, controlled study 10 stable end-stage renal disease patients were randomly allocated to 30 sessions of post-dilutional on-line HDF with three types of steam-sterilized membranes: DIAPES HF800, polysulfone and polyamide. Blood flow rate was 250 ml/min and treatment time was 240 min. Pre-treatment beta(2)m and albumin plasma concentrations did not differ between the three groups. The concentration of the two proteins was determined before and after treatment in plasma as well as in the continuously collected haemodiafiltrate. Tolerance of all treatments was very good, without any side-effects for all filters. The mean plasma reduction rate of beta(2)m was 77 +/- 1% for DIAPES HF800 and polysulfone whereas it was 71 +/- 1% for polyamide (P < 0.05). The mean beta(2)m amount removed and found in the haemodiafiltrate per session was 230 +/- 14 mg for DIAPES HF800, 186 +/- 13 mg for polysulfone and 147 +/- 13 mg for polyamide (P < 0.05 between each pair of membranes). The same ranking was obtained for albumin removed and found in haemodiafiltrate per session for the three membranes: 5.7 +/- 0.4, 3.5 +/- 0.4 and 1.0 +/- 0.4 g, respectively. Although DIAPES HF800 showed the highest value for albumin in haemodiafiltrate the mean post-treatment plasma albumin was higher after the treatment with DIAPES HF800 compared with the other membranes (P < 0.05). On-line HDF has shown to achieve plasma reduction rates for beta(2)m of up to 77% for the DIAPES HF800 membrane and for polysulfone. The amounts of beta(2)m and albumin in haemodiafiltrate were much higher for DIAPES HF800 than for the other two membranes indicating a greater permeability for molecules up to a molecular weight of 66.5 kDa. This could, at least theoretically, offer the advantage also to remove uraemic toxins in the molecular weight range of albumin or of albumin-bound toxins. The future must show whether this will counterbalance the loss of albumin.


Prevalence of gabapentin in drug overdose postmortem toxicology testing results.
The goal of this study was to establish and compare baseline data on the prevalence of gabapentin identified through postmortem toxicology testing among drug overdose decedents in several geographically diverse states/jurisdictions with differing levels of drug overdose fatality burdens in 2015. Death certificates and postmortem toxicology result reports from five U.S. jurisdictions were used to identify residents who died from drug overdoses in year 2015 and to calculate prevalence rates of gabapentin in postmortem toxicology by jurisdiction. On average, 22% of all drug overdose decedents in our study tested positive for gabapentin. The percentage of gabapentin-positive overdose deaths varied significantly among jurisdictions: 4% in Northeast Tennessee, 7% in Maricopa County, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky (p < 0.0001). Among the drug overdose decedents who tested positive for opioids (including heroin), 26% also tested positive for gabapentin, with significant variation among states/jurisdictions (p < 0.0001). There was a significant difference in the gender distribution among drug overdose decedents who tested positive for gabapentin (46% male) vs. those who tested negative for gabapentin (65% male) (p < 0.0001). In Kentucky, gabapentin was listed as a contributing drug on the death certificate in 40% of the overdose deaths with gabapentin-positive toxicology; in North Carolina this percentage was 57%. Routine gabapentin postmortem testing and linking of death certificate, medical examiner, coroner, toxicology, and prescription history data will provide more reliable information on the extent of gabapentin misuse, diversion, and implications for clinical care.


Signal integration enhances the dynamic range in neuronal systems.
The dynamic range measures the capacity of a system to discriminate the intensity of an external stimulus. Such an ability is fundamental for living beings to survive: to leverage resources and to avoid danger. Consequently, the larger is the dynamic range, the greater is the probability of survival. We investigate how the integration of different input signals affects the dynamic range, and in general the collective behavior of a network of excitable units. By means of numerical simulations and a mean-field approach, we explore the nonequilibrium phase transition in the presence of integration. We show that the firing rate in random and scale-free networks undergoes a discontinuous phase transition depending on both the integration time and the density of integrator units. Moreover, in the presence of external stimuli, we find that a system of excitable integrator units operating in a bistable regime largely enhances its dynamic range.


COVID-19 mortality rate in children is U-shaped.
Children are known to be better protected from COVID-19 than adults, but their susceptibility patterns and the risk relative to other diseases are insufficiently defined. Here, we found that the COVID-19 mortality rate is U-shaped in childhood: it initially decreases, reaching the minimum at the ages 3-10 years, and then increases throughout life. All-cause mortality and mortality from other diseases, such as pneumonia and influenza, show a similar pattern; however, childhood mortality rates from COVID-19 are considerably lower than from other diseases, with the best relative protection achieved at the youngest ages. Consistent with this, the fraction of COVID-19 deaths among all deaths increases as a function of age throughout childhood and the entire life. We discuss implications of the elevated postnatal COVID-19 risk and lower childhood COVID-19 mortality compared to other diseases.


