Simultaneous Liver Kidney Transplant in Elderly Patients With Chronic Kidney Disease: Is There an Appropriate Upper Age Cutoff?
The aging of liver transplant (LT) recipients, the weighting of the model for end-stage liver disease score, and the increased prevalence of nonalcoholic steatohepatitis has led to an increased number of older LT recipients with pre-LT chronic kidney disease (CKD). There are limited data on the impact of increased recipient age on post-simultaneous liver-kidney (SLK) transplant outcomes among patients with CKD, leading some centers to employ subjective age cutoffs for potential SLK recipients. We evaluated United Network for Organ Sharing data of adult SLK recipients from February 27, 2002, to December 31, 2018, restricted to recipients with ≥90 days of waiting time and CKD (estimated glomerular filtration rate persistently <60 mL/min/1.73 m2 for ≥90 d using the modification of diet in renal disease-4 equation). We fit mixed-effects Cox regression models (center as random effect) to evaluate the association of recipient age and patient survival. Among 3146 SLK recipients with CKD, nearly two-thirds were 50-64 years of age, while 465 (14.8%) and 93 (3.0%) were 65-69 years and ≥70 years, respectively. Compared with nondiabetic SLK recipients aged 50-59 years, SLK recipients ≥70 years of age without diabetes (hazard ratio, 1.97; 95% CI, 1.20-3.23; P = 0.007) and with diabetes (hazard ratio, 1.90; 95% CI, 1.16-3.09; P = 0.01) had higher mortality compared with the reference group. In absolute terms, SLK recipients ≥70 years of age had 25% lower patient survival at 5 years compared to recipients aged 40-49 years. Although careful selection is required of any SLK recipient, especially those with increased comorbidities, there are no objective data to justify a specific age cutoff <70 years among potential SLK recipients with CKD.


Assessment of serum macro and trace element homeostasis and the complexity of inter-element relations in bipolar mood disorders.
Bipolar disorders are complex neuropsychiatric in nature and are clinically classified as Type I, Type II, and Type V. The etiological factors include environmental-genetic inter-relations. Trace metals play a significant role in neurological disorders. There is very limited information on the role of macro and trace elements in bipolar disorders. Trace elements namely Na, K, S, Ca, Mg, P, Cu, Fe, Zn, Mn and Al were analyzed in serum samples of 3 bipolar types: bipolar I, bipolar II and bipolar V with a control group using inductively coupled plasma-atomic emission spectrometry (ICP-AES). The patients were assessed as per the standard diagnostic criteria and classified into the bipolar type I, II hypomanic, II depressives and V. In bipolar I (mania), Na, K, P, Cu, Al and Mn were increased significantly (p<0.001). In bipolar II hypomania, Na, S, Al and Mn were increased significantly (p<0.02), while in bipolar II depression, Na, K, Cu and Al were increased (p<0.001). In bipolar V, Na, Mg, P, Cu, and Al were increased significantly (p<0.002), though S (p<0.00001), Fe (p<0.002) and Zn (p<0.004) were decreased in all 3 bipolar groups. There is a disturbance in the charge distribution and element-element interdependency in bipolar serum when compared to controls. These results suggest that there is a definite imbalance in macro and trace element homeostasis as evidenced by element inter-relationships in serum samples of bipolar groups when compared to controls.


What difficulties do people with mild intellectual disabilities experience when seeking medical help from their GP? A qualitative study.
People with intellectual disabilities often have low health literacy as a result of their limited language comprehension. The aim of this study was to explore the difficulties Dutch people with intellectual disabilities experience during the process of considering and seeking medical help from their GP. The study was intended as input for an online intervention supporting health literacy. A qualitative study, in which 12 semi-structured interviews were conducted with people with mild intellectual disabilities and 4 with relatives of people with mild intellectual disabilities. The interviews were analysed following the principles of thematic analysis. Difficulties were experienced in the following activities: assessing and proactively reacting to health complaints, processing health information, communicating with a GP and retaining information from the consultation. Support workers and relatives play an important role in all these activities. To increase the capacity of people with intellectual disabilities to manage their health and seek care from their GP, it is important to support them in the activities they find difficult. Recommendations resulting from the study have been incorporated in an online intervention.


Elevated CO2 and drought alter tissue water relations of birch (Betula populifolia Marsh.) seedlings.
The effect of increasing atmospheric CO2 concentrations on tissue water relations was examined in Betula populifolia, a common pioneer tree species of the northeastern U.S. deciduous forests. Components of tissue water relations were estimated from pressure volume curves of tree seedlings grown in either ambient (350 μl l-1) or elevated CO2 (700 μl l-1), and both mesic and xeric water regimes. Both CO2 and water treatment had significant effects on osmotic potential at full hydration, apoplasmic fractions, and tissue elastic moduli. Under xeric conditions and ambient CO2 concentrations, plants showed a decrease in osmotic potentials of 0.15 MPa and an increase in tissue elastic moduli at full hydration of 1.5 MPa. The decrease in elasticity may enable plants to improve the soil-plant water potential gradient given a small change in water content, while lower osmotic potentials shift the zero turgor loss point to lower water potentials. Under elevated CO2, plants in xeric conditions had osmotic potentials 0.2 MPa lower than mesic plants and decreased elastic moduli at full hydration. The increase in tissue elasticity at elevated CO2 enabled the xeric plants to maintain positive turgor pressures at lower water potentials and tissue water contents. Surprisingly, the elevated CO2 plants under mesic conditions had the most inelastic tissues. We propose that this inelasticity may enable plants to generate a favorable water potential gradient from the soil to the plant despite the low stomatal conductances observed under elevated CO2 conditions.


Modern approach to the diagnosis and treatment of tuberculosis in children.
Tuberculosis in children remains an important infectious disease in the United States, with 1261 cases reported in 1985. The percentage of extrapulmonary manifestations is increasing. Advances in the diagnosis and treatment of tuberculosis in children have lagged behind those in adults owing to diminished familiarity with the disease and difficulty in performing clinical studies in children. Tuberculosis in the United States now occurs mainly in clusters of high-risk people, such as the foreign born, Hispanics, blacks, Native Americans, and the impoverished. In general, the diagnosis of tuberculosis is epidemiologic, supported by the chest roentgenogram, skin test, and, most important, contact tracing. As the rate of drug-resistant tuberculosis increases, greater effort should be made to obtain cultures. New advances, such as DNA probes and serodiagnosis, may improve diagnostic accuracy, especially for extrapulmonary tuberculosis. Noncompliance is the major problem in treating tuberculosis, and greater effort should be directed toward novel treatment approaches in children, such as twice-weekly supervised therapy and shorter, more intense durations of therapy.


Identifying the Potential for Robotics to Assist Older Adults in Different Living Environments.
As the older adult population grows and becomes more diverse, so will their needs and preferences for living environments. Many adults over 65 years of age require some assistance [1, 2]; yet it is important for their feelings of well-being that the assistance not restrict their autonomy [3]. Not only is autonomy correlated with quality of life [4], autonomy enhancement may improve functionality [2, 5]. The goal of this paper is to provide guidance for the development of technology to enhance autonomy and quality of life for older adults. We explore the potential for robotics to meet these needs. We evaluated older adults' diverse living situations and the predictors of residential moves to higher levels of care in the United States. We also examined older adults' needs for assistance with activities of daily living (ADLs), instrumental activities of daily living (IADLs), and medical conditions when living independently or in a long-term care residence. By providing support for older adults, mobile manipulator robots may reduce need-driven, undesired moves from residences with lower levels of care (i.e., private homes, assisted living) to those with higher levels of care (i.e., skilled nursing).


Obstetric haemorrhage in the perioperative environment.
Massive haemorrhage remains a serious complication of childbirth despite advances in knowledge and surgical technique, with the number of mothers dying in the UK from haemorrhage appearing to be on the increase.


Activation of human nuclear receptors by perfluoroalkylated substances (PFAS).
Perfluoralkylated substances (PFAS) such as perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS) are used to produce, e.g., surface coatings with water- and dirt-repellent properties. These substances have been shown to be hepatotoxic in rodents, and the mechanism of action is mostly attributed to the PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). In the present study, we investigated by using luciferase-based reporter gene assays whether PFOA, PFOS and six alternative PFAS can activate, in addition to PPARα, eight other human nuclear receptors. All tested PFAS except for perfluorobutanesulfonic acid (PFBS) were able to activate human PPARα. Perfluoro-2-methyl-3-oxahexanoic acid (PMOH) and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were weak agonists of human PPARγ. The other human nuclear receptors (PPARδ, CAR, PXR, FXR, LXRα, RXRα and RARα) were not affected by any PFAS tested in this study. Although PMOH was more effective than PFOA in stimulating PPARα in the transactivation assay, it was less effective in stimulating PPARα-dependent target gene expression in human HepG2 hepatocarcinoma cells. Notably, any effect observed in this in vitro study only occurred at concentrations higher than 10 μM of the respective PFAS which is in all cases several magnitudes above the average blood concentration in the Western population. Thus, the results suggest that nuclear receptor activation may only play a minor role in potential PFAS-mediated adverse effects in humans.


Surface antigens on equine sarcoid cells and normal dermal fibroblasts as assessed by xenogeneic antisera.
To characterise the expression of surface antigens on equine sarcoid cells compared to normal equine fibroblasts, immune sera were produced in rabbits against transformed cells of a virus-containing sarcoid cell line (Mc-1) and normal dermal fibroblasts, respectively. The specificities of the sera were analysed by antibody-dependent cellular cytotoxicity against 51Cr-labelled target cells using human lymphocytes as effector cells. Anti-Mc-1 antiserum induced strong cytotoxicity against transformed cells of two sarcoid cell lines (Mc-1 and Bay Mc-1), whereas the cytotoxicity against transformed cells of equine testis, or against cells grown in short term or primary cultures derived either from sarcoids or normal dermis was low or absent. In contrast, anti-normal dermal fibroblasts antiserum did not induce antibody-dependent cellular cytotoxicity against Mc-1 or Bay Mc-1 but reacted strongly against both normal fibroblasts and primary cultured cells derived from sarcoids. The apparent specificity of the anti-Mc-1-induced cytotoxicity was confirmed by absorption of the anti-serum with either normal dermal fibroblasts and equine testis cells or Mc-1 cells. Immunoprecipitation of 125I-surface labelled Mc-1 cells by absorbed anti-serum and analysis by SDS-PAGE and autoradiography revealed that anti-Mc-1 antibodies reacted with at least four surface components with a wide range of molecular weights. Immunofluorescence with rabbit anti-human beta 2mu serum indicated that Mc-1 cells in contrast to equine lymphocytes and fibroblasts did not express class 1 major histocompatibility complex antigens.(ABSTRACT TRUNCATED AT 250 WORDS)


[Photocinematography of moving objects utilizing pulsed and continuous x-ray radiation].
The paper described advantages of pulsed X-radiation over the continuous one. Experimental technique employed with a roentgen-diagnostic unit is depicted. It is shown that the use of pulsed X-radiation helps to substantially cut down the radiation load on the physician and the patient and to heighten the resolution of the moving organs image.


