Surgical treatment of pelvic organ prolapse in women aged ≥75 years in Hong Kong: a multicentre retrospective study.
Pelvic organ prolapse (POP) is common among older women. With the increasing lifespan and emphasis on quality of life worldwide, older women increasingly prefer surgical treatment for POP. We reviewed the surgical treatment of POP in older women to characterise its safety, effectiveness, and the type most often selected. This multicentre, retrospective study was conducted at four hospitals between 2013 and 2018. Included patients were aged ≥75 years and had undergone POP surgery. We compared patient demographic characteristics, POP severity, and surgical outcomes between reconstructive and obliterative surgeries; these comparisons were also made among vaginal hysterectomy plus pelvic floor repair (VHPFR), transvaginal mesh surgery (TVM), vaginal hysterectomy (VH) plus colpocleisis, and colpocleisis alone. In total, 343 patients were included; 84.3% and 15.7% underwent reconstructive and obliterative surgeries, respectively. Overall, 246 (71.7%), 43 (12.5%), 20 (5.8%), and 34 (9.9%) patients underwent VHPFR, TVM, VH plus colpocleisis, and colpocleisis alone, respectively. Patients who were older (81.9 vs 79.6 y; P=0.001), had vault prolapse (38.9% vs 3.5%; P<0.001), and had medical co-morbidities (37% vs 4.8%; P<0.001) chose obliterative surgery more frequently than reconstructive surgery. Obliterative surgeries had shorter operative time (73.5 min vs 107 min; P<0.001) and fewer surgical complications (9.3% vs 28.0%; P=0.003). Vaginal hysterectomy plus pelvic floor repair had the highest rate of surgical complications (most were minor), while colpocleisis alone had the lowest rate (30.1% vs 8.8%; P=0.01). Pelvic organ prolapse surgeries were safe and effective for older women. Colpocleisis may be appropriate as primary surgery for fragile older women.


Geometry of the nuclear envelope determines its flexural stiffness.
During closed mitosis in fission yeast, growing microtubules push onto the nuclear envelope to deform it, which results in fission into two daughter nuclei. The resistance of the envelope to bending, quantified by the flexural stiffness, helps determine the microtubule-dependent nuclear shape transformations. Computational models of envelope mechanics have assumed values of the flexural stiffness of the envelope based on simple scaling arguments. The validity of these estimates is in doubt, however, owing to the complex structure of the nuclear envelope. Here, we performed computational analysis of the bending of the nuclear envelope under applied force using a model that accounts for envelope geometry. Our calculations show that the effective bending modulus of the nuclear envelope is an order of magnitude larger than a single membrane and approximately five times greater than the nuclear lamina. This large bending modulus is in part due to the 45 nm separation between the two membranes, which supports larger bending moments in the structure. Further, the effective bending modulus is highly sensitive to the geometry of the nuclear envelope, ranging from twofold to an order magnitude larger than the corresponding single membrane. These results suggest that spatial variations in geometry and mechanical environment of the envelope may cause a spatial distribution of flexural stiffness in the same nucleus. Overall, our calculations support the possibility that the nuclear envelope may balance significant mechanical stresses in yeast and in cells from higher organisms.


Circulatory effects evoded by 'physiological' increases of arterial osmolality.
The effects of moderate arterial hyperosmolality (+20 mOsm/kg H2O), produced by short term intravenous hypertonic infusion, on vascular resistance in skin, skeletal muscle, intestine, and kidney were analyzed in the anesthetized cat. Vascular resistance decreased in all four regions in response to the hypertonicity both before and after regional sympathectomy and the effects were not significantly altered by beta-adreno-ceptor blockade. Arterial blood pressure rose during the hypertonic infusion despite the decreased vascular resistance and an unchanged heart rate, indicating an increased stroke volume and cardiac output. Similar increases of arterial osmolality are known to occur in heavy exercise and in hemorrhage. The present results may therefore suggest that blood borne hyperosmolality is a factor which can contribute to the overall cardiovascular adjustments in these situations.


