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Background: While a palliative approach is generally perceived to be an integral part of the intensive care unit (ICU), the provision of palliative care in this setting is challenging. This review aims to identify factors (barriers and facilitators) influencing a palliative approach in intensive care settings, as perceived by health care professionals., Method: A systematic mixed-methods review was conducted. Multiple electronic databases were used, and the following search terms were utilized: implementation, palliative care, and intensive care unit. In total, 1843 articles were screened, of which 24 met the research inclusion/exclusion criteria. A thematic synthesis method was used for both qualitative and quantitative studies., Results: Four key prerequisite factors were identified: (a) organizational structure in facilitating policies, unappropriated resources, multi-disciplinary team involvement, and knowledge and skills; (b) work environment, including physical and psychosocial factors; (c) interpersonal factors/barriers, including family and patients' involvement in communication and participation; and (d) decision-making, e.g., decision and transition, goal conflict, multidisciplinary team communication, and prognostication., Conclusion: Factors hindering the integration of a palliative approach in an intensive care context constitute a complex interplay among organizational structure, the care environment and clinicians' perceptions and attitudes. While patient and family involvement was identified as an important facilitator of palliative care, it was also recognized as a barrier for clinicians due to challenges in shared goal setting and communication.

Optical properties of four model systems (Na-, K-, Rb- or Cs-doped quasi-two-dimensional X 1.95 Al 1.95 Si 2.05 O 8.00 ; X  =  Na, K, Rb, or Cs) used to study the metal-insulator transition (MIT) in a deformable lattice are investigated. The doping evolution of the optical absorption band(s) originating from small bipolarons show strong variations depending on the electron-lattice coupling strength [Formula: see text]. Despite the increasing number density of small (bi)polarons, the Na-system remains a stubborn (bi)polaronic insulator due to strong [Formula: see text], while the other three systems show closing of the respective mobility gaps giving way to conducting phases with differing properties. These interesting evolutions and dynamical properties are compared and discussed. We conjecture that the manifestation of anomalous electronic transport properties and Mooij correlations near the MIT or superconductor-insulator transition in systems with non-negligible electron-lattice coupling effects may be linked to the coexistence of competing polaronic phases and the dynamical intertwining of the deformable lattice and the random electronic potential.

Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. However, the mechanisms controlling AIS assembly remain poorly defined. We performed differential proteomics and found nuclear mitotic apparatus protein 1 (NuMA1) is downregulated in AIS-deficient neonatal mouse brains and neurons. NuMA1 is transiently located at the AIS during development where it interacts with the scaffolding protein 4.1B and the dynein regulator lissencephaly 1 (Lis1). Silencing NuMA1 or protein 4.1B by shRNA disrupts AIS assembly, but not maintenance. Silencing Lis1 or overexpressing NuMA1 during AIS assembly increased the density of AIS proteins, including ankyrinG and neurofascin-186 (NF186). NuMA1 inhibits the endocytosis of AIS NF186 by impeding Lis1's interaction with doublecortin, a potent facilitator of NF186 endocytosis. Our results indicate the transient expression and AIS localization of NuMA1 stabilizes the developing AIS by inhibiting endocytosis and removal of AIS proteins., (© 2019 Torii et al.)

Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na + and K + channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons.

The myelin proteolipid protein gene (PLP1) encodes the most abundant protein present in myelin from the central nervous system (CNS). Its expression must be tightly controlled as evidenced by mutations that alter PLP1 dosage; both overexpression (elevated PLP1 copy number) and lack thereof (PLP1 deletion) result in X-linked genetic disorders in man. However, not much is known about the mechanisms that govern expression of the human gene. To address this, transgenic mice were generated which utilize human PLP1 (hPLP1) sequences (proximal 6.2 kb of 5'-flanking DNA to the first 38 bp of exon 2) to drive expression of a lacZ reporter cassette. LoxP sites were incorporated around a 1.5-kb section of hPLP1 intron 1 since it contains sequence orthologous to the wmN1 region from mouse which, previously, was shown to augment expression of a minimally-promoted transgene coincident with the active myelination period of CNS development. Eight transgenic lines were generated with the parental, 6.2hPLP(+)Z/FL, transgene. All lines expressed the transgene appropriately in brain as evidenced by staining with X-gal in white matter regions and olfactory bulb. Removal of the "wmN1" region from 6.2hPLP(+)Z/FL with a ubiquitously expressed Cre-driver caused a dramatic reduction in transgene activity. These results demonstrate for the first time that the wmN1 enhancer region: (1) is functional in hPLP1; (2) works in collaboration with its native promoter-not just a basal heterologous promoter; (3) is required for high levels of hPLP1 gene activity; (4) has a broader effect, both spatially and temporally, than originally projected with mPlp1., (© 2018 Wiley Periodicals, Inc.)