State of the art in (semi-)synthesis of Ubiquitin- and Ubiquitin-like tools.
Protein ubiquitination is a key post-translational modification in regulating many fundamental cellular processes and dysregulation of these processes can give rise to a vast array of diseases. Unravelling the molecular mechanisms of ubiquitination hence is an important area in current ubiquitin research with as aim to understand this enigmatic process. The complexity of ubiquitin (Ub) signaling arises from the large variety of Ub conjugates, where Ub is attached to other Ub proteins, Ub-like proteins, and protein substrates. The chemical preparation of such Ub conjugates in high homogeneity and in adequate amounts contributes greatly to the deciphering of Ub signaling. The strength of these chemically synthesized conjugates lies in the chemo-selectivity in which they can be created that are sometimes difficult to obtain using biochemical methodology. In this review, we will discuss the progress in the chemical protein synthesis of state-of-the-art Ub and Ub-like chemical probes, their unique concepts and related discoveries in the ubiquitin field.


Differential antitumor activity and toxicity of isomeric 1,2-diaminocyclohexane platinum (II) complexes.
Acquired resistance is a main drawback of using cisplatin in cancer chemotherapy; however, analogs containing the 1,2-diaminocyclohexane (DACH) ligand can overcome this resistance. Because DACH can exist as the trans-1R,2R, trans-1S,2S or cis isomer, the antitumor activity and toxicity of individual isomers of both DACH(sulfato)Pt(II) and DACH(1,1-cyclobutanedicarboxylato)Pt(II) complexes have been examined. At optimal doses, differences in antitumor activities among the three isomers were moderately dependent on the in vivo tumor models (L1210/0, L1210/DDP, B16 and M5076). However, differences in efficacy among these isomers were greatly modulated by the sulfate or 1,1-cyclobutanedicarboxylate (CBDCA) leaving ligands. Thus, the trans isomers (R,R and/or S,S) of the sulfate complex generally had greater activities than the corresponding cis form, while the cis configuration appeared to be superior in the complex containing the CBDCA ligand. The isomers were also compared for their potential to elicit myelosuppression and kidney toxicity. Of the six isomers investigated, cis-DACH(CBDCA)Pt(II) was myelosuppressive, and the corresponding R,R and S,S isomers were mildly nephrotoxic. No such toxicities were apparent with any of the sulfate complexes. From these studies, particularly with the cisplatin-resistant L1210/DDP cell line, the R,R isomers are evidently the most interesting. However, it is possible that other leaving ligands or tumor models may indicate either S,S- or cis-DACH as the isomer worthy of greater interest.


Perforation of the common bile duct during endoscopic sphincterotomy: recognition on computed tomography and successful percutaneous treatment.
Retroperitoneal common bile duct (CBD) perforation is a rare complication of endoscopic retrograde cholangiopancreatography (ERCP). We describe such a case with delayed diagnosis made by computed tomography (CT) and successful percutaneous management of the injury.


Metabolomic profiles and health-promoting functions of Camellia drupifera mature-seeds were revealed relate to their geographical origins using comparative metabolomic analysis and network pharmacology approach.
To insight into the chemical components and their health-promoting function of Camellia drupifera mature-seeds (CMS) in Hainan and Liangguang, UPLC-MS/MS- and HS-SPME/GC-MS-based metabolomic analyses and network pharmacology approaches were combined preformed to Camellia drupifera mature-seeds samples (CMSSs). Totally, 1057 metabolites were identified, of which 76 and 99 metabolites were annotated as key active ingredients in Traditional Chinese Medicines and the active pharmaceutical ingredients for seven human disease-resistance, respectively. Comparative analysis revealed different metabolomic profiles of CMSSs from Hainan and Liangguang. KEGG annotation and enrichment analysis showed secondary metabolic pathways, especially "flavone and flavonol biosynthesis", were played important roles. Finally, 22 metabolites that only detected in CMSSs from Hainan or Liangguang were explored as potential indicators to separate CMS from Hainan out of Liangguang. Our findings enhanced the understanding of chemical compositions of CMS and provided valuable information for the healthy development of oil-tea Camellia industry in Hainan.


Novel cases of Tunisian patients with mutations in the gene encoding 17β-hydroxysteroid dehydrogenase type 3 and a founder effect.
17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed almost exclusively in the testis and converts Δ4-androstene-3,17-dione to testosterone. Mutations in the HSD17B3 gene causing 17β-HSD3 deficiency are responsible for a rare recessive form of 46, XY Disorders of Sex Development (46, XY DSD). We report novel cases of Tunisian patients with 17β-HSD3 deficiency due to previously reported mutations, i.e. p.C206X and p.G133R, as well as a case with the novel compound heterozygous mutations p.C206X and p.Q176P. Moreover, the previously reported polymorphism p.G289S was identified in a heterozygous state in combination with a novel non-coding variant c.54G>T, also in a heterozygous state, in a male patient presenting with micropenis and low testosterone levels. The identification of four different mutations in a cohort of eight patients confirms the generally observed genetic heterogeneity of 17β-HSD3 deficiency. Nevertheless, analysis of DNA from 272 randomly selected healthy controls from the same geographic area (region of Sfax) revealed a high carrier frequency for the p.C206X mutation of approximately 1 in 40. Genotype reconstruction of the affected pedigree members revealed that all p.C206X mutation carriers harbored the same haplotype, indicating inheritance of the mutation from a common ancestor. Thus, the identification of a founder effect and the elevated carrier frequency of the p.C206X mutation emphasize the importance to consider this mutation in the diagnosis and genetic counseling of affected 17β-HSD3 deficiency pedigrees in Tunisia.


Effect of three enteral diets with different protein contents on protein metabolism in critically ill infants: a randomized controlled trial.
The optimal intake to improve protein metabolism without producing adverse effects in seriously ill infants has yet to be established. The aim of our study was to analyse whether an increased protein intake delivered through enteral nutrition would be associated with an improvement in nitrogen balance and serum protein levels in critically ill infants. We conducted a multicentre, prospective randomized controlled trial (December 2016-June 2019). The sample consisted of critically ill infants receiving enteral nutrition assigned randomly to 3 protein content groups: standard diet (1.7 g/dL), protein-enriched diet (2.7 g/dL) and high protein-enriched diet (5.1 g/dL). Blood and urine tests were performed, and we assessed nitrogen balance at baseline and at 3-5 days of the diet. We analysed variations in nitrogen balance and serum protein levels (total protein, albumin, transferrin, prealbumin, and retinol-binding protein) throughout the study period. Ninety-nine infants (33 per group) completed the study. We did not find any differences were between groups in demographic characteristics, severity scores or prescribed medications, except for corticosteroids, administered in a higher proportion of patients in the third group. We observed significant increases in prealbumin and retinol-binding protein levels in patients receiving the protein-enriched and high protein-enriched diets at 3-5 days compared to baseline. The nitrogen balance increased in all groups, but the differences were not significant in the high protein-enriched group. There were no differences in gastrointestinal tolerance. Patients fed high protein-enriched formula had higher levels of serum urea, with a higher incidence of hyperuraemia in this group. Enteral administration of higher amounts of protein improves serum protein levels in critically ill children. A protein intake of 2.2 g/kg/day is generally safe and well tolerated, whereas an intake of 3.4 g/kg/day may produce hyperuraemia in some patients.


Necessity of capillary modes in a minimal model of nanoscale hydrophobic solvation.
Modern theories of the hydrophobic effect highlight its dependence on length scale, emphasizing the importance of interfaces in the vicinity of sizable hydrophobes. We recently showed that a faithful treatment of such nanoscale interfaces requires careful attention to the statistics of capillary waves, with significant quantitative implications for the calculation of solvation thermodynamics. Here, we show that a coarse-grained lattice model like that of Chandler [Chandler D (2005)Nature437(7059):640-647], when informed by this understanding, can capture a broad range of hydrophobic behaviors with striking accuracy. Specifically, we calculate probability distributions for microscopic density fluctuations that agree very well with results of atomistic simulations, even many SDs from the mean and even for probe volumes in highly heterogeneous environments. This accuracy is achieved without adjustment of free parameters, because the model is fully specified by well-known properties of liquid water. As examples of its utility, we compute the free-energy profile for a solute crossing the air-water interface, as well as the thermodynamic cost of evacuating the space between extended nanoscale surfaces. These calculations suggest that a highly reduced model for aqueous solvation can enable efficient multiscale modeling of spatial organization driven by hydrophobic and interfacial forces.


Prospective trial on telemonitoring of geriatric cancer patients using handheld devices.
Randomized trials indicate that electronic or app-based assessment of patient-reported outcomes may improve outcomes in cancer patients. To analyze if an app-based follow-up would be accepted by elderly cancer patients, we conducted a single-center prospective feasibility study (NCT03196050). Cancer patients (≥60 years) without concurrent uncontrolled severe medical conditions and a Karnofsky performance status (KPS) ≥70 were eligible if they were able to use the smartphone app. The primary endpoint was compliance over 1 year, calculated as patient-specific and study date-specific response rate to questions sent as push notifications; in this interim analysis, we report on 4‑month data. Secondary outcomes included a comparison of a subjective health status item (SPHS) with the physician-rated KPS. Out of 225 patients screened, 54 patients agreed to participate and 29 activated the app and participated in the study. The mean age was 66 years (61-78). The individual compliance rate averaged at 58.3% (standard deviation SD = 35%). Daily compliance was 53.3% on average (SD = 10.8%) and declined over time. The average percentage of patients who sent answers at least weekly was 75.0% (SD = 14.8%) and declined from 100% in week 1 to 53.8% in week 17 post-enrollment. Secondary outcomes indicated that questionnaires such as the EORTC-QLQ-C30 are accepted via app and that there is a significant moderate correlation between the SPHS and KPS scores (r = 0.566; p < 0.001). Our data indicate that an app-based follow-up incorporating EORTC questionnaires might be possible in highly selected elderly cancer patients with modest compliance rates. Further trials should aim at an increased participation rate.


