Sex- and Age-related Differences in Spinal Degeneration: An Anatomical and Magnetic Resonance Imaging Study of the Human Spine.
A precise anatomical understanding of the morphology of the spine is indispensable for neck and low back pain therapy including rehabilitation. However, few studies have directly addressed spinal morphology with a focus on the height of the vertebral body and discs. The aim of the current study was to analyze sex- and age-related changes in the spine by measuring the distance between adjacent centers of the intervertebral disc spaces from the posterior aspect in cadavers and by using magnetic resonance imaging (MRI) measurements at the cervical and lumbar vertebral levels. In the cadaveric study, the posterior distance between the adjacent centers of the disc spaces was measured for 58 spinal canals. The equivalent distances were examined using MRI in 370 and 660 subjects who presented with neck pain and back pain, respectively. The distance between the adjacent centers of the intervertebral disc spaces in male cadavers was larger than that in female cadavers from C3 to L5/S1. The MRI results showed that the distance between the adjacent centers of the intervertebral disc spaces decreased with age in all spinal areas in men and women. Cadaveric values were significantly lower than the MRI values in men, whereas in women, no significant differences were observed. These results suggest that age-related changes in the cervical and lumbar spine are associated with differences between men and women in the degrees of progressive vertebral body and disc degeneration.


Dissociating cognitive and affective empathy across psychopathy dimensions: The role of interoception and alexithymia.
This study examined the associations between psychopathy dimensions (triarchic phenotypes and classical factors), empathy domains (cognitive and affective), and interoception (interoceptive attention and accuracy) while accounting for the putative role of alexithymia. A community sample (n = 515) completed an online survey encompassing: Triarchic Psychopathy Measure (boldness, meanness, disinhibition); Levenson Self-Report Psychopathy Scale (primary and secondary psychopathy); Body Perception Questionnaire (interoceptive attention); Interoceptive Accuracy Scale; Toronto Alexithymia Scale. Hierarchical linear regression models were implemented for hypothesis-driven analyses examining the associations between psychopathy, empathy, and interoception while controlling for sex, age, and alexithymia. Exploratory path models were employed to investigate alexithymia and/or cognitive empathy as mediators between interoception and psychopathy. Our results largely confirmed the postulated empathy profiles across psychopathy dimensions, as meanness and primary psychopathy displayed a broad empathy impairment, while disinhibition and secondary psychopathy were only associated with diminished cognitive empathy. Importantly, boldness displayed a unique pattern (enhanced cognitive empathy and reduced affective empathy), further reinforcing its importance within the constellation of psychopathy traits. Contrary to our hypotheses, self-perceived interoceptive attention and accuracy were not associated with either psychopathy dimension after controlling for alexithymia. However, interoceptive accuracy and alexithymia were associated with cognitive empathy, while alexithymia was also positively related to all psychopathy dimensions (as expected), despite the unexpected strong and negative association with boldness. Exploratory analyses suggested significant indirect effects (mediation) between interoceptive accuracy and psychopathy via alexithymia and/or cognitive empathy. These mediating effects must be interpreted with caution and future studies should be designed to formally test this model.


Selective immunosuppressive action of a factor produced by colon cancer cells.
A soluble substance (HT29 factor) produced by HT29 colon cancer cells markedly suppresses mitogen-induced T-cell proliferation and interleukin-2 production. In this study the range of T-cell functions susceptible to the inhibitory effects of the HT29 factor was evaluated. Serum-free conditioned medium was collected from confluent cultures of HT29 cancer cells, concentrated, and subjected to gel filtration chromatography and anion exchange chromatography, resulting in 24.4-fold purification of the HT29 factor with 31% yield. This factor abolished the development of lymphokine-activated killer cells when present during activation of peripheral blood lymphocytes by interleukin-2 but did not affect the lysis of target cells by normal effectors when added in the lysis stage only. The HT29 factor did not affect the generation of concanavalin A-induced suppressor lymphocytes, even though it markedly inhibited synthesis of DNA, RNA, and protein as well as expression of the CD25 (Tac) antigen during mitogen activation of T-cells. The HT29 factor itself did not induce suppressor cells. These results indicate that the immunosuppressive action of the HT29 factor is selective.


Development of a 15-item odour discrimination test (Düsseldorf Odour Discrimination Test).
A key function of the olfactory system is the detection of differences in odour quality. Therefore, a test was developed to assess odour discrimination ability in normosmic humans. Out of six monomolecular substances (capric acid, coumarin, eugenol, geraniol, phenylethyl alcohol, and vanillin) quaternary mixtures were prepared. Within one item, three odour mixtures were presented (triangle forced-choice procedure). The deviant odour contained the same substances as the two remaining odours; however, the proportions were changed. Study 1 (120 participants) aimed to select items that contribute to a high internal consistency. Study 2 (104 participants) assessed test-retest reliability, parallel test reliability and test validity. Out of 45 items, a 15-item test (Düsseldorf Odour Discrimination Test, DODT) with an internal consistency of 0.61 and medium item difficulties was prepared. The test-retest reliability of the DODT was 0.66 (test interval = 4 weeks) and the parallel test reliability 0.42. The DODT correlated significantly with the University of Pennsylvania Smell Identification Test and to a lesser extent with the phenylethyl alcohol odour threshold test. As the DODT did not correlate with the odour discrimination test of the Sniffin' Sticks, the two tests seem to measure different performances of the olfactory system.


Analysis of Surface Plasmon Resonance Curves with a Novel Sigmoid-Asymmetric Fitting Algorithm.
The present study introduces a novel curve-fitting algorithm for surface plasmon resonance (SPR) curves using a self-constructed, wedge-shaped beam type angular interrogation SPR spectroscopy technique. Previous fitting approaches such as asymmetric and polynomial equations are still unsatisfactory for analyzing full SPR curves and their use is limited to determining the resonance angle. In the present study, we developed a sigmoid-asymmetric equation that provides excellent curve-fitting for the whole SPR curve over a range of incident angles, including regions of the critical angle and resonance angle. Regardless of the bulk fluid type (i.e., water and air), the present sigmoid-asymmetric fitting exhibited nearly perfect matching with a full SPR curve, whereas the asymmetric and polynomial curve fitting methods did not. Because the present curve-fitting sigmoid-asymmetric equation can determine the critical angle as well as the resonance angle, the undesired effect caused by the bulk fluid refractive index was excluded by subtracting the critical angle from the resonance angle in real time. In conclusion, the proposed sigmoid-asymmetric curve-fitting algorithm for SPR curves is widely applicable to various SPR measurements, while excluding the effect of bulk fluids on the sensing layer.


Biochemical and molecular characterization of bovine fertilin alpha and beta (ADAM 1 and ADAM 2): a candidate sperm-egg binding/fusion complex.
Fertilin alpha and beta (previously known as PH-30 alpha and beta) are sperm surface proteins implicated in sperm-egg binding and membrane fusion. In this work we report the purification, characterization, and cloning of the bovine homologues of fertilin alpha and beta. Immunofluorescence and Western blotting, using polyclonal antibodies made against guinea pig fertilin, identified likely bovine fertilin alpha and beta homologues. These candidates were purified under nondenaturing conditions using lectin and ion-exchange chromatography and were subjected to amino acid sequence analysis. Degenerate oligonucleotides made from bovine N-terminal protein sequences and from guinea pig fertilin sequences were used to isolate clones encoding bovine fertilin alpha and beta from a bovine testis cDNA library. The predicted proteins have the same domain organization as guinea pig fertilin alpha and beta: pro, metalloprotease-like, disintegrin-like, and cysteine-rich domains, followed by an EGF-like repeat, a transmembrane domain, and a cytoplasmic tail. In contrast to the reported sequence of guinea pig fertilin alpha, the mature, proteolytically processed bovine fertilin alpha subunit contains a complete disintegrin-like domain, and a potential amphipathic beta strand, which may be involved in sperm-egg fusion. Gradient sedimentation experiments suggest that the fertilin alpha/beta heterodimer may be present on the sperm surface as a higher-order oligomer.


[Meningeal carcinomatosis. Review of 30 cases].
The clinical features of 30 patients with carcinomatous meningitis caused by solid tumors are reported. The most common originating sites of tumors were lung (12 cases) and breast (9 cases). Headache was the most common presenting symptom and there was involvement in more than one level of neuro-axis in 53% of cases. The CSF from the first lumbar puncture was abnormal in all cases; pleocytosis and an increased protein level in CSF were of great diagnostic value when a positive cytology was absent. Only three patients were treated with intrathecal chemotherapy, with a median survival of six weeks since the onset of symptoms.


Circular RNA PLCE1 promotes epithelial mesenchymal transformation, glycolysis in colorectal cancer and M2 polarization of tumor-associated macrophages.
Plentiful studies have clarified that circular RNAs (circRNAs) are crucial in colorectal cancer (CRC)'s occurrence and development, but its function has not been fully elucidated. The purpose of this study was to investigate the biological functions of circPLCE1 on epithelial mesenchymal transformation (EMT) and glycolysis in CRC, and tumor-associated macrophage (TAM) polarization. The results affirmed augment of circPLCE1 and γ-Actin Gene (ACTG1) but decline of miR-485-5p in CRC. Knockdown circPCLE1 refrained CRC proliferation, glucose consumption, lactic acid and pyruvate production, M2 macrophage markers (IL-10, MRC1), N-cadherin, Snail, reduced the proportion of CD206+ and CD168+ macrophages, but expedited M1 macrophage markers (TNF-α, IL-6) and E-cadherin, while descending miR-485-5p expedited EMT, glycolysis in CRC and TAM M2 polarization . Additionally, it was affirmed that the repression or motivation of depressive or elevated circPCLE1 on EMT, glycolysis in CRC and TAM M2 polarization were reversed via facilitated ACTG1 and miR-485-5p, separately. Mechanism studies have clarified that circPCLE1 as a competitive endogenous RNA adsorbed miR-485-5p to mediate ACTG1. It was assured that refrained circPCLE1 constrained CRC tumor growth, EMT and TAM M2 polarization. In brief, circPCLE1 expedites EMT, glycolysis in CRC and TAM M2 polarization via modulating the miR-485-5p/ACTG1 axis, and is supposed to be a latent molecular target for CRC therapy later.