This study aimed to determine the effect of seminal vesicle extract administration to increase the concentration and motility of spermatozoa and testosterone level of kacang goat. The experiment was arranged using a randomly completely block design (RCBD). Three kacang goats were used and each goat received three treatments namely P0 (2 mL of 0.9% NaCl), P1 (1.5 mL Capriglandin, PGF2α), and P2 (2 mL of seminal vesicle extract, EVS). Semen and blood were collected two days post-treatment to measure the concentration and motility of spermatozoa and testosterone level. Testosterone levels were measured with enzyme-linked immunosorbent assay (ELISA). Duration between treatments was one week after semen collection. The result showed that the average spermatozoa concentration (x10 6 ) in P0; P1; and P2 respectively were 2,763.0±395.0; 2,060.00±678.2; and 2,387.0±442.7 (P>0.05), while the spermatozoa motility score in P0; P1; and P2 respectively were 3.7±1.1, 3.4±0.5, and 3.4±0.5 (P>0.05). The mean testosterone levels in P0, P1, and P2 respectively were 10.27±5.42, 18.51±19.46, and 29.57±12.96 ng/mL (P<0.05). It can be concluded that administration of EVS did not increase concentration and motility of spermatozoa but increased the level of testosterone in kacang goat.

Objectives (1) To describe the clinical, demographic and polysomnographic (PSG) characteristics of children with very severe obstructive sleep apnea (OSA) without significant comorbidities; (2) to assess the outcomes following tonsillectomy and adenoidectomy (T&A); and (3) to determine predictors of persistence of OSA after T&A. Study Design Case series with chart review. Setting Tertiary-level freestanding children's hospital. Subjects and Methods Seventy-four children aged 2 to 12 years who underwent T&A for very severe OSA (obstructive apnea-hypopnea index [AHI] >30) were included. Children with significant comorbidities were excluded. PSG variables were compared pre- and post-T&A using statistical tests. Factors affecting OSA resolution and persistence were studied. Results The mean (95% confidence interval) age was 4.3 (3.8-4.7) years with the majority black or Hispanic (64/74, 86%). The mean decrease in AHI after T&A was 49 (43-58) ( P < .001). Complete resolution of OSA, defined by an AHI <1, or an AHI <5 was seen in 32% (24/74) and 80% (59/74), respectively. Total sleep time (TST) greater than 5 minutes with end-tidal CO 2 >50 mm Hg was strongly associated with persistent OSA. The decrease in AHI post-T&A was best predicted by higher preoperative oxygen saturation (SpO 2 ) nadir and lower TST with SpO 2 <90% ( R 2 = 0.24, P < .001). Conclusions T&A is associated with a significant improvement but not resolution of very severe OSA. The severity of baseline hypercapnia and hypoxemia may best predict persistent OSA after T&A. The study supports obtaining routine post-T&A PSG in children with very severe OSA.

The control of NFκB in CNS neurons appears to differ from that in other cell types. Studies have reported induction of NFκB in neuronal cultures and immunostaining in vivo, but others have consistently detected little or no transcriptional activation by NFκB in brain neurons. To test if neurons lack some component of the signal transduction system for NFκB activation, we transfected cortical neurons with several members of this signaling system along with a luciferase-based NFκB-reporter plasmid; RelA was cotransfected in some conditions. No component of the NFκB pathway was permissive for endogenous NFκB activity, and none stimulated the activity of exogenous RelA. Surprisingly, however, the latter was inhibited by cotransfection of NFκB-inducing kinase (NIK). Fluorescence imaging of RelA indicated that co-expression of NIK sequestered RelA in the cytoplasm, similar to the effect of IκBα. NIK-knockout mice showed elevated expression of an NFκB-reporter construct in neurons in vivo. Cortical neurons cultured from NIK-knockout mice showed elevated expression of an NFκB-reporter transgene. Consistent with data from other cell types, a C-terminal fragment of NIK suppressed RelA activity in astrocytes as well as neurons. Therefore, the inhibitory ability of the NIK C-terminus was unbiased with regard to cell type. However, inhibition of NFκB by full-length NIK is a novel outcome that appears to be specific to CNS neurons. This has implications for unique aspects of transcription in the CNS, perhaps relevant to aspects of development, neuroplasticity, and neuroinflammation. Full-length NIK was found to inhibit (down arrow) transcriptional activation of NFκB in neurons, while it elevated (up arrow) activity in astrocytes. Deletion constructs corresponding to the N-terminus or C-terminus also inhibited NFκB in neurons, while only the C-terminus did so in astrocytes. One possible explanation is that the inhibition in neurons occurs via two different mechanisms, including the potential for a neuron-specific protein (e.g., one of the 14-3-3 class) to create a novel complex in neurons, whereas the C-terminus may interact directly with NFκB. [Structure of NIK is based on Liu J., Sudom A., Min X., Cao Z., Gao X., Ayres M., Lee F., Cao P., Johnstone S., Plotnikova O., Walker N., Chen G., and Wang Z. (2012) Structure of the nuclear factor κB-inducing kinase (NIK) kinase domain reveals a constitutively active conformation. J Biol Chem. 287, 27326-27334); N-terminal lobe is oriented at top]., (© 2016 International Society for Neurochemistry.)