Abnormalities in the levels of extracellular and tissue amino acids in the brain of the seizure-susceptible rat.
Basal and high potassium-stimulated release of endogenous amino acids was measured using brain dialysis in the hippocampus of urethane-anesthetized seizure-resistant (SR) and seizure-susceptible (SS) rats. Moreover, the tissue level of amino acids was determined in the hippocampus, sensorimotor cortex, cerebellum and corpus striatum. The basal extracellular concentration of amino acids did not differ between SR and SS rats. However, aspartate release was higher, and taurine and phosphoethanolamine release was lower in SS rats during stimulation with 100 mM K+. Several strain differences were observed with regard to regional tissue levels of amino acids. Aspartate was significantly elevated in the hippocampus, cortex and cerebellum of SS animals, and the catecholamine precursor tyrosine was diminished in all regions examined. Other disparities included a depressed gamma-aminobutyrate concentration in the hippocampus and cortex, slightly increased levels of phosphoethanolamine in the cerebellum and minor decreases in striatal and cortical taurine. Glutamate, glutamine, serine and alanine concentrations were not significantly altered in any brain area of the SS rat. The results confirm and extend previous findings on abnormalities in aspartate, taurine and phosphoethanolamine regulation in this model. In addition, decreased availability of tyrosine may provide a partial explanation for the well-documented deficiency in cerebral norepinephrine in the SS strain.


Some examples of the MRA application in trading of radionuclide products and radioecological monitoring.
Three examples of bilateral cooperation connected with trading of radionuclide products and radioecological monitoring, are discussed. The example in the field of trading is related to the shipment of Russian sources with a high specific activity of 60Co applied for radiation therapeutics to the UK. The examples in the field of radioecological monitoring concern the establishment of equivalence between the 235U reference standards used in Russia and the USA to classify SNM monitors and ensure radiation safety at salvage of the "Kursk" nuclear-powered submarine. The works accomplished are interpreted in the sense of interaction between the NMIs relative to the Mutual Recognition Arrangement (MRA) ideology. It is suggested to coordinate closely the metrological and applied aspects of the MRA when planning the key comparisons and actualizing the CMC Tables.


Reflex seizures in patients with malformations of cortical development and refractory epilepsy.
Malformations of cortical development (MCDs) are usually highly epileptogenic, and their hyperexcitability could facilitate the occurrence of reflex seizures. We sought to characterize reflex seizures in patients with MCDs and refractory epilepsy. Clinical, electrographic, and neuroimaging data were reviewed in eight patients with MCDs who had reflex seizures reproduced during presurgical evaluation. All eight patients had both reflex and spontaneous seizures. In six, however, drop attacks or axial myoclonic seizures occurred only upon specific sensory stimulation. Reflex seizures were induced by more than one type of stimulus in most patients, but anatomofunctional correlations could usually be invoked. Six patients had significant intellectual impairment. Surgical resection controlled seizures in two patients. Reflex seizures in patients with MCDs may be medically refractory and may often manifest as drop attacks or axial myoclonus. Surgical resection of focal lesions can bring reflex seizures under control. Putative mechanisms related to the relatively low frequency of reflex seizures in MCDs are discussed.


Children's value-based decision making.
To effectively navigate their environments, infants and children learn how to recognize events predict salient outcomes, such as rewards or punishments. Relatively little is known about how children acquire this ability to attach value to the stimuli they encounter. Studies often examine children's ability to learn about rewards and threats using either classical conditioning or behavioral choice paradigms. Here, we assess both approaches and find that they yield different outcomes in terms of which individuals had efficiently learned the value of information presented to them. The findings offer new insights into understanding how to assess different facets of value learning in children.


The Joint Commission's "improving organizational performance" standards for home infusion therapy providers.
In today's homecare environment, optimizing operational efficiency and making data-driven decisions is essential. Home infusion therapy organizations that are accredited by the Joint Commission on Accreditation of Healthcare Organizations (Joint Commission) will find a heavy emphasis on the standards for improving organizational performance during the homecare survey process. The standards from the "Improving Organizational Performance" chapter are reviewed, and the Joint Commission's requirements for meeting the intent of the standards are discussed.


Postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in the retina of the golden hamster.
The histochemical method was used to investigate the postnatal development of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) -positive neurons in retinas of the golden hamster. NADPH-d-positive neurons were discernible in the retina at postnatal day (P)1. From P4 onward to adulthood, when the retina acquired its laminated characteristics, NADPH-d- positive neurons were observed in the inner nuclear layer (INL) and the ganglion cell layer (GCL). Results showed that NADPH-d-positive neurons in INL and GCL followed different time courses and patterns in their development. NADPH-d-positive neurons in INL underwent a sharp increase from P4 to P8 (3.6-fold), followed by a decrease to 46% of the maximum at P12. This value was maintained relatively constant to the adult level. The mean diameters of NADPH-d-positive neurons in INL, which were smaller than those in the GCL for all ages, increased from P8 to P12 and from P20 to adulthood. As for neurons in the GCL, the increase in cell number was not so apparent for the earlier postnatal days until P20; thereafter, an obvious increase to the adult level was observed. The mean diameters of the NADPH-d-positive cell bodies in the GCL increased with age, except for P16-P20, during which time there was a slight and insignificant decrease. The tendency of changes in cell density was basically similar to that of the total number for both the INL and the GCL. Between P12 and P20, the density distribution map of the NADPH-d-positive neurons underwent dramatic changes: The highest density shifted from the upper central retina at the earlier postnatal days to the lower central retina in the adult. The two waves of increase in NADPH-d-positive neurons coincide with the process of axonal elongation and synaptogenesis and the acquisition of visual function and experience. It is suggested that these NADPH-d-positive neurons are related to these two developmental events.


An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin.
Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination with cimetidine can produce objective antitumor responses in some patients with advanced renal cell carcinoma. The purpose of this report is to review the clinical development of coumarin, with or without cimetidine, with special reference to renal cell carcinoma (RCC). Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented. The rationale and study design of an active randomized, double-blinded, placebo-controlled trial of coumarin for RCC are discussed. A progress report is given for an ongoing phase I trial of oral 7-hydroxycoumarin, the major human metabolite of coumarin.


Low dosage of prednisone acetate combined with doxycycline in the treatment of chronic endometritis in patients with repeated implantation failure.
To retrospectively investigate whether the oral administration of prednisone acetate with doxycycline increases the cure rate of chronic endometritis (CE) and improves in vitro fertilization (IVF) outcomes in patients with repeated implantation failure (RIF) with CE. In total, 352 patients with RIF were investigated, 128 of whom were diagnosed with CE by hysteroscopy and endometrial immunohistochemical analysis. The patients with CE were divided into CD138-positive high-power field (HPF) counts of 1-2 and ≥3. Forty-five patients were orally administered prednisone acetate tablet 5 mg daily and doxycycline 100 mg twice daily for 14 consecutive days (group A), and 55 patients were administered doxycycline 100 mg orally twice daily for 14 days (group B) and underwent repeated endometrial sampling and histological assessment. Twenty-eight patients (group C) did not receive any treatment. The cure rate of CE and final reproductive outcomes of the frozen-thawed embryo transfer cycle were compared. The total cure rate, cure rate of patients with CE(CD138+ HPF counts: 1-2), and cure rate of patients with CE(CD138+ HPF counts: ≥3) showed no significant difference between groups A and B. Logistics regression analysis indicated that the implantation rate, human chorionic gonadotropin (hCG)-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on day 30 (D30), and ongoing pregnancy rate was significantly higher in group A than in group C. For CE-cured patients after the treatment, the implantation rate, hCG-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on D30, and ongoing pregnancy rate were significantly higher in group A than in group B. CE is closely related to RIF occurrence, and the combined oral administration of prednisone acetate and doxycycline can be a treatment option for patients with RIF with CE and improves reproductive outcomes, although it does not improve the CE cure rate compared with doxycycline treatment alone.


Various cells of the immune system and intestine differ in their capacity to reduce hexavalent chromium.
The cells of the immune system form a strong line of defence against foreign substances. The present study was undertaken to investigate the capacity of different cells of Wistar rats to reduce potentially carcinogenic hexavalent chromium (Cr-VI) into less toxic trivalent chromium in vitro. 5 x 10(6) cells were incubated with 10 or 25 microg ml(-1) of Cr (VI) in the form of K2Cr2O7 at 37 degrees C in the presence of 5% CO2 in air. At various time periods the remaining amount of Cr (VI) was measured and the percentage of Cr (VI) reduced was calculated. Among the single cell suspensions from the splenic cells a peak reduction of 55% was observed with the total spleen cells, 40% with the B-lymphocyte-enriched subpopulation, 10% with T-lymphocytes and 24% with the macrophages. The reduction by splenic and peritoneal macrophages was similar. Total thymocytes reduced 54% of the Cr (VI). Since the most common route of entry of chromium is through drinking water and food, intestinal cells were also investigated. Among the intestinal cells the maximum reduction of 100% (of 10 microg ml(-1)) was observed with the upper villus cells and 72% with the middle villus cells while reduction was the least (4%) with the crypt cells. The reduction in the intestinal loop in situ was 100%. The time taken by each cell type for the peak reduction to Cr (VI) was markedly different. The findings thus show that the capacity of different cells in the body differs vastly in their capacity and time taken to reduce hexavalent chromium. The most efficient handling of Cr (VI) by the intestine, due to the presence of a variety of cells and bacteria, protects the body from its adverse effects.