PfADA2, a Plasmodium falciparum homologue of the transcriptional coactivator ADA2 and its in vivo association with the histone acetyltransferase PfGCN5.
The transcriptional coactivator ADA2 is an evolutionarily conserved component of histone acetyltransferase (HAT) complexes involved in chromatin remodeling and transcriptional regulation in eukaryotes. The Plasmodium falciparum homologue, PfADA2, has a 7737 bp open reading frame, encoding a protein of 2578 amino acids with an ADA2-like domain located near the C-terminus. The annotated PfADA2 in the parasite genome is Pf10_143, located on chromosome 10. Sequence analysis demonstrated the presence of an ADA2 homologue in each Plasmodium species selected for genome sequencing. Mapping of the 5' transcriptional initiation sites suggested that PfADA2 transcription was initiated from multiple sites. Northern analysis detected a major transcript of approximately 8.5 kb in erythrocytic stage parasites. An antiserum raised against the internal ADA2-like domain detected multiple proteins from mixed blood stages, suggesting that PfADA2 may be proteolytically processed. In comparison, affinity-purified anti-GCN5 antibodies reacted with a major protein of approximately 200 kDa and immunoprecipitated proteins from the parasite lysate with HAT activity similar to that of the recombinant GCN5. Moreover, this GCN5-like HAT activity could also be precipitated with anti-PfADA2 antibodies, indicating that PfADA2 is associated with PfGCN5 in vivo. To illustrate whether PfADA2 could functionally replace the yADA2, complementation experiments were performed. However, the ADA2-like domain of PfADA2 failed to rescue the yeast ada2(-) mutant, probably due to significant divergence between the two genes. Taken together, these results indicate the presence of PfADA2-PfGCN5 complex(es) in the malaria parasite, which may have conserved functions in chromatin remodeling and gene regulation.


Phenolic Acid-based Poly(anhydride-esters) as Antioxidant Biomaterials.
Poly(anhydride-esters) comprised of naturally occurring, non-toxic phenolic acids, namely syringic and vanillic acid, with antioxidant properties were prepared via solution polymerization methods. Polymer and polymer precursor physiochemical properties were characterized, including polymer molecular weight and thermal properties. In vitro release studies illustrated that polymer hydrolytic degradation was influenced by relative hydrophobicity and degree of methoxy substitution of the phenolic acids. Further, the released phenolic acids were found to maintain antioxidant potency relative to free phenolic acid controls as determined by a 2,2-diphenyl-1-picrylhydrazyl assay. Polymer cytotoxicity was assessed with L929 fibroblasts in polymer-containing media; appropriate cell morphology and high fibroblast proliferation were obtained for the polymers at the lower concentrations. These polymers deliver non-cytotoxic levels of naturally occurring antioxidants, which could be efficacious in topical delivery of antioxidant therapies.


Functional significance of prorenin internalization in the rat heart.
Intracardiac renin is considered to be involved in the pathogenesis of cardiac hypertrophy, fibrosis, and myocardial infarction. Cardiac renin is predominantly derived from the circulation, because preprorenin is not expressed locally and uptake of renin has been demonstrated. One mechanism of internalization recently described involves the mannose-6-phosphate receptor and requires glycosylation of renin. Based on previous observations, we considered the existence of another pathway of uptake, not requiring glycosylation and predominantly involving prorenin. This hypothesis and its functional consequences were investigated in vitro and in vivo. We demonstrate that isolated adult cardiomyocytes internalize unglycosylated prorenin, which is followed by the generation of angiotensins. We further show that transgenic rats, expressing the ren-2(d) renin gene in an inducible manner, exhibit markedly enhanced levels of unglycosylated renin within intracellular compartments in the heart as a consequence of the induction of hepatic transgene expression and the rise of circulating unglycosylated prorenin levels. Because in this model severe cardiac damage occurs as a consequence of the rise of circulating prorenin levels, internalization of prorenin into cardiac cells is likely to play a key role in this process.


[Results of artificial immunization of Rh-negative persons for the production of anti-D(RhO)-antibodies].
By means of a recording sheet the data about 62 artificially immunised male persons are evaluated retrospectively. 51 of them (82.3%) were anti-D-antibodies, with 41 of them having a high titer sufficient for gaining plasma. 2/3 of all test persons formed an accompanying antibody anti-C. In order to avoid this, persons of Rh-formula Cde may be included into artificial immunisation. An anti-E as an accompanying antibody was found in 2/3 of those test persons who had received injections of cDE blood. The blood of this Rh-formula will yield better immunising results than cDe blood. It was only in three immunised persons (4.8%) that side effects with a light or medium course of seriousness could be observed. It is necessary to develop immunobiological investigation methods to recognize those persons prior to the arteficial immunisation, who are suitable or unsuitable for anti-D-antibody formation.


Sialolithiasis of minor salivary glands: a clinical and histopathological study.
Sialolithiasis is one of the most common disorders of particular major salivary glands. It is caused by sialolith within the ducts or parenchyma of particularly major salivary glands. Although sialolithasis is not uncommon, it often is clinically misdiagnosed when minor salivary glands are affected. This article describes the clinical and microscopic findings of nine cases of sialolithiasis of minor salivary glands. The lesions frequently appeared as single and asymptomatic nodules in middle-aged patients. Only three sites were affected: four lesions were found in the upper lip, three in the buccal mucosa, and two in the lower lip. The most common clinical hypotheses for diagnosis were mucocele, sialoadenitis, and benign salivary gland tumor. Sialolithiasis of minor salivary glands was misdiagnosed frequently. It should be considered as a possible diagnosis when swelling of the oral tissues is observed.


Population-based study of severe trauma due to electrocution in the Calgary Health Region, 1996-2002.
Severe trauma arising from electrocution is uncommon, and we wished to study the incidence, risk factors and outcome to identify potential areas of prevention. We therefore studied an active population of adult victims of severe electrical trauma in a large area of Canada (the Calgary Health Region [CHR]). From 3 databases, we collected data on all adult (> or = 18 yr) residents of the CHR who suffered electrical injury associated with an Injury Severity Score of 12 or greater or died as a result of electrocution between Apr. 1, 1996, and Mar. 1, 2002. Of particular interest were the incidence, the age and sex of the victims, the mechanism, the type of electrical power and the outcome. Ten cases of severe electrical trauma were identified (2.4 per 1 million population annually). Victims' ages were a mean (and standard deviation) of 38.2 (10.3) years. All 10 victims were male for an annual sex-specific incidence of 4.9 per 1 million people. Men aged 18-49 years were nearly 3 times more likely to be victims of electrocution than older men, although this result was not statistically significant (6.1 v. 2.1 per 1 million annually; relative risk 2.9; 95% confidence interval 0.4-127.5). All episodes of electrocution were unintentional, and 7 were occupationally related. All 10 electrocutions resulted from domestically generated current, and 9 were related to power-line exposure. Overall, 6 patients died for a death rate due to severe electrical trauma of 1.4 per 1 million people annually. This population-based study demonstrates that severe electrocution is rare but is associated with death in the majority of cases in this large Canadian region.


The effects of Ghana's capitation policy on hospital Under-5 mortality in the Ashanti Region.
The study estimated the capitation policy's effect on the under-5 mortality (U5MR) rate in hospitals in Ashanti Region. We used an interrupted time series design to estimate the impact from secondary data obtained from the DHIMS-2 database. Monthly under-5 deaths and the number of live births per month were extracted and entered into Stata 15.0 for analyses. The U5MR was calculated by dividing the number of live deaths by the number of live births for each of the 60 months of the study. Health facilities of the Ashanti Region with Data in the DHIMS 2. the level and trend of U5MR for 31 months during the Capitation Policy implementation (January 2015 to July 2017) were compared with the level and trend 29 months after the withdrawal of the capitation policy (August 2017 to December 2019). changes in trend or level of U5MR after the withdrawal of capitation. During the capitation policy, monthly U5MR averaged 10.71 +/-2.71 per 1000 live births. It declined to 0.03 deaths per 1000 live births (p=0.65). After the policy withdrawal, the immediate (increase of 0.01 per 1000live births) and the trend (decline of 0.13 deaths per 1000 live births per month) were still not statistically significant. We conclude that the capitation policy did not appear to have influenced under-5 mortality in the Ashanti Region. The design of future healthcare payment models should target quality improvement to reduce under-5 mortalities. None declared.


Passing the clinical baton: 6 principles to guide the hospitalist.
Hospitalist systems make it increasingly common for responsibility for a patient to be passed from one physician to another. During such transfers, patients' outcomes and satisfaction can benefit from better communication between hospitalists and the primary care physicians whose patients they care for. We propose 6 principles to guide such communication, to ensure that critical information about patients is not lost and to optimize the quality of care. We also discuss special considerations for patients discharged to a skilled nursing facility or to home with home care.


H2 Binding, Splitting, and Net Hydrogen Atom Transfer at a Paramagnetic Iron Complex.
While diamagnetic transition metal complexes that bind and split H2 have been extensively studied, paramagnetic complexes that exhibit this behavior remain rare. The square planar S = 1/2 FeI(P4N2)+ cation (FeI+) reversibly binds H2/D2 in solution, exhibiting an inverse equilibrium isotope effect of KH2/ KD2 = 0.58(4) at -5.0 °C. In the presence of excess H2, the dihydrogen complex FeI(H2)+ cleaves H2 at 25 °C in a net hydrogen atom transfer reaction, producing the dihydrogen-hydride trans-FeII(H)(H2)+. The proposed mechanism of H2 splitting involves both intra- and intermolecular steps, resulting in a mixed first- and second-order rate law with respect to initial [FeI+]. The key intermediate is a paramagnetic dihydride complex, trans-FeIII(H)2+, whose weak FeIII-H bond dissociation free energy (calculated BDFE = 44 kcal/mol) leads to bimetallic H-H homolysis, generating trans-FeII(H)(H2)+. Reaction kinetics, thermodynamics, electrochemistry, EPR spectroscopy, and DFT calculations support the proposed mechanism.