Objective: To compare the changes in buccolinugal inclination of mandibular canines and intercanine distance in patients treated with clear aligners to those treated with preadjusted edgewise appliances., Materials and Methods: The buccolingual inclination of mandibular canines and the intercanine distance were measured on pre- and posttreatment cone-beam computed tomograms of 30 patients who had been treated with clear aligners and 30 patients who had been treated with fixed preadjusted edgewise appliances. Differences between the aligner and fixed appliance groups and between pre- and posttreatment measurements were tested for statistical significance., Results: In both groups, most of the mandibular canines had positive buccolingual inclinations (ie, their crowns were positioned lateral to their roots) both before and after treatment. While there was no difference between the groups pretreatment, the posttreatment buccolingual inclination was significantly greater in the aligner group. In the fixed appliance group, the canines became more upright with treatment, while the buccolingual inclination did not change significantly in the clear aligner group. The intercanine distance did not differ between the groups either before or after treatment. However, it increased significantly over the course of treatment in the aligner group, whereas it did not change significantly in the fixed appliance group., Conclusions: Orthodontic treatment with clear aligners tends to increase the mandibular intercanine distance with little change in inclination in contrast to treatment with fixed appliances, which leaves the intercanine distance unchanged but leads to more upright mandibular canines.

Objective: Assess the need for folate testing, frequency of corrective action, and determine reference level for serum folate., Methods: Serum folate levels in 5313 samples from 4448 patients, and clinical data were reviewed for patient characteristics and for (a) evidence of corrective action in patients with serum folate values <5.5 ng/mL, and (b) differences in patients with serum folate levels <5.5 ng/mL and patients with levels >25.7 ng/mL., Results: The prevalence of serum folate levels, in patients, <3.0, <4.0, <5.5, <7.0 and <13.0 ng/mL was 0.58%, 1.55%, 4.9%, 9.98% and 43.21% respectively. Patients with serum folate levels <5.5 ng/mL had lower serum albumin and hemoglobin. In 64% of patients with serum folate >25.7 ng/mL the sample was collected after supplementation with folic acid. Of the 128 patients with serum folate <5.5 ng/mL documentation of supplementation was present in only 38.9%., Conclusions: Serum folate levels are below the current "normal" level of 3.0 ng/mL in a larger proportion of tertiary care patients than that reported for ambulatory patients. In patients with folate deficiency, corrective action is lacking in >60% of the patients. Since serum folate levels ≥13.0 ng/mL are needed for optimal prevention of neural tube defects in the embryo/fetus, we propose that normal serum folate level should be designated to be ≥13.0 ng/mL.

Although the myelin proteolipid protein gene (PLP1) encodes the most abundant protein in central nervous system (CNS) myelin, not much is known about the mechanisms that govern expression of the human gene (hPLP1). Much more is known about the processes that regulate Plp1 gene expression in rodents. From studies with Plp1-lacZ transgenic mice, it was determined that the first intron of mouse Plp1 (mPlp1) is required to attain high levels of expression in brain, concurrent with the active myelination period. Other studies have suggested that within mPlp1 intron 1 (>8 kb) lie several regions with enhancer-like activity. To test whether these sequences (and possibly others) in hPLP1 intron 1 are functional, deletion-transfection analysis was performed with hPLP1-lacZ constructs that contain various portions of the intron, or lack it altogether. Results presented here demonstrate the importance of hPLP1 intron 1 in achieving maximal levels of expression in the immortalized oligodendroglial cell line, Oli-neu. Deletion analysis indicates that the intron contains multiple positive regulatory elements which are active in Oli-neu cells. Some of these elements appear to be functionally conserved between human and mouse, while others are not. Furthermore, our studies demonstrate that multiple splice variants can be formed due to inclusion of extra (supplementary) exons from what is classically thought of as hPLP1 intron 1. Thus, splicing of these novel exons (which are not recognized as such in mPlp1 due to lack of conserved splice sites) must utilize factors common to both human and mouse since Oli-neu cells are of mouse origin., (© The Author(s) 2015.)

The small intestine participates in lipid digestion, metabolism and transport. Cytosolic malic enzyme 1 (ME1) is an enzyme that generates NADPH used in fatty acid and cholesterol biosynthesis. Previous work has correlated liver and adipose ME1 expression with susceptibility to obesity and diabetes; however, the contributions of intestine-expressed ME1 to these conditions are unknown. We generated transgenic (Tg) mice expressing rat ME1 in the gastrointestinal epithelium under the control of the murine villin1 promoter/enhancer. Levels of intestinal ME1 protein (endogenous plus transgene) were greater in Tg than wildtype (WT) littermates. Effects of elevated intestinal ME1 on body weight, circulating insulin, select adipocytokines, blood glucose, and metabolism-related genes were examined. Male Tg mice fed a high-fat (HF) diet gained significantly more body weight than WT male littermates and had heavier livers. ME1-Tg mice had deeper intestinal and colon crypts, a greater intestinal 5-bromodeoxyuridine labeling index, and increased expression of intestinal lipogenic (Fasn, Srebf1) and cholesterol biosynthetic (Hmgcsr, Hmgcs1), genes. The livers from HF diet-fed Tg mice also exhibited an induction of cholesterol and lipogenic pathway genes and altered measures (Irs1, Irs2, Prkce) of insulin sensitivity. Results indicate that gastrointestinal ME1 via its influence on intestinal epithelial proliferation, and lipogenic and cholesterologenic genes may concomitantly impact signaling in liver to modify this tissue's metabolic state. Our work highlights a new mouse model to address the role of intestine-expressed ME1 in whole body metabolism, hepatomegaly, and crypt cell proliferation. Intestinal ME1 may thus constitute a therapeutic target to reduce obesity-associated pathologies.