Psychometric examination of the Daily Spiritual experiences Scale.
Despite the burgeoning research literature addressing spirituality and its measurements, few instruments have undergone rigorous reliability and validity testing. This study contributed to determining the reliability and validity of the 16- and 6-item Daily Spiritual Experiences Scale (DSES) in a convenience sample of African Americans ages 34-85. Data were collected via self-administered questionnaire including the DSES and sociodemographic variables thought to influence spiritual experiences. Data were analyzed using paired t-tests, ANOVA, inter-class correlation coefficients, Pearson's correlation, and Cronbach's alpha. Both versions were stable over time, internally consistent, and the forms were equivalent and valid in an all-African American sample.


Hepatitis patients lost to follow-up at a liver centre in a tertiary care hospital of Karachi, Pakistan--a cross-sectional descriptive study.
To investigate the causes for loss-to-follow-up of hepatitis patients at a liver centre of a tertiary care hospital. A representative sample of 165 patients who were lost to follow-up during 2009 to 2010 was chosen and a cross-sectional descriptive study was performed. All hepatitis patients included were screened for antibody to hepatitis C virus (HCV Ab) and hepatitis B virus surface antigen (HbsAg), and were tested through polymerase chain reaction (PCR) and genotyping. Laboratory investigations, ultrasounds, personal habits, visits to hakeems and use of other alternative medications, occupations and income per month, education, and other basic information was also recorded. Those who did not return for follow-up were contacted and inquired about their reasons for loss-to-follow-up. Based on this data, the patients were categorised into four different groups according to reasons of loss to follow up: non-compliance, alternative medication, monetary issue and poor prognosis. The entire sample size of 165 patients who were lost to follow-up was included in the study. 14 (8.5%) patients were hepatitis B virus (HBV) positive. Of these patients, 1 (7.1%) was lost due to alternative medication and the rest (n=13; 92.9%) were lost to follow-up due to non-compliance. Amongst the 151 (91.5%) hepatitis C virus (HCV) positive patients, 2 (1.3%) were lost due to monetary issues, 17 (11.3%) were lost due to alternative medication, 4 (2.6%) were lost due to poor prognosis and 128 (84.8%) were lost due to non-compliance. This study shows that most patients were lost to follow-up due to non-compliance. It is important for physicians to design better counselling programmes to make the patient compliant enough to go through the complete treatment.


[Understanding Qi: its development and clinical application to nursing practices].
This paper analyzed the historical origins of the Qi concept and assesses its possible contributions to the development of complementary therapy and new nursing practices. In order to clarify the Qi concept and measure its theoretical/clinical potentials, this study analyzed both historical data and experimental research that adopt and apply the concept. These include modern/contemporary research measuring its effects in promoting mental and physical health. Using the method of cross-cultural comparison, this study analyzed diverse approaches to the Qi concept and sought to find common features among the approaches. A historical, cross-cultural analysis revealed several fundamental similarities between Qi theories that have developed in the east and the holistic concepts that have evolved in the western traditions. Especially, the analysis of the more recent research on the Qi concept shows ample possibilities of its future contributions to the development of new diagnostic applications and the promotion of overall human health. The historical study of the Qi concept found some key common factors in the diverse philosophical traditions in the east and the west. Considering the growing popularity of complementary therapy among health professionals and the general public, the Qi concept and its clinical applications are expected to promote human health. In this context, this research contributes to developing new nursing practices based on the concept by clarifying its philosophical origins and theoretical backgrounds.


[Current status of nutritional care provision to burnt patients: processes audit of a burnt patients department from a tertiary hospital].
Response of the burned patient to surgical medical treatment might depend not only upon the damages brought about by thermal aggression, namely, increased metabolic requirements, onset of the Systemic Inflamatory Response Syndrome, and microbial infections, but also the cultural practices embedded within nutritional care institutional processes. To assess how conduction of nutritional care processes of assessment and intervention may influence therapeutical effectiveness indicators of hospital Burn Services. STUDY SERIES: Forty-two patients with a Burn Body Surface Area (BBSA)>10% assisted at the Burn Service of the "Hermanos Ameijeiras" Clinical Surgical Hospital (La Habana, Cuba), between January 2001-December 2003. Nutritional care of assessment and intervention conducted upon the burn patient were audited after reviewing clinical charts. The audited processes were declared as Completed (or not). Completeness of the process was related to complications and mortality rates, and length of hospital stay predicted from BBSA. Nutritional care processes of assessment and intervention were completed in 49.4% and 22.6% of the audited charts, respectively. Prospective recording of patient's body weight was associated with lower mortality. Early nutritional assessment and sufficient energy supply to patients with BBSA>20% were associated with lower complications rates and better compliance with BBSA-predicted length of stay. This work is the first enquiry into the behaviour of the institution's Burn Service, in anticipation of the design and implementation of a medical care Continuous Quality Improvement Program. In spite of the current state of nutritional care processes completeness, their observance might favorably influence the Service's effectiveness indicators.