Acute myeloid leukemia treatment in patients over 60 years of age. Comparison of symptomatic, palliative, and aggressive therapy.
State-of-art of aggressive treatment of acute myeloid leukemia (AML) in patients older than 60 years is one of the least satisfactory topics of present-day hematology. This fact led us to ask the following questions: Does it make sense to administer aggressive treatment to older patients with AML? Could it be that we only complicate the rest of the life of these older patients with AML, by using aggressive treatment? Would they not benefit more from palliative or symptomatic therapy? What is the quality of life of older patients with AML like? Therefore, to try to answer these questions, we performed the next analysis. A retrospective analysis was performed including (without any selection) all consecutive patients over 60 years of age who were treated with AML in our centre from 1998 till 2003. We have analyzed data from 137 elderly patients who were diagnosed with AML (excluding acute promyelocytic leukemia). Median survival from diagnosis in the aggressive (curative) therapy group was 4 months, in palliative therapy group 2 months and in symptomatic therapy group 0.8 months. Patients receiving curative therapy spent in a hospital (in-patient stay) 70% (median) of their life after diagnosis of AML, patients receiving palliative treatment 64% (median) of their life after diagnosis, and patients receiving symptomatic treatment 100% (median), respectively. Only marginal advantage in the median overall survival is observed in the group of aggressively treated patients.


Fibroblasts in Head and Neck Squamous Cell Carcinoma Associated With Perineural Invasion Have High-Level Nuclear Yes-Associated Protein (YAP) Expression.
We retrospectively studied the expression of Yes-associated protein (YAP) using immunohistochemical staining in 10 cases of head and neck squamous cell carcinoma with associated perineural invasion. We find that fibroblasts in areas associated with perineural invasion show higher levels of nuclear YAP compared to fibroblasts in the stroma of normal mucosa, with a median cell count of 35.4 per high-power field in the former and 3.9 in the latter. No differences were observed between the expression of YAP phosphorylated at Ser127 in the tumoral stroma compared to that in the normal mucosa, with a median cell count expression of 4.9 in the former versus 5.0 in the latter. Therefore, a strong and increased nuclear YAP expression in fibroblasts associated with perineural invasion in head and neck squamous cell carcinoma suggests that YAP-mediated transcription programs in these fibroblasts may contribute to perineural invasion.


Trends in suicide risk associated with hospitalized psychiatric illness: a case-control study based on Danish longitudinal registers.
In light of the consistent reduction in suicide rate during the past 20 years in Denmark, this study aims to investigate trends in suicide risk associated with hospitalized psychiatric illness and to explore differences in the changes with regard to clinical phases of illness, sex, age, and diagnosis. This population-based study includes all of 21,169 suicides in Denmark during the years 1981 through 1997 and 423,128 controls matched for sex, age, and time (using a nested case-control design). Personal data on psychiatric history and socioeconomic status were retrieved from Danish longitudinal registers. Data were analyzed using conditional logistic regression. This study shows that the reduction in suicide rate is generally faster among individuals with a history of psychiatric admission than among individuals without such a history. However, this substantial reduction is mainly accounted for by the reduction among patients who had been discharged from psychiatric hospitals for more than 1 year. For patients who had been discharged from hospitals within 1 year, the reduction is similar to that of the general population; while for patients hospitalized for treatment at the time of suicide or the index date, the reduction in suicide rate is relatively slower. Such trends hold for all diagnostic groups. Further analyses stratified by age indicate that the faster reduction in suicide rate associated with history of hospitalized psychiatric illness is more pronounced among patients aged 36 years and older. The reduction in suicide rate is substantial for patients who have been discharged from psychiatric hospitals for more than 1 year and for middle-aged and older patients. Recent improvement in psychiatric care and treatment and promotion of new generation antidepressants may contribute to these changes.


Homology modeling, virtual screening, molecular docking, and dynamics studies for discovering Staphylococcus epidermidis FtsZ inhibitors.
Staphylococcus epidermidis is the most common cause of medical device-associated infections and is an opportunistic biofilm former. Among hospitalized patients, S. epidermidis infections are the most prevalent, and resistant to most antibiotics. In order to overcome this resistance, it is imperative to treat the infection at a cellular level. The present study aims to identify inhibitors of the prokaryotic cell division protein FtsZ a widely conserved component of bacterial cytokinesis. Two substrate binding sites are present on the FtsZ protein; the nucleotide-binding domain and the inter-domain binding sites. Molecular modeling was used to identify potential inhibitors against the binding sites of the FtsZ protein. One hundred thirty-eight chemical entities were virtually screened for the binding sites and revealed ten molecules, each with good binding affinities (docking score range -9.549 to -4.290 kcal/mol) compared to the reference control drug, i.e., Dacomitinib (-4.450 kcal/mol) and PC190723 (-4.694 kcal/mol) at nucleotide and inter-domain binding sites respectively. These top 10 hits were further analyzed for their ADMET properties and molecular dynamics simulations. The Chloro-derivative of GTP, naphthalene-1,3-diyl bis(3,4,5-trihydroxybenzoate), Guanosine triphosphate (GTP), morpholine and methylpiperazine derivative of GTP were identified as the lead molecules for nucleotide binding site whereas for inter-domain binding site, 1-(((amino(iminio)methyl)amino)methyl)-3-(3-(tert-butyl)phenyl)-6,7-dimethoxyisoquinolin-2-ium, and Chlorogenic acidwere identified as lead molecules. Molecular dynamics simulation and post MM/GBSA analysis of the complexes revealed good protein-ligand stability predicting them as potential inhibitors of FtsZ (Figure 1). Thus, identified FtsZ inhibitors are a promising lead compounds for S. epidermidis related infections.


Full-length nisin immunity protein NisI from Lactococcus lactis in a lipid-free form: crystallization and X-ray analysis.
NisI is a lantibiotic-binding lipoprotein that is specific for nisin. Nisin-producing microorganisms use NisI as an immunity protein for self-protection against nisin. Here, the purification, crystallization and preliminary X-ray diffraction of full-length NisI from Lactobacillus lactis in a lipid-free form (NisI22-C) are reported. Importantly, reductive methylation of the lysine residues in NisI22-C was essential for initial crystallization. Only methylated NisI22-C crystallized. The optimized crystals of methylated NisI22-C were grown in 30-40 mM ammonium sulfate, 0.1 M sodium acetate pH 4.6, 16-18% PEG 4000 at 295 K and diffracted to 1.9 Å resolution. The crystal belonged to space group P212121, with unit-cell parameters a = 45.99, b = 76.67, c = 76.39 Å, α = β = γ = 90.0°. Assuming the presence of one molecule in the asymmetric unit, the estimated Matthews coefficient (VM) is 2.58 Å3 Da-1 and the estimated solvent content is 52.3%.


The Complete Mechanism of an Aldol Condensation.
Although aldol condensation is one of the most important organic reactions, capable of forming new C-C bonds, its mechanism has never been fully established. We now conclude that the rate-limiting step in the base-catalyzed aldol condensation of benzaldehydes with acetophenones, to produce chalcones, is the final loss of hydroxide and formation of the C═C bond. This conclusion is based on a study of the partitioning ratios of the intermediate ketols and on the solvent kinetic isotope effects, whereby the condensations are faster in D2O than in H2O, regardless of substitution.


Maternal blood mitochondrial DNA copy number and placental abruption risk: results from a preliminary study.
Oxidative stress and impaired placental function - pathways implicated in the pathogenesis of placental abruption - have their origins extending to mitochondrial dysfunction. To the best of our knowledge, there are no published reports of associations of placental abruption with circulating mitochondrial DNA (mtDNA) copy number - a novel biomarker of systemic mitochondrial dysfunction. This pilot case-control study was comprised of 233 placental abruption cases and 238 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in maternal whole blood samples collected at delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). There was some evidence of an increased odds of placental abruption with the highest quartile of mtDNA copy number (P for trend = 0.09) after controlling for confounders. The odds of placental abruption was elevated among women with higher mtDNA copy number (≥336.9) as compared with those with lower values (<336.9) (adjusted OR = 1.60; 95% CI 1.04-2.46). Women diagnosed with preeclampsia and with elevated mtDNA copy number had a dramatically increased odds of placental abruption as compared with normotensive women without elevated mtDNA copy number (adjusted OR = 6.66; 95% CI 2.58-17.16). Maternal mitochondrial dysfunction appears to be associated with placental abruption in the presence of preeclampsia. Replication in other studies, particularly prospective cohort studies and those that allow for tissue specific assessment of mitochondrial dysfunction (e.g., the placenta) are needed to further understand cellular and genomic biomarkers of normal and abnormal placental function.


Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review.
Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. Systematic review. RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.


What is a preclinical pregnancy loss?
To evaluate the contribution of embryo quality to preclinical loss rates after in vitro fertilization (IVF)/embryo transfer (ET) pregnancy, multiple gestation, and clinical loss rates were compared to preclinical pregnancy loss rates over a 3-year period. The pregnancy outcomes after 1675 fresh ETs from 1994 to 1997 were studied. While establishment of a clinical pregnancy confirms uterine receptivity, multiple gestation rates reflect embryo quality. Because the majority of clinical losses are chromosomally abnormal, clinical loss rates serve as another indicator of embryo quality. The overall preclinical pregnancy loss rate was 5% (78/1675) of ETs and 17% (78/472) of pregnancies. During the 3-year period the pregnancy rates per ET increased from 19 to 36% (P < 0.0001), multiple gestation rates increased from 21 to 48% (P < 0.008), clinical loss rates decreased from 20 to 6% (P < 0.0001), and preclinical pregnancy loss rates remained unchanged from 13 to 19% (P = 0.1). Preclinical pregnancy loss more likely reflects abnormalities in uterine receptivity rather than embryo quality. If recurrent preclinical pregnancy loss occurs after IVF/ET, evaluation for abnormalities of uterine receptivity should be performed.