The self-organizing map is a kind of artificial neural network used to map high dimensional data into a low dimensional space. This paper presents a self-organizing map for interval-valued data based on adaptive Mahalanobis distances in order to do clustering of interval data with topology preservation. Two methods based on the batch training algorithm for the self-organizing maps are proposed. The first method uses a common Mahalanobis distance for all clusters. In the second method, the algorithm starts with a common Mahalanobis distance per cluster and then switches to use a different distance per cluster. This process allows a more adapted clustering for the given data set. The performances of the proposed methods are compared and discussed using artificial and real interval data sets., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Claudins are the main sealing proteins of the intercellular tight junctions and play an important role in cancer cell progression and dissemination. This study examined and compared the expression of claudin-1 by immunohistochemistry in 60 squamous cell carcinomas of different tissue types and normal 33 controls, arranged in 2 tissue microarray slides. A score was generated to classify claudin-1 expression into negative, low, medium, and high. Most squamous cell carcinomas (91.67%) showed positive membranous staining. Medium to high claudin-1 expression was prevalent in carcinomas from the head-neck, skin, and genitourinary regions and was less frequent in other locations. An inverse correlation was noted between claudin-1 expression and tumor grade in tumors of the genitourinary and breast-gynecologic regions. Of the normal organs, significant claudin-1 expression was present mainly in the skin whereas other epithelial tissues had only minimal to low expression levels. Claudin-1 expression in squamous cell carcinoma varies in organ-specific manner reflecting influence of local factors and different mechanisms of claudin-1 expression. Knowledge of this fact is important in planning biologic therapy targeting claudin-1.

The renovation of a building will certainly affect the quality of air in the vicinity of where associated activities were undertaken, this includes the quality of air inside the building. Indoor air pollutants such as particulate matter, heavy metals, and fine fibers are likely to be emitted during renovation work. This study was conducted to determine the concentration of heavy metals, asbestos and suspended particulates in the Biology Building, at the Universiti Kebangsaan, Malaysia (UKM). Renovation activities were carried out widely in the laboratories which were located in this building. A low-volume sampler was used to collect suspended particulate matter of a diameter size less than 10 μm (PM₁₀) and an air sampling pump, fitted with a cellulose ester membrane filter, were used for asbestos sampling. Dust was collected using a small brush and scope. The concentration of heavy metals was determined through the use of inductively coupled plasma-mass spectroscopy and the fibers were counted through a phase contrast microscope. The concentrations of PM₁₀ recorded in the building during renovation action (ranging from 166 to 542 μg m⁻³) were higher than the value set by the Department of Safety and Health for respirable dust (150 μg m⁻³). Additionally, they were higher than the value of PM₁₀ recorded in indoor environments from other studies. The composition of heavy metals in PM₁₀ and indoor dust were found to be dominated by Zn and results also showed that the concentration of heavy metals in indoor dust and PM₁₀ in this study was higher than levels recorded in other similar studies. The asbestos concentration was 0.0038 ± 0.0011 fibers/cc. This was lower than the value set by the Malaysian Department of Occupational, Safety and Health (DOSH) regulations of 0.1 fibers/cc, but higher than the background value usually recorded in indoor environments. This study strongly suggests that renovation issues need to be considered seriously by relevant stakeholders within the university in order to ensure that the associated risks toward humans and indoor environment are eliminated, or where this is not feasible, minimized as far as possible.

Background and Objectives: Previous in vitro and clinical studies showed that the urea mass transfer-area coefficient (K(o)A) increased with increasing dialysate flow rate. This observation led to increased dialysate flow rates in an attempt to maximize the delivered dose of dialysis (Kt/V(urea)). Recently, we showed that urea K(o)A was independent of dialysate flow rate in the range 500 to 800 ml/min for dialyzers incorporating features to enhance dialysate flow distribution, suggesting that increasing the dialysate flow rate with such dialyzers would not significantly increase delivered Kt/V(urea)., Design, Setting, Participants, & Measurements: We performed a multi-center randomized clinical trial to compare delivered Kt/V(urea) at dialysate flow rates of 600 and 800 ml/min in 42 patients. All other aspects of the dialysis prescription, including treatment time, blood flow rate, and dialyzer, were kept constant for a given patient. Delivered single-pool and equilibrated Kt/V(urea) were calculated from pre- and postdialysis plasma urea concentrations, and ionic Kt/V was determined from serial measurements of ionic dialysance made throughout each treatment., Results: Delivered Kt/V(urea) differed between centers; however, the difference in Kt/V(urea) between dialysate flow rates of 800 and 600 ml/min was NS by any measure (95% confidence intervals of -0.064 to 0.024 for single-pool Kt/V(urea), -0.051 to 0.023 for equilibrated Kt/V(urea), and -0.029 to 0.099 for ionic Kt/V)., Conclusions: These data suggest that increasing the dialysate flow rate beyond 600 ml/min for these dialyzers offers no benefit in terms of delivered Kt/V(urea).