The burden of and risk factors for active trachoma in the North and South Wollo Zones of Amhara Region, Ethiopia: a cross-sectional study.
Trachoma is a disease of the eye, caused by the bacteria Chlamydia trachomatis, which can lead to blindness if left untreated. Ethiopia is one of the most trachoma-affected countries in the world. The objective of this study was to determine the prevalence of and associated risk factors for active trachoma among children in selected woredas of North and South Wollo Zones in Amhara Region, Ethiopia. This study was a community-based, cross-sectional study, which was conducted from October to December 2014 among children aged 1-8. A four-stage random cluster sampling technique was employed to select the study areas and participants. From each selected household, one child was clinically assessed for active trachoma. A structured questionnaire was used to collect sociodemographic, behavioral, and clinical data. Multivariate logistic regression analysis was used to analyze the association between predictor variables and active trachoma. The overall prevalence of active trachoma among 1358 children was found to be 21.6% (95% CI: 19.4-23.8%). When analyzed by the presence or absence of individual WHO simplified system signs of active trachoma, trachomatous inflammation-follicular cases constituted18% (95% CI: 15.9-20.2%), while 4.7% (95% CI: 3.6-5.8%) were trachomatous inflammation-intense cases. Ocular discharge (aOR = 5.2; 95% CI: 3.3-8.2), nasal discharge (aOR = 1.8; 95% CI: 1.2-2.7), time taken to fetch water (aOR = 0.02; 95% CI: 0.01-0.05), frequency of hand and face washing (aOR = 4.4; 95% CI: 1.1-17.8), and access to a latrine (aOR = 0.006; 95% CI: 0.001-0.030) were found to be independently associated with the presence of active trachoma. There is a high burden of active trachoma among children in the study areas. Lack of personal hygiene and limited access to a safe water supply and latrines were associated with increased prevalence of active trachoma. In order to reduce the burden of active trachoma, facial cleanliness and environmental improvement components of the SAFE strategy should be upgraded in the study areas.


HLA class I (Bg) antigens on red cells of SLE patients: a serological study with polyclonal and monoclonal antibodies.
The enhanced HLA class I (Bg) on red blood cells (RBC) of many patients with systemic lupus erythematosus has allowed a significant correlation to be made between their HLA-B types and haemagglutination reactivity with lymphocytotoxic anti-HLA-B sera stimulated by pregnancy alone. Therefore the class I expression on these RBC relates to classical, rather than non-classical, class I gene products. Studies of class I expression on RBC by means of monoclonal antibodies (MAb) to epitopes on the heavy polypeptide chain and beta 2-microglobulin (beta 2m) have suggested that the complete extracellular structure is present. The specific effect of chloroquine in 'stripping HLA' from RBC had been assumed to support the concept that HLA class I was adsorbed from plasma. However, from our data, we conclude that HLA class I is an intrinsic membrane component. We suggest that the action of chloroquine is to remove beta 2m alone, which prevents normal class I expression and also results in conformational changes to the class I heavy chain, but that it is not capable of removing the membrane-bound heavy chain.


Assessing the structure-activity relationships of fluorotelomer unsaturated acids and aldehydes with glutathione. Reactivity of glutathione with fluorotelomer unsaturated acids and aldehydes.
Fluorotelomer alcohols (FTOHs) have been shown to degrade via abiotic and biotic mechanisms to perfluorocarboxylates (PFCAs) which are environmentally persistent and bioaccumulate in humans and wildlife depending on their chain length. Fluorotelomer unsaturated aldehydes (FTUALs) and acids (FTUCAs) are intermediate metabolites that form from the degradation of FTOHs. Their potential for toxicity is not yet defined and may be more significant compared to PFCAs. Past studies have shown that these intermediates form adducts with glutathione (GSH). The purpose of this study was to further assess the reactivity of these intermediate compounds. In vitro experiments were carried out in an aqueous buffer system (pH 7.4) where FTUCAs and FTUALs of varying chain lengths were reacted with GSH. To quantify the reactivity of FTUCAs and FTUALs, unreacted free GSH was derivatized with 5,5'-dithiobis(2-nitrobenzoic acid), its absorbance measured at 412 nm, and the percentage of unconjugated free GSH evaluated over time. EC50 values were obtained for the reactions of GSH with acrolein and methyl methacrylate to assess the accuracy of the method, as well as for acrylic acid, FTUCAs, and FTUALs. The results of this study indicated that α,β-unsaturated aldehydes are comparatively the most reactive and reaction with GSH may be influenced by the length of the fluorinated tail. This is the first study to examine the relationship of FTUCAs and FTUALs with biological nucleophiles by quantifying their intrinsic reactivity.


Measurement of the average path length of gamma-rays in samples using scattered radiation.
A method for measuring the average path length traversed by gamma-rays in a sample is presented. In this method the amount of radiation scattered within the sample at small angles and registered in the spectrum is measured. It is shown that the increase in counts in an energy interval close to the energy of the emitted gamma-rays, relative to the value attained in the absence of the interaction between the gamma-rays and the sample, is proportional to the average path length in the sample. Measurements of the average path length in samples of cylindrical geometry with various dimensions and at several energies are presented and compared with the predicted values. The differences between the measured and predicted values are discussed.


Serum insulin and ECG abnormalities suggesting coronary heart disease in the populations of Mauritius and Nauru: cross-sectional and longitudinal associations.
Cross-sectional associations between insulin and ECG abnormalities suggestive of 'possible' and 'probable' coronary heart disease (CHD) in the populations of Nauru (n = 568) and Mauritius (n = 3280) have been examined in both non-diabetic and diabetic subjects. Additionally, the longitudinal relationship between baseline insulin and incident ECG abnormalities has been explored in non-diabetic Nauruans (n = 177) over 5 years. Age-adjusted mean 2-hour serum insulin was generally higher in subjects with ECG abnormalities than those with a normal ECG, but the difference was significant only for non-diabetic Mauritian men (p < 0.01). There was no clear association between prevalence of ECG abnormalities and quintiles of fasting or 2-hr insulin in Mauritians, and in non-diabetic Nauruans there was a non-significant positive association between prevalence of ECG abnormalities and tertiles of 2-hr insulin. Logistic regression analyses showed a slight positive association between 2-hr insulin and ECG abnormalities in non-diabetic Mauritians (p = 0.06 in males, p = 0.09 in females), and non-diabetic male Nauruans (p = 0.054) independent of possible confounders. Fasting insulin was not associated in any group. In longitudinal analyses in Nauruans there were no significant differences in mean baseline fasting or 2-hr serum insulin between subjects who maintained a normal ECG and those who developed abnormalities consistent with 'possible CHD' (there were no changes suggestive of 'probable CHD'). The incidence of ECG changes suggesting 'possible CHD' was slightly higher in the upper tertile of baseline fasting insulin in both sexes and 2-hr insulin in females, but when other factors were accounted for, multiple logistic regression analyses did not support this finding. Data from the populations of Mauritius and Nauru do not support a major role for serum insulin in ECG abnormalities suggestive of CHD.


Nanoscale Elasto-Capillarity in the Graphene-Water System under Tension: Revisiting the Assumption of a Constant Wetting Angle.
Wetting highly compliant surfaces can cause them to deform. Atomically thin materials, such as graphene, can have exceptionally small bending rigidities, leading to elasto-capillary lengths of a few nanometers. Using large-scale molecular dynamics (MD), we have studied the wetting and deformation of graphene due to nanometer-sized water droplets, focusing on the wetting angle near the vesicle transition. Recent continuum theories for wetting of flexible membranes reproduce our MD results qualitatively well. However, we find that when the curvature is large at the triple-phase contact line, the wetting angle increases with decreasing tension. This is in contrast to existing macroscopic theories but can be amended by allowing for a variable wetting angle.


Associations Between Selenium Content in Hair and Kashin-Beck Disease/Keshan Disease in Children in Northwestern China: a Prospective Cohort Study.
The objective of this study was to investigate the relationship between selenium content in hair and the incidence of Kashin-Beck disease (KBD) and Keshan disease (KD) in China. A prospective cohort study was conducted among children aged 5-12 years with different levels of low-selenium (group 1, Se ≤ 110 ng/g; group 2, 110 < Se ≤ 150 ng/g; and group 3, 150 < Se ≤ 200 ng/g) or selenium-supplemented (group 4, Se > 200 ng/g) exposure. A person-years approach was used to calculate the incidence and rate of positive clinical signs. Relative risk (RR), attributable risk, and etiologic fraction were used to determine the strength of association between selenium and disease incidence. Seven new KBD cases were diagnosed during 3-year follow-up. Positive clinical signs of KBD were found in 17.78 (95% confidence interval [CI] 14.27-21.29) cases per 100 person-years in group 1, 13.28 (9.82-16.74) in group 2, 12.95 (9.34-16.56) in group 3, and 8.18 (5.50-10.85) in group 4. Compared with group 4, the RR (95% CI) of groups 1, 2, and 3 were 2.17 (1.48-3.19), 1.62 (1.07-2.47), and 1.58 (1.03-2.43), respectively. Positive clinical signs of KD were 25.90 (18.62-33.18) cases per 100 person-years in group 1, 5.66 (1.26-10.06) in group 2, 4.60 (0.20-9.00) in group 3, and 14.62 (8.54-20.69) in group 4. Compared with group 4, the RR (95% CI) were 1.77 (1.07-2.93), 0.39 (0.16-0.93), and 0.31 (0.11-0.89), respectively. In children, the onset of KBD was negatively correlated with selenium content within a certain range. However, there may be a U-shaped association between selenium content and KD in children.


Polygenic risk of Alzheimer's disease in the Faroe Islands.
The Faroe Islands are a geographically isolated population in the North Atlantic with a similar prevalence of Alzheimer's disease (AD) and all-cause dementia as other European populations. However, the genetic risk underlying AD and other dementia susceptibility has yet to be elucidated. Forty-nine single-nucleotide polymorphisms (SNPs) were genotyped in 174 patients with AD and other dementias and 159 healthy controls. Single variant and polygenic risk score (PRS) associations, with/without APOE variability, were assessed by logistic regression. Performance was examined using receiver operating characteristic area under the curve (ROC AUC) analysis. APOErs429358 was associated with AD in the Faroese cohort after correction for multiple testing (odds ratio [OR] 6.32, 95% confidence interval [CI] 3.98-10.05, p = 6.31e-15 ), with suggestive evidence for three other variants: NECTIN2 rs41289512 (OR 2.05, 95% CI 1.20-3.51, p = 0.01), HLA-DRB1 rs6931277 (OR 0.67, 95% CI 0.48-0.94, p = 0.02) and APOE rs7412 [ε2] (OR 0.28, 95% CI 0.11-0.73, p = 0.01). PRSs were associated with AD with or without the inclusion of APOE (PRS+APOE OR = 4.5, 95% CI 2.90-5.85, p = 4.56e-15 , and PRS-APOE OR = 1.53, 95% CI 1.21-1.98, p = 6.82e-4 ). AD ROC AUC analyses demonstrated a PRS+APOE AUC = 80.3% and PRS-APOE AUC = 63.4%. However, PRS+APOE was also significantly associated with all-cause dementia (OR = 3.39, 95% CI 2.51-4.71, p = 2.50e-14 ) with an AUC = 76.9%, that is, all-cause dementia showed similar results albeit less significant. In the Faroe Islands, SNP analyses highlighted APOE and immunogenomic variability in AD and dementia risk. PRS+APOE , based on 25 SNPs/loci, had excellent sensitivity and specificity for AD with an AUC of 80.3%. High PRSs were also associated with an earlier onset of late-onset AD.