Resveratrol-loaded chitosan-pectin core-shell nanoparticles as novel drug delivery vehicle for sustained release and improved antioxidant activities.
Resveratrol, chemically known as 3,5,4'-trihydroxy-trans-stilbene, is a natural polyphenol with promising multi-targeted health benefits. The optimal therapeutic uses of resveratrol are limited due to its poor solubility, rapid metabolism and low bioavailability. To address the issues, we have encapsulated resveratrol inside the nanosized core made of chitosan and coated this core with pectin-shell in order to fabricate a drug delivery vehicle which can entrap resveratrol for a longer period of time. The core-shell nanoparticles fabricated in this way were characterized with the help of Fourier transform infrared spectrometer, field-emission scanning electron microscope, field-emission transmission electron microscopy/selected area electron diffraction, high-resolution transmission electron microscope, dynamic light scattering and zeta potential measurements. In vitro drug release study showed the ability of the core-shell nanoparticles to provide sustained release of resveratrol for almost 30 h. The release efficiency of the drug was found to be pH dependent, and a sequential control over drug release can be obtained by varying the shell thickness. The resveratrol encapsulated in a nanocarrier was found to have a better in vitro antioxidant activity than free resveratrol as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. This work finally offers a novel nano-based drug delivery system.


Effect of Oral Administration of Weissella confusa on Fecal and Plasma Ethanol Concentrations, Lipids and Glucose Metabolism in Wistar Rats Fed High Fructose and Fat Diet.
In previous investigations, Weissella confusa was shown to lack the metabolic pathway from fructose to mannitol and to produce ethanol when cultivated in the presence of fructose. Hence, we assessed the effect of oral administration of W. confusa (strain NRRL-B-14171) on blood and fecal ethanol concentrations, glucose and lipid metabolism and traits of the metabolic syndrome in Wistar rats (n=27) fed diets with two different fat and fructose levels and with or without the addition of W. confusa during a total intervention time of 15 weeks (105 days). From week 1 to 6, rats were given a medium fructose and fat (MFru-MF) diet containing 28% fructose and 10% fat without the addition of W. confusa (control group, n=13) or mixed with 30 g per kg diet of lyophilized W. confusa (10.56 ± 0.20 log CFU/g; W. confusa group, n=14). From week 7 to 15, the percentage of dietary fructose and fat in the control and W. confusa group was increased to 56% and 16%, respectively (high fructose-high fat (HFru-HF) diet). In HFru-HF-fed rats, W. confusa was detected in feces, regardless of whether W. confusa was added to the diet or not, but not in rats receiving the MFru-MF diet without added W. confusa or in an additional control group (n=10) fed standard rat food without fructose, increased fat content and W. confusa. This indicates that fecal W. confusa may be derived from orally administered W. confusa as well as - in the case of high fructose and fat intake and obesity of rats - from the intestinal microbiota. As shown by multifactorial ANOVA, blood ethanol, the relative liver weight, serum triglycerides, and serum cholesterol as well as fecal ethanol, ADH, acetate, propionate and butyrate, but not lactate, were significantly higher in the W. confusa - compared to the control group. This is the first in vivo trial demonstrating that heterofermentative lactic acid bacteria lacking the mannitol pathway (like W. confusa) can increase fecal and blood ethanol concentrations in mammals on a high fructose-high fat diet. This may explain why W. confusa resulted in hyperlipidemia and may promote development of NAFLD in the host.


Mechanical capacity of esophagogastric anastomosis at early postoperative stage.
The tensile strength of esophagogastric anastomosis was measured in 20 dogs. In case of 32 other animals the preparations were histologically examined, too. Mechanical tolerance was found significant from the 7th postoperative day on, reaching its maximum on the 15th day with no later change. An explanation is sought in the prevalence of the elastic elements growing in direct proportion to the time elapsing after operation. This role of the elastic fibres has not yet been reported in the available literature.


Villous adenomas and carcinoma of the duodenum in Gardner's syndrome.
Patients with Gardner's syndrome are increasingly found to have polyps on routine upper gastrointestinal endoscopy, and their risk of developing periampullary carcinoma is between 3-12%. We report a 45 year old man with Gardner's syndrome who presented with periampullary carcinoma 5 years after colectomy. Review of the literature amassed another 21 cases of periampullary carcinoma in patients with Gardner's syndrome.


Radiofrequency Ablation in Primary Aldosteronism.
The radiofrequency ablation (RFA) technique has been extensively used in the treatment of primary malignancies and metastases and has been recently deployed for the treatment of unilateral primary aldosteronism (PA) as an alternative to whole unilateral adrenalectomy.Current evidence comparing RFA with unilateral adrenalectomy in the treatment of PA so far has been variable, with studies being retrospective and small-scale, but it remains a very attractive option as a potentially less invasive treatment option compared to adrenalectomy.This review article describes the procedure, and provides evidence and the possible future direction of RFA in the treatment of unilateral PA.


Hypoxia and acidosis impair cGMP synthesis in microvascular coronary endothelial cells.
To characterize the effects of ischemia on cGMP synthesis in microvascular endothelium, cultured endothelial cells from adult rat hearts were exposed to hypoxia or normoxia at pH 6.4 or 7.4. Cellular cGMP and soluble (sGC) and membrane guanylyl cyclase (mGC) activities were measured after stimulation of sGC (S-nitroso-N-acetyl-penicillamine) or mGC (urodilatin) or after no stimulation. Cell death (lactate dehydrogenase release) was negligible in all experiments. Hypoxia at pH 6.4 induced a rapid approximately 90% decrease in cellular cGMP after sGC and mGC stimulation. This effect was reproduced by acidosis. Hypoxia at pH 7.4 elicited a less pronounced (approximately 50%) and slower reduction in cGMP synthesis. Reoxygenation after 2 h of hypoxia at either pH 6.4 or 7.4 normalized the response to mGC stimulation but further deteriorated the sGC response; normalization of pH rapidly reversed the effects of acidosis. At pH 7.4, the response to GC stimulation correlated well with cellular ATP. We conclude that simulated ischemia severely depresses cGMP synthesis in microvascular coronary endothelial cells through ATP depletion and acidosis without intrinsic protein alteration.


Speech-in-Speech Recognition and Spatially Selective Attention in Children and Adults.
Purpose Knowing target location can improve adults' speech-in-speech recognition in complex auditory environments, but it is unknown whether young children listen selectively in space. This study evaluated masked word recognition with and without a pretrial cue to location to characterize the influence of listener age and masker type on the benefit of spatial cues. Method Participants were children (5-13 years of age) and adults with normal hearing. Testing occurred in a 180° arc of 11 loudspeakers. Targets were spondees produced by a female talker and presented from a randomly selected loudspeaker; that location was either known, based on a pretrial cue, or unknown. Maskers were two sequences comprising spondees or speech-shaped noise bursts, each presented from a random loudspeaker. Speech maskers were produced by one male talker or by three talkers, two male and one female. Results Children and adults benefited from the pretrial cue to target location with the three-voice masker, and the magnitude of benefit increased with increasing child age. There was no benefit of location cues in the one-voice or noise-burst maskers. Incorrect responses in the three-voice masker tended to correspond to masker words produced by the female talker, and in the location-known condition, those masker intrusions were more likely near the cued loudspeaker for both age groups. Conclusions Increasing benefit of the location cue with increasing child age in the three-voice masker suggests maturation of spatially selective attention, but error patterns do not support this idea. Differences in performance in the location-unknown condition could play a role in the differential benefit of the location cue.


Aggression classification and treatment response.
This preliminary study investigated whether the aggression subtypes derived from the Aggression Questionnaire (AQ) are related to treatment response. The subjects were 28 aggressive conduct-disordered children (25 males, 3 females), ranging in age from 9.8 to 17.0 years (mean age = 12.69 years), who participated in a double-blind, placebo-controlled study of lithium as a treatment for reducing aggression. We used the Predatory-Affective Index of the AQ to classify subjects into "predatory" (planned) or "affective" (explosive) subtypes of aggression and then related this classification to treatment response. This index did not differentiate placebo baseline responders from nonresponders. However, the Index did significantly differentiate responders and nonresponders during the experimental treatment period, regardless of whether they received lithium or placebo. Treatment response was associated with a more affective and less predatory subtype of aggression. To the best of our knowledge, this is the first study in children to show an association between the aggression subtype and treatment response.


Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target Protein Profiling.
The identification of the molecular targets and mechanisms underpinning the beneficial or detrimental effects of small-molecule leads and drugs constitutes a crucial aspect of current drug discovery. Over the last two decades, three-hybrid (3H) systems have progressively taken an important position in the armamentarium of small molecule-target protein profiling technologies. Yet, a prerequisite for successful 3H analysis is the availability of appropriate chemical inducers of dimerization. Herein, we present a comprehensive and critical overview of the chemical dimerizers specifically applied in both yeast and mammalian three-hybrid systems for small molecule-target protein profiling within the broader scope of target deconvolution and drug discovery. Furthermore, examples and alternative suggestions for typical components of chemical dimerizers for 3H systems are discussed. As illustrated, more tools have become available that increase the sensitivity and efficiency of 3H-based screening platforms. Hence, it is anticipated that the great potential of 3H systems will further materialize in important contributions to drug discovery.


