Monoclonal antibodies which identify carbohydrate-defined MHC class I epitopes.
Eleven different monoclonal antibodies specific for H-2K- and H-2D-encoded Class I molecules have been screened to determine Class I epitopes dependent on both carbohydrate and protein structures. Monoclonal antibodies have been identified which bind to carbohydrate-defined antigens encoded by both the H-2K and H-2D gene regions. Sensitivity to glycosidases versus pronase has been used to classify antigens both expressed as cell surface molecules and when prepared as detergent solubilized antigen. Several simple sugars have also been found to act as inhibitors of antibodies which bind to carbohydrate-defined sites. The genetic control of carbohydrate antigen expression by H-2K- and H-2D-linked genes has been verified since a specific antibody does not bind to H-2Kb or H-2Db molecules encoded by several mutant strains of mice containing single amino acid substitutions in their protein product. All of these data are consistent with Class I antigenic structures being encoded in carbohydrate as well as protein moieties.


Overexpression of the transcriptional repressor complex BCL-6/BCoR leads to nuclear aggregates distinct from classical aggresomes.
Nuclear inclusions of aggregated proteins have primarily been characterized for molecules with aberrant poly-glutamine repeats and for mutated or structurally altered proteins. They were termed "nuclear aggresomes" and misfolding was shown to promote association with molecular chaperones and proteasomes. Here, we report that two components of a transcriptional repressor complex (BCL-6 and BCoR) of wildtype amino acid sequence can independently or jointly induce the formation of nuclear aggregates when overexpressed. The observation that the majority of cells rapidly downregulate BCL-6/BCoR levels, supports the notion that expression of these proteins is under tight control. The inclusions occur when BCL-6/BCoR expression exceeds 150-fold of endogenous levels. They preferentially develop in the nucleus by a gradual increase in aggregate size to form large, spheroid structures which are not associated with heat shock proteins or marked by ubiquitin. In contrast, we find the close association of BCL-6/BCoR inclusions with PML bodies and a reduction in aggregation upon the concomitant overexpression of histone deacetylases or heat shock protein 70. In summary, our data offer a perspective on nuclear aggregates distinct from classical "nuclear aggresomes": Large complexes of spheroid structure can evolve in the nucleus without being marked by the cellular machinery for protein refolding and degradation. However, nuclear proteostasis can be restored by balancing the levels of chaperones.


Effectiveness of a health education curriculum for secondary school students--United States, 1986-1989.
The issue of MMWR introduces a new series, "Effectiveness in Disease and Injury Prevention." Future reports in this section will 1) highlight preventive measures that have proven effective and economical in public health and clinical practice and 2) describe how those measures can be integrated more effectively and economically within public health and clinical practice. In addition, reports will address needs, opportunities, and methods for assessing preventive measures. The following report summarizes the evaluation of a school health education curriculum developed to reduce selected health-risk behaviors among young persons.


Re-programming pullulan for targeting and controlled release of doxorubicin to the hepatocellular carcinoma cells.
A novel bioconjugate for hepatocellular carcinoma (HCC) targeting was obtained by pullulan re-programming, which involves the backbone oxidation and conjugation of targeting peptide and doxorubicin (Doxo) through a releasable linker. Preliminary in vivo studies showed that the oxidation of 40 glucopyranose units (GPU) out of 100 remarkably reduced the pullulan unspecific liver tropism. This oxidized polymer was functionalized with PreS1 to selectively target the HCC and with rhodamine (Rhod) as label to perform in vitro cell up-take investigations. PreS1 and Rhod were conjugated to the aldehydes present along the oxidized pullulan backbone through a 3.4 and 2kDa PEG spacer, respectively, and by reductive amination. The resulting PreS1-Pull-Rhod contained a mean of 8 PreS1 per oxidized pullulan chain. Cell culture studies were performed by using HepG2/SERPINB3 cells that overexpress the serpine B3 receptor and control HepG2/EMPTY cells that do not overexpress the receptor. A comparative study by cytofluorimetry and confocal microscopy performed using PreS1-Pull-Rhod and Pull-Rhod (control polymer) showed that PreS1 conveys to the conjugate high cell selectivity. Afterwards, the oxidized pullulan was exploited to generate a targeted drug delivery system by conjugation of Doxo to the polymer backbone through a hydrazone pH-sensitive bond and NH2-PEG3.4 kDa-PreS1. The PreS1-Pull-Doxo conjugate showed a two-fold increase of anticancer activity with respect to the control Pull-Doxo towards HepG2/SERPINB3 cells.


Natural history of visual outcome in central retinal vein occlusion.
To investigate systematically the natural history of visual outcome in central retinal vein occlusion (CRVO). Cohort study. Six hundred sixty-seven consecutive patients (30 patients had both eyes involved resulting in 697 eyes) with CRVO first seen in the authors' clinic from 1973 through 2000. At the first visit, all patients underwent a detailed ophthalmic and medical history and a comprehensive ophthalmic evaluation. Visual evaluation was carried out by recording visual acuity, using the Snellen visual acuity chart, and assessing visual fields with a Goldmann perimeter. The same ophthalmic evaluation was performed at each follow-up visit. Central retinal vein occlusion was classified into nonischemic (588 eyes) and ischemic (109 eyes) types at the initial visit based on functional and morphologic criteria. Visual acuity and visual fields. Of the eyes first seen within 3 months, visual acuity was 20/100 or better in 78% with nonischemic CRVO and in only 1% with ischemic CRVO (P < 0.0001), and visual field defects were minimal or mild in 91% and 8%, respectively (P < 0.0001). Final visual acuity, on resolution of macular edema, was 20/100 or better in 83% with nonischemic CRVO and in only 12% with ischemic CRVO (P < 0.0001), and visual field defects were minimal or mild in 95% and 18%, respectively (P < 0.0001). On resolution of macular edema, in eyes with initial visual acuity of 20/70 or worse, visual acuity improved in 59% with nonischemic CRVO, with no significant (P = 0.55) improvement in ischemic CRVO. Similarly, on resolution of macular edema, in eyes with moderate to severe initial visual field defect, improvement was seen in 86% of nonischemic CRVO eyes, but no significant (P = 0.83) improvement was seen in eyes with ischemic CRVO. In nonischemic CRVO, development of foveal pigmentary degeneration, epiretinal membrane, or both, was the main cause of poor final visual acuity. This shows that initial presentation and the final visual outcome in the 2 types of CRVO are entirely different. A clear differentiation of CRVO into nonischemic and ischemic types, based primarily on functional criteria, is crucial and fundamental in determining visual outcome. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.


Lymphoepithelial cysts of the pancreas:a management dilemma.
Pancreatic lymphoepithelial cysts (LECs) are rare, benign lesions that are typically unexpected post-operative pathological findings. We aimed to review clinical, radiological and pathological features of LECs that may allow their pre-operative diagnosis. Histopathology databases of two large pancreatic units were searched to identify LECs and notes reviewed to determine patient demographic details, mode of presentation, investigations, treatment and outcome. Five male and one female patients were identified. Their median age was 60 years. Lesions were identified on computed tomography performed for abdominal pain in two patients, and were incidentally observed in four patients. Five LECs were located in the tail and one in the body of the pancreas, with a median cyst size of 5 cm. Obtaining cyst fluid was difficult and a largely acellular aspirate was yielded. The pre-operative diagnosis was mucinous cystic neoplasm in all patients. This series of patients were treated distal pancreatectomy and splenectomy. A retrospective review of radiological examinations suggested that LECs have a relatively low signal on T2 imaging and a high signal intensity on T1 weighted images. LECs appear more common in elderly males, and are typically incidental, large, unilocular cysts. Close attention to signal intensity on MRI may allow pre-operative diagnosis of these lesions.


Ionic liquid expedites partition of curcumin into solid gel phase but discourages partition into liquid crystalline phase of 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes.
The hydrolysis of curcumin in alkaline and neutral buffer conditions is of interest because of the therapeutic applicability of curcumin. We show that hydrolysis of curcumin can be remarkably suppressed in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. The fluorescence of curcumin sensitively detects the phase transition temperature of liposomes. However, at greater concentrations, curcumin affects the phase transition temperature, encouraging fusion of two membrane phases. The interaction of curcumin with DMPC is found to be strong, with a partition coefficient value of Kp = 2.78 × 10(5) in the solid gel phase, which dramatically increases in the liquid crystalline phase to Kp = 1.15 × 10(6). The importance of ionic liquids as green solvents has drawn interest because of their toxicological effect on human health; however, the impact of ionic liquids (ILs) on liposomes is not yet understood. The present study establishes that ILs such as 1-methyl-3-octylimidazolium chloride (moic) affect the permeability and fluidity of liposomes and thus influence parition of curcumin into DMPC liposomes, helping in the solid gel phase but diminishing in the liquid crystalline phase. The Kp value of curcumin does not change appreciably with moic concentration in the solid gel state but decreases with moic concentration in the liquid crystalline phase. Curcumin, a rotor sensitive to detect phase transition temperature, is applied to investigate the influence of ionic liquids such as 1-methyl-3-octylimidazolium chloride, 1-buytl-3-methyl imadazolium tetrafluoroborate, and 1-benzyl-3-methyl imidazolium tetrafluoroborate on DMPC liposome properties. 1-Methyl-3-octylimidazolium chloride lowers the phase transition temperature, but 1-buytl-3-methyl imidazolium tetrafluoroborate and 1-benzyl-3-methyl imidazolium tetrafluoroborate do not perceptibly modify the phase transition temperature; rather, they broaden the phase transition.


Days in A/R.
Medicare rules and practices' smart billing have cut collection time dramatically, but can it drop any further? Oh, yes, say the techies.