Acute immobilization stress reduces (+/-)DOI-induced 5-HT2A receptor-mediated head shakes in rats.
Acute immobilization stress induced by taping four limbs, applying tail pinch stress and electric foot shock stress immediately reduced the frequency of head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)DOI), a 5-HT2A/C agonist in rats. Immobilization stress due to the use of cylinder restraint and forced swimming did not affect 5-HT2A-mediated behavior. Acute immobilization stress did not affect [3H]ketanserin binding to the 5HT2A receptor in the prefrontal cortex and hippocampus. Presynaptic serotonergic lesions with 5,7-dihydroxytryptamine(5,7-DHT) did not affect the reduction in 5-HT2A-mediated behavior after acute immobilization stress. The decreases in head shake frequency after acute immobilization stress by taping were attenuated by pretreatment with diazepam (2.5 mg/kg IP): This attenuation was reversed by pretreatment with flumazenil (10 mg/kg IP). The reduction in (+/-)DOI-induced 5-HT2A-mediated behavior caused by stress may be related to a change in agonist affinity to the receptor or changes in other neurotransmitter systems or the effect of PI turnover.


Epithelial peptide antibiotics.
Surfaces of higher eukaryotes such as plants, invertebrates, and vertebrates, including humans, are normally covered with microorganisms but usually are not infected by them. The reason, apart from physical barriers, is the production of gene-encoded antimicrobial peptides by epithelial cells. Many novel antimicrobial peptides have been discovered recently in the epithelia of plants, insects, amphibians, and cattle, and, more recently, also in humans. In situ hybridization studies indicate a rather organ-specific expression of the genes for peptide antibiotics, which, due to their antimicrobial spectrum and conditions of expression, may also define the physiologic microflora. Some epithelial antimicrobial peptides are constitutively expressed; others are inducible, either by the presence of microorganisms via as of yet not well characterized elicitor receptors or by endogenous proinflammatory cytokines. Most antimicrobial peptides kill microorganisms by forming pores in the cell membrane, and the sensitivity of some peptide antibiotics towards cholesterol, a major mammalian cell membrane constituent, may indicate why these peptide antibiotics are not toxic for mammalian cells. Thus, it seems to be difficult for microorganisms to acquire resistance, making these peptides very attractive for therapeutic use as antibiotics. The first clinical studies are very promising, and after solving the problems of a large-scale biotechnical synthesis, which is more complicated due to the principally suicidal activity of these peptides, a number of new natural structure-based peptides may be developed. Furthermore, discovery of the inducibility of many antimicrobial peptides may also lead to the development of compounds that elicit epithelial defense reactions by stimulating the synthesis of endogenous peptide antibiotics.


What Is the Spatial Extent of a Bemisia tabaci Population?
Effective pest management depends on basic knowledge about insect dispersal patterns and gene flow in agroecosystems. The globally invasive sweet potato whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is considered a weak flier whose life history nonetheless predisposes it to frequent dispersal, but the scale over which populations exchange migrants, and should therefore be managed, is uncertain. In this review, we synthesize the emergent literature on B. tabaci population genetics to address the question: What spatial scales define B. tabaci populations? We find that within-species genetic differentiation among sites is often low, and evidence of population structuring by host plant or geography is rare. Heterozygote deficits prevail among populations, indicating that migrants from divergent populations are frequently sampled together. Overall, these results suggest that there is high ongoing gene flow over large spatial extents. However, genetic homogeneity typical of recently invading populations could obscure power to detect real isolation among populations. Genome-wide data collected systematically across space and time could distinguish signatures of invasion history from those of ongoing gene flow. Characterizing the spatial extent of B. tabaci populations could reveal whether insecticide rotations can be tailored to specific commodities or if coordination across linked commodities and regions is justified.


Mucus secretions from a conditionally reprogrammed primary endocervical cell culture.
To determine if the secretions collected from a conditionally reprogrammed primary endocervical cell culture are suitable surrogates for mucus studies. Experimental. University research center. Female rhesus macaque (n = 2). None. Quantitative proteomic analysis using tandem mass tag mass spectrometry liquid chromatography/tandem mass spectrometry. We identified 3,047 proteins, common proteins present in both primary endocervical cell cultures and the mucus of rhesus macaques. We found a 71% overlap in the top 500 most prevalent proteins in the samples. Cell culture secretions contained many essential mucus proteins, including MUC5B, the primary mucin of the endocervix. Similarities in secreted proteins suggest that conditionally reprogrammed primary endocervical cells could be used to study mucus secretion in vitro.


Implementation and evaluation of a pandemic simulation exercise among undergraduate public health and nursing students: A mixed-methods study.
In addition to overwhelming the healthcare system, pandemics have enormous societal and economic costs. To better train future healthcare professionals and develop collaborations across healthcare disciplines, pandemic simulations have been incorporated into undergraduate healthcare professional curricula. The purpose of this study was to assess the usefulness of a pandemic simulation in preparing the future healthcare professionals during large-scale pandemic disasters. This was a mixed-methods, cross-sectional study. The study was conducted at a 4-year public university in rural Texas. The students (n = 89) participated in a simulation exercise that mirrored a real influenza pandemic that facilitated interactions among various first responders. Participants completed pre- and post-tests of knowledge survey questions pertaining to areas of situational awareness, communication effectiveness and public health knowledge, and the 27-item Nursing Anxiety and Self-Confidence with Clinical Decision-Making Scale. The majority (76%) of the participants were between the ages of 18 to 24, Caucasians (74.2%) and female (87.6%). The results of the paired t-test showed increased situational awareness [t = 7.17(76), p < 0.001], effective communication [t = 7.130(75), p < 0.001], and public health knowledge [t = 8.77 (74), p < 0.001] following the pandemic simulation. Significant improvement in situational awareness, effective communication, and public health knowledge was demonstrated by the undergraduate public health and nursing students in handling disasters through the simulation exercise. The study results demonstrated value in incorporating simulation as an effective teaching strategy in preparing future healthcare professionals.


A simple, general method for detecting retroviral RNAs expressed in cells.
A simple, efficient method has been developed for detecting retroviral RNAs expressed in cells. In this method, total RNAs or poly A+ RNAs extracted from various human cells are separated by electrophoresis and hybridized with synthetic oligonucleotides corresponding to the 3'-terminal 18 nucleotides of various tRNAs. Genomic and subgenomic RNAs of HTLV-I and HTLV-II in virus-infected cells and of xenotropic murine leukemia virus expressed in human lung cancer cells were easily detected with the tRNA(Pro)-derived oligonucleotide probe. This technique can be used to search for unidentified retroviruses expressed in human cancer cells and tissues.


Robotic-assisted Posterior Urethroplasty: Outcomes From 105 Men in a Single-center Experience.
To determine surgical outcomes in a large of cohort men undergoing robotic-assisted posterior urethroplasty (RPU), which has been described in small series as a viable option. We performed a retrospective review of all 105 men who underwent RPU from October 2014 to August 2022 at a single institution. We evaluated postoperative outcomes, including complications; surgical success defined as no need for reintervention; and incontinence requiring artificial urinary sphincter placement. We performed descriptive statistics and chi-square testing to determine if outcomes were associated with certain posterior urethral disease etiologies. Mean follow-up time was 18.7months. Over half of patients (57.1%) received prior pelvic radiation. The most common reconstructive techniques were excision and primary anastomosis (n = 45, 30.0%), resitting of the bladder neck (n = 26, 24.8%), Y-V plasty (n = 21, 20.0%), and buccal mucosal graft urethroplasty (n = 14, 13.3%). Forty-one patients (39.0%) required a combined abdominoperineal approach. Seven patients (6.7%) had ≥CD grade 3 complications within 30days. Thirty patients (28.6%) developed incontinence with subsequent artificial urinary sphincter placement. One-quarter (24.8%) of patients required at least one subsequent surgical reintervention. In the largest RPU cohort to date, surgical success rates were similar and continence rates were improved compared to open surgery and align with existing robotic series, adding to the growing body of evidence demonstrating advantages of RPU.


Molecular diagnosis of autoimmune blistering diseases.
Autoimmune bullous diseases are the best-characterized autoimmune skin diseases. Molecular diagnosis of these diseases has become possible due to the identification of their target autoantigens over the past three decades. In this review, we summarize methodology for categorizing autoimmune bullous diseases by means of combinations of direct and indirect immunofluorescence techniques using normal human skin sections, rat bladder sections and COS7 cells transfected with desmocollins 1-3 encoded vectors, enzyme-linked immunosorbent assays and immunoblotting with normal human epidermal extracts, dermal extracts, purified proteins from cell cultures and recombinant proteins.


Parents' perception on the use of augmentative and alternative communication by children with complex communication needs in Malaysia.
Children with developmental disabilities who have complex communication needs (CCN) frequently need to use augmentative and alternative communication (AAC) to communicate effectively and efficiently. Speech-language pathologists (SLPs) often work closely with parents and other professionals when deciding on the best AAC system to introduce to these children. This study aimed to describe the use of AAC by children with CCN in Malaysia as reported by their parents. An online survey distributed for this study was completed by 235 parents. Most of the parents of children with CCN who participated in this study reported that their children used low-tech AAC systems. A majority of respondents were satisfied with their child's AAC system. Parental satisfaction was positively associated with the frequency of use and whether the use of AAC helped parents understand the child better. Challenges reported by parents when using AAC and the reason some families abandoned the use of AAC were similar. Examples of challenges include parents having limited time and the child lacking the motivation to use the AAC system. The findings of this study suggest the importance of SLPs actively involving parents in the selection of their children's AAC system so they are agreeable with the system introduced and continuously supporting children and their families to encourage and sustain the use of AAC. Implications for rehabilitationSpeech-language pathologists (SLPs) can create communication opportunities for the child to use augmentative and alternative communication (AAC) and experience success, teach parents how to incorporate AAC into the family's daily routine and activities, and reduce the demands on parents by preparing the AAC materials and programming the AAC system where possible.SLPs can provide ongoing support to school teachers to equip them with the necessary knowledge and skills to support the use of AAC in the classroom.