Inhibition of parathyroid hormone bioactivity by human parathyroid hormone (PTH)-(3-84) and PTH-(8-84) synthesized in Escherichia coli.
Human PTH (hPTH)-(3-84) and hPTH-(8-84) were synthesized in Escherichia (E.) coli when the cells were transformed with a multicopy plasmid in which the transcription of human preproPTH cDNA is directed by the E. coli lac promoter. PTH fragments were extracted from cells and purified by reverse phase HPLC. PTH bioactivity and PTH antagonist activity were estimated in a renal cytochemical bioassay. hPTH-(3-84) and hPTH-(8-84) exhibited less than 1% and less than 0.1%, respectively, of the biological activity of synthetic hPTH-(1-84). hPTH-(8-84) had 1% of the PTH inhibitory activity of synthetic [Nle8,18,Tyr34]bovine PTH-(3-34)amide, whereas hPTH-(3-84) was 100 times more active as a PTH inhibitor than the synthetic bovine PTH-(3-34) analog. The latter has so far been recognized as the most potent PTH antagonist in vitro. A 5-fold molar excess of hPTH-(3-84) over hPTH-(1-84) completely blocked the biological action of intact hPTH-(1-84) in the renal cytochemical bioassay. These findings suggest that the carboxyl-terminal portion of the intact hPTH-(1-84) molecule contributes importantly to inhibitor potency.


The combined catalytic action of solid acids with nickel for the transformation of polypropylene into carbon nanotubes by pyrolysis.
The effects of both organically modified montmorillonite (OMMT) and Ni(2)O(3) on the carbonization of polypropylene (PP) during pyrolysis were investigated. The results from TEM and Raman spectroscopy showed that the carbonized products of PP were mainly multiwalled carbon nanotubes (MWNTs). Surprisingly, a combination of OMMT and Ni(2)O(3) led to high-yield formation of MWNTs. X-ray powder diffraction (XRD) and GC-MS were used to investigate the mechanism of this combination for the high-yield formation of MWNTs from PP. Brønsted acid sites were created in degraded OMMT layers by thermal decomposition of the modifiers. The resultant carbenium ions play an important role in the carbonization of PP and the formation of MWNTs. The degradation of PP was induced by the presence of carbenium ions to form predominantly products with lower carbon numbers that could be easily catalyzed by the nickel catalyst for the growth of MWNTs. Furthermore, carbenium ions are active intermediates that promote the growth of MWNTs from the degradation products with higher carbon numbers through hydride-transfer reactions. The XRD measurements showed that Ni(2)O(3) was reduced into metallic nickel (Ni) in situ to afford the active sites for the growth of MWNTs.


Mapping quantitative trait loci for cross-sectional geometry at the femoral neck.
A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X. Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees. A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately. Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males). This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.


A comparison of carteolol and nadolol in the treatment of stable angina pectoris.
In a multicenter, dose-ranging, double-blind study, 63 patients diagnosed as having stable angina pectoris were randomly assigned to treatment with carteolol (33 patients) or nadolol (30 patients). Following a 2 to 4-week dose-ranging period, an optimal dose was determined for each patient and treatment with that dose continued for 6 weeks. Data from all 63 patients were analyzed for drug safety; data for 52 patients (27 carteolol and 25 nadolol) were analyzed for drug efficacy. The most commonly chosen dosage levels were 20 mg of carteolol and 80 mg of nadolol. There were no statistically significant differences between the carteolol and nadolol groups in changes in exercise tolerance as reflected by time to onset of angina, end-point of exercise, and onset of 1 mm ST segment change on ECG. Both drugs significantly suppressed tachycardia and double product during treadmill exercise. The nadolol-treated group demonstrated a significantly greater reduction in resting heart rate (18.7 bpm) as compared with the carteolol-treated group (3.1 bpm). Carteolol possesses intrinsic sympathomimetic activity (ISA), which may account for the fact that carteolol effectively reduces exercise-induced tachycardia while producing relatively little effect on resting heart rate. The frequency of anginal attacks and the use of sublingual nitroglycerin were reduced to a similar extent in both treatment groups. The most commonly reported side effect in both treatment groups was asthenia.(ABSTRACT TRUNCATED AT 250 WORDS)


Cycle threshold values are inversely associated with poorer outcomes in hospitalized patients with COVID-19: a prospective, observational cohort study conducted at a UK tertiary hospital.
This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus disease 2019 (COVID-19). Demographic and outcome data were collected prospectively for all adult patients who tested positive for severe acute respiratory syndrome coronavirus-2 on admission to the University Hospitals North Midlands NHS Trust between 1 February and 1 July 2020. Nasopharyngeal swab samples were obtained, and a valid Ct value was determined for all patients using the Viasure reverse transcription polymerase chain reaction assay, validated by Public Health England, on admission to hospital. Multi-variable logistic regression results based on data from 618 individuals demonstrated a significant inverse relationship between the odds of death and Ct values (adjusted odds ratio 0.95, 95% confidence interval 0.92-0.98, P=0.001). The association remained highly significant after adjusting for known clinical risk factors for COVID-19.