The use of immortalized cells has been instrumental as a tool with which to study gene regulation. However, it is crucial to understand the status of a given cell line, especially when investigating the regulation of genes whose expression is developmentally regulated. Several immortalized cell lines have been derived from primary cultures of mouse oligodendrocytes. Two such cell lines, N20.1 and Oli-neu, were characterized here in terms of their relative expression of myelin genes at both the mRNA level and the protein level. Analysis of the splice isoforms expressed by the myelin proteolipid protein (Plp1), myelin basic protein (Mbp), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp) genes, along with the relative amount of protein expressed by these genes, suggests that the cell lines are representative of immature oligodendrocytes, although Oli-neu cells appear to be farther along the differentiation pathway compared with N20.1 cells. Previous studies have shown that the developmental increase in Plp1 gene expression that occurs during the active myelination period is governed by transcription regulatory elements present within the first intron. The responsiveness of one of these elements, the so-called antisilencer/enhancer (ASE), was investigated in both cell lines. Results presented here suggest that the ASE has a much more potent effect in Oli-neu cells. Thus, the two cell lines appear to be at different stages and will be useful as a means to study transcription regulatory elements whose influence changes during development., (Copyright © 2011 Wiley-Liss, Inc.)

A 53-year-old man developed a deep venous thrombus (DVT) and pulmonary embolism (PE) shortly after an open Roux-en-Y gastric bypass was performed. He later suffered a life-threatening gastrointestinal bleed while on anticoagulation for the DVT. Thus, anticoagulation was held and an inferior vena cava (IVC) filter (G2, Bard Inc., Tempe, AZ, USA) was placed for PE prophylaxis. About 10 days after filter placement, he presented with severe low back pain and syncope. He also presented with hypotension and anuria unresponsive to intravenous fluids. A STAT non-contrast CT scan of the abdomen revealed that his IVC filter had migrated from an infrarenal to a suprarenal position. Given the high clinical suspicion for renal vein thrombosis, an attempt at IVC filter retrieval was made. The filter could not be retrieved because it was embedded in a large IVC thrombus that extended from the hepatic veins down to the common iliac veins. The patient received nearly 4 days of tPA that was administered at the site of the thrombus with a long thrombolytic catheter (UNIFUSE, Angiodynamics, Queensbury, NY, USA). While his creatinine peaked at 7.6 on hospital Day 4, he eventually began to produce urine and his creatinine had declined to his baseline of 1.0 on follow-up 1 month later. About 18 months after admission, his creatinine had further declined to 0.8. We report the first published case of acute renal failure due to bilateral renal vein thrombosis in the setting of IVC filter migration and thrombosis. This report highlights an important, but rare complication of IVC filter placement as well as the non-operative management of acute bilateral renal vein thrombosis.

Introduction: The vague term of capitellar fractures is still frequently used to designate articular coronal fractures of the distal humeral epiphysis. The use of eponyms for their descriptions may cause confusion. Recent publications describe a wide variety of fracture types and recommend new classifications based on the operative findings. We report our results of surgical treatment of 12 cases of these fractures in comparison to recent series of the literature., Methods: Twelve patients (seven female and five male with a mean age of 31 years and 6 months) have been treated for articular coronal fractures of the distal humeral epiphysis between 1994 and 2004. A retrospective analysis of the radiographs and the operative notes permits their differentiation into 3 types according to the classification of Dubberley et al. (2006): ten fractures of type 1, one fracture of type 2 and one fracture of type 3. All fractures underwent open reduction and internal fixation, except for one case, which was initially missed and operated, therefore, by excision of the articular fragment with a delay of 6 weeks. All patients were clinically evaluated according to the index of performance of Morrey et al. (1993). In addition, a radiological assessment based on the scale of Knirk and Jupiter (1986) for elbow osteoarthritis was performed., Results: The mean follow-up was 9 years. The clinical evaluation showed seven excellent results (six cases of type 1 and one case of type 3 with a score of 100 points for each one), two good (type 1 with 80 and 85 points of respective scores) and three fair (two cases of type 1 with 65 and 60 points of respective scores and one case of type 2 with a score of 65 points). The radiological evaluation showed seven elbows of grade 0 (six cases of type 1 and one case of type 3), four elbows of grade 1 (type 1) and one elbow of grade 2 (type 2)., Discussion: Articular coronal fractures of the distal humerus are rare. The classification of Dubberley et al. (2006) [7] is comprehensive and allows inclusion of all varieties of these fractures. In addition, it is the only one that indicates the surgical approach according to the fracture type. However, to do so, a preoperative CT-scan is highly recommended. The more the fracture line extends medially to involve the trochlea (types 2 and 3), the less a lateral approach is sufficient and the more a combined lateral and medial or a posterior transolecranon approach is mandatory. An internal fixation using conventional small fragment screws inserted from posterior to anterior is feasible when the articular fragment has a sufficient subchondral bone thickness. A direct anteroposterior fixation is better achieved using headless screws buried beneath the cartilaginous surface; it is particularly helpful when the articular fragment has a thin sub-chondral cancellous bone component. Excision is reserved for comminuted fractures, those not amenable to fixation, very thin or osteoporotic fragments, and for the late diagnosed fracture.