Triplane fractures of the distal tibial epiphysis.
Triplane distal tibial fractures can occur as two-, three-, or four-part fractures with or without a fibular fracture. Diagnosis of the particular anatomy of each fracture is ascertained by plain radiographs; if the fracture is displaced 2 mm or more on any view, anteroposterior and lateral tomograms and, if possible, a limited computerized tomography (CT) scan should be done. A plaster cast in situ for non-displaced fractures or closed reduction for displaced fractures should be attempted first by internal rotation and anterior movement of the fibular metaphyseal piece. Failure to obtain and/or maintain an adequate closed reduction (less than 2 mm displacement), determined by plain radiographs, is an indication for operative treatment. Operative treatment consists of screw fixation for the metaphyseal fragment alone in two-part fractures and both metaphyseal and epiphyseal screw fixation in three-part fractures. Associated fibular fractures may also require internal fixation. The prognosis is generally good if adequate reduction has been achieved by closed or open means.


Impact of Malnutrition Status on Muscle Parameter Changes over a 5-Year Follow-Up of Community-Dwelling Older Adults from the SarcoPhAge Cohort.
This study aimed to assess the impact of malnutrition on the 5-year evolution of physical performance, muscle mass and muscle strength in participants from the SarcoPhAge cohort, consisting of community-dwelling older adults. The malnutrition status was assessed at baseline (T0) according to the "Global Leadership Initiatives on Malnutrition" (GLIM) criteria, and the muscle parameters were evaluated both at T0 and after five years of follow-up (T5). Lean mass, muscle strength and physical performance were assessed using dual X-ray absorptiometry, handgrip dynamometry, the short physical performance battery test and the timed up and go test, respectively. Differences in muscle outcomes according to nutritional status were tested using Student's t-test. The association between malnutrition and the relative 5-year change in the muscle parameters was tested using multiple linear regressions adjusted for several covariates. A total of 411 participants (mean age of 72.3 ± 6.1 years, 56% women) were included. Of them, 96 individuals (23%) were diagnosed with malnutrition at baseline. Their muscle parameters were significantly lower than those of the well-nourished patients both at baseline and after five years of follow-up (all p-values < 0.05), except for muscle strength in women at T5, which was not significantly lower in the presence of malnutrition. However, the 5-year changes in muscle parameters of malnourished individuals were not significantly different than those of well-nourished individuals (all p-values > 0.05).


Diffusion archeology for diffusion progression history reconstruction.
Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring - perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data.


A novel mutation of SETBP1 in atypical chronic myeloid leukemia transformed from acute myelomonocytic leukemia.
To investigate an oncogenic mutation of SETBP1 in the evolution from acute myelomonocytic leukemia (M4) to secondary aCML. Clinical data and molecular studies were analyzed of paired aCML and 'normal'DNA from a case with M4. We identified a mutation in SETBP1 (encoding a p.Asp868Ala alteration). The analysis of paired sample indicated that SETBP1 mutation was acquired during leukemic evolution.


Abobotulinum toxin A (Dysport) and botulinum toxin type A (Botox) for purposeful induction of eyelid ptosis.
Chemodervation with abobotulinum toxin A (Dysport) and botulinum toxin type A (Botox) is finding an expanding role in functional and cosmetic cases. We describe the use of chemodenervation with abobotulinum toxin A for functional corneal protection in two cases and botulinum toxin type A for facial symmetry after Bell's palsy in one patient. The first case is a 75-year-old female with a nonhealing corneal erosion in her right eye secondary to epithelial basement membrane corneal dystrophy who underwent injection of 24 units of abobotulinum toxin A to the right Muller's muscle and levator palpebrae superioris to induce a protective ptosis. The second case is a 40-year-old male with corneal decompensation in the right eye after penetrating keratoplasty who underwent similar injection at both sites. The third case is a 46-year-old Asian female with history of Bell's palsty affecting her right side and causing mild left eyelid retraction who was injected 3 units of botulinum toxin type A to her Muller's muscle for lid positioning. Chemodenervation is used in these cases to purposefully induce ptosis by careful injection to Muller's muscle and the levator palpebrae superioris for functional and cosmetic purposes.


In-silico identification of cardiovascular disease-related SNPs affecting predicted microRNA target sites.
MicroRNAs (miRNAs) are small RNAs that play an important role in the regulation of gene expression. miRNA dysregulation has been associated with phenotypic changes, including cardiovascular diseases (CVDs). The aim of the study was to obtain a list of single nucleotide polymorphisms (SNPs) related to CVDs, with computationally predicted effect on miRNA binding sites, which would verify the hypothesis that miRNA dysregulation can lead to the development of CVDs. SNPs, CVDs, and miRNAs were the 3 factors subjected to analysis. Based on the publicly available databases, we created a set of SNPs associated with the phenotype of interest and of SNPs located in known miRNA binding sites. We then merged the records assigned by the same SNP, which allowed us to indicate miRNA target sites, whose variants may be associated with CVDs. The results were supplemented with the additional data such as miRNA and mRNA coexpression, differences in the expression between various tissues, and Expression Quantitative Trait Locus analysis. Only in-silico methods, on the basis of publically available information tools and databases, were used. We obtained a list of 47 entries, constituting unique miRNA-SNP allele-phenotype linkages. Computational approach supports the hypothesis of the linkage between alterations in miRNA function and numerous CVDs. Given the high frequency of SNP incidence, this pathomechanism may be common in the population. Although the obtained results need to be further experimentally validated, limiting the number of interactions to the most probable ones will facilitate the identification of clinically significant associations.


Mechanism for candidacidal activity in macrophages activated by recombinant gamma interferon.
Candidacidal activity in macrophages activated by recombinant gamma interferon was examined kinetically in relation to acidification of phagolysosomes. In resident peritoneal macrophages (PMPs) of BALB/c mice, enhanced killing activity against Candida albicans was demonstrated after incubation with 100 U of gamma interferon per ml for 24 h but not after incubation for 48 to 72 h. Conversely, increased generation of H2O2 was exhibited in PMPs incubated from 48 to 72 h but not in PMPs incubated for 24 h. In normal PMPs, fusion of lysosomes to candida-containing phagosomes was readily accomplished and phagosome-lysosome fusion was not enhanced further by activation. The candidacidal substance was extracted from granule-rich fractions of either normal or activated PMPs by using citric acid (pH 2.7) in equal amounts; the substance showed a noncationic, heat-stable protein nature. In addition, when phagolysosomal pH was determined by flow cytometry of intraphagolysosomal fluorescein isothiocyanate-labeled C. albicans, phagolysosomes with low pH (less than 4.0) were detected in about 40% of PMPs activated for 24 h but not in those activated for 72 h or in normal PMPs. Moreover, increasing the intralysosomal pH with NH4Cl resulted in a significant reduction of candidacidal activity in activated PMPs. These results indicate that the candidacidal activity of gamma interferon-activated PMPs correlates well with enhanced acidification of their phagolysosomes and suggest that the candidacidal activity of activated PMPs is independent from reactive oxygen molecules and is mediated by proteinaceous substance(s) generated only in a strong acidic milieu of phagolysosomes by activation.


[Diagnostic value of selective small bowel enteroclysis in imageology of intestinal obstruction: clinical analysis of 98 cases].
To improve the diagnosticability of selective enteroclysis in the area of intestinal obstruction, by reviewing the cases of selective intestinal enteroclysis through a naso-intestinal decompression tube, and evaluating its diagnostic concordance level and the influence factors. The selective enteroclysis was different from traditional enteroclysis; it utilized a naso-intestinal decompression long tube to perform local intestinal opacification. In the four years between Apr. 2008 and Apr. 2012, 98 cases of selective intestinal enteroclysis were analyzed retrospectively, and diagnostic concordance value was made between the radiologic diagnosis and the final clinical diagnosis recorded in the medical history according to an evaluating criterion. Five scores were used in the evaluating system: 0 meant that the enteroclysis had no valuable information to provide; 0.25 meant that the enteroclysis could prompt the occurring of obstruction, but could not provide the information of location and cause; 0.50 meant that the enteroclysis could find the location of obstruction, but could not determine the cause; 0.75 meant that the enteroclysis could provide some valuable analysis of the causes of the obstruction, and very close to the final clinical diagnosis; 1.00 meant that the complete concordance between the enteroclysis diagnosis and the final clinical diagnosis. The influence factors would also be considered to improve the competence of the selective enteroclysis in the diagnosis of intestinal obstruction. In the 98 cases, 53.1% had definite abdominal operative history. The most common cause of obstruction was conglutination between intestinal loops when discharged from hospital, almost occupying 50%. In this group of cases, the most common types were ileum obstruction (47.6%), multiple location obstruction (41.7%) and incomplete obstruction (59.5%). Conglutination and stricture of the intestinal was the common radiologic appearance (61.9%). There were 50 cases with higher concordance scoring 0.75 or 1.00, in comparison, there were 25 cases with lower concordance scoring 0 or 0.25. The difference between the two groups had statistical significance. As a combination of traditional enteroclysis and naso-intestinal decompression tube, selective intestinal enteroclysis could exert higher diagnostic ability than that of traditional enteroclysis and also could break through the limitations of traditional enteroclysis in the condition of intestinal obstruction. This method has higher diagnostic concordance and could provide valuable information in obstruction location, extent, severity and possible causes. The main factor influencing the effectiveness of the examination is the location of the decompression tube and dynamic observation would be very helpful and important.


Single- and double-row repair for rotator cuff tears - biology and mechanics.
We critically review the existing studies comparing the features of single- and double-row repair, and discuss suggestions about the surgical indications for the two repair techniques. All currently available studies comparing the biomechanical, clinical and the biological features of single and double row. Biomechanically, the double-row repair has greater performances in terms of higher initial fixation strength, greater footprint coverage, improved contact area and pressure, decreased gap formation, and higher load to failure. Results of clinical studies demonstrate no significantly better outcomes for double-row compared to single-row repair. Better results are achieved by double-row repair for larger lesions (tear size 2.5-3.5 cm). Considering the lack of statistically significant differences between the two techniques and that the double row is a high cost and a high surgical skill-dependent technique, we suggest using the double-row technique only in strictly selected patients.