Accurate measurements of fetal hemoglobin for neonates with different gestational ages.
The purposes of this study were to examine the accuracy of fetal hemoglobin (Hb F, alpha2gamma2) as quickly measured by a hemoximeter but verified by high performance liquid chromatography [HPLC, including Hb F total (Hb Ft), acetylated Hb F (Hb F1), and non acetylated Hb F ( Hb F*)], and to predict the Hb F levels for different gestational weeks of neonates. Thirty-nine neonates of predominantly Hispanic and African American ethnicity, with gestational ages ranging from 25 to 38 weeks, were investigated. Analyses were performed on 163 blood samples that were pure neonates' blood before the transfusion of any adult blood. Two neonates had increased Hb C [beta6(A3)Glu-->Lys, GAC-->AAG] levels (1.67-2.79%) and one neonate whose mother drank alcohol during pregnancy, had elevated Hb A2 levels (0.12-0.14%). After excluding these data points, the mean Hb F were overestimated by hemoximeter, 118.4 +/- 8.77% vs. 92.6 +/- 2.77% by HPLC (mean difference: 25.8 +/- 7.71%, p = <0.001). Mean Hb F1 was 10.5 +/- 2.28%. Hb F levels decreased as gestational age increased (p <0.001 for Hb Ft and Hb F*; p = <0.05 for Hb F1). A multivariate regression model for Hb F prediction was established with the best R2. The gestational age and post birth hours in the prediction of Hb Ft was included when Hb F could be determined at the clinical settings. Future studies may be needed to account for Hb F1 when measuring Hb F levels to assess oxygenation status in (pre term) neonates.


Contrast transesophageal echocardiography in diagnosing congenital enlargement of the right atrium--a case report.
Congenital malformation of the right atrium or the coronary sinus is rare, and cases are classified into 1 of the following 4 categories: (1) congenital enlargement of right atrium, (2) single diverticulum, (3) multiple diverticula of the right atrium, and (4) diverticulum of the coronary sinus. This report presents a 63-year-old man with cardiomegaly and no chest symptoms. A chest radiograph revealed an enlarged cardiac silhouette with a prominent right heart border. Although a transesophageal echocardiography revealed marked enlargement of the right atrium, neither further anomaly nor massive regurgitation was observed. The systolic pulmonary artery pressure derived from the peak velocity of mild tricuspid regurgitation was 38 mm Hg. Secondary enlargement of the right atrium due to atrial septal defect or pulmonary venous connection anomaly was deemed negligible by use of transesophageal contrast echocardiography, and primary enlargement of the right atrium was confirmed. Transesophageal echocardiography using ultrasound contrast was determined to be feasible for diagnosing congenital malformation of the right atrium.


Mutations affecting the activity of toxic shock syndrome toxin-1.
Toxic shock syndrome toxin-1 (TSST-1), the potent staphylococcal exoprotein linked to most cases of the toxic shock syndrome, is a V beta-restricted T-cell mitogen (a so-called "superantigen"). TSST-ovine (TSST-O) is a natural variant of TSST-1, and is produced by certain ovine mastitis-associated strains of Staphylococcus aureus. Compared to TSST-1, TSST-O is only weakly mitogenic for leporine or murine splenocytes. It differs from TSST-1 at 7 amino acid residues over its 194 amino acid length. Terminus shuffling between the two proteins has suggested that their C-terminal differences (T69, Y80, E132, and I140 in TSST-1; 169, W80, K132, and T140 in TSST-O) are in part responsible for their discrepant mitogenic properties. In order to explore further the functional consequences of altering TSST-1 at residues 132 and 140, we engineered point mutants of TSST-1 at those positions. The mutant proteins were purified to homogeneity from culture supernants of a nontoxigenic strain of S. aureus using a combination of ultrafiltration, liquid-phase isoelectric focusing, and ion-exchange chromatography. The mutants retained global structural integrity as evidenced by circular dichroism spectroscopy, their preserved resistance to trypsin digestion, and their preserved binding to a neutralizing murine monoclonal antibody. The mutants were then tested for mitogenicity for human T-cells: The mutant I140T was approximately as active as wild-type TSST-1, while the mutant E132D was about 10-fold attenuated. On the other hand, the mutants E132A or E132K were each at least 1000-fold attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypereosinophilia as a Preclinical Sign of Tongue Squamous Cell Cancer in a Gastric Cancer Patient with Complete Remission.
Although parasitic infestations and allergic disorders are the most common causes of eosinophilia it may also occompany malignant diseases. Many studies suggested that eosinophilia is related to tumor dissemination or necrosis. We are presenting a case; 10 months after gastric carcinoma operation who had severe eosinophilia with bone marrow and skin infiltration that gave response to steroid therapy. After three months, tongue squamous cell carsinoma as a second malignancy occurred in our patient that the eosinophilia could be the preclinical sign of the second cancer.