A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.
Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.


Distinguishing isomeric aldohexose-ketohexose disaccharides by electrospray ionization mass spectrometry in positive mode.
The identification of the structure of carbohydrates is challenging because of their complex composition of monosaccharide units, linkage position and anomeric configuration. We used a combination of principle component analysis (PCA) and tandem mass spectrometry (MS/MS), including collision-induced dissociation (CID) and higher energy collision dissociation (HCD), to distinguish four aldohexose-ketohexose isomers, sucrose, turanose, maltulose, and palatinose, which are composed of glucose and fructose. The electrospray ionization (ESI)-MS/MS spectra of the lithium and sodium adducts of the glucopyranosyl fructose (Glc-Fru) isomers were recorded on two independent mass spectrometers using CID (MicroTOF QII) and HCD (Q-Exactive Orbitrap). The differences between the fragment ions were evaluated by the PCA models. The glycosidic bond cleavage mechanism of lithiated sucrose was verified by a deuterium-labeling experiment combined with density functional theory calculations (Gaussian 09). The main fragment ions in the MS/MS spectra from the glycosidic bond decomposition, cross-ring cleavage (-90 Da), and dehydration of the precursor ions of m/z 349 ([M+Li](+)) and m/z 365 ([M+Na](+)) were observed. Surprisingly, cross-ring cleavage and dehydration of the precursor ions were rarely observed in both lithiated and sodiated sucrose. There were significant differences in the fragmentation patterns and relative abundances of fragment ions in second-order mass spectrometry, which allowed discriminant models to be constructed for the alkali adducts and collision modes. Glc-Fru isomers were discriminated in the PCA score plots for their lithium and sodium adducts by using different collision modes. The results showed that HCD-MS/MS is an ideal tool for differentiating lithium adducts, whereas, CID-MS/MS is better for discriminating sodium adducts. The hydrogen migration of the hydroxyl group at C3 of the fructose unit caused the glycosidic bond decomposition of lithiated sucrose.


Colocalization of nestin and vimentin/desmin in skeletal muscle cells demonstrated by three-dimensional fluorescence digital imaging microscopy.
During skeletal muscle development three intermediate filament proteins are expressed: nestin, vimentin, and desmin. Vimentin and desmin belong to the class III intermediate filaments and are closely related to each other, whereas nestin is a more distantly related, class VI, intermediate filament. It was previously observed by conventional immunocytochemistry that the intracellular patterns of nestin, desmin, and vimentin appeared indistinguishable, despite nestin's more distant evolutionary relationship. We here extend this analysis by applying three-dimensional fluorescence digital imaging microscopy to compare the intracellular distribution of nestin with that of desmin, vimentin, actin, and tubulin in G6 human fetal skeletal muscle cells. We show that in vitro differentiation of G6 cells can produce an intermediate filament expression pattern similar to that observed during myogenesis in vivo, i.e., downregulation of vimentin but not of nestin and desmin during myotube maturation. The image analysis demonstrated that the degree of overlap between nestin and desmin/vimentin was very extensive in myoblasts and in multinucleate myotubes in all regions of the cells. In contrast, nestin did not colocalize with tubulin or actin in G6 myoblasts. In particular, nestin immunoreactivity was not detected at the microtubule-organizing center, and it was only sparsely observed at the cell periphery where actin stress fibers were seen. Our data lend further support to the notion that nestin interacts very closely with the two more distantly related class III intermediate filament proteins desmin and vimentin in the entire muscle cell, before and after myotube formation. A comparison of conserved amino acid residues in the different IFs suggest that charged amino acid residues in the alpha-helical rod domain may play a role in the interaction.


Initial description of immune reconstitution inflammatory syndrome involving the thyroid gland in an immunocompromised patient.
Abscess formation in the thyroid gland is particularly a rare phenomenon and presents a medical and surgical dilemma especially in HIV seropositive patients. The authors report a case of a paradoxical tuberculous abscess immune reconstitution inflammatory syndrome involving the thyroid gland in a 37-year-old woman who presented 12 weeks after initiation of antiretroviral therapy at the Infectious Diseases Institute, Kampala, Uganda. The patient is still undergoing treatment.


Renal response to vasopressin in premature infants: what is new?
Clinical and experimental data indicate that the neonatal pituitary is capable of responding with arginine vasopressin (AVP) release to physiological stimulation and pathological events commonly seen in the perinatal period. The limited concentrating performance of the newborn kidney is thought, therefore, to be accounted for by the diminished end-organ responsiveness to AVP and the inability of the immature kidney to generate and maintain deep corticopapillary osmotic gradient. Evidence has been provided to indicate that in low birth weight premature infants the impaired renal tubular sodium transport, the renal salt wasting and late hyponatremia, and the increased renal prostaglandin production may be important factors in attenuating renal response to AVP.