Assessment of cancers' diagnostic stage in a Deaf community - survey about 4363 Deaf patients recorded in French units.
Deaf people represent 0.1% of the French population and their access to public health campaigns is limited due to their frequent illiteracy and the infrequent use of sign language in campaigns. There is also a lack of general health knowledge in spite of the existence of French Deaf Care Units (UASS). The aim of this study is to assess the average diagnostic stage of cancer in the Deaf Community and discuss deafness as a contributing factor. Four thousand three hundred sixty-three Deaf patients recorded in five UASS, 80 diagnosed between 2005/01/01 and 2014/12/31 were selected from medical records and/or ICD-10 coding. Data regarding cancers were extracted, grouped by stage and compared to literature. Statistical significance was tested with Fisher's Exact Test. Eighty patients were selected. Most cancers were diagnosed at advanced stages: of 11 prostate cancers, 46% were locally advanced and 18% were metastatic. (In the general population, this was respectively 3% and 10.4% (p < 0.01)). Of six colorectal cancers, 67% were diagnosed at stage III and 33% at stage IV. (Respectively 20.6% and 26.6% (p = 0.03) in the general population). In contrast, of the 15 breast cancers, 93% were diagnosed at stages T1-T3 that was earlier than in the general population (p = 0.43). In this study, we observed a delay cancer diagnosis among Deaf people. Complicated and/or non-systematic screening procedures for cancers would be involved. Which is most likely the result of many factors (communication, medical knowledge). Increasing UASS coverage and health information campaigns in sign language could assist in earlier cancer diagnosis.


Adsorption and Biodegradation of Aromatic Chemicals by Bacteria Encapsulated in a Hydrophobic Silica Gel.
An adsorbent silica biogel material was developed via silica gel encapsulation of Pseudomonas sp. NCIB 9816-4, a bacterium that degrades a broad spectrum of aromatic pollutants. The adsorbent matrix was synthesized using silica precursors methyltrimethoxysilane and tetramethoxysilane to maximize the adsorption capacity of the matrix while maintaining a highly networked and porous microstructure. The encapsulated bacteria enhanced the removal rate and capacity of the matrix for an aromatic chemical mixture. Repeated use of the material over four cycles was conducted to demonstrate that the removal capacity could be maintained with combined adsorption and biodegradation. The silica biogel can thus be used extensively without the need for disposal, as a result of continuous biodegradation by the encapsulated bacteria. However, an inverse trend was observed with the ratio of biodegradation to adsorption as a function of log Kow, suggesting increasing mass-transport limitation for the most hydrophobic chemicals used (log Kow > 4).


Holmium-YAG laser: impact of pulse energy and frequency on local fluid temperature in an in-vitro obstructed kidney calyx model.
During laser lithotripsy, energy is transmitted to both the stone and the surrounding fluid. As the energy is delivered, the temperature will rise. Temperatures ≥60 ° C can cause protein denaturation. The objective of this study is to determine the time it takes from body temperature (37°C) to 60°C at various laser power settings. A Flexiva TracTip 200 optical fiber was submerged alongside a negative temperature coefficient-type thermistor in 4 mL of saline in a glass test tube. A Lumenis VersaPulse Powersuite 100-W holmium:yttrium aluminum garnet laser was activated at 0.2- to 1.5-J pulse energies, 6- to 50-Hz frequencies, and 2- to 22.5-W average power. Temperature readings were recorded every second from 37°C until 60°C. Time and heating rate were measured. The procedure was repeated three times for each setting. Average time from 37°C to 60°C for settings (1) 0.2 J/50 Hz, (2) 0.6 J/6 Hz, (3) 1 J/10 Hz, and (4) 1.5 J/10 Hz was 60.3, 172.7, 58, and 43.3 s, respectively. Time from 37°C to 60°C decreased as frequency increased for every given pulse energy. Average heating rate increased proportionally to power from 0.06°C/s at 2 W to 0.74°C/s at 22.5 W. During laser lithotripsy, there is a rapid increase in the temperature of its surrounding fluid and temperatures ≥60 ° C may be reached. This could have local tissue effects and some caution with higher power settings should be employed especially where irrigation is limited. Further studies incorporating irrigation and live tissue models may aid to further define the risks.


Preliminary study of confocal laser endomicroscopy for in vitro specimens of the endometrium.
This study observed and described the morphological characteristics of the endometrium of the resected uterus using confocal laser endomicroscopy. This included benign endometrium, non-atypical endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma, thereby laying a foundation for finding the precise localization and resection of endometrial lesions, given the feasibility of confocal laser endomicroscopy-assisted hysteroscopy. This prospective study included 32 patients who underwent hysterectomy. We used confocal laser endomicroscopy to observe the endometrium of resected uteruses and described the characteristics of endometrium in different states by comparing histopathological findings (primary objects). The secondary objects of observation were the myometrium, endocervical canal, and surface of the external os of the cervix. A total of 32 patients who underwent hysterectomy for different diseases were included: 9 with endometrial carcinoma (5 with endometrioid carcinoma, 1 with endometrial serous carcinoma, 2 with clear cell carcinoma, and 1 with carcinosarcoma), 2 with atypical endometrial hyperplasia, 9 with benign diseases, 7 with cervical cancer, and 5 with ovarian cancer and borderline tumor. The dynamic images of the endometrium were observed and recorded using probe-based confocal laser endomicroscopy (pCLE). Considering histopathology as the gold standard, the diagnostic concordance rate of pCLE was 96.9% in patients with endometrial carcinoma and precancerous lesions and 100% in patients with endometrial carcinoma. Confocal laser endomicroscopy provides real-time high-resolution images of the benign endometrium and endometrial lesions. Compared with histopathology, confocal laser endomicroscopy has high diagnostic accuracy and may become an auxiliary examination tool for hysteroscopy, as it is useful for early identification of endometrial lesions, real-time diagnosis of tumor, and detection of tumor boundaries for complete tumor resection. These findings can lay a foundation for the feasible use of fertility-sparing local excision of tumor lesions by hysteroscopy.


[Effects of biochar addition into soils in semiarid land on water infiltration under the condition of the same bulk density].
Making clear the effects of biochar addition on soil water infiltration process can provide the scientific basis for the evaluation of the influence of biochar application on soil hydrology in semi-arid region. In this paper, through the soil column simulation method in laboratory, the effects of biochar of three sizes (1-2 mm, 0.25-1 mm and ≤ 0.25 mm) at 4 doses (10, 50, 100 and 150 g x kg(-1)) on the cumulative infiltration, the permeability and the stable infiltration rate of two different soils (anthrosol and aeolian sandy soil) were studied. The results showed that the infiltration capacity of the anthrosol was obviously increased compared to the control, however, the one in the aeolian sandy soil was decreased due to the biochar addition. At 100 minutes after infiltration starting, the averaged cumulative infiltration was increased by 25.1% in the anthrosol with comparison to the control. Contrarily, the averaged cumulative infiltration was decreased by 11.1% in the aeolian sandy soil at 15 minutes after infiltration starting. When the dose was the same, biochar with different particle sizes improved the infiltration for the anthrosol, but for the different dose treatments, the particle size of biochar which showed the greatest improvement was different. As for the aeolian sandy soil, the infiltration increased at the dose of 10 g x kg(-1) after the addition of biochar with different particle sizes, while decreased at the higher dose of 50, 100 and 150 g x kg(-1). The cumulative infiltration of the aeolian sandy soil was decreased with the increase in addition amount of biochar with the same particle size, while it was not so for the anthrosol. The determination coefficient fitted by the Philip infiltration model ranged from 0.965 to 0.999, suggesting this model was suitable for the simulation of soil water infiltration process after biochar application. Statistical analysis of main effects showed that the biochar particle size, the biochar addition amount, and the interactive effect had statistically significant effect on the soil permeability and stable infiltration rate in the two soils. In conclusion, the biochar had different effects on the soils with different textures, moreover, there was a positive correlation relationship between the impact and the addition amount.


[Newer pathophysiologic considerations and treatment of neonatal respiratory distress syndrome (RDS)].
RDS is the major cause of morbidity and mortality in preterm infants. Hochheim first noted the pathologic appearance of the lungs with RDS in 1903, which included alveolar collapse associated with dilatation of the alveolar ducts and terminal bronchioles. This important finding now can be best explained by the newer model of pulmonary micromechanics proposed by Weibel and Bachofen. In this model, alveoli are not individual structures, but subunits of the alveolar duct system. The alveolar stability requires particular properties of both the fibrous skeleton and the alveolar surfactant film. With increasing surface forces resulting from surfactant deficiency, the alveolar volumes and surface areas decrease, more septal segments are folded up between the adjacent ducts, thereby widening the duct system and terminal bronchioles. In this situation, the shear forces triggered by mechanical ventilation cause damage of the terminal airways with increased permeability of plasma proteins into the airspaces, which tends to aggravate alveolar instability further. Exogenous surfactant replacement produced excellent results which decreased the pulmonary complications of RDS significantly with no adverse effects. In the not too distant future this therapy will be regularly practiced in NICU.


Microbiology of chronic suppurative otitis media in children.
The aerobic microorganisms present in 51 middle ears of 36 children with chronic suppurative otitis media without cholesteatoma were evaluated. Specimens were taken directly from the middle ear through a patent perforation or tympanostomy tube and cultured using standard techniques. Twenty-three microbiologic species were identified, with Pseudomonas aeruginosa being the most prevalent (67% of ears) and the only organism in 31% of ears. The initial treatment of all patients was intravenous administration of an antimicrobial selected on the basis of culture and susceptibility reports; this treatment was successful in all but four children, who subsequently required tympanomastoid surgery. These results indicate that medical therapy, based on the results of culture and susceptibility studies, provides a viable alternative to major mastoid surgery in the management of chronic suppurative otitis media without cholesteatoma.