Hexagonal Layer Manganese Metal-Organic Framework for Photocatalytic CO2 Cycloaddition Reaction.
A novel manganese metal-organic framework (Mn-MOF) termed UAEU-50 assembled from a benzenedicarboxylate linker (BDC) and trinuclear manganese clusters was synthesized and fully characterized using different spectroscopic and analytic techniques (e.g., X-ray powder diffraction, UV-vis diffuse reflectance spectroscopy, thermogravimetric analysis, scanning electron microscopy, and energy-dispersive X-ray spectroscopy). UAEU-50 adopted a hexagonal layer structure and exhibited superior thermal stability and robust chemical stability. Photocatalytic activities of UAEU-50 were investigated using the cycloaddition of CO2 to different epoxides, forming cyclic carbonates. Impressively, UAEU-50 can transform up to 90% photocatalytic CO2 conversion to cyclic carbonates in the visible-light region at ambient conditions.


Attenuated total reflection Fourier transform infrared and polarization spectroscopy of in vivo human skin ablated, layer by layer, by erbium:YAG laser.
The results of an experimental study of the possibilities of monitoring erbium yttrium aluminum garnet laser-mediated ablation of human epidermis with the use of Fourier transform infrared (FTIR) spectroscopy and spectral polarization techniques are presented. The attenuated total reflection (ATR) method was used for FTIR spectroscopic measurements. Spectral polarization monitoring of the ablation was carried out by analyzing the spectra of the degree of residual linear polarization of a probe light diffusely reflected from the laser-treated region of skin. It was found that the analysis of FTIR spectra allows monitoring of the water and protein contents in the subsurface layers of the treated skin, while the degree of residual polarization measured at the wavelengths of maximal absorption of hemoglobin is sensitive to changes in the epidermis thickness and the blood content in the dermal layer (the degree of erythema).


[Traumatic rupture of the spleen. Histopathologic findings].
The most common causes of splenic rupture are blunt injury and surgical intervention in abdominal cavity. Morphological investigation of the spleen often shows but a small capsular laceration as well as haemorrhage and granulocytic infiltration in microscopy of its margins. The laceration may be sometimes difficult to find. There are two types of microscopical haemorrhage. One in sinus-lacking subcapsular tissue zone, the other in deeper layers. In this case the tissue haemorrhage is diffuse, sometimes within or around the marginal zone. The sinuses are neither collapsed nor obturated by any material even close to margins of the wound.


Serial body composition by bioimpedance analysis in a diabetic subject with rapid insulin-induced weight gain--a case report.
Insulin treatment is well known to induce progressive body weight gain. However, rapid weight increase due to transient fluid accumulation is rare. Bioelectrical impedance analysis (BIA) is a convenient method for determining body composition and water content. We report an 18-year-old diabetic female with rapid insulin-induced weight gain due to excessive body water retention, found by serial BIA measurement. The patient was admitted to our hospital due to uncontrolled diabetes. She had an initial body weight of 55 kg and height of 165 cm. However, a weight gain of 6.5 kg was noted one week after starting insulin injections and further increased to 8 kg after the second week. Finally a net weight increase of 4 kg from fat and lean mass was attained after two months. The weekly BIA data showed that most of the initial weight gain came from water retention, peaking on day 14 and recovering afterwards. Rapid weight gain shortly after insulin therapy may be due to excessive but reversible water retention, detected by repeated BIA measurements.