White rice husk ash (RHA), an agriculture waste containing crystalline tridymite and alpha-cristobalite, was used as a silica source for zeolite Beta synthesis. The crystallization of zeolite Beta from RHA at 150 degrees C in the presence of tetraethylammonium hydroxide was monitored by XRD, FTIR and (29)Si MAS NMR techniques. It was found that zeolite Beta started to form after 12h and the complete crystallization of zeolite Beta phase was achieved after 2d. XRD, (29)Si MAS NMR and solid yield studies indicate that the transformation mechanism of silica present in RHA to zeolite Beta involves dissolution of the ash, formation of an amorphous aluminosilicate after 6h of crystallization, followed by dissolution in the mother liquor and final transformation to pure zeolite Beta crystals.

Use of sequencing-based genotyping as a diagnostic assay for human immunodeficiency virus (HIV) antiretroviral resistance is increasing. Periodic evaluation of the proficiency of laboratories performing this assay should be established. It is important to identify components of the assay that influence the generation of reliable sequencing data and that should and can be monitored. A model was developed to determine what parameters were reasonable and feasible for assessing the performance of genotyping assays. Ten laboratories using the genotyping platform, HIV-1 Genotyping System (HGS) v. 1 and software versions 1.1 or 2.0, participated in two rounds of testing. For each round, each group was sent a panel consisting of three clinical samples to sequence in real time. Six months later, seven laboratories using the TRUGENE HIV-1 Genotyping Kit participated in a separate round, working with both panels at the same time. Analysis of the data showed that one main indicator of genotyping proficiency was achievement of > or =98% sequence homology of a sample tested to a group consensus sequence for that sample. A second was concordant identification of codons at sites identified with resistance mutations in the sample, although scoring of these criteria is still undetermined from this study. These criteria are applicable to all sequence-based genotyping platforms and have been used as a baseline for assessing the performance of genotyping for the determination of antiretroviral resistance in our ongoing proficiency program.

Laboratory-bred females of Culex quinquefasciatus, Aedes aegypti and Aedes albopictus from the insectarium, Unit of Medical Entomology, Institute for Medical Research were used in the experiment. The late third stage of the F0 larvae which survived the high selection pressure of malathion, permethrin and temephos were reared and colonies were established from adults that emerged. Cx. quinquefasciatus larvae were subjected to selection by malathion and permethrin for 40 generations, Ae. aegypti larvae to malathion, permethrin and temephos for 32 generations and Ae. albopictus larvae were selected against malathion and permethrin for 32 generations and 20 generations against temephos. The rate of resistance development was measured by LC50 value. Cx. quinquefasciatus larvae developed higher resistance to malathion and permethrin compared to Ae. aegypti and Ae. albopictus. On the whole, permethrin resistance developed at a faster rate than malathion and temephos.

The surfaces of NaY zeolite particles were modified by the alkylsilylation of n-octadecyltrichlorosilane (OTS). Two kinds of modified NaY zeolites were prepared; one with its external surface partially and the other fully covered with alkylsilyl groups. Since the size of OTS is bigger than the pore diameter of NaY, it is attached on the external surface, leaving the internal pore accessible to adsorbate molecules. As a result of alkylsilylation, the adsorption properties of these sorbents were improved. The adsorption properties of these materials were tested by their reaction in a mixture of paraquat and blue dye. The results demonstrate that the alkysilylated NaY materials are capable of simultaneous adsorption of paraquat and blue dye. Paraquat was selectively adsorbed into the internal pore of the zeolite whereas the dye on the externally attached alkylsilyl groups of the sorbent; displaying the unique bimodal amphiphilic character of the alkylsilylated NaY zeolites.

Purpose: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol., Patients and Methods: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor., Results: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P =.014) and a 60% reduction in risk of disease progression (P =.014) for women with such mutations. However, these striking risk reductions increased over time (P <.02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome., Conclusion: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.

This is the case of a young woman, 16-year-old, calling to our Department because of the appearance, in the floor of the mouth, of a mass progressively growing until about 5 cm diameter. Through fine needle biopsy was diagnosed of epidermoid cyst. Despite its size and infrahyoid site was removed successfully. Perusal review of last years bibliography and its variants.

Point mutations and inserts in the beta3-beta4 region of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are associated with resistance to nucleoside analog inhibitors. This report describes HIV-1 strains from seven patients that were found to have a 3-bp deletion in the beta3-beta4 region of the RT gene. These patient strains also had a mean of 6.2 drug resistance-associated mutations in their RT genes (range, 3 to 10 mutations). The deletion was most frequently found in strains with the Q151M mutation. Nonnucleoside RT inhibitor mutations were found in six of seven strains. Culture-based drug sensitivity assays showed that deletion-containing isolates had reduced susceptibility to four to eight RT inhibitors. Site-directed mutagenesis experiments showed that the deletion alone conferred reduced susceptibility to nucleoside analogs. Changes in the three-dimensional models of the RT deletion mutants were consistently observed at the beta3-beta4 loop and at helices C and E in both the presence and the absence of dTTP. Loss of hydrogen bonds between the RT and dTTP were also observed in the RT deletion mutant. These results suggest that the deletion in the RT gene contributes to resistance to several nucleoside analogs through a complex interaction with other mutations in the RT gene.