Hip Spine Syndrome Negatively Impacts Arthroscopic Outcomes in the Management of Femoroacetabular Impingement Syndrome: A Systematic Review.
To determine whether the presence of spine pathology affects clinical outcomes after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) in the setting of hip-spine syndrome (HSS) METHODS: A systematic review of PubMed and Cochrane was conducted. Primary research articles evaluating patient-reported outcomes (PRO) after hip arthroscopy for FAIS in the presence of concomitant spine pathology were considered RESULTS: Literature review identified 12 studies meeting criteria. In 2109 FAIS patients undergoing hip arthroscopy, 591 had concomitant spine pathology. Baseline PROs in the hip-spine (modified Harris Hip Score [mHHS]: 39.8-65.29 vs 56.9-78.8, 8 studies; non-arthritic hip score [NAHS]: 42.2-51.5 vs 68.2-75.2, 4 studies; hip outcome score-activities of daily living [HOS-ADL]: 45.9-71.1 vs 49.3-89.51, 9 studies; hip outcome score-Sport (HOS-Sport): 22.8-49.6 vs 50.6-73.1, 3 studies; international hip outcome tool-33 [iHOT-12]: 38.0 vs 66.0, 1 study; visual analog scale [VAS] Pain: 6.43-6.56 vs 1.18-3.60, 3 studies; VAS Satisfaction: 7.18-7.46 range at follow-up, 2 studies) and control (mHHS: 39.3-64.9 vs 70.2-92.6, 6 studies; NAHS: 42.8-54.2 vs 74.0-87.1, 4 studies; HOS-ADL: 59.0-76.4 vs 75.4-97.1, 4 studies; HOS-Sport: 38.1-55.1 vs 60.9-93.9, 3 studies; iHOT-12: 43.4 vs 89.8, 1 study; VAS Pain: 6.18-6.22 vs 1.82-3.44, 2 studies; VAS Satisfaction: 7.74-8.22 range at follow up, 2 studies). Minimal clinically important difference threshold rates achieved in the hip-spine (44.1-86.7, 4 studies) cohorts were significantly lower than control (79.4-88.2%; 4 studies) cohorts in 3 studies. Patient-acceptable symptomatic state threshold rates achieved in the hip-spine (42-63.5, 3 studies) cohorts were significantly lower than control (58.8-81.0, 3 studies) in 1 study. There was no statistical difference in complication and reoperation rates between cohorts CONCLUSION: FAIS patients with concomitant HSS have improved but inferior outcomes after hip arthroscopy compared to patients without HSS LEVEL OF EVIDENCE: IV, systematic review.


Association of psychological distress with psychological factors in rescue workers within two months after a major earthquake.
Studies of the health of rescue workers after a major disaster have frequently focused on posttraumatic stress disorder. This study aimed to determine the characteristics of psychological distress and its psychosocial predictors in rescue workers within a 2-month period after an earthquake that struck central Taiwan on September 21, 1999. A total of 1,104 rescue workers serving in the earthquake were enrolled in the study. Psychological distress was measured using the Brief Symptom Rating Scale (BSRS), personality traits using the Maudsley Personality Inventory (MPI), and family function using APGAR (adaptability, partnership, growth, affection, and resolve) indexes. These measurements were performed within 2 months of the earthquake. Univariate and multivariate analyses were applied to examine the association between psychological distress and various psychosocial factors. BSRS assessment revealed severe psychological distress in 137 (16.4%) subjects. The most common symptom dimension was phobic-anxiety (18.7%), followed by hostility (17.6%), obsessive-compulsive symptoms (16.2%), depression (14.9%), paranoid ideation (14.2%), interpersonal sensitivity (13.3%), psychoticism (11.9%), anxiety (10.8%), additional symptoms (8.5%), and somatization (6.2%). Pre-disaster major life events (R2 = 0.03) and most of the factor scores of the MPI (including moodiness, anxiety-prone, outgoing, conscientiousness, activity, and sociability factors; R2 = 0.25) predicted the severity of psychological distress. Time of arrival at the scene, previous exposure, age, and family function had no or trivial predictive power. The results of this study indicated that prevalence of general psychological distress is high among rescue workers in the first 2 months after a major earthquake. Personality traits and pre-disaster life adjustment had a dominant predictive power for psychological distress. Immediate psychosocial intervention should be considered to ameliorate the distress related to disaster rescue work.


Eliminating Systematic Errors in DFT via Connectivity-Based Hierarchy: Accurate Bond Dissociation Energies of Biodiesel Methyl Esters.
We present a computational study focusing on the determination of accurate bond dissociation energies (BDEs) involved in the combustion of biodiesel methyl esters. We have adapted our previously developed efficient error-cancellation protocols, based on the systematic "connectivity-based hierarchy" (CBH), to derive accurate BDEs of biodiesel molecules at a modest computational cost. Using DFT energies on the full biodiesel molecule in conjunction with accurate G4 energies on the small fragments involved in the CBH reaction schemes, systematic errors in the DFT methods can be cancelled efficiently. Herein, we apply our G4-corrected ΔCBH-2 and ΔCBH-3 schemes in conjunction with several popular DFT methods to determine accurate bond dissociation energies of different C-C, C-H, and C-O bonds in biodiesel surrogate molecules. We first evaluate the performance of different DFT methods using a test set of 21 reactions involving various bond dissociations in small to medium biodiesel surrogates (up to methyl decanoate, a C10-methyl ester) by calibration against accurate values calculated with multireference methods (MRACPF2), reported by Carter and co-workers. The CBH-2 corrections for all tested dispersion-corrected functionals yield mean absolute deviations (MADs) in a narrow range of 1.3-1.5 kcal/mol, the best performance being obtained for B97-D3 and ωB97X-D functionals (MAD = 1.3 kcal/mol). Further, significant improvement yielding a MAD of only 0.9 kcal/mol is obtained using the G4-corrected CBH-3 scheme. Finally, the protocol has been applied to derive accurate BDEs of eight different bonds in the larger biodiesel molecule, methyl linolenate, yielding a MAD of only 1.13 kcal/mol using the ΔCBH-3 error correction scheme. The results suggest that our protocol in conjunction with different DFT methods should be broadly applicable to yield accurate BDEs for a variety of large biodiesel molecules.


Conversion of protein farnesyltransferase to a geranylgeranyltransferase.
Posttranslational modifications are essential for the proper function of a number of proteins in the cell. One such modification, the covalent attachment of a single isoprenoid lipid (prenylation), is carried out by the CaaX prenyltransferases, protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type-I (GGTase-I). Substrate proteins of these two enzymes are involved in a variety of cellular functions but are largely associated with signal transduction. These modified proteins include members of the Ras superfamily, heterotrimeric G-proteins, centromeric proteins, and a number of proteins involved in nuclear integrity. Although FTase and GGTase-I are highly homologous, they are quite selective for their substrates, particularly for their isoprenoid diphosphate substrates, FPP and GGPP, respectively. Here, we present both crystallographic and kinetic analyses of mutants designed to explore this isoprenoid specificity and demonstrate that this specificity is dependent upon two enzyme residues in the beta subunits of the enzymes, W102beta and Y365beta in FTase (T49beta and F324beta, respectively, in GGTase-I).


Effect of amnioinfusion for meconium stained amniotic fluid on perinatal outcome.
To see the effect of amnioinfusion on perinatal outcome in cases of meconium staining of liquor. This study was conducted in department of Obstetrics and Gynaecology, unit 1, Jinnah Postgraduate Medical Centre, Karachi, from 1st January 1998 to 31st December 2000. Four hundred patients were included in this study, assigning 200 for amnioinfusion and 200 as control. All patients were matched in both the groups with respect to age, antenatal booking, parity, gestational age, stage of labour, colour of amniotic fluid and fetal birth weight. Both the groups were found to be comparable. The rate of Caesarean section was found to be 37% in amnioinfusion group, which collaborates with other international studies. The fetal outcome was better i.e. 91% alive and healthy, after amnioinfusion due to dilution of meconium stained amniotic fluid with physiological solutions. The perinatal outcome was recorded by Apgar score at 5 minutes. The perinatal morbidity and mortality both were significantly lowered and was found to be 6% as compared to 14% in control, which was also noticed by less number of admissions in nursery i.e. 12% and perinatal deaths. The incidence of meconium aspiration syndrome was found to be 56% in control and was reduced to 22% after amnioinfusion in the other arm of the study. These results are very encouraging and suggestion can be safely made that in future amnioinfusion will be the ideal method of preventing fetal distress due to meconium stained amniotic fluid.


Preclinical and clinical study results of the combination of paclitaxel and 5-fluorouracil/folinic acid in the treatment of metastatic breast cancer.
Results of phase II studies have demonstrated high efficacy and low toxicity for a weekly schedule of high-dose 5-fluorouracil/folinic acid (5-FU/FA) when given to intensively pretreated patients with metastatic breast cancer. In a phase I/II study of outpatients, we have added paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this regimen in an attempt to improve the results. Patients were treated weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36) with high-dose 5-FU 2.0 g/m2 by 24-hour infusion with FA 500 mg/m2 given as a 2-hour infusion prior to 5-FU. Paclitaxel 175 mg/m2 by 3-hour infusion was administered on days 1 and 22 prior to 5-FU/FA. Each cycle comprised 6 weeks followed by 2 weeks rest; the number of cycles depended on response and toxicity. To date, 40 patients have been entered into this trial during phase II. Pretreatment included adjuvant chemotherapy among 12 patients, prior chemotherapy for metastasis in nine patients, and both adjuvant therapy and treatment for metastasis in 19 patients. Of 24 anthracycline-pretreated patients, 20 had anthracycline-resistant disease. The observed toxicities were of mild to moderate intensity, especially with regard to myelosuppression. Thirty-four patients have been evaluable for response. Response rates included 3% complete response (one of 34 patients) and 50% partial response (17 of 34 patients) for an overall response rate of 53% (95% confidence interval, 37% to 69%). Additionally, 41% (14 of 34 patients) had stable disease and 6% had progressive disease (two of 34 patients). Among 20 anthracycline-resistant patients, 55% responded (11 of 20 patients). The median number of treatment cycles per patient was three (range, one to five); time to maximum response, 2 months (range, 1 to 5 months); and remission duration, 9 months (range, 2 to 17 months). Median time to progression was 10 months (range, 3 to 17 months). In conclusion, the combination of paclitaxel with weekly high-dose 5-FU/FA is well tolerated as second-line treatment of metastatic breast cancer, with high activity, even in patients with anthracycline-resistant disease. The regimen can be administered safely on an outpatient basis.