The Impact of Demographic Factors and Blood Sugar Control on the Incidence of Urinary Tract Infections in Khorramabad in 2013.
Diabetes is one of the most serious metabolic disorders to affect different organs in the body. Patients with diabetes are hence at risk of developing other problems. Urinary tract infections (UTI) are one of the problems that occur more commonly in diabetic patients than in others. There are several risk factors that lead to the incidence of UTI in diabetic patients. We conducted this study to determine the effect of different factors on the incidence of UTI in diabetic patients in order to decrease the incidence of this problem. In this cross-sectional study, data concerning 233 patients who were referred to the largest diabetes center in Khorramabad, Lorestan province, Iran, were recorded. The relationships between various factors and the incidence of UTI in these patients were evaluated using SPSS version 16. We used chi-square and logistic regression to analyze the data. A P < 0.05 was considered to be statistically significant. The incidence of UTI increased significantly with increasing age (P = 0.009). The incidence of UTI was higher among females than among males, and it was higher among unemployed people than among those in other occupations. The prevalence of UTI among patients who control their diabetes through diet and exercise was lower than that among those undergoing other types of treatment; however, no significant relationship was found between the different types of oral medication and the incidence of UTI. We did not find any relationship between the incidence of UTI in diabetic patients and other factors such as literacy, marital status, BMI, addiction, history of hospitalization, and level of HbA1c. We found that age, gender, occupation, and the type of medication used are all risk factors for the incidence of UTI in diabetic patients. Other factors such as literacy, marital status, addiction, and history of hospitalization did not have any significant association with the incidence of UTI in diabetic patients.


Propofol Compared to Midazolam Sedation and to General Anesthesia for Percutaneous Microwave Ablation in Patients with Hepatic Malignancies: A Single-Center Comparative Analysis of Three Historical Cohorts.
In percutaneous ablation procedures, periprocedural pain, unrest and respiratory concerns can be detrimental to achieve a safe and efficacious ablation and impair treatment outcome. This study aimed to compare the association between anesthetic technique and local disease control in patients undergoing percutaneous microwave ablation (MWA) of colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). This IRB-exempted single-center comparative, retrospective analysis of three cohorts analyzed 90 patients treated for hepatic malignancies from January 2013 until September 2018. The local tumor progression-free survival (LTPFS), safety and periprocedural pain perception were assessed using univariate and multivariate Cox proportional hazard regression analyses to correct for potential confounders. In 114 procedures (22 general anesthesia; 32 midazolam; 60 propofol), 171 liver tumors (136 CRLM; 35 HCC) were treated with percutaneous MWA. Propofol and general anesthesia were superior to midazolam/fentanyl sedation regarding LTPFS (4/94 [4.3%] vs. 19/42 [45.2%] vs. 2/35 [5.7%]; P < 0.001, respectively). Local tumor progression rate was 14.6% (25/171). Eighteen tumors (72.0%) were retreated by ablation. Of them, 14 (78%) were previously treated with midazolam. Propofol versus midazolam (P < 0.001), general anesthesia versus midazolam (P = 0.016), direct postprocedural visual analog pain score above 5 (P = 0.050) and more than one tumor per procedure (P = 0.045) were predictors for LTPFS. Multivariate analysis revealed that propofol versus midazolam (HR 7.94 [95% CI 0.04-0.39; P < 0.001]) and general anesthesia versus midazolam (HR 6.33 [95% CI 0.04-0.69; P = 0.014]) were associated with LTPFS. Pain during and directly after treatment was significantly worse in patients who received midazolam sedation (P < 0.001). Compared to propofol and general anesthesia, midazolam/fentanyl sedation was associated with an increased periprocedural perception of pain and lower local tumor progression-free survival. To reduce the number of repeat procedures required to eradicate hepatic malignancies, general anesthesia and propofol sedation should be favored over midazolam.


A 48,XXY,+21 Down syndrome patient with additional paternal X and maternal 21.
The origin of meiotic nondisjunction of the extra chromosomes X and 21 was studied in a patient with the karyotype 48,XXY,+21 using DNA polymorphisms. The extra chromosome X was the result of paternal first meiotic nondisjunction of X and Y. The extra chromosome 21 was derived from the mother. The meiotic error in the mother most probably occurred in meiosis II. Thus, this is a combination caused by the chance occurrence of two independent events.


[Antibiotic profylaxis in obstetrics].
Nosocomial infections increase health care costs significantly and they are a real threat for all hospitalised patients as well. Surgical procedures affect imunological integrity in patients and increase risk of contamination and subsequent incidence of surgical site infections (SSIs). Antibiotic profylaxis according to recent trials has been shown to be effective in reducing the risks of postoperative infectious complications particularly in women undergoing cesarean section, termination of pregnancy in I. and II. trimester and repair of extensive obstetric perineal injuries. Benefit of antibiotic profylaxis hasn t been proven in procedures such as amniocentesis, cerclage and manual uterine evacuation. The routine antibiotic administration isnt recommanded in cases of spontaneous preterm labour without membrane rupture due to an increased risk of worse long-term outcome of children.The authors present also recent studies regarding antivirotic profylaxis in pregnant women with hepatitis B and herpes genitalis recidivans. In the end of the article differences in antimicrobial administration in obese women and in patients with penicillin allergy anamnesis are mentioned.


Integration of IR-808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging.
Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS2 nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS2 nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.


Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex.
Arterial bifurcations represent preferred locations for aneurysm formation, especially when they are associated with variations in divider geometry. The authors hypothesized a link between basilar apex aneurysms and basilar bifurcation (α) and vertebrobasilar junction (VBJ) angles. The α and VBJ angles were measured in 3D MR and rotational angiographic volumes using a coplanar 3-point technique. Angle α was compared between age-matched cohorts in 45 patients with basilar artery (BA) aneurysms, 65 patients with aneurysms in other locations (non-BA), and 103 nonaneurysmal controls. Additional analysis was performed in 273 nonaneurysmal controls. Computational fluid dynamics (CFD) simulations were performed on parametric BA models with increasing angles. Angle α was significantly wider in patients with BA aneurysms (146.7° ± 20.5°) than in those with non-BA aneurysms (111.7° ± 18°) and in controls (103° ± 20.6°) (p < 0.0001), whereas no difference was observed for the VBJ angle. A wider angle α correlated with BA aneurysm neck width but not dome size, which is consistent with CFD results showing a widening of the impingement zone at the bifurcation apex. BA bifurcations hosting even small aneurysms (< 5 mm) had a significantly larger α angle compared with matched controls (p < 0.0001). In nonaneurysmal controls, α increased with age (p < 0.0001), with a threshold effect above 35 years of age and a steeper dependence in females (p = 0.002) than males (p = 0.04). The α angle widens with age during adulthood, especially in females. This angular widening is associated with basilar bifurcation aneurysms and may predispose individuals to aneurysm initiation by diffusing the flow impingement zone away from the protective medial band region of the flow divider.


How to understand real net ultrafiltration and its association with low blood pressure in critically ill patients with renal replacement therapy.
The concept of net ultrafiltration (UFNET) mentioned in the paper by Murugan et al. in a recent issue of Critical Care does not equate to the real UFNET in patients with renal replacement therapy initiation. Furthermore, the baseline blood pressure among the groups had a statistically significant difference. Both of these two factors may affect the final results. Thus, we should be cautious interpreting the conclusions.


Hierarchical information fusion for global displacement estimation in microsensor motion capture.
This paper presents a novel hierarchical information fusion algorithm to obtain human global displacement for different gait patterns, including walking, running, and hopping based on seven body-worn inertial and magnetic measurement units. In the first-level sensor fusion, the orientation for each segment is achieved by a complementary Kalman filter (CKF) which compensates for the orientation error of the inertial navigation system solution through its error state vector. For each foot segment, the displacement is also estimated by the CKF, and zero velocity update is included for the drift reduction in foot displacement estimation. Based on the segment orientations and left/right foot locations, two global displacement estimates can be acquired from left/right lower limb separately using a linked biomechanical model. In the second-level geometric fusion, another Kalman filter is deployed to compensate for the difference between the two estimates from the sensor fusion and get more accurate overall global displacement estimation. The updated global displacement will be transmitted to left/right foot based on the human lower biomechanical model to restrict the drifts in both feet displacements. The experimental results have shown that our proposed method can accurately estimate human locomotion for the three different gait patterns with regard to the optical motion tracker.


Measuring function and health status in rheumatic disease clinical trials.
We have summarized the limitations of traditional outcome measures in rheumatology, reviewed the growing field of measures emphasizing the patient's perception of improvement, and provided guidelines for choosing a specific instrument for a clinical trial. Newer measures have measurement properties equal to or surpassing traditional measures, but no one ADL or quality-of-life instrument can be used to assess outcome in every situation as no one test can indicate success of a treatment in a chronic disease. An instrument needs to be judged by the following criteria: Is it metrically sound? Does it fit the socio-demographic characteristics of the target population? Does it measure the specific changes which are likely to be affected by the treatment? Will it capture or measure the expected changes?


Changes in the oral cavity might reflect psychological disorders in some patients.
The treatment of oral dysesthesias, such as burning mouth syndrome, can be challenging. Patient acceptance of the role of psychological etiological factors might be improved if there are clinical signs that patients could confirm themselves, which could be used as reinforcement of clinical discussions. Published associations between psychological disorder and various oral signs and symptoms are not suited to this purpose, as they are ambiguous in origin and implication. Others, used clinically in this situation, are not supported by published literature. Therefore, the purpose of this study was to determine if a demonstrable relationship could be established between psychological profile and the appearance and function of the oral cavity. Seventy-nine participants underwent an oral examination and completed a Depression Anxiety Stress Scale-21 questionnaire. Correlations were calculated between clinical variables and the raw Depression Anxiety Stress Scale scores. Univariate analyses determined variables with significant differences between a high-risk and normal group, and multiple logistic regression models were calculated for these. Various oral signs and symptoms were found to correlate with depression, anxiety, and/or stress, with some predictive of psychological disturbance. These signs and symptoms might be used to reinforce the psychological aspects of an oral dysesthesia.