Smoking and the health gap in minorities.
Over the past decade, tobacco companies have targeted minority populations when advertising and promoting their products, containing the most widely available, legal addictive drug in the United States. This has contributed to a greater prevalence of cigarette smoking among some minorities and lower-income groups. Black males are more likely to smoke than white males and more often they smoke high-tar cigarettes. They are also less likely to quit smoking. Compared to the national average, a greater proportion of Hispanic males smoke, but not Hispanic females. Smoking prevalence rates among Asians and Native Americans are available from local surveys but there are no reliable national estimates. Blacks experience substantially higher rates of mortality and morbidity from all causes, heart disease, stroke, and smoking-related cancers as well as adverse pregnancy outcomes. Substantially lower rates of death from heart disease, stroke, and cancers are observed among Asians and Native Americans than among whites. Disparities in cigarette smoking among racial and ethnic groups do not mirror the observed racial and ethnic disparities in mortality. Other health risk factors, access to medical care and premature death from other causes, may partially explain the morbidity/mortality gap between minorities and nonminorities. Reliable national estimates on smoking prevalence and morbidity and mortality among minorities are needed. The role of tobacco use in the etiology of diseases that are disproportionately prevalent among minorities should be studied. Culturally sensitive and acceptable smoking interventions should be developed with the involvement of minorities.


Anti-Markovnikov Hydroamination of Alkenes with Aqueous Ammonia by Metal-Loaded Titanium Oxide Photocatalyst.
A completely new route was established to synthesize valuable primary amines from alkenes by using aqueous ammonia, that is, a simple photocatalytic hydroamination of alkenes using aqueous ammonia with a metal-loaded TiO2 photocatalyst. Although the photochemical hydroamination prefers to form amines according to the Markovnikov rule, the new photocatalytic hydroamination gives anti-Markovnikov products predominantly. With an Au-loaded TiO2 photocatalyst, the amine yield reached up to 93% and the regioselectivity of anti-Markovnikov products was above 98%. The reaction mechanism was proposed for the new photocatalytic hydroamination.


Myocardial β-Catenin-BMP2 signaling promotes mesenchymal cell proliferation during endocardial cushion formation.
Abnormal endocardial cushion formation is a major cause of congenital heart valve disease, which is a common birth defect with significant morbidity and mortality. Although β-catenin and BMP2 are two well-known regulators of endocardial cushion formation, their interaction in this process is largely unknown. Here, we report that deletion of β-catenin in myocardium results in formation of hypoplastic endocardial cushions accompanying a decrease of mesenchymal cell proliferation. Loss of β-catenin reduced Bmp2 expression in myocardium and SMAD signaling in cushion mesenchyme. Exogenous BMP2 recombinant proteins fully rescued the proliferation defect of mesenchymal cells in cultured heart explants from myocardial β-catenin knockout embryos. Using a canonical WNT signaling reporter mouse line, we showed that cushion myocardium exhibited high WNT/β-catenin activities during endocardial cushion growth. Selective disruption of the signaling function of β-catenin resulted in a cushion growth defect similar to that caused by the complete loss of β-catenin. Together, these observations demonstrate that myocardial β-catenin signaling function promotes mesenchymal cell proliferation and endocardial cushion expansion through inducing BMP signaling.


Pancreatoduodenectomy in a public versus private teaching hospital is comparable with some minor variations.
The impact of the public and private hospital systems on major abdominal operations that are demanding on clinical resources, such as pancreatic surgery, has not been explored in an Australian setting. This study examines the perioperative outcome of patients undergoing pancreatoduodenectomy (PD) at a major public and private hospital. Patients undergoing PD between January 2004 and October 2015 were classified based on their health insurance status and location of where the surgery was performed. Clinical variables relating to perioperative outcome were retrieved and compared using univariate and multivariate analyses. Four hundred and twenty patients underwent PD of whom 232 patients (55%) were operated on in the private hospital. Overall, there was no difference in morbidity and mortality in the public versus the private hospital. However, there were variations in public versus private hospital, this included longer duration of surgery (443 min versus 372 min; P < 0.001), increased estimated blood loss (683 mL versus 506 mL; P < 0.001) and more patients requiring perioperative blood transfusion (25% versus 13%; P = 0.001). Of the 10 complications compared, post-operative bleeding was higher in the private hospital (11% versus 5%; P = 0.051) and intra-abdominal collections were more common in the public hospital (11% versus 5%; P = 0.028). Independent predictive factors for major complications were American Society of Anesthesiologists score (odds ratio (OR) = 1.91; P = 0.050), patients requiring additional visceral resection (OR = 3.36; P = 0.014) and post-operative transfusion (OR = 3.37; P < 0.001). The hospital type (public/private) was not associated with perioperative outcome. Comparable perioperative outcomes were observed between patients undergoing PD in a high-volume specialized unit in both the public and private hospital systems.


Predicting adverse outcomes in elective coronary artery bypass graft surgery using pre-operative troponin I levels.
Cardiac troponins are frequently measured as part of the pre-operative work-up of patients prior to coronary artery bypass graft surgery (CABG). The utility of measuring these levels in elective patients, and the clinical implication of an abnormal result are unclear. The following study investigates the relationship between cardiac troponin I (cTnI) measured as part of a routine pre-operative work-up and outcomes following CABG. From January 2010 to December 2012, 378 patients underwent isolated, elective CABG and had cTnI measured prospectively, as part of their pre-operative work-up. Patients were divided into normal (Group I) and elevated (Group II) cTnI groups. Pre-operative, operative and post-operative data were obtained from our institution's prospectively collected database. Elevated cTnI was present in 47 patients (12.4%) pre-operatively. Intra-operative variables did not differ between the elevated cTnI and control groups. Both 30-day mortality (Group I: 0.9% v Group II: 6.4%, p=0.03) and cardiac arrest (Group I: 1.5% v Group II: 8.5%, p=0.01) were significantly more frequent in the elevated cTnI group. In multivariable analysis, elevated cTnI remained a predictor for cardiac arrest (OR 5.8, 95% CI 1.2 - 29.2). Patients presenting for elective CABG frequently have elevated cTnI on pre-operative work-up. These patients may be at a greater risk of 30-day mortality and cardiac arrest. Routine pre-operative measurement of cTnI may alert clinicians to a higher operative risk.


Vector competence of Aedes aegypti and Culex quinquefasciatus from the metropolitan area of Guadalajara, Jalisco, Mexico for Zika virus.
Zika virus (ZIKV) is a mosquito-borne pathogen discovered in the late 40's in Uganda during a surveillance program for yellow fever. By 2014 the virus reached Eastern Island in the Americas, and two years later, the virus spread to almost all countries and territories of the Americas. The mosquito Aedes aegypti has been identified as the main vector of the disease, and several researchers have also studied the vector competence of Culex quinquefasciatus in virus transmission. The aim of the present study was to evaluate the vector competence of Ae. aegypti and Cx. quinquefasciatus in order to understand their roles in the transmission of ZIKV in Guadalajara, Jalisco, Mexico. In blood feeding laboratry experiments, we found that Ae. aegypti mosquitoes showed to be a competent vector able to transmit ZIKV in this area. On the other hand, we found that F0 Cx. quinquefasciatus mosquitoes are refractory to ZIKV infection, dissemination and transmission.


Regulation of fat body mitochondrial respiration in Periplaneta americana by a novel factor from the corpus cardiacum.
Respiration of fat body (Periplaneta americana) mitochondria is increased by pretreatment of the tissue with corpus cardiacum (CC) extract. The magnitude of the increase depends on the type of substrate supplied for oxidation. With 5 mM pyruvate the respiration increased 22%, decreasing to 0 with 1 mM pyruvate. In contrast, 50 microM and 0.2 mM palmitic acid supported an increase in CC-stimulated respiration of 14 and 44%, respectively. Unlike crude CC extract, the synthetic hyperglycemic peptides CCI and CCII failed to alter the respiratory activity of fat body mitochondria. In common with the action of CC extract pretreatment of the fat body in vitro with 10(-5) M cyclic AMP, 10(-5) M 8-bromo-cyclic AMP, or 10(-5) M forskolin increased mitochondrial respiration approximately 30%. Octopamine (10(-4) M) elicited a response similar to that obtained with CC extract. Neither 10(-5) M cyclic AMP nor 10(-5) M 8-bromo-cyclic AMP stimulated respiration when applied directly to the mitochondria. These results suggest that the factor in CC extract manifests its effect intracellularly through the activation of a cyclic AMP-dependent protein kinase. This interpretation is also based on the finding that diamide, an inhibitor of protein kinase, inhibits CC-dependent and cyclic AMP-dependent mitochondrial respiration. The physiological role of the CC factor responsible is not known.


Post-traumatic stress disorder and its treatment in children and adolescents.
This article reviews current concepts of and treatments for post-traumatic stress disorder (PTSD) in children and adolescents. We discuss the DSM-IV-TR diagnostic criteria and their applicability to children and adolescents. We also review the history of PTSD and the development of its diagnostic criteria. We present the concept of complex trauma and trauma's effect on the developing child and describe a new diagnosis labeled developmental trauma disorder that would better describe children and adolescents who have been exposed to abuse and neglect. Finally, we summarize psychotherapeutic and psychopharmacologic approaches to treating PTSD in children and adolescents. More research is needed on the diagnosis and treatment of PTSD in children and adolescents.


In vivo fluorescence imaging of β-amyloid plaques with push-pull dimethylaminothiophene derivatives.
In vivo fluorescence imaging of β-amyloid (Aβ) plaques in the brain is expected to be used as a new method for detecting Alzheimer's disease (AD). We synthesized novel push-pull dimethylaminothiophenyl (DTM) derivatives and evaluated their utility as in vivo fluorescence imaging probes targeting Aβ plaques. As a result, we found that DTM-2 is a promising fluorescent probe for Aβ plaques in the AD brains.


Clinical characteristics and outcomes of people with severe mental disorders hospitalized due to COVID-19: A nationwide population-based study.
Hospitalized COVID-19 patients with severe mental illness (SMI) have worse outcomes than counterparts without SMI. Barriers in access to acute care medical procedures among SMI patients may partially explain this phenomenon. Here, we examined differences in critical care admission and in-hospital mortality between hospitalized COVID-19 patients with and without SMI. This population-based study used Spain's nationwide electronic health records. Based on International Classification Diseases, Tenth Revision, ICD-10-CM codes, we identified all patients aged ≥15 years hospitalized due to COVID-19 between July 1st-December 31st, 2020, and compared patients with and without SMI in terms of (i) critical care admission and (ii) in-hospital mortality - overall and stratified by age. We used logistic regression models including sex, age, and comorbidity burden as measured by Charlson Comorbidity Index Score as covariates. Of 118,691 hospital admissions due to COVID-19 of people aged ≥15 years, 1512 (1.3%) included a diagnosis of SMI. Compared to non-SMI patients, SMI patients had higher in-hospital mortality (OR,95%CI: 1.63,1.42-1.88) and were less frequently admitted to critical care (OR,95%CI: 0.70,0.58-0.85). Admission to critical care in SMI patients was lower than for non-SMI counterparts only among individuals aged ≥60 years. The magnitude of the difference in in-hospital mortality between SMI and non-SMI patients decreased as age increased. Individuals with SMI had reduced critical care admission and increased in-hospital mortality compared non-SMI counterparts, suggesting that differences in delivery of acute care medical procedures may partially explain higher risk of negative outcomes among COVID-19 patients with SMI.