Diode-pumped continuous wave tunable and graphene Q-switched Tm:LSO lasers.
We have investigated the lasing characteristics of Tm:LSO crystal in three operation regimes: continuous wave (CW), wavelength tunable and passive Q-switching based on graphene. In CW regime, a maximum output power of 0.65 W at 2054.9 nm with a slope efficiency of 21% was achieved. With a quartz plate, a broad wavelength tunable range of 145 nm was obtained, corresponding to a FWHM of 100 nm. By using a graphene saturable absorber mirror, the passively Q-switched Tm:LSO laser produced pulses with duration of 7.8 μs at 2030.8 nm under a repetition rate of 7.6 kHz, corresponding to pulse energy of 14.0 μJ.


Multifocal diffuse glomus tumor. A case report of glomangiomyoma and review of the literature.
The case examined was a multifocal diffuse glomus tumor covering most of the right leg of a 24-year-old woman. The lesion, present at birth, had never caused any symptoms. Macroscopically, it had a simulangiomatous aspect, whereas histologically it was identified as a glomangiomyoma. The Authors have examined 26 (46.4%) of the 56 cases of multiple tumors reported to date. Multiple glomus tumors are benign lesions, which generally appear at an early age (70% by the age of 20), with no clear distinction between the two sexes. The lesions usually occur on the upper limbs, which account for 80% of the cases. Pain is reported in half of the cases. There are 3 histological types: "sensu strictu" glomus tumor, glomangioma and glomangiomyoma; the glomangioma being the most frequent (80.8%) as compared to 19.2% for the glomangiomyomatosis type. No case of "sensu strictu" glomus tumor was observed.


Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing.
Limit size systems are defined as the smallest achievable aggregates compatible with the packing of the molecular constituents in a defined and energetically stable structure. Here we report the use of rapid microfluidic mixing for the controlled synthesis of two types of limit size lipid nanoparticle (LNP) systems, having either polar or nonpolar cores. Specifically, limit size LNP consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine (POPC), cholesterol and the triglyceride triolein were synthesized by mixing a stream of ethanol containing dissolved lipid with an aqueous stream, employing a staggered herringbone micromixer. Millisecond mixing of aqueous and ethanol streams at high flow rate ratios (FRR) was used to rapidly increase the polarity of the medium, driving bottom-up synthesis of limit size LNP systems by spontaneous assembly. For POPC/triolein systems the limit size structures consisted of a hydrophobic core of triolein surrounded by a monolayer of POPC where the diameter could be rationally engineered over the range 20-80 nm by varying the POPC/triolein ratio. In the case of POPC and POPC/cholesterol (55/45; mol/mol) the limit size systems achieved were bilayer vesicles of approximately 20 and 40 nm diameter, respectively. We further show that doxorubicin, a representative weak base drug, can be efficiently loaded and retained in limit size POPC LNP, establishing potential utility as drug delivery systems. To our knowledge this is the first report of stable triglyceride emulsions in the 20-50 nm size range, and the first time vesicular systems in the 20-50 nm size range have been generated by a scalable manufacturing method. These results establish microfluidic mixing as a powerful and general approach to access novel LNP systems, with both polar or nonpolar core structures, in the sub-100 nm size range.


Vibronic couplings and coherent electron transfer in bridged systems.
A computational strategy to analyze the dynamics of coherent electron transfer processes in bridged systems, involving three or more electronic states, is presented. The approach is based on partitioning of the Hilbert space of the time independent basis functions in subspaces of increasing dimensionality, which allows us to easily check the convergence of the time dependent wave function. Vibronic couplings are determined by Duschinsky's analysis of the equilibrium position displacements, carried out using the equilibrium geometries and normal modes of the redox partners obtained at the DFT computational level.


Impact of the COVID-19 Pandemic Surge on Radiation Treatment: Report From a Multicenter New York Area Institution.
During the COVID-19 surge months of March and April 2020, our New York multicenter health system experienced an influx of cases with COVID-19. We sought to study the impact of the surge period on patients with cancer prescribed radiation treatment (RT). We reviewed our secure departmental quality assurance database for all patients who underwent RT planning simulations from March 6, 2020, through April 30, 2020. A priority level between 1 and 3 was prospectively assigned to each case based on faculty consensus to determine which patients required immediate RT. In May 2020, each faculty physician again retrospectively reviewed their patients from the database and provided additional commentary on how the COVID-19 pandemic had affected each patient's care. All statistics are descriptive. A total of 412 RT courses in 406 unique patients were simulated for linear accelerator-based external beam RT. The median age was 66 years. Treatment intent was curative in 70.6% and palliative in 29.4%. Of the 412 cases, 66.7% were priority 1, 25% priority 2, and 7.8% priority 3. Two hundred thirty-nine cases (58%) underwent standard-of-care diagnosis, workup, and treatment plan. Seventeen patients (4.1%) electively canceled their RT, and 17 others (4.1%) electively delayed RT start. Thirty-four (8.3%) were prescribed hypofractionation to shorten their RT course, and 22 (5.3%) had a change in modality. Incomplete or delayed workup was identified in 19 cases (4.6%). The COVID-19 pandemic surge resulted in 42% of our patients having a non-standard-of-care pathway. This outcome demonstrates a significant impact of the COVID-19 crisis on routine cancer care.


Transcriptomic analysis of the interaction between Helianthus annuus and its obligate parasite Plasmopara halstedii shows single nucleotide polymorphisms in CRN sequences.
Downy mildew in sunflowers (Helianthus annuus L.) is caused by the oomycete Plasmopara halstedii (Farl.) Berlese et de Toni. Despite efforts by the international community to breed mildew-resistant varieties, downy mildew remains a major threat to the sunflower crop. Very few genomic, genetic and molecular resources are currently available to study this pathogen. Using a 454 sequencing method, expressed sequence tags (EST) during the interaction between H. annuus and P. halstedii have been generated and a search was performed for sites in putative effectors to show polymorphisms between the different races of P. halstedii. A 454 pyrosequencing run of two infected sunflower samples (inbred lines XRQ and PSC8 infected with race 710 of P. halstedii, which exhibit incompatible and compatible interactions, respectively) generated 113,720 and 172,107 useable reads. From these reads, 44,948 contigs and singletons have been produced. A bioinformatic portal, HP, was specifically created for in-depth analysis of these clusters. Using in silico filtering, 405 clusters were defined as being specific to oomycetes, and 172 were defined as non-specific oomycete clusters. A subset of these two categories was checked using PCR amplification, and 86% of the tested clusters were validated. Twenty putative RXLR and CRN effectors were detected using PSI-BLAST. Using corresponding sequences from four races (100, 304, 703 and 710), 22 SNPs were detected, providing new information on pathogen polymorphisms. This study identified a large number of genes that are expressed during H. annuus/P. halstedii compatible or incompatible interactions. It also reveals, for the first time, that an infection mechanism exists in P. halstedii similar to that in other oomycetes associated with the presence of putative RXLR and CRN effectors. SNPs discovered in CRN effector sequences were used to determine the genetic distances between the four races of P. halstedii. This work therefore provides valuable tools for further discoveries regarding the H. annuus/P. halstedii pathosystem.


Quality assessments for cancer centers in the European Union.
Cancer centers are pressured to deliver high-quality services that can be measured and improved, which has led to an increase of assessments in many countries. A critical area of quality improvement is to improve patient outcome. An overview of existing assessments can help stakeholders (e.g., healthcare professionals, managers and policy makers) improve the quality of cancer research and care and lead to patient benefits. This paper presents key aspects of assessments undertaken by European cancer centers, such as: are assessments mandatory or voluntary? Do they focus on evaluating research, care or both? And are they international or national? A survey was sent to 33 cancer centers in 28 European Union member states. Participants were asked to score the specifics for each assessment that they listed. Based on the responses from 19 cancer centers from 18 member states, we found 109 assessments. The numbers have steadily increased from 1990's till 2015. Although, a majority of assessments are on patient-care aspects (n = 45), it is unclear how many of those include assessing patient benefits. Only few assessments cover basic research. There is an increasing trend towards mixed assessments (i.e., combining research and patient-care aspects) The need for assessments in cancer centers is increasing. To improve efforts in the quality of research and patient care and to prevent new assessments that "reinvent the wheel", it is advised to start comparative research into the assessments that are likely to bring patient benefits and improve patient outcome. Do assessments provide consistent and reliable information that create added value for all key stakeholders?


Percutaneous Closure of Perimembranous Ventricular Septal Defect with Modified Double-disk Occluder: What Is the Outcome at 10-year Follow-up?
Percutaneous closure of perimembranous ventricular septal defect is one of the greatest challenges in interventional cardiology. The long-term follow-up data are still limited. This report presents our experience in percutaneous closure of perimembranous ventricular septal defect with modified double-disk occluder. The study is a retrospective analysis of cases from the Changhai Hospital clinic database. We reviewed the clinic database from December 2001 to December 2005. We included 117 patients who underwent percutaneous closure of perimembranous ventricular septal defects. Procedural data and complications were assessed by an expert panel of cardiologists. Device implantation was successfully accomplished in 113 of a total 117 patients (96.6%). The mean age was 31.1 ± 12.5 years (range 2-56 years). The patients were followed for a period of 86-134 months. The diameter of defect was 2-15 mm (mean 4.9 ± 2.9 mm). The ventricular septal defect rim below the aortic valve was 1-5 mm. The mean diameter of device used was 6.9 ± 3.7 (range 4-24 mm). Four patients presented complete atrio-ventricular block within 1 week after the procedure and recovered within 3 weeks. No other patient encountered serious adverse events during the follow-up. Percutaneous closure of ventricular septal defect is safe and effective in most selected patients with modified double-disk occluder. Additional studies with larger cohorts and longer follow-up are needed to evaluate its safety.