Synthesis of fused energetic compounds using structural modification from local carbonyl to hydroxylamine/hydrazone.
This work presents the successful synthesis of a series of fused energetic compounds using the strategy of structural modification from local carbonyl to hydroxylamine, hydrazone or methylamine. Hydroxylamine-substituted compound 2 exhibits high density, high detonation performance and low sensitivities as a secondary explosive.


Split-Cre recombinase effectively monitors protein-protein interactions in living bacteria.
The ability of Cre recombinase to excise genetic material has been used extensively for genome engineering in prokaryotic and eukaryotic cells. Recently, split-Cre fragments have been described that advance control of recombinase activity in mammalian cells. However, whether these fragments can be utilized for monitoring protein-protein interactions has not been reported. In this work, we developed a protein-fragment complementation assay (PCA) based on split-Cre for monitoring and engineering pairwise protein interactions in living Escherichia coli cells. This required creation of a dual-fluorescent reporter plasmid that permits visualization of reconstituted Cre recombinase activity by switching from red to green in the presence of an interacting protein pair. The resulting split-Cre PCA faithfully links cell fluorescence with differences in binding affinity, thereby allowing the facile isolation of high-affinity binders based on phenotype. Given the resolution of its activity and sensitivity to interactions, our system may prove a viable option for poorly expressed or weakly interacting protein pairs that evade detection in other PCA formats. Based on these findings, we anticipate that our split-Cre PCA will become a highly complementary and useful new addition to the protein-protein interaction toolbox.


N-doped photocatalytic titania thin films on active polymer substrates.
Active polymer substrates have found their way in the semiconductor industry as a base layer for flexible electronics, as well as in sensor and actuator applications. The optimum performance of these systems may be affected by dirt adsorbed on its surface, which can also originate mechanisms for the degradation of the polymer. Titanium dioxide (titania) semiconductor photocatalytic thin films have been deposited by unbalanced reactive magnetron sputtering on one of the most applied and investigated electroactive polymer: poly(vinilidene fluoride), PVDF. In order to increase the photocatalytic efficiency of the titania coatings, a reduction of the semiconductor band-gap has been attempted by using a nitrogen doping. Rutherford Backscattering Spectroscopy was used in order to assess the composition of the titania thin films, whereas Heavy Ion Elastic Recoil Detection Analysis provided the evaluation of the doping level of nitrogen. X-ray Photoelectron Spectroscopy provided valuable information about the cation-anion binding within the semiconductor lattice. The photocatalytic performance of the titania films have been characterized by decomposing an organic dye illuminated with combined UV/visible light.


Detection of early gastric cancer by panendoscopy.
With the implementation of a small-caliber panendoscope which was made according to our suggestion, we gradually replaced the conventional barium meal as the first line of the upper gastrointestinal tract examination by panendoscopy after 1976. The efficacy of panendoscopy for the early detection of gastric cancer in our 8-yr experience was investigated. In 910 matched pairs of patients subjected to "screening" fluoroscopy or panendoscopy two and six cases of early gastric cancer were detected respectively. Panendoscopy was superior to fluoroscopy in its sensitivity for detection of gastric cancer (86.4% vs. 80.0%), in its specificity (99.5% vs. 97.0%) and in its low false-positive rate (17.4% vs. 69.2%). After 1976, the detection of early gastric cancer increased year by year. The frequency of early gastric cancer detected by panendoscopy was about three times that of early gastric cancer detected by fluoroscopy (61.5% vs. 21.7% of all cancer). Early cancer located in the proximal third of the stomach and superficial esophageal cancer were detected only by panendoscopy. All gastric cancers that were overlooked by panendoscopy were in the gastric body. How to prevent such overlooking is discussed. In 24,000 panendoscopies we have encountered six complications (0.03%). The cost of panendoscopy and fluoroscopy is 6,500 yen and 11,000 yen respectively.


Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer.
Photodynamic therapy (PDT) has been proven to be a minimally invasive and effective therapeutic strategy for cancer treatment. It can be used alone or as a complement to conventional cancer treatments, such as surgical debulking and chemotherapy. The mitochondrion is an attractive target for developing novel PDT agents, as it produces energy for cells and regulates apoptosis. Current strategy of mitochondria targeting is mainly focused on utilizing cationic photosensitizers that bind to the negatively charged mitochondria membrane. However, such an approach is lack of selectivity of tumor cells. To minimize the damage on healthy tissues and improve therapeutic efficacy, an alternative targeting strategy with high tumor specificity is in critical need. Herein, we report a tumor mitochondria-specific PDT agent, IR700DX-6T, which targets the 18kDa mitochondrial translocator protein (TSPO). IR700DX-6T induced apoptotic cell death in TSPO-positive breast cancer cells (MDA-MB-231) but not TSPO-negative breast cancer cells (MCF-7). In vivo PDT study suggested that IR700DX-6T-mediated PDT significantly inhibited the growth of MDA-MB-231 tumors in a target-specific manner. These combined data suggest that this new TSPO-targeted photosensitizer has great potential in cancer treatment. Photodynamic therapy (PDT) is an effective and minimally invasive therapeutic technique for treating cancers. Mitochondrion is an attractive target for developing novel PDT agents, as it produces energy to cells and regulates apoptosis. Current mitochondria targeted photosensitizers (PSs) are based on cationic molecules, which interact with the negatively charged mitochondria membrane. However, such PSs are not specific for cancerous cells, which may result in unwanted side effects. In this study, we developed a tumor mitochondria-targeted PS, IR700DX-6T, which binds to translocator protein (TSPO). This agent effectively induced apoptosis in TSPO-positive cancer cells and significantly inhibited tumor growth in TSPO-positive tumor-bearing mice. These combined data suggest that IR700DX-6T could become a powerful tool in the treatment of multiple cancers that upregulate TSPO.


Evaluation of Web sites on management of pain in children.
Increasingly, consumers access the Internet for information about their health problems and treatments and to learn more about their health care. Although Web sites can be valuable resources, the information may not be accurate or current. The purpose of this project was to evaluate the quality of Web sites for parents on the management of children's pain. The Health Information Technology Institute criteria were used to evaluate 40 Web sites identified from two search engines: MSN and Google. After the evaluation process was completed, the readability of the sites was determined. Of the 40 sites, 29 (72.5%) provided useful information for parents searching to educate themselves about pain management. Other sites advertised the pain management services of their facility or were not relevant for patient education. The reading levels of the Web sites ranged from grade 7.7 to 12; the mean reading grade level of the 40 sites was 10.8, too high for many consumers. This article discusses the role of the nurse in evaluating health Web sites and teaching patients how best to use the Web for their health information.


Giant Polarization Sensitivity via the Anomalous Photovoltaic Effect in a Two-Dimensional Perovskite Ferroelectric.
Polarization sensitivity, which shows great potential in photoelectric detection, is expected to be significantly improved by the ferroelectric anomalous photovoltaic (APV) effect. However, it is challenging to explore new APV-active ferroelectrics due to severe polarization fatigue induced by the leakage current of photoexcited carriers. For the first time, we report a strong APV effect in a 2D hybrid perovskite ferroelectric assembled by alloying mixed organic cations, (HA)2(EA)2Pb3Br10 (1, where HA+ is n-hexylammonium and EA+ is ethylammonium), which has a large spontaneous polarization ∼3.8 μC/cm2 and high a Curie temperature ∼378 K. Its ferroelectricity allows a strong APV effect with an above-bandgap photovoltage up to 7.4 V, which exceeds its bandgap (∼2.7 eV). Most strikingly, based on the dependence on polarized-light angle, this strong APV effect renders the highest level of polarization sensitivity with a giant current ratio of ∼25, far beyond other 2D single-phase materials. This study sheds light on the exploration of APV-active ferroelectrics and inspires their future high-performance optoelectronic device applications.


Antiplatelet therapy: an alternative to heparin for blunt carotid injury.
Blunt carotid injuries (BCIs) are uncommon. Most single-center studies are small and highlight the use of anticoagulation for treatment. In a retrospective review, we identified 22 patients who presented with BCI and assessed neurologic and survival outcomes on the basis of injury grade and treatment with anticoagulation or antiplatelet therapy. Patient demographics were identified using the trauma registry at a single Level I trauma center. Chart reviews assessed neurologic function, modalities used for diagnosis, and treatment. Neurologic outcomes were graded good (minimal to no deficit), fair (moderate deficit needing some assistance), poor (requiring institutionalization), and dead. Twenty-two adult trauma patients were diagnosed with BCI, for an incidence of 0.45% in the 8-year study period. All BCI patients underwent head computed tomography and four-vessel cerebral arteriography. Eight patients were not anticoagulated, five because of intracranial injuries, two who had surgical CCA repairs, and one with an aortic injury. Full anticoagulation with heparin was attempted in seven patients, with four major bleeding complications requiring cessation of heparin and blood transfusions. Seven patients received antiplatelet therapy. No difference in neurologic outcome was observed between those receiving anticoagulation and those receiving antiplatelet therapy. Bleeding complications from full anticoagulation were higher than with antiplatelet agents (p = 0.05). Contrary to previous reports, we did not observe improved outcomes with full anticoagulation compared with antiplatelet therapy. Anticoagulation was associated with increased extracranial bleeding complications. The risks and possible benefits, as well as timing, of anticoagulation or antiplatelet therapy for BCI should be carefully weighed by the major care providers of the patient with multiple injuries.


Embryonic development of mouse external genitalia: insights into a unique mode of organogenesis.
The mammalian external genitalia are specialized appendages for efficient copulation, internal fertilization and display marked morphological variation among species. In this paper, we described the embryonic development of mouse genital tubercle (GT), an anlage of the external genitalia utilizing the scanning electron microscope (SEM) analysis. It has been shown that the Distal Urethral Epithelium (DUE) may fulfill an essential role in the outgrowth control of the GT. Our present SEM analysis revealed a small distal protrusion at the tip of the GT of normal embryos as well as some morphological differences between male and female embryonic external genitalia. Previous analysis shows that the teratogenic dose of Retinoic Acid (RA) induces a drastic marformation of the urethral plate, but not gross abnormalities for GT outgrowth. Interestingly, a small distal protrusion at the tip of GT was clearly observed also after RA treatement. Furthermore, we showed that treatment with anti-androgen flutamide resulted in the demasculinization of the GT in males. The unique character of GT development and the sexual dimorphism are discussed.