While many point mutations in the HIV-1 reverse transcriptase (RT) confer resistance to antiretroviral drugs, inserts or deletions in this gene have not been previously characterized. In this report, 14 RT inhibitor-treated patients were found to have HIV-1 strains possessing a 6-basepair insert between codons 69 and 70 of the RT gene. Known drug resistance mutations were also observed in these strains, with T215Y appearing in all strains. Genotypic analysis indicated that the inserts had substantial nucleotide variability that resulted in relatively restricted sets of amino acid sequences. Linkage of patients' treatment histories with longitudinal sequencing data showed that insert strains appeared during drug regimens containing ddI or ddC, with prior or concurrent AZT treatment. Drug susceptibility tests of recombinant patient isolates showed reduced susceptibility to nearly all nucleoside RT inhibitors. Site- directed mutagenesis studies confirmed the role of the inserts alone in conferring reduced susceptibility to most RT inhibitors. The addition of AZT-associated drug resistance mutations further increased the range and magnitude of resistance. These results establish that inserts, like point mutations, are selected in vivo during antiretroviral therapy and provide resistance to multiple nucleoside analogs.

NKX2.1 is a member of the NK2 family of homeodomain-containing transcriptional factors which binds to and activates the promoters of thyroid and pulmonary epithelial genes. We have cloned and sequenced twelve human lung NKx2.1 cDNAs. To elucidate the origin of Nkx2.1 transcripts, we also cloned and sequenced a 12 kb human Nkx2.1 genomic clone. Alignment of cDNA sequences with the genomic clone showed that contrary to previous reports, the human Nkx2.1 gene is organized into three exons and two introns. The newly discovered exon I contains an ATG codon that falls in frame with the previously identified Nkx2.1 initiator ATG codon on one of the cDNAs, designated 5E. Northern blot analysis shows that an mRNA of approximately 2.5 kb in size, homologous to 5E, is expressed in both lung and thyroid. The deduced amino acid sequence of the longest open reading frame on 5E is identical to NKX2.1 with the exception of a 30 amino acid N-terminal extension. Coupled in vitro transcription/translation of the 5E cDNA confirms that the open reading frame is translated into a contiguous polypeptide of 44 kDa. Analysis of Nkx2.1 genomic DNA fragments suggest that at least two independent regions, one within the first intron and the other 5' of the first exon may mediate the basal promoter activity of the Nkx2.1 gene in lung epithelial cells.

Background: The conventional method for diagnosis of fragile X syndrome has been amplification of the trinucleotide repeat region of the FMR-1 gene by polymerase chain reaction (PCR) and Southern blot analysis to detect full expansion and hypermethylation. "Stuttering" resulting from incomplete amplification is still observed in the PCR products despite the use of reagents that reduce the secondary structure of the GC-rich template. In addition, PCR products can be detected by autoradiography only after 1 to 2 days of exposure. By combination of a recently reported amplification protocol with fluorescence detection of PCR products in an automated DNA sequencer, the PCR protocol for amplification of trinucleotide repeats was simplified. This modified protocol is highly reproducible, more accurate, and less costly than the conventional protocol because of the elimination of radioisotopes from the PCR. Methods and Results: PCRs were conducted with betaine and Pfu DNA polymerase. This improved PCR protocol allowed immediate detection of PCR products in agarose gels containing ethidium bromide. Stuttering was completely eliminated and fragments of up to 1kb ( approximately 250 repeats) were visible in agarose gels. PCR products were automatically detected by laser fluorescence in an automated DNA sequencer by inclusion of a fluorescently-labeled primer in the PCR reaction. A short electrophoresis run of 100 minutes in denaturing acrylamide gels was sufficient to give high resolution of fragments with higher accuracy and sensitivity than conventional detection by autoradiography. Conclusions: A simple, nonradioactive protocol that is more rapid and less expensive than the conventional PCR protocol for the detection of trinucleotide repeats has been developed. By use of this detection protocol, fragment sizes containing up to 100 repeats could be detected, alleles differing by one trinucleotide repeat were clearly resolved, and heterogeneous repeat patterns such as those present in mosaics could be discriminated. This protocol has been adapted to the amplification and detection of at least two other classes of trinucleotide repeats [(CAG)(n) and (CTG)(n)], suggesting that it may be a universal protocol for PCR amplification and detection of trinucleotide repeats.