Internal limiting membrane peeling as prophylaxis of macular pucker formation in eyes undergoing retinectomy for severe proliferative vitreoretinopathy.
The purpose of this was to analyze the effect of internal limiting membrane (ILM) peeling on the anatomical and functional outcomes in patients undergoing retinectomy for proliferative vitreoretinopathy-related retinal detachment, especially regarding the postoperative development of macular pucker. In all, a consecutive and prospective series of 84 eyes of 84 patients were included in the study. All eyes underwent retinectomy with silicone oil tamponade for retinal detachment because of proliferative vitreoretinopathy. In Group A (33 eyes), the ILM was also peeled; in Group B (51 eyes), the ILM was left intact. Each patient gave consent to be included in the study, and no patient was lost to follow-up. Postoperatively, careful slit-lamp examination with a contact lens was used to determine whether primary ILM peeling was effective in preventing macular pucker formation. Various statistical methods were used to analyze the significance of the results with a P value of ≤ 0.05 interpreted as significant. In Group A, the mean age of the patients was 57.2 ± 12.8 years and in Group B 54.6 ± 14.5 years. Median follow-up in Group A was 28.2 ± 7.2 months and in Group B 27.4 ± 6.5 months. The mean time interval between the last retinectomy and silicone oil removal was 9.2 ± 6.1 months in Group A and 8.8 ± 3.0 months in Group B. The mean follow-up after silicone oil removal was 17.4 ± 10.3 months in Group A and 15.1 ± 9.3 months in Group B. The mean logarithm of the minimum angle of resolution visual acuity at the final follow-up visit was 1.89 ± 0.87 in Group A and 1.85 ± 0.83 in Group B (P = 0.6, t-test). Extramacular epiretinal cellular proliferation occurred in 3 eyes (9%) in Group A in the first month after retinectomy and in 3 eyes (5.8%) in Group B (P = 0.27, Fisher exact test). These epiretinal membranes, extending to the edge of the retinotomy, were stable during the follow-up period. No case of macular pucker was observed in Group A, but macular pucker was observed in 9 eyes (17.6%) in Group B at the final examination (P = 0.008, Fisher exact test). Primary peeling of the ILM allowed complete removal of all the epiretinal membranes and successfully prevented the development of macular pucker. Retinectomy and silicone oil tamponade proved an effective treatment modality for eyes with retinal detachment due to proliferative vitreoretinopathy.


Low molecular weight heparins in cardiovascular medicine.
Cardiovascular diseases are the major cause of morbidity and mortality in the Western countries and their prevalence is increasing in developing world. The final biological evolution of atherosclerotic process, supporting development and progression of cardiovascular diseases, is thrombosis. In the most recent years several clinical trails have established that low molecular weight heparins play a major role in the area of prevention and treatment of arterial and venous thrombosis. It is now established, that low molecular weight heparins are efficacious and safe anticoagulant options for patients with deep vein thrombosis, pulmonary embolism, unstable angina and non-ST-segment elevation myocardial infarction. In addition, low molecular weight heparins play a major role to prevent thromboembolic events in patients with chronic diseases (e.g. due to cerebrovascular ischemic events, cancer) and in patients undergoing surgical interventions. Clinical trials have also shown that low molecular weight heparins might play a role in the treatment of patients with ST-segment elevation acute myocardial infarction, in the prevention of thrombotic events in patients with congestive heart failure, and in patients undergoing percutaneous coronary interventions. The combined use of low molecular weight heparins with fibrinolysis and other antithrombotic agents has been also studies in a number of clinical trials. This review summarises the results of the most recent clinical studies regarding the use of low molecular weight heparins in prevention and treatment of cardiovascular diseases.


[Treatment of multiple recession-type defects in a young patient with esthetic demands].
Treatment of gingival recession has become an important therapeutic issue due to the increasing number of cosmetic demands from patients. Frequently, gingival recessions affect groups of adjacent teeth. In order to optimize the esthetic result all the contiguous recessions should be treated at the same time. The purpose of this article is to compare some techniques of root coverage in a patient with Miller class 1 recessions. A mean of 80% of root exposure was covered using the free gingival graft and free connective tissue graft with repositioned flap compared to 67% using coronally positioned flap over a connective tissue graft. In conclusion, partial root coverage and gingival augmentation with a good esthetic appearance were obtained by a one-step connective tissue graft procedure.


Does colchicine work? The results of the first controlled study in acute gout.
We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients.


The influence of basal cartilage calcification on dynamic juxtaarticular stress transmission.
Dynamic finite element analysis is used to elucidate the manner in which juxtaarticular stress distributions depend on the transitional mechanical properties of the calcified cartilage layer. A finite element model is used to study how these stresses change in response to the thinning of the articular cartilage layer associated with tidemark advancement. The finite element results indicate that shear stress levels within the deepest layer of articular cartilage are increased when tidemark advancement with concomitant cartilage-thinning and calcified cartilage/subchondral plate thickening is modeled. The cartilage-thinning associated with tidemark advancement, observed both clinically and experimentally, may be an explanation for what has previously been considered wear-related thinning.


Noncompliance with drug therapy for chronic obstructive pulmonary disease: a risk factor for hospitalization?
To determine if patients who were noncompliant with prescribed medications for chronic obstructive pulmonary disease (COPD) had higher rates of hospitalization. A retrospective case-control study was performed in a tertiary-care university-affiliated Veterans Administration Health Care System setting. Subjects included 93 patients hospitalized for exacerbation of COPD and 93 controls with a diagnosis of COPD who did not require hospitalization. Utilizing pharmacy prescription fill records, medication noncompliance rates of patients who required hospitalization for exacerbation of COPD were compared with patients who did not require such hospitalization. The mean noncompliance ratio for the hospitalized patients was lower than the ratio for the controls (0.19 vs. 0.20) although the difference was not statistically significant (P = .95). There was no statistically significant difference between the demographics of the two groups. However, the patients who were hospitalized had a significantly greater number of COPD and nonCOPD medications (P < .0001, P < .0001) prescribed. They also had significantly more nonCOPD admissions and lengths of stay (P = .02, P = .01). At the levels of medication noncompliance observed in this population, there was no difference in rates of hospitalization. Hospitalization could be attributed to other causes such as severity of illness and existence of other comorbid conditions. The effects of environmental pollution and cigarette smoking were not studied. chronic obstructive pulmonary disease; hospitalization, noncompliance; risk factors.


Follicular Helper T-Cell-Based Classification of Endometrial Cancer Promotes Precise Checkpoint Immunotherapy and Provides Prognostic Stratification.
Despite the fact that management of EC is moving towards four TCGA-based molecular classifications, a pronounced variation in immune response among these molecular subtypes limits its clinical use. We aimed to investigate the determinant biomarker of ICI response in endometrial cancer (EC). We characterized transcriptome signatures associated with tumor immune microenvironment in EC. Two immune infiltration signatures were identified from the TCGA database (n = 520). The high- and low-infiltration clusters were compared for differences in patient clinical characteristics, genomic features, and immune cell transcription signatures for ICI prediction. A Lasso Cox regression model was applied to construct a prognostic gene signature. Time-dependent receiver operating characteristic curve, Kaplan-Meier curve, nomogram, and decision curve analyses were used to assess the prediction capacity. The efficacy of potential biomarker was validated by the Karolinska endometrial cancer cohort (n = 260). Immune signature profiling suggested that T follicular helper-like cells (Tfh) may be an important and favorable factor for EC; high Tfh infiltration showed potential for clinical use in the anti-PD-1 treatment. A Tfh Infiltration Risk Model (TIRM) established using eight genes was validated, and it outperformed the Immune Infiltration Risk Model. The TIRM had a stable prognostic value in combination with clinical risk factors and could be considered as a valuable tool in a clinical prediction model. We identified CRABP1 as an individual poor prognostic factor in EC. The Tfh-based classification distinguishes immune characteristics and predicts ICI efficacy. A nomogram based on Tfh-related risk score accurately predicted the prognosis of patients with EC, demonstrating superior performance to TCGA-based classification.


Bacteriological cultures of removed intrauterine devices and pelvic inflammatory disease.
Intrauterine devices (IUDs) are highly effective, long-term methods of contraception. Although evidence of a direct association between IUD use and pelvic inflammatory disease (PID) is scarce, concerns about PID related to IUDs use has limited their use throughout the world. We designed this study to examine the effect of IUDs on PID. For the study, we recruited 200 participants from among women who requested an IUD as a means of contraception. The IUDs were removed 36 months later or in case of PID. No PID cases were recorded during the follow-up period. Prior to IUD insertion, 121 women (60.5%) had symptoms and/or signs of lower genital tract infection, whereas during the follow-up period 179 women (89.5%) had symptoms and/or signs of lower genital tract infection. The Papanicolaou smears were negative for Actinomyces throughout the study period. Also, cultures for sexualy transmitted disease microorganisms were negative throughout the study period. Following IUD removal, 189 IUD cultures (94.5%) were positive. The bacterial flora of the removed IUDs consisted of common aerobic and anaerobic microorganisms that do not account for PID. The most common microorganisms identified were Staphylococcus coagulase negative, Eschericia coli, and Enterococcus faecalis. IUDs are a very effective and safe method of contraception if potential recipients are selected carefully. Culture of the removed IUDs and therapeutic management of women with positive cultures are not recommended when women are asymptomatic for PID.