Precision cell delivery in biphasic polymer systems enhances growth of keratinocytes in culture and promotes their attachment on acellular dermal matrices.
Current approaches for precision deposition of cells are not optimized for moist environments or for substrates with complex surface topographic features, for example, the surface of dermal matrices and other biomaterials. To overcome these challenges, an approach is presented that utilizes cell confinement in phase-separating polymer solutions of polyethylene glycol and dextran to precisely deliver keratinocytes in well-defined colonies. Using this approach, keratinocyte colonies are produced with superior viability, proliferative capacity, and barrier formation compared with the same number of cells dispersedly seeded across substrate surfaces. It is further demonstrated that keratinocytes delivered in colonies to the surface of acellular dermal matrices form an intact epidermal basal layer more rapidly and more completely than cells delivered by conventional dispersed seeding. These findings demonstrate that delivery of keratinocytes in phase-separating polymer solutions holds potential for enhancing growth of keratinocytes in culture and production of functional skin equivalents.


An anti-predator response in the great tit (Parus major): Is it tuned to predator risk?
Two semi-quantitative predictions about the intensity of defence against a predator based on the associated costs and benefits as a function of predator species, were examined in great tits (Parus major) feeding nestlings. One premise was that defence behaviour is adaptive. Defence comprised of vocalizing and homing in on a live raptor near the nest hole. The intensity of defence as judged by two measures of approaching (Minimum Distance, Average Distance) varies with the species of raptor, i.e. sparrowhawk ♀ (Accipiter nisus), pigmy owl (Glaucidium perlatum), and tawny owl (Strix aluco). With the exception of the response to the pigmy owl, defence intensities proved to conform to both predictions; the tits correctly assessed the relative overall risk from each predator ("predator pressure") i.e. its degree of specialization on great tits, and the immediate risk of defence. The failure to verify the predictions regarding the pigmy owl is thought to derive from our incomplete assessment of the cost function and/or from the response being mal-adaptive.The male takes a greater risk, exceeding the female's by an amount independent of the species of raptor. The sexual difference remains functionally unexplained.


The adipokine/ceramide axis: key aspects of insulin sensitization.
Until recently, sphingolipid physiology was primarily the domain of oncologists and immunologists. However, mounting evidence implicates ceramides and their derivatives in various aspects of metabolism via directly impacting the insulin receptor as well as modulating cell survival and proliferation. More recent observations suggest a strong link between a number of adipokines and ceramide catabolism. Here, we aim to briefly review the available data on the established metabolic effects of sphingolipids in various cell types and will discuss how adipokines exert a critical influence on the steady state levels of these lipid mediators.


Integrated Internal Stabilization for Saddle Nose Surgery.
Correction of Saddle nose deformity is one of the most challenging issues in facial plastic surgery. In this study, a single structure in the form of L-strut was attempted to be created by using one 0.035" Kirschner wire and an autologous costal graft out of the 10th and 11th ribs. This study involved 13 cases, most of whom were traumatic. The corrective surgical techniques used in this study will be described in detail. There was no warping, no rejection, and no infection in the created L-strut and patients' satisfaction was very good during the follow up period. Surgical correction of a saddle-shaped nose using the described technique seems to be an acceptable and uncomplicated technique, and the cosmetic result is totally acceptable.


Integrated multiomics analysis of chromosome 19 miRNA cluster in bladder cancer.
With 46 microRNAs (miRNAs) embedded tandemly over a distance of ~100 kb, chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster in the human genome. The C19MC is transcribed from a long noncoding genomic region and is usually expressed simultaneously at a higher level. Hence, we performed an integrative multiomics data analysis to examine C19MC regulation, expression patterns, and their impact on bladder cancer (BCa). We found that 43 members of C19MC were highly expressed in BCa. However, its co-localization with recurrent copy number variation (CNV) gain was not statistically significant to implicate its upregulation. It has been reported that C19MC expression is regulated by a well-established CpG island situated 17.6 kb upstream of the transcription start site, but we found that CpG probes at this island were hypomethylated, which was not statistically significant in the BCa cohort. In addition, the promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients. Further, C19MC targeted 42 tumor suppressor (TS) genes that were downregulated, of which 15 were significantly correlated with patient survival. Our findings suggest that transcription factors and chromatin modifiers at the promoter region may regulate C19MC overexpression. The upregulated C19MC members, transcription regulators, and TS genes can be further exploited as potential diagnostic and prognostic indicators as well as for therapeutic management of BCa.


Multi-functional bio-film based on sisal cellulose nanofibres and carboxymethyl chitosan with flame retardancy, water resistance, and self-cleaning for fire alarm sensors.
Flexible and environmentally friendly bio-based films have attracted significant attention as next-generation fire-responsive sensors. However, the low structural stability, durability, and flame retardancy of pure bio-based films limit their application in outdoor and extreme environments. Here, we report the design of a sustainable bio-based composite film assembled from carboxymethyl-modified sisal fibre microcrystals (C-MSF), carboxymethyl chitosan (CMC), graphene nanosheets (GNs), phytic acid (PA), and trivalent iron ions (Fe3+). Cross-linking between Fe3+ and the C-MSF/CMC matrix and the formation of PA-Fe3+ complexes on the surface of the film imparted excellent mechanical properties, chemical stability, self-cleaning ability, and flame retardancy to the bio-film. Furthermore, the bio-film produced a reversible and sensitive response to temperature at 55.3-214.1 °C, and a fire alarm system made from the bio-film had a fire-response time of 4.6 s. In addition, the char layer of the bio-film retained a stable cyclic response to temperature, enabling it to serve as a fire resurgence sensor with a response time of 2.3 s and recovery time of 11.2 s. This work provides a simple pathway for the fabrication of self-cleaning, flame retardant, and water-resistant bio-films that can be assembled into fire alarm systems for the real-time monitoring of fire accidents and resurgence.


National Comprehensive Cancer Network Guidelines for Pediatric Acute Lymphoblastic Leukemia.
The National Comprehensive Cancer Network has recently published the first pediatric guidelines for the management of children, adolescent and young adults with acute lymphoblastic leukemia (ALL). The recommendations for diagnosis, work up, genetic evaluation, treatment and follow up of pediatric ALL have been provided. Genetic risk factors and newer therapeutic agents have been discussed. We highlight the major points in the guidelines.


A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population.
Inflammation is now considered critical in the pathogenesis of myocardial infarction. One of the mechanisms regulating the inflammatory process is the ubiquitin-proteasome system. We investigated whether variants of the 20S proteasome are associated with susceptibility to myocardial infarction and found a common SNP (minor allele frequency of 0.35) in the proteasome subunit alpha type 6 gene (PSMA6) conferring risk of myocardial infarction in the Japanese population (chi(2) = 21.1, P = 0.0000044, 2,592 affected individuals versus 2,851 controls). We replicated this association in another panel of myocardial infarction and control subjects, although its relevance to other ethnic groups remains to be clarified. The SNP, located in the 5' untranslated region of exon 1 in this gene, enhanced the transcription of PSMA6. Moreover, suppression of PSMA6 expression using short interfering RNA in cultured cells reduced activation of the transcription factor NF-kappaB by stabilizing phosphorylated IkappaB. Our results implicate this PSMA6 SNP as a previously unknown genetic risk factor for myocardial infarction.


Effectiveness of intraoperative optical coherence tomography on vitrectomy for proliferative diabetic retinopathy.
We sought to verify the effect of intraoperative optical coherence tomography (iOCT) on vitrectomy for the treatment of proliferative diabetic retinopathy (PDR). Retrospective study. We reviewed 178 eyes with PDR treated with 25-gauge vitrectomy by a single surgeon between April 2013 and December 2017. In total, 98 eyes of 77 patients with PDR (mean age, 52.5 ± 11.7 years) treated with vitrectomy using iOCT (iOCT group) and 80 eyes of 60 patients with PDR (mean age, 53.1 ± 10.9 years) treated without iOCT (non-iOCT group) were included in the study. To determine the effects of combining vitrectomy with iOCT, a comparison was made of patients treated with this combination and patients treated with vitrectomy without iOCT. The effects of these treatments were assessed on the basis of intraoperative complications, reoperation ratios, postoperative complications, operation times, and postoperative visual acuity. The operation time was significantly reduced for the iOCT group (72.9 ± 23.9 min) when compared with the non-iOCT group (91.3 ± 31.2 min) (P = .001). The incidences of intraoperative complications, reoperation, and postoperative complications did not differ significantly between the 2 groups (P = .542, 0.258, and 0.860 respectively). Six months after surgery, the postoperative visual acuity did not differ significantly between the 2 groups (P = .508). Multiple linear regression analysis revealed that the operation time was significantly correlated with iOCT (beta [standard partial regression coefficient] = - 0.28, P < .001), the fibrovascular proliferative membrane (beta = 0.17, P = .009), cataract surgery (beta = 0.22, P = .016), preoperative retinal photocoagulation (beta = - 0.14, P = .021), intraoperative complications (beta = 0.16, P = .023), and posterior vitreous detachment (beta = - 0.14, P = .04). Use of iOCT reduced the operation time without affecting the incidence rates of intraoperative and postoperative complications, reoperation ratios, or postoperative visual acuities in patients who underwent vitreous surgery for PDR.


A ring-expansion approach to roseophilin.
[reaction: see text] Preparation of a cyclopentenone-fused pyrrolophane, which serves as a model for the tricyclic core of roseophilin (1), is described. The synthetic scheme features a palladium-catalyzed annulation and oxidative cleavage sequence to provide a macrocyclic ketoester (17). Modified Paal-Knorr pyrrole synthesis and Friedel-Crafts acylation complete the pyrrolophane model system (20).