A multidimensional approach to homosexual identity.
The existing developmental stage models of homosexual identity do not consider the diversity of human sexual experience. The stage models stem from an essentialist perspective, in which the process of homosexual identity formation is largely a matter of becoming aware of one's underlying, or real, sexual orientation. Once homosexual orientation is identified, the only legitimate outcome is to develop homosexual identity and eventually incorporate that identity as one aspect of the total self. In this paper, we are concerned with those people for whom the stage models are inadequate in describing their experience of sexual identity development. The social constructionist perspective holds that the process of identity formation is a continual, two-way interactive process between the individual and the social environment, and that the meanings the individual gives to these factors influence the development of self-constructs and identity. Sexual identity develops within this contextual framework and, because it is influenced by continual interaction, is fluid over time and experience, throughout one's life. Our model does not rely on the existing developmental models of homosexual identity; rather, our model looks at desire, behavior, and identity as three separate constructs related to sexual identity. We posit that from the social constructionist viewpoint, there is in fact no true endpoint to sexual identity development.


Synaptic vesicles are "primed" for fast clathrin-mediated endocytosis at the ribbon synapse.
Retrieval of synaptic vesicles can occur 1-10 s after fusion, but the role of clathrin during this process has been unclear because the classical mode of clathrin-mediated endocytosis (CME) is an order of magnitude slower, as during retrieval of surface receptors. Classical CME is thought to be rate-limited by the recruitment of clathrin, which raises the question: how is clathrin recruited during synaptic vesicle recycling? To investigate this question we applied total internal reflection fluorescence microscopy (TIRFM) to the synaptic terminal of retinal bipolar cells expressing fluorescent constructs of clathrin light-chain A. Upon calcium influx we observed a fast accumulation of clathrin within 100 ms at the periphery of the active zone. The subsequent loss of clathrin from these regions reflected endocytosis because the application of a potent clathrin inhibitor Pitstop2 dramatically slowed down this phase by ~3 fold. These results indicate that clathrin-dependent retrieval of synaptic vesicles is unusually fast, most probably because of a "priming" step involving a state of association of clathrin with the docked vesicle and with the endosomes and cisternae surrounding the ribbons. Fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP) showed that the majority of clathrin is moving with the same kinetics as synaptic vesicle proteins. Together, these results indicate that the fast endocytic mechanism operating to retrieve synaptic vesicles differs substantially from the classical mode of CME operating via formation of a coated pit.


GCHap: fast MLEs for haplotype frequencies by gene counting.
GCHap quickly finds maximum likelihood estimates (MLEs) of frequencies of haplotypes given genotype information on a random sample of individuals. It uses the gene counting method but by excluding haplotypes with zero MLE at an early stage, this implementation uses many orders of magnitude less space and time than naive implementations. A second program, ApproxGCHap, is provided to give alternate estimates for data sets with large numbers of loci or large amounts of missing genotypes. The Java classes and Javadocs pages for GCHap can be obtained from bioinformatics.med.utah.edu/~alun


Cross- cultural validation of the Brazilian Portuguese version of the Social Phobia Inventory (SPIN): study of the items and internal consistency.
The objective of the present study was to carry out the cross- cultural validation for Brazilian Portuguese of the Social Phobia Inventory, an instrument for the evaluation of fear, avoidance and physiological symptoms associated with social anxiety disorder. The process of translation and adaptation involved four bilingual professionals, appreciation and approval of the back- translation by the authors of the original scale, a pilot study with 30 Brazilian university students, and appreciation by raters who confirmed the face validity of the Portuguese version, which was named ' Inventário de Fobia Social' . As part of the psychometric study of the Social Phobia Inventory, analysis of the items and evaluation of the internal consistency of the instrument were performed in a study conducted on 2314 university students. The results demonstrated that item 11, related to the fear of public speaking, was the most frequently scored item. The correlation of the items with the total score was quite adequate, ranging from 0.44 to 0.71, as was the internal consistency, which ranged from 0.71 to 0.90. The authors conclude that the Brazilian Portuguese version of the Social Phobia Inventory proved to be adequate regarding the psychometric properties initially studied, with qualities quite close to those of the original study. Studies that will evaluate the remaining indicators of validity of the Social Phobia Inventory in clinical and non-clinical samples are considered to be opportune and necessary.


Fatal glioblastoma multiforme in a patient with neurofibromatosis type I: the dilemma of systematic medical follow-up.
Neurofibromatosis type I (NF1) is one of the most prevalent genetic diseases of the nervous system. Although the majority of NF1 patients are only mildly affected, the risk of developing malignancies is significantly increased in this population. Here, we present a 9-year-old girl with clinical stigmata of NF1 and a rapidly evolving glioblastoma multiforme. Molecular genetic analysis uncovered a novel missense mutation in Exon 32 of the NF1 gene [c.6032C>A(p.Ala2011Glu)]. The girl's death 3 days after diagnosis of the brain tumor exemplifies that NF1 still is a life-threatening disease despite its generally benign course in most patients. However, it remains questionable if a fatal course as reported here can be prevented by routine MRI screening.


Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.
The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. Reports in amputees describing phantom limb pain demonstrate a positive correlation between pain intensity and the amount of primary somatosensory cortex (S1) reorganization. Of note, this S1 reorganization has also been shown to reverse with pain reduction. It is unknown whether a similar association between S1 reorganization and pain intensity exists in subjects with SCI. The aim of this investigation was to determine whether the degree of S1 reorganization following SCI correlated with on-going neuropathic pain intensity. In 20 complete SCI subjects (10 with neuropathic pain, 10 without neuropathic pain) and 21 control subjects without SCI, the somatosensory cortex was mapped using functional magnetic resonance imaging during light brushing of the right little finger, thumb and lip. S1 reorganization was demonstrated in SCI subjects with the little finger activation point moving medially towards the S1 region that would normally innervate the legs. The amount of S1 reorganization in subjects with SCI significantly correlated with on-going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.


Molecular pathogenesis of diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous clinicopathologic entity accounting for 30% of non-Hodgkin's lymphomas. The pathogenesis of DLBCL is complex and heterogeneous. Recent studies using analysis of global gene expression with DNA microarrays and the classical molecular approaches demonstrate presence of several DLBCL subtypes characterized by different cells of origin, cytogenetic and molecular aberrations, and distinct pathogenesis. This review summarizes the progress in understanding of DLBCL biology and presents a state-of-the-art overview of DLBCL molecular pathogenesis.


Initial outcomes of an augmented competing stimulus assessment.
Competing stimulus assessments (CSAs) are designed to identify stimuli that, when made freely available, reduce problem behavior. Although CSAs have demonstrated utility, identifying competing stimuli can be difficult for some individuals. The current study describes outcomes from an augmented CSA (A-CSA) for 6 consecutively encountered cases with treatment-resistant subtypes of automatically maintained problem behavior. When test stimuli were made freely available, only between 0 and 1 effective competing stimuli were identified for each case. Prompting and response blocking were temporarily employed in succession to promote engagement with stimuli and disrupt problem behavior. When those procedures were withdrawn and stimuli made freely available, the number of effective competing stimuli increased in all 6 cases. Findings suggest that procedures designed to promote engagement and disrupt problem behavior may allow the A-CSA to be a platform not only for identifying competing stimuli, but also for actively establishing competing stimuli.


Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alpha-tocopherol.
A kinetic model of vitamin E transport in humans is described using data from our studies with deuterium-labeled stereoisomers of alpha-tocopherol (RRR- and SRR-). In normal subjects, both alpha-tocopherols are present at similar concentrations in chylomicrons, but by 24 hr, RRR-alpha-tocopherol is at higher plasma concentrations because RRR-alpha-tocopherol is preferentially incorporated into very low density lipoproteins, which are then secreted into plasma. In three nondiscriminator patients with familial isolated vitamin E deficiency, the fractional disappearance rates (mean +/- SD) of deuterium-labeled RRR- and SRR-alpha-tocopherols in plasma were 1.4 +/- 0.6 and 1.3 +/- 0.3 pools per day, respectively (difference, 0.1 +/- 0.3). In these patients, plasma concentrations of both RRR- and SRR-alpha-tocopherols decreased similarly to SRR-alpha-tocopherol in controls. In six controls, fractional disappearance rates of deuterium-labeled RRR-alpha-tocopherol (0.4 +/- 0.1 pool per day) were significantly (P < 0.01) slower than for SRR- (1.2 +/- 0.6). The differences (0.8 +/- 0.6 pool per day) between these two rates in controls estimate the rate at which RRR-alpha-tocopherol, which had left the plasma, was returned to the plasma. Although plasma labeled RRR-alpha-tocopherol concentrations in controls appear to change slowly, these data show that both RRR- and SRR-alpha-tocopherols leave the plasma rapidly, but only RRR-alpha-tocopherol is returned to the plasma, likely in nascent very low density lipoproteins. This recycling of RRR-alpha-tocopherol accounts for nearly 1 pool of alpha-tocopherol per day.


Development and characterization of mouse hybridomas.
Cell fusion protocols that were developed by Kohler and Milstein in the mid-1970s and aimed at producing and characterization of mouse monoclonal antibodies (MAbs) remain the gold standard of hybridoma development. Despite tremendous progress in using MAbs in multiple research, diagnostic, and therapeutic areas, major experimental flaws in designing and carrying out hybridoma experimentation often result in the production of hybridomas exhibiting poor growth parameters and secreting low-specificity and low-affinity antibodies. This methodology chapter is built around the conventional hybridoma protocol, with a special emphasis on tissue culture and biochemical techniques aimed at producing truly monospecific and highly active mouse MAbs.