Glasgow Coma Scale on admission as predictor of neurological sequelae at discharge and acute respiratory failure in patients with heatstroke.
Transient neuronal dysfunction may occur in most brain regions with heatstroke (HS). This study aimed to explore the prognostic significance of initial Glasgow Coma Scale (GCS) scores in HS. Retrospective data regarding HS were obtained from six hospitals. The primary outcome was neurological sequelae at discharge. Secondary outcomes included acute respiratory failure (ARF) and intensive care unit (ICU) admission. Logistic regression models and random forest imputation were used to assess the independent association between GCS score and outcomes. Interaction and stratified analyses of body temperature (BT) at 0.5 hours were also conducted. Receiver operating characteristic curves and decision curve analysis were used to estimate prognostic values. Of 206 patients, 44 (21.36%) had neurological sequelae at discharge. The mean ± standard deviation initial GCS score was 8.17 ± 4.05. After adjustment for confounders, GCS, as a continuous variable, was significantly related to neurological sequelae at discharge [odds ratio (OR): 0.65; 95% confidence interval (CI): 0.50-0.85; P = 0.002], ARF (OR: 0.76; 95% CI: 0.66-0.87; P = 0.001), and ICU admission (OR: 0.68; 95% CI: 0.53-0.87; P = 0.003). These relationships were consistent in the random forest imputation cohort. The OR between GCS and neurological sequelae at discharge was much lower (P = 0.048) in participants with BT at 0.5 hours ≤39°C than in those with BT at 0.5 hours >39°C. The GCS and National Early Warning Score (NEWS) had similar prognostic ability for all outcomes, whereas the net benefits were greater with the GCS compared with the NEWS. Initial GCS score was an independent prognostic factor for neurological sequelae at discharge in HS. Rapid cooling played a positive role in this relationship. Key messages What is already known on this topic Brain damage caused by heatstroke (HS) can be transient or result in irreversible injury. Early recognition of those at risk of death or developing neurological complications is very important for improving the outcomes of HS. What this study adds Initial Glasgow Coma Scale (GCS) score was an independent prognostic factor for neurological sequelae at discharge, acute respiratory failure, and intensive care unit (ICU) admission in HS. Rapid cooling played a positive role in this relationship. How this study might affect research, practice, or policy The GCS upon emergency department admission can be a useful predictor of prognosis in patients with HS.


Bone morphogenetic proteins and their antagonists: the sclerostin paradigm.
Sclerosteosis and Van Buchem disease are two closely related sclerosing disorders, characterized by progressive bone thickening due to increased bone formation. Sclerosteosis is due to premature termination mutations in the SOST gene, whereas Van Buchem disease has been associated with a 52 kb deletion downstream of the SOST gene that most likely inhibits SOST gene transcription. The gene product, sclerostin, is an osteocyte-expressed negative regulator of bone formation with amino acid sequence similarity with the DAN family of secreted glycoproteins, that share the capacity to antagonize bone morphogenetic protein (BMP) activity. The exact mechanism, however, by which sclerostin inhibits osteoblastic bone formation is still uncertain. While it binds BMPs and antagonizes their bone forming capacity, it cannot antagonize all BMP responses. Sclerostin's mechanism of action is, therefore, distinct from that described for classical BMP antagonists. The restricted expression of sclerostin and the exclusive bone phenotype of good quality of patients with sclerosteosis or Van Buchem disease provide the basis for the development of therapeutics that stimulate bone formation, such as, for example, an antibody against sclerostin.


Stiffness dependent separation of cells in a microfluidic device.
Abnormal cell mechanical stiffness can point to the development of various diseases including cancers and infections. We report a new microfluidic technique for continuous cell separation utilizing variation in cell stiffness. We use a microfluidic channel decorated by periodic diagonal ridges that compress the flowing cells in rapid succession. The compression in combination with secondary flows in the ridged microfluidic channel translates each cell perpendicular to the channel axis in proportion to its stiffness. We demonstrate the physical principle of the cell sorting mechanism and show that our microfluidic approach can be effectively used to separate a variety of cell types which are similar in size but of different stiffnesses, spanning a range from 210 Pa to 23 kPa. Atomic force microscopy is used to directly measure the stiffness of the separated cells and we found that the trajectories in the microchannel correlated to stiffness. We have demonstrated that the current processing throughput is 250 cells per second. This microfluidic separation technique opens new ways for conducting rapid and low-cost cell analysis and disease diagnostics through biophysical markers.


Full potential energy curve for N2 by the reduced multireference coupled-cluster method.
Relying on a 56-dimensional reference space and using up to the correlation-consistent, polarized, valence-quadruple-zeta (cc-pVQZ) basis sets, the reduced multireference (RMR) coupled-cluster method with singles and doubles (CCSD), as well as its perturbatively corrected version for secondary triples [RMR CCSD(T)], is employed to generate the full potential energy curves for the nitrogen molecule. The resulting potentials are then compared to the recently published accurate analytic potential based on an extensive experimental data analysis [R. J. Le Roy et al., J. Chem. Phys. 125, 164310 (2006)], and the vibrational term values of these potentials are compared over the entire well. A comparison with single-reference CCSD and CCSD(T) results, as well as with earlier obtained eight-reference RMR CC results, is also made. Excellent performance of RMR CCSD, and its systematic improvement with the increasing dimension of the reference space employed, is demonstrated. For the first 19 vibrationally excited levels, which are based on experimentally observed bands, we find an absolute average deviation of 8 cm(-1) from the computed RMR CCSD/cc-pVQZ values. The perturbative correction for triples increases this deviation to 126 cm(-1), but only to 61 cm(-1) when extrapolated to the basis set limit. Both RMR CCSD and RMR CCSD(T) potentials perform well when compared to the experiment-based analytic potential in the entire range of internuclear separations.


Finite element analysis of the possible mechanism of cervical lesion formation by occlusal force.
Recently, various authors have proposed the interesting idea that occlusal force may be a principal factor in cervical lesions of the tooth. It is speculated that the lateral force in non-ideal mastication causes the tooth to bend and that the resulting tensile stress damages the enamel surface. In this study, we carried out stress analysis on the upper central incisor and the lower first molar using the plastic-elastic deformation theory with two-dimensional finite element method (FEM). The essential feature that the tensile yield strength is much smaller than the compressive one was taken into account. Our results suggested that oblique loading on the tooth stretches the enamel surface near the cemento-enamel junction and causes plastic deformation which eventually leads to the cervical lesion.


Comparison of Different 2D and 3D-QSAR Methods on Activity Prediction of Histamine H3 Receptor Antagonists.
Histamine H3 receptor subtype has been the target of several recent drug development programs. Quantitative structure-activity relationship (QSAR) methods are used to predict the pharmaceutically relevant properties of drug candidates whenever it is applicable. The aim of this study was to compare the predictive powers of three different QSAR techniques, namely, multiple linear regression (MLR), artificial neural network (ANN), and HASL as a 3D QSAR method, in predicting the receptor binding affinities of arylbenzofuran histamine H3 receptor antagonists. Genetic algorithm coupled partial least square as well as stepwise multiple regression methods were used to select a number of calculated molecular descriptors to be used in MLR and ANN-based QSAR studies. Using the leave-group-out cross-validation technique, the performances of the MLR and ANN methods were evaluated. The calculated values for the mean absolute percentage error (MAPE), ranging from 2.9 to 3.6, and standard deviation of error of prediction (SDEP), ranging from 0.31 to 0.36, for both MLR and ANN methods were statistically comparable, indicating that both methods perform equally well in predicting the binding affinities of the studied compounds toward the H3 receptors. On the other hand, the results from 3D-QSAR studies using HASL method were not as good as those obtained by 2D methods. It can be concluded that simple traditional approaches such as MLR method can be as reliable as those of more advanced and sophisticated methods like ANN and 3D-QSAR analyses.


[Limited resection for small peripheral lung cancer using intraoperative pathologic examination].
From 1996 to 2002, we performed intentional limited resection for small peripheral lung cancer using intraoperative pathologic examination. Wedge resection was performed in patients who had small peripheral adenocarcinoma (< or = 20 mm), suspected of being Noguchi type A or B, and confirmed by intraoperative pathologic examination. Extended segmentectomy was performed in the rest of patients (tumor diameter < or = 20 mm), and not suspected of being Noguchi type A or B. Hilar and mediastinal lymph nodes sampling was performed in this group. If lymph node metastasis was detected by the intraoperative pathologic examination, the surgical procedures was converted into a lobectomy with lymph node dissection. Limited resection was performed in 27 patients, wedge resection in 8, and extended segmentectomy in 19. All patients received wedge resection are alive without sign of recurrence. In extended segmentectomy, 17 patients are alive with no evidence of disease, 1 patient died of non-pulmonary disease, and 1 patient is alive with recurrent disease. The overall survival rate at 5 years was 100% in wedge resection, 91% in extended segmentectomy, and 79% in standard lobectomy. We conclude that limited resection for small peripheral lung cancer using intraoperative pathologic examination may be safe and effective procedure.


The characteristics of infections in crush syndrome.
To analyze the results of clinical and bacteriological examinations of crush syndrome patients admitted to our institute after the Marmara earthquake. Data were collected retrospectively from patients' files. Forty patients are included. Their mean age was 31.5 +/- 13.5 years and 18 were male. Their mean time under the rubble was 13.1 +/- 14.4 h. Fasciotomies were performed on 41 extremities of 30 patients. One hundred and twelve (mean 2.9 +/- 1.9 samples/patient) bacteriological samples were collected from wounds (51), blood (23), urine (25) and catheters (13). Microbial growth was detected in 67 samples from 38 (95%) patients. Non-fermenting Gram-negative bacilli, Gram-positive cocci, Enterobacteriaciace and yeast-like fungi were isolated in 67%, 17%, 12% and 4% of the samples, respectively. Acinetobacter (36%) and Pseudomonas aeruginosa (21%), the major bacterial isolates from wound infections, were resistant to carbapenems and sensitive to quinolones. As the hospitalization period increased, other infections supervened. Gram-positive cocci and non-fermenting Gram-negative bacilli were detected in six blood and seven catheter samples and methicillin-resistant Staphylococcus aureus was the major isolate. Nine (22%) of the patients died due to sepsis despite all supportive therapies. Infections are still major factors in crush syndrome-related deaths.