Synthetic sandwich culture of 3D hepatocyte monolayer.
The sandwich culture of hepatocytes, between double layers of extra-cellular matrix (ECM), is a well-established in vitro model for re-establishing hepatic polarity and maintaining differentiated functions. Applications of the ECM-based sandwich culture are limited by the mass transfer barriers induced by the top gelled ECM layer, complex molecular composition of ECM with batch-to-batch variation and uncontrollable coating of the ECM double layers. We have addressed these limitations of the ECM-based sandwich culture by developing an 'ECM-free' synthetic sandwich culture, which is constructed by sandwiching a 3D hepatocyte monolayer between a glycine-arginine-glycine-aspatic acid-serine (GRGDS)-modified polyethylene terephthalate (PET) track-etched membrane (top support) and a galactosylated PET film (bottom substratum). The bioactive top support and bottom substratum in the synthetic sandwich culture substituted for the functionalities of the ECM in the ECM-based sandwich culture with further improvement in mass transfer and optimal material properties. The 3D hepatocyte monolayer in the synthetic sandwich culture exhibited a similar process of hepatic polarity formation, better cell-cell interaction and improved differentiated functions over 14-day culture compared to the hepatocytes in collagen sandwich culture. The novel 3D hepatocyte monolayer sandwich culture using bioactive synthetic materials may readily replace the ECM-based sandwich culture for liver tissue engineering applications, such as drug metabolism/toxicity testing and hepatocyte-based bioreactors.


The Role of Algae Extract (Ulva lactuca and Solieria chordalis) in Fishmeal Substitution in Gibel Carp (Carrassius auratus gibeilo).
The function of algae extract (AE) in fishmeal (FM) substitution with plant proteins in the diets of Gibel carp (Carrassius auratus gibeilo) was investigated during a 56-day trial. Diets 1 and 2 contained 10% FM, Diets 3 and 4 contained 5% FM, and Diet 5 and 6 contained 0% FM. In contrast, Diets 2, 4, and 6 were supplemented with 0.2% AE. The results showed that FM reduction inhibited growth performance, while AE supplementation alleviated growth inhibition. FM reduction significantly decreased the crude protein levels of the whole body, while the contents of whole-body lipids were significantly decreased with AE supplementation. There were no significant changes in ALB, ALP, ALT, AST, TP, GLU, GLU, and TC in plasma. FM reduction with AE supplementation mitigated the decrease in antioxidant capacity by heightening the activity of antioxidant enzymes and related gene expressions, which mitigated the decrease in immune capacity by affecting the expression of inflammatory factors. In summary, AE supplementation could alleviate the negative effects of FM reduction in Gibel carp.


Pharmacological and immunohistochemical evidence for serotonergic modulation of cholinergic nucleus basalis neurons.
Identified electrophysiologically by low threshold bursts and transient outward rectification, cholinergic nucleus basalis neurons were recorded and labelled intracellularly in guinea-pig basal forebrain slices. By means of a triple labelling immunofluorescent technique, serotonin-immunoreactive fibres were visualized in close proximity to the soma and dendrites of the biocytin-labelled, choline acetyl transferase (ChAT)-immunoreactive cells. By bath application, 5-hydroxytryptamine (5-HT) produced a direct hyperpolarization of the identified cells which was mimicked by 5-HT1A receptor agonists, suggesting that it may inhibit the tonic firing but also modulate the low threshold bursting of the cholinergic nucleus basalis neurons.


A rare vascular ring caused by an aberrant right subclavian artery concomitant with the common carotid trunk: a report of two cases.
In this report, we describe two rare cases with aortic branching anomalies. One was a 7-year-old girl who had an incomplete vascular ring caused by the presence of left aortic arch and aberrant, retroesophageal right subclavian artery associated with the common carotid trunk. The other was a 6-year-old boy who had a right aortic arch and mirror image branches of the former case. Both were asymptomatic and discovered incidentally. Three-dimensional surface rendering magnetic resonance angiography was used to confirm the diagnosis. Surgical intervention was not performed in either case because of lack of vascular ring-related symptoms. The incidence, clinical symptoms, pathogenesis and management of this rare vascular ring are discussed below.


[Peroxidase-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of 2,4-dinitrosoresorcinol and polydisulfide derivatives of resorcinol and 2,4-dinitrosoresorcinol].
A comparative study of the kinetics of peroxidase-catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of 2,4-dinitrosoresorcinol (DNR), its polydisulfide derivative [poly(DNRDS)], and resorcinol polydisulfide [poly(RDS)], substances that competitively inhibit the formation of TMB conversion product, was carried out. The inhibition constants, Ki for DNR, poly(DNRDS), and poly(RSD) were determined at 20 degrees C and pH 6.4 to be 110, 13.5, and 0.78 microM, respectively. The stoichiometric coefficients of inhibition were calculated to be 0.38 and 76 for poly(DNRDS) and poly(RDS), respectively. In the pH range 6.4-7.0, the initial rates of the peroxidative oxidation of TMB, and its mixtures with DNR and poly(DNRDS) and the Ki value for poly(RDS) substantially decreased with increasing pH. The kinetic parameters of poly(RDS) (Ki 0.22-0.78 microM and f76) suggest that it is the most efficient inhibitor of peroxidase oxidation of TMB: in micromolar concentrations, it completely stops this process and can be used in EIA.


Role of immature myeloid cells in mechanisms of immune evasion in cancer.
Tumor affects myelopoiesis by inhibiting the process of differentiation/maturation of antigen-presenting cells from their myeloid precursors and by stimulating an accumulation of immature myeloid cells in cancer patients and tumor-bearing mice. These immature myeloid cells can contribute greatly to tumor progression and promote tumor evasion from immune attack: i) by inhibiting development of adaptive immune responses against tumor in lymphoid organs; ii) by migrating into tumor site and differentiating there into highly immune suppressive tumor-associated macrophages. Immature myeloid cells and tumor-associated macrophages utilize different JAK/STAT signaling pathways and different mechanisms to control T cell responses, which include increased production of TGF-beta, reactive oxygen species, peroxynitrites, as well as enhanced L-arginine metabolism. Understanding of precise mechanisms, which tumors use to affect differentiation of APC from myeloid cell precursors and inhibit T cell responses, could help to develop new approaches for cancer therapy and substantially improve efficiency of existing cancer vaccination strategies.


Lanthanide(III)-phosphatidic acid complexes: binding site heterogeneity and phase separation.
The luminescent lanthanides are potentially useful probes of cation-induced events involving phospholipid membranes. In this work, the spectroscopic properties of Tb3+, Ce3+ and Eu3+ are shown to be complementary in defining three forms of complex with phosphatidic acid vesicles. Ce3+, in particular, is useful for studying dilute cation-lipid complexes because it has strong excitation bands in the near ultraviolet. In addition to providing a means for detecting chemically distinct forms of lanthanide-lipid complexes, the luminescence can be used to monitor cation-induced lateral segregation. Ce3+ to Tb3+ energy transfer was observed at lanthanide levels as low as 1:1000 Ln3+/phosphatidic acid, indicating clustering or phase separation. Initial clustering occurs on a subsecond timescale, followed by a much slower aggregation continuing for several minutes to hours. Addition of a chelator results in slow release of the lanthanides. In the case of the dioleoylphosphatidic acid complexes, release is bimodal and indicative of cation entrapment; dimyristoylphosphatidic acid complexes exhibit this behavior only at high temperatures. These observations are consistent with the relative tendencies of these two lipids to form the HII phase. This work sets the foundation for experiments designed to determine the size of nucleation sites for cation-induced events such as intramembrane inverted micelle formation and membrane fusion.


Is positive-contrast myelography of value in acute cervical spinal cord injury?
Positive-contrast myelography in 30 patients with acute cervical spinal cord injury has not provided any information of clinical value. Reference to the literature does not provide a definite set of indications for myelography in acute spinal cord injury. An attempt has therefore been made to evaluate the indications for this procedure. The potential hazards of myelography in patients with acute spinal cord injury are discussed. Specific contra-indications are described. Difficulties in the radiological interpretation of the usual myelographic appearances in spinal cord injury are mentioned. The advantages of negative-contrast myelography are briefly described. It is concluded that there is a very limited indication for positive-contrast myelography in acute spinal cord injury.


Emergence of family medicine in Ethiopia [corrected]: an international collaborative education model.
Family Medicine (FM) is a new specialty in Ethiopia. The first seven family physicians graduated in February 2016 from the inaugural residency programme at Addis Ababa University. Cooperation amongst Ethiopian and expatriate decision-makers and physicians was needed to begin the programme. Intentional replacement of expatriates with Ethiopian family physicians has begun. Barriers include lack of understanding of FM and the human and financial resources needed for scaling up the programme. Regular programme review with resident physician involvement has allowed the FM training programme to adapt and fit the Ethiopian context. Further successes will result from ongoing support and advocacy from the Federal Ministry of Health and other Ethiopian, African, and international primary care organisations.


Trends in consuming alcoholic beverages among adolescents and young adults of school age: sexes differences.
To analyze the tendency of alcoholic beverage consumption among adolescents and young adults at school age according to their sexes. This is a trend research study in public schools of the municipality of Petrolina, between 2014 and 2016, with 3146 students aged between 12 and 24 years old. The instrument was constituted by socio-economic inquiry and the Youth Risk Behavior Survey. Trends were assessed using the Centers for Disease Control and Prevention recommended approach. The analyses were conducted using logistic regression, with a statistical significance of 0.05. Close to 56% of the adolescents had already tried some alcoholic beverage, most of which had contact after 13 years of age. The prevalence of binge drinking ranged between 17% and 25%. The percentage of girls who tried alcohol before 13 years old remained similar over the three years (p = 0.943). The prevalence of this behavior was stabilized at around 20%. There was a trend to decrease in the prevalence of boys who reported having tried alcohol before 13 years old (p = 0.014). The percentage of boys who reported involvement in binge drinking in the past 30 days remained stable at around 20% over the years (p = 0.951). The girls' data revealed a significant decrease in binge drinking (p = 0.019). The general analysis suggests a trend towards stabilization of consumption among boys, and an increase among girls.


Hemodynamic and cardiac metabolic changes during nicardipine-induced myocardial ischemia.
After 10 mg nicardipine IV a patient with stable angina developed chest pain and ST-segment depression accompanied by excessive tachycardia, low arterial blood pressure, and initially decreased coronary sinus blood flow. Measurements of arterial concentrations and cardiac exchanges of lactate, glucose, free fatty acids, glutamate, and alanine showed alterations indicative of severe ischemia.