Reaching soldiers with untreated substance use disorder: lessons learned in the development of a marketing campaign for the Warrior Check-Up study.
The Warrior Check-Up, a confidential telephone-delivered intervention, is designed to reach active-duty soldiers with untreated substance-use disorder at a large U.S. military base. This paper describes the development and successful implementation of the study's marketing strategies at the recruitment period's midpoint (2010-2012). Qualitative analyses of focus groups (n = 26) and survey responses (n = 278) describe the process of campaign design. Measures of demographics, media exposure, post-traumatic stress, anxiety and depression gathered from callers (n = 172) are used in quantitative analysis assessing the campaign's success in reaching this population. Implications, limitations, and suggestions for future research are discussed. Department of Defense provided study funding.


Ta(CNDipp)6 : An Isocyanide Analogue of Hexacarbonyltantalum(0).
Hexakis(2,6-diisopropylphenylisocyanide)tantalum is the first isocyanide analogue of the highly unstable Ta(CO)6 and represents the only well-defined zerovalent tantalum complex to be prepared by conventional laboratory methods. Two prior examples of homoleptic Ta0 complexes are known, Ta(benzene)2 and Ta(dmpe)3 , dmpe=1,2-bis(dimethylphosphano)ethane, but these have only been accessed via ligand co-condensation with tantalum vapor in a sophisticated metal-atom reactor. Consistent with its 17-electron nature, Ta(CNDipp)6 undergoes facile one-electron oxidation, reduction, or disproportionation reactions. In this sense, it qualitatively resembles V(CO)6 , the only paramagnetic homoleptic metal carbonyl isolable under ambient conditions.


Stereospecificity in metallocene catalyzed acrylate polymerizations: the chiral orientation of the growing chain selects its own chain end enantioface.
The mechanism of stereocontrol in the site-controlled stereospecific polymerization of methyl methacrylate (MMA) with C2- and CS-symmetric zirconocenes is investigated with a DFT based approach. Our model explains the experimentally observed isospecificity in MMA polymerization with the C2-symmetric rac-C2H4(Ind)2Zr-based system as well as the experimentally observed syndiospecificity in MMA polymerization with the CS-symmetric Me2C(Cp)(Flu)Zr-based system. In both cases, the chiral metallocene induces a chiral orientation of the ester enolate growing chain. In turn, the chirally oriented growing chain selects its own enantioface. Comparison with the mechanism of stereocontrol operative in the case of propene polymerization by the same zirconocenes is performed to stress similarities and differences. Although analogies are expected, surprising differences also exist. The most peculiar is that the in the case of 1-olefins, the enantioselective event is selection between the enantiofaces of the prochiral monomer. Instead, in the case of acrylates, the enantioselective event is selection between the enantiofaces of the prochiral growing chain.


Culturally Responsive Pain Management for Black Older Adults.
HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS XX contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "XXXX XXXX XXXXXX XXXXXXX XXXX XXXX XXX XXX XXXX XX" found on pages XX-XX, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until MONTH XX, 20XX. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. XXX 2. XXX DISCLOSURE STATEMENT Neither the planners nor the author have any conflicts of interest to disclose. The management of pain for Black older adults has received inadequate attention by health care professionals despite evidence of greater pain intensity, depressive symptoms, and functional disability compared with White American older adults. Pain management for this population may be significantly improved with more careful attention to the provision of culturally responsive care. As professionals concerned with the optimization of health and reduction of suffering throughout the lifespan, nurses have an ethical, moral, and professional responsibility to provide culturally responsive care to the populations they serve-particularly when clear disparities in health exist. By considering how culture affects important health beliefs, values, preferences, and customs, and integrating this understanding into practice, quality of life is likely to be improved. [Journal of Gerontological Nursing, xx(x), xx-xx.].


Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells.
Nucleocytoplasmic transport refers to the import and export of large molecules from the cell nucleus. Recently, a number of studies have shown a connection between amyotrophic lateral sclerosis (ALS) and impairments in the nucleocytoplasmic pathway. ALS is a neurodegenerative disease affecting the motor neurons and resulting in paralysis and ultimately in death, within 2-5 years on average. Most cases of ALS are sporadic, lacking any apparent genetic linkage, but 10% are inherited in a dominant manner. Recently, hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene were identified as a genetic cause of ALS and frontotemporal dementia (FTD). Importantly, different groups have recently proposed that these mutants affect nucleocytoplasmic transport. These studies have mostly shown the final outcome and manifestations caused by HREs on nucleocytoplasmic transport, but they do not demonstrate nuclear transport dysfunction in real time. As a result, only severe nucleocytoplasmic transport deficiency can be determined, mostly due to high overexpression or exogenous protein insertion. This protocol describes a new and very sensitive assay to evaluate and quantify nucleocytoplasmic transport dysfunction in real time. The rate of import of a NLS-NES-GFP protein (shuttle-GFP) can be quantified in real time using fluorescent microscopy. This is performed by using an exportin inhibitor, thus allowing the shuttle GFP only to enter the nucleus. To validate the assay, the C9orf72 HRE translated dipeptide repeats, poly(GR) and poly(PR), which have been previously shown to disrupt nucleocytoplasmic transport, were used. Using the described assay, a 50% decrease in the nuclear import rate was observed compared to the control. Using this system, minute changes in nucleocytoplasmic transport can be examined and the ability of different factors to rescue (even partially) a nucleocytoplasmic transport defect can be determined.