Anterior cervical discectomy versus corpectomy for multilevel cervical spondylotic myelopathy: a meta-analysis.
This is a meta-analysis to compare the results between anterior cervical discectomy fusion (ACDF) and anterior cervical corpectomy fusion (ACCF) for the patients with multilevel cervical spondylotic myelopathy (MCSM). Systematic review and meta-analysis of cohort studies between ACDF with plate fixation and ACCF with plate fixation for the treatment of MCSM. An extensive search of literature was performed in PubMed, Mediline, Embase and the Cochrane library. The following outcome measures were extracted: JOA scores, fusion rate, cervical lordosis (C2-7), complications, blood loss and operation time. Data analysis was conducted with RevMan 5.0. Four cohorts (six studies) involving 258 patients were included in this study. The pooled analysis showed that there was no significant difference in the postoperative JOA score [WMD = -0.14 (-1.37, 1.10), P = 0.83], fusion rate [OR = 0.84 (0.15, 4.86), P = 0.85] between two group. However, there was significant difference in the cervical lordosis [WMD = 3.38 (2.52, 4.23), P < 0.00001], surgical complication rate and instrument related complication rate (P = 0.01, 0.005 respectively), blood loss [WMD = -52.53 (-73.53, -31.52), P < 0.00001], and operation time [WMD = -14.10 (-20.27, -7.93), P < 0.00001]. As compared with ACCF with plate fixation, ACDF with plate fixation showed no significant differences in terms of postoperative JOA score, fusion rate, but better improved cervical lordosis, lower complication and smaller surgical trauma. As the limitations of small sample and short follow-up in this study, it still could not be identified whether ACDF with plate fixation is more effective and safer than ACCF with plate fixation.


Patient Experience of Antimuscarinic Treatment for Overactive Bladder: A Qualitative Exploration of Online Forum Content.
Antimuscarinic medications are often discontinued, and there is a paucity of data regarding patient experience of medications within this class. The objective of this study is to qualitatively explore patient experience of antimuscarinic medications used for overactive bladder using reviews on Drugs.com. We examined reviews prior to February 2, 2020 (available since 2008) for oral antimuscarinic medications. User content was reviewed qualitatively via inductive content analysis. Investigators coded third-party impressions, categorizing each review as positive, mostly positive, mostly negative, or negative. The prevalence of side effects, themes, and impressions are described, with comparisons by drug using χ2, Mann-Whitney U, and Kruskal-Wallis tests, as appropriate. Correlation between ordinal and categorical variables was performed using Tau and Spearman correlation coefficients, respectively. We analyzed 469 user reviews. 68.2% reported symptom improvement. The most common side effects were dry mouth (29%) and fatigue (10.7%). Fewer neurologic side effects were reported in the solifenacin (13.9%) and trospium (none) groups (P = 0.009). Tolterodine and trospium immediate release had lower rates of ears, nose, and throat side effects (22.5% and 26.2%, respectively, P = 0.001.) Analysis of themes suggested 2 domains driving overall satisfaction: improvement and side effects. Improvement was associated with a positive satisfaction score (ρ = 0.64, P < 0.001) and gestalt impression (ρ = 0.74, P < 0.001). The factors that most negatively affected these measures were persistent symptoms followed by gastrointestinal side effects (P < 0.001). Our data suggest important differences within this class of medication both in terms of side effects and patient satisfaction. Furthermore, symptom improvement is the leading factor for patient satisfaction, whereas gastrointestinal side effects are associated with dissatisfaction.


Influences of School Latino Composition and Linguistic Acculturation on a Prevention Program for Youth.
This study examined how ethnic composition and linguistic acculturation within schools affected the efficacy of a youth substance use prevention model program. Data come from a randomized trial of the keepin' it REAL program, using a predominantly Mexican American sample of middle school students in Phoenix, Arizona. Schools were randomly assigned to a control group or to one of three culturally tailored intervention versions. We hypothesized that school ethnic and linguistic acculturation composition (percent Latino, percent non-English speaking at home) and individual level of linguistic acculturation jointly would moderate the efficacy of the prevention program, as indicated by students' alcohol, marijuana, and cigarette use. Using multilevel linear modeling and multiple imputation techniques to manage clustered data and attrition, results showed that desired program effects varied by the linguistic acculturation level of the school, the program version, and individual acculturation level. The Latino intervention version was more efficacious in schools with larger percentages of non-English speaking families, but only among less linguistically acculturated Latino students. There were no significant school level program effects connected to the percentage of Latino students at school, the other versions of the program, or among more linguistically acculturated students.


HIV infection in the United States household population aged 18-49 years: results from 1999-2006.
Data from the National Health and Nutrition Examination Surveys (NHANES). The prevalence of HIV infection among adults aged 18-49 years residing in households in the United States was 0.47% for the period 1999-2006. Men were more likely to be HIV positive than women. Race/ethnic disparities in HIV infection were also seen. Non-Hispanic blacks were more likely to be HIV positive than all other race/ethnic groups. Infection with HSV-2 was significantly associated with HIV infection among the total population aged 18-49 years and especially so among the non-His-panic black population. In 1999-2006, nearly one-quarter of HIV-positive individuals but only 1% of the HIV-negative individuals aged 18-49 years had low CD4 counts (a marker of decreased immune function). Approximately one-third of HIV-positive persons had healthy immune systems as compared with 90% among those HIV negative.


Substance use patterns among first-year college students: secondary effects of a combined alcohol intervention.
This study explored secondary effects of a multisite randomized alcohol prevention trial on tobacco, marijuana, and other illicit drug use among a sample of incoming college students who participated in high school athletics. Students (n = 1,275) completed a series of Web-administered measures at baseline during the summer before starting college and 10 months later. Students were randomized to one of four conditions: a parent-delivered intervention, a brief motivation enhancement intervention (Brief Alcohol Screening and Intervention for College Students [BASICS]), a condition combining the parent intervention and BASICS, and assessment-only control. A series of analyses of variance evaluating drug use outcomes at the 10-month follow-up assessment revealed significant reductions in marijuana use among students who received the combined intervention compared to the BASICS-only and control groups. No other significant differences between treatment conditions were found for tobacco or other illicit drug use. Our findings suggest the potential utility of targeting both alcohol and marijuana use when developing peer- and parent-based interventions for students transitioning to college. Clinical implications and future research directions are considered.


Fate of direct and inverted repeats in the RNA hypermutagenesis reaction.
RNA hypermutagenesis results from cDNA synthesis in the presence of highly biased dNTP precursor concentrations and preferentially exploits human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Such reaction conditions slow down DNA synthesis, which might be conducive to strand transfer and deletion. This has been investigated. A 6 bp inverted repeat nested between 10 bp repeats was efficiently deleted at dCTP concentrations typically used. Inter- or intramolecular strand transfer between 10 bp repeated sequences separated by runs of templated G residues occurred, but at lower concentrations. If RNA hypermutagenesis of a sequence containing direct and inverted repeats is unavoidable, avian myeloblastosis virus (AMV) reverse transcriptase could be used, as strand transfer occurs with much diminished dCTP substrate dependence.


Sickness Impact Profile (SIP) Score, a Good Alternative Instrument for Measuring Quality of Life in Patients with Ileal Urinary Diversions.
To determine the effectiveness of the use of the SIP score and the quality of life impairment in patients with ileal conduit and orthotropic ileal derivations by Hautmann and AbolEnein/Ghoneim. Prospectively evaluated 146 patients in different age groups. In 66 patients ileal conduit derivation was performed, in 20 patients orthotropic derivation using Hautman technique was recorded and in 20 of them AbolEnein/Ghoneim was used. Prior to examining patients with urinary diversions, 40 patients with minor urological symptoms not requiring any active treatment, were surveyed in order to validate SIP score. Six months after the operation, all patients with urinary diversions filled the SIP score questionnaire. Using Crombach's Alpha equation the high reliability of SIP questionnaire was proven. Average scale value was 0,93. Using descriptive statistics mean values of all categories and dimensions of the SIP questionnaire of examined patients were determined, calculated according to the questionnaire manual being converted to percentage. Total value of SIP score for the ileal conduit group was 34,76% and in orthotropic derivation 18,52% respectively. For Hautmann procedure total SIP score was 18,35% and for AbolEnein/Ghoneim 18,7%. In the control group total SIP score was 9%. The most influential dimensions on the total score of ileal conduit were physical and psycho-social, while independent dimension did not significantly influent total SIP score. Taking into consideration the lack of questionnaires on quality of life for urinary derivations, SIP score as a general disease influence to the quality of life questionnaire represents a reliable alternative for objectification and quantification of the quality of life upon urinary derivation. According to this instrument, orthotropic derivations provide significantly better quality of life compared to ileal conduit.


Anatomophysiologic basis of tetralogy of Fallot and its clinical implications.
Tetralogy of Fallot is the most frequent cyanotic congenital cardiopathy. Its physiopathology has been progressively described which has made better treatment possible. The four characteristic morphologic abnormalities are: interventricular communication, subpulmonary stenosis, biventricular origin of the aortic valve and right ventricular hypertrophy, which are the direct result of the antero-cephalad deviation of the ventricular septal outlet and hypertrophy of the septoparietal trabeculations. These anatomic abnormalities result in decreased pulmonary blood flow, leading to hypoxia and cyanosis. The main determinants of pulmonary blood flow are the source of the blood flow to the lungs, the severity and functional behaviour of the subpulmonary obstruction, the right ventricular and arterial systemic pressures and the ductus arteriosus. The mechanism of cyanotic spells is not clear. Increases in infundibular contractility, peripheral vasodilatation and right ventricular mechanoreceptor stimulation are some of the proposed mechanisms. There are two surgical strategies in newborns/children: a staged approach (with a palliative procedure followed by the complete repair) or early complete repair. There are arguments for and against each of these strategies, and the debate about the ideal treatment continues. In conclusion, the correct understanding of this cardiopathy's physiopathology is essential to improving the child's treatment. This review is particularly contemporary and relevant issue because one must always bear in mind the physiopathology of the original disease in order to correctly follow-up a new patient population: adults with surgically corrected Tetralogy of Fallot.