We are interested in determining whether premature birth alters expression of counterregulatory cytokines which modulate lung inflammation. Production of proinflammatory cytokines tumor necrosis factor alpha. IL-1 beta, and IL-8 is regulated in part by the antiinflammatory cytokine IL-10. For preterm newborns with hyaline membrane disease, deficiencies in the ability of lung macrophages to express antiinflammatory cytokines may predispose to chronic lung inflammation. We compared the expression of pro- and antiinflammatory cytokines at the mRNA and protein level in the lungs of preterm and term newborns with acute respiratory failure from hyaline membrane disease or meconium aspiration syndrome. Four sequential bronchoalveolar lavage (BAL) samples were obtained during the first 96 h of life from all patients. All patients rapidly developed an influx of neutrophils and macrophages. Over time, cell populations in both groups became relatively enriched with macrophages. The expression of proinflammatory cytokine mRNA and/or protein was present in all samples from both patient groups. In contrast, IL-10 mRNA was undetectable in most of the cell samples from preterm infants and present in the majority of cell samples from term infants. IL-10 concentrations were undetectable in lavage fluid from preterm infants with higher levels in a few of the BAL samples from term infants. These studies demonstrate that 1) IL-10 mRNA and protein expression by lung inflammatory cells is related to gestational age and 2) during the first 96 h of life neutrophil cell counts and IL-8 expression decrease in BAL from term infants, but remain unchanged in BAL samples from preterm infants.

The effects of exposure to solvents on serum bile acids were investigated by comparing a group of apprentice vehicle spray painters (exposed group) with one of apprentice electricians. Apprentice spray painters from the study were subdivided into high- and low-solvent-exposure groups. Concentrations of individual serum bile acids (SBA) were measured and compared with conventional liver function tests (LFTs). Total, free, glycine- and taurine-conjugated SBA were consistently found to be present at higher levels in the spray painters than in the electricians, even at the beginning of the apprenticeship. Total SBA tended to increase in spray painters with increasing years of exposure during the apprenticeship, but this was significant at only one time point. No rises were observed over the sampling period in electricians. The mean values of individual and total SBA concentrations were all found to be higher in the high-exposure group than in the low-exposure group, with some differences reaching statistical significance. None of the routine liver biochemistry parameters was different between spray painters and electricians. gamma-Glutamyl transferase (GGT) was the only enzyme found to be significantly different between the high- and low-exposure groups, but all values were within the normal range. This study suggests that occupational exposure even to low levels of solvent mixtures results in increases in SBA. The increased SBA may be indicative of a subclinical liver dysfunction. Alternatively, they may reflect solvent exposure only, with the raised levels having no pathologic implication or consequence.

TTF-1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. In vitro, TTF-1 can activate the promoter of thyroid- and pulmonary-specific genes. We postulated that TTF-1 not only is essential for the activation of tissue-specific genes, but also may directly participate in epithelial cell morphogenesis. To test this postulate, we used an antisense oligonucleotide inhibitory strategy in an in vitro model of embryonic mouse lung branching morphogenesis. This strategy suppressed TTF-1 translation and inhibited lung branching morphogenesis. The resulting abnormal phenotype was characterized by hyperplastic and unorganized proliferation of epithelial cells in the airways. The mesenchymal compartment of the lung appeared to be unaffected. These results demonstrate, for the first time, that the expression of a homeoprotein transcriptional regulator is necessary for lung epithelial morphogenesis.

Background: Chemotherapy given by continuous infusion may have different toxicity profiles and different degrees of therapeutic efficacy than when given by bolus administration. The potential therapeutic benefits of continuous infusion chemotherapy and the advantages of outpatient treatment led us to study a continuous infusion of ifosfamide with mesna and oral etoposide., Methods: The authors performed a Phase I-II trial in which 9 g/m2 ifosfamide was administered for 6 days and 10.5 g/m2 mesna was administered for 7 days, both by continuous infusion, in combination with 50 mg/m2/d oral etoposide for 8 days in 21 patients with sarcomas or other solid tumors. Courses were repeated every 28 days., Results: A total of 65 treatment cycles were given. Only six patients required hospitalization for treatment, all because of an initial poor performance status, and most carried out normal activities on an ambulatory basis. Treatment was stopped during the first course in five patients because of central nervous system toxicity, each with a poor pretreatment performance status; neurologic recovery was complete in each patient. The dose of etoposide was decreased by 20% in 11 patients and unchanged in 7 following the first treatment. Hematologic toxicity was predominantly manifested by leukopenia. An absolute neutrophil count less than 500 neutrophils/microliters occurred in 22 of 50 cycles; thrombocytopenia (platelets less than 100,000/microliters) was seen in two patients, requiring platelet transfusion in one. Neutropenic fevers occurred in 13 of 65 cycles; in 4 of these, cultures demonstrated a bacterial infection. Nausea and vomiting were mild. Objective responses occurred in 6 of 16 patients with soft tissue sarcomas (6 partial responses [PR]) (95% confidence interval, 15-65%), and 3 of 5 bone sarcomas, all of whom had been previously treated with doxorubicin and dacarbazine., Conclusions: The authors concluded that ifosfamide and mesna given by ambulatory continuous intravenous infusion with wearable pump systems in combination with oral etoposide was well tolerated and showed substantial anti-tumor activity. This combination represents a rational therapeutic approach to patients with advanced soft tissue sarcomas and may have application to other malignancies.