Effect of the use of rubber dam versus cotton rolls on marginal adaptation of composite resin fillings to acid-etched enamel.
The effect of the use of rubber dam and the use of cotton rolls on the marginal adaptation of composite resin fillings to acid-etched enamel was investigated in vivo. Each of 35 patients received one hybrid and one microfilled resin filling placed in front teeth under rubber dam and one hybrid and one microfilled resin filling placed with cotton rolls and saliva suction equipment as moisture control. Marginal adaptation was investigated, by means of SEM replica technique, 1 week and 1 year after insertion of the fillings. The similarity in marginal adaptation to the acid-etched margins of fillings made with or without rubber dam indicated that sufficient dryness in the supragingival area can be achieved under the conditions used in the present study. With both moisture control methods the hybrid resin fillings showed statistically significantly better marginal adaptation than the microfilled restorations, both after 1 week and after 1 year. The size and the volume of the marginal defects increased markedly for both filling materials at the 1-year examination compared with the 1-week registrations.


Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle.
Overactive bladder is a highly prevalent clinical condition that is often caused by bladder outlet obstruction (BOO). Increased coupling of bladder smooth muscle cells (BSMC) via gap junctions has been hypothesized as a mechanism for myogenic bladder overactivity in BOO, although little is known about the regulatory system underlying such changes. Here, we report the involvement of basic fibroblast growth factor (bFGF) and connexin 43, a bladder gap junction protein, in bladder overactivity. BOO created by urethral constriction in rats resulted in elevated bFGF and connexin 43 levels in the bladder urothelium and muscle layer, respectively, and muscle strips from these bladders were more sensitive than those from sham-operated controls to a cholinergic agonist. In vitro bFGF treatment increased connexin 43 expression in cultured rat BSMC via the ERK 1/2 pathway. This finding was supported by another in vivo model, where bFGF released from gelatin hydrogels fixed on rat bladder walls caused connexin 43 upregulation and gap junction formation in the muscle layer. Bladder muscle strips in this model showed increased sensitivity to a cholinergic agonist that was blocked by inhibition of gap junction function with alpha-glycyrrhetinic acid. Cystometric analyses of this model showed typical features of detrusor overactivity such as significantly increased micturition frequency and decreased bladder capacity. These findings suggest that bFGF from the urothelium could induce bladder hypersensitivity to acetylcholine via gap junction generation in the smooth muscle, thereby contributing to the myogenic overactivity of obstructed bladders.


Restless legs syndrome due to brainstem stroke: A systematic review.
Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases PubMed and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in patients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.


Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone.
Mononuclear phagocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophages produce a vast array of regulatory and chemotactic cytokines. Interleukin-8 (IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammatory events. In this investigation, we describe the effects of prostaglandin E2 (PGE2) and dexamethasone (Dex) on IL-8 mRNA and protein expression from lipopolysaccharide (LPS)-treated human peripheral blood monocytes (PBM) and alveolar macrophages (AM). We demonstrate the dose-dependent suppression of IL-8 from LPS-stimulated PBM by PGE2. Treatment of stimulated PBM with 10(-6) M PGE2 resulted in maximal inhibition, causing 60% suppression of both IL-8 mRNA and extracellular protein levels. In contrast, PGE2 (10(-6) to 10(-8) M) did not significantly alter IL-8 mRNA or protein expression from LPS-treated AM. Treatment of LPS-stimulated PBM and AM with Dex (10(-6) to 10(-8) M) resulted in 75% decline in IL-8 mRNA and extracellular protein from either cell population. Pretreatment of PBM with PGE2 or Dex 1 or 2 h before LPS stimulation caused a significant suppression of steady-state IL-8 mRNA levels; however, administration of either of these modulators 1 or 2 h after LPS stimulation failed to have an inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Morphological and Morphometric Analysis of Superior Articular Facet of Atlas Vertebra.
The first cervical vertebra, also referred to as the atlas, forms a vital part of the craniovertebral junction (CVJ). The anatomy of the atlas is essential to understand the basis for CVJ anomalies and their surgical correction. The present study was undertaken to provide accurate morphometry and describe the morphological variations of the superior articular facet (SAF) of the atlas. Methods: In this observational, cross-sectional study, the length and width of the SAF of 150 atlas were measured using a digital caliper. The variations in the morphology of the SAF in the same bones were also recorded. Z-test was applied to find the statistically significant difference between the measurements of the SAF of the atlas on the right and left sides. p-value ≤ 0.05 was considered statistically significant. The width of the SAF of the atlas was found to be significantly (p < 0.001) greater on the left side (8.76 mm to 14.84 mm) compared to the right (7.67 mm to 14.83 mm). The mean length of the SAF was 21.1 mm and 21.9 mm on the left and right sides, respectively. Morphologically, four variations of superior articular facets were noted: oval, bilobed, kidney, and dumbbell shaped. The most common variation was an oval-shaped facet with a prevalence of 66.7% on the left side and 57.3% on the right. The least common variation was the bilobed facet, with a prevalence of 4% on the left side and 8.7% on the right. The width of the SAF of the atlas was statistically significant on the left side. Morphologically, four types of variations were observed in the shape of the SAF. Knowledge of the morphological and morphometric variations of the SAF can be of help during surgical approaches at the CVJ.


Use of flowering gene FLOWERING LOCUS T (FT) homologs in the phylogenetic analysis of bambusoid and early diverging grasses.
A nuclear gene, FLOWERING LOCUS T (FT) homolog, was cloned from Phyllostachys meyeri as PmFT. Its putative copy number was estimated as four by Southern blot analysis, and the two copies were completely sequenced. Twenty-seven FT homolog sequences of bambusoid and early diverging grasses comprised 172-bp exons, and 357- to 785-bp introns exhibited 0-58.9% pairwise divergence with six modal levels. Parsimony analyses of the FT homologs rooted at Pharus virescens produced six equally parsimonious trees. In the strict consensus tree, five clades were resolved; they were affected by divergence of the intron region rather than exon region. The basal clade was Puelioideae, followed by Olyreae clade including Oryza sativa. Streptogyneae clade combined the Olyreae clade with terminal sister clades of the Bambuseae, i.e., pantropical bamboos and East Asiatic temperate bamboos. The global topology suggested that FT homologs are significant for resolving the tribe level. However, the phylogeny of FT homologs does not resolve monophyly in Bambusoideae because of intercalary positioning by Streptogyneae clade. We discussed the role of FT homologs in controlling the inflorescence architecture and position of Streptogyneae in the bamboo phylogeny.


Adipose tissue-derived mesenchymal stem cells for breast tissue regeneration.
With an escalating incidence of breast cancer cases all over the world and the deleterious psychological impact that mastectomy has on patients along with several limitations of the currently applied modalities, it's plausible to seek unconventional approaches to encounter such a burgeoning issue. Breast tissue engineering may allow that chance via providing more personalized solutions which are able to regenerate, mimicking natural tissues also facing the witnessed limitations. This review is dedicated to explore the utilization of adipose tissue-derived mesenchymal stem cells for breast tissue regeneration among postmastectomy cases focusing on biomaterials and cellular aspects in terms of harvesting, isolation, differentiation and new tissue formation as well as scaffolds types, properties, material-host interaction and an in vitro breast tissue modeling.


The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties.
Several rich sources of polyphenols stimulate the endothelial formation of nitric oxide (NO), a potent vasoprotecting factor, via the redox-sensitive activation of the PI3-kinase/Akt pathway leading to the phosphorylation of endothelial NO synthase (eNOS). The present study examined the molecular mechanism underlying the stimulatory effect of epicatechins on eNOS. NO-mediated relaxation was assessed using porcine coronary artery rings in the presence of indomethacin, and charybdotoxin plus apamin, inhibitors of cyclooxygenases and EDHF-mediated responses, respectively. The phosphorylation level of Akt and eNOS was assessed in cultured coronary artery endothelial cells by Western blot, and ROS formation using dihydroethidine. (-)-Epigallocatechin-3-O-gallate (EGCg) caused endothelium-dependent relaxations in coronary artery rings and the phosphorylation of Akt and eNOS in endothelial cells. These responses were inhibited by membrane-permeant analogues of superoxide dismutase and catalase, whereas native superoxide dismutase, catalase and inhibitors of major enzymatic sources of reactive oxygen species including NADPH oxidase, xanthine oxidase, cytochrome P450 and the mitochondrial respiration chain were without effect. The EGCg derivative with all hydroxyl functions methylated induced neither relaxations nor the intracellular formation of ROS, whereas both responses were observed when the hydroxyl functions on the gallate moiety were present. In conclusion, EGCg causes endothelium-dependent NO-mediated relaxations of coronary artery rings through the Akt-dependent activation of eNOS in endothelial cells. This response is initiated by the intracellular formation of superoxide anions and hydrogen peroxide, and is critically dependent on the gallate moiety and on the presence of hydroxyl functions possibly through intracellular auto-oxidation.


Rice gall dwarf virus exploits tubules to facilitate viral spread among cultured insect vector cells derived from leafhopper Recilia dorsalis.
Rice gall dwarf virus (RGDV), a member of the family Reoviridae, causes repeated epidemics in rice fields in southern China. An RGDV isolate collected from Guangdong Province (southern China) is mainly transmitted by leafhopper vector Recilia dorsalis in a persistent-propagative manner. The infection by RGDV induces the formation of virus-containing tubules in the plant host and insect vector. In this study, we established continuous cell cultures of the leafhopper R. dorsalis to investigate the functional role of these tubules within the insect vector. Cytopathologic studies revealed that the tubules, which comprised viral non-structural protein Pns11 and contained viral particles, were able to protrude from the surface of cultured leafhopper cells. Tubule-like structures formed in non-host insect cells after the expression of Pns11 in a baculovirus system, suggesting that Pns11 was the minimal viral factor required for the formation of the tubules induced by RGDV infection. In cultured leafhopper cells, knockdown of Pns11 expression from RNA interference, induced by synthesized dsRNA from the Pns11 gene, abolished the formation of such tubules, preventing the direct cell-to-cell spread of RGDV without significant effects on viral multiplication. All these results show that RGDV exploits virus-containing tubules to facilitate viral spread among its insect vector cells.