Identification and immunoregulatory function of neuromedin U (Nmu) in the Japanese pufferfish Takifugu rubripes.
In this study, immunoregulatory function of neuromedin U (Nmu) in the teleost fish Fugu (Takifugu rubripes) was characterized. Three splicing variants of nmu mRNA encoding preproNMUs consisting of 164 (Nmu1), 139 (Nmu2), and 129 (Nmu3) amino acid residues were found in Fugu.The biologically active C-terminal region of Fugu Nmu showed high homology among fish and other vertebrate NMUs. The genomic organization of Fugu nmu differed from those of zebrafish and mammals. However, in phylogenetic analysis, Fugu Nmu formed a cluster with NMUs of other vertebrates, in addition to neuromedin S. The splicing variants of mRNA were identified in various tissues. Nmu-21 and Nmu-9 were purified as endogenous peptides from Fugu intestine. The synthetic Nmu-21 peptide activated phagocytic cells, and elevated the expression of cytokine mRNA in peripheral blood leukocytes.


Integrated computational approach to vibrationally resolved electronic spectra: anisole as a test case.
A new general and effective procedure to compute Franck-Condon spectra from first principles is exploited to elucidate the subtle features of the vibrationally resolved optical spectra of anisole. Methods based on the density functional theory and its time-dependent extension for electronic excited states [B3LYP6-311+G(d,p) and TD-B3LYP6-311+G(d,p)] have been applied to geometry optimizations and harmonic frequency calculations. Perturbative anharmonic frequencies [J. Chem. Phys. 122, 014108 (2005)] have been calculated for the ground state, and the Duschinsky matrix elements have been used to evaluate the corresponding anharmonic corrections for the first excited electronic state. The relative energetics of both electronic states has been refined by single point calculations at the coupled clusters (CC) level with the aug-cc-pVDZ basis set. Theoretical spectra have been evaluated using a new optimized implementation for the effective computation of Franck-Condon factors. The remarkable agreement between theoretical and experimental spectra allowed for revision of some assignments of fundamental vibrations in the S(1) state of anisole.


NF-kappaB functions in the nervous system: from development to disease.
The transcription factor nuclear factor-kappaB (NF-kappaB) is an ubiquitously expressed dimeric molecule with post-translationally regulated activity. Its role in the immune system and host defense has been well characterized over the last two decades. In contrast, our understanding of the function of this transcription factor in the nervous system (NS) is only emerging. Given their cytoplasmic retention and nuclear translocation upon stimulus, NF-kappaB members are likely to exert an important role in transduction of signals from synaptic terminals to nucleus, to initiate transcriptional responses. This report describes recent findings deciphering the diverse functions of NF-kappaB in NS development and activity, which range from the control of cell growth, survival and inflammatory response to synaptic plasticity, behavior and cognition. Particular attention is given to the specific roles of NF-kappaB in the various cells of the NS, e.g. neurons and glia. Current knowledge of the contribution of NF-kappaB to several neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's diseases is also summarized.


Photolysis of oxalyl chloride (ClCO)2 at 193 nm: emission of CO(v<or=6, J<or=60) detected with time-resolved Fourier-transform spectroscopy.
Upon photolysis of oxalyl chloride at 193 nm, time-resolved and rotationally resolved emission of CO(v<or=6, J<or=60) in the spectral region 1850-2350 cm(-1) was detected with a step-scan Fourier-transform spectrometer under nearly collisionless conditions. Boltzmann-type rotational distributions of CO correspond to temperatures 3520+/-110 (v=1) to 2300+/-610 K (v=6), with an average rotational energy of 23+/-2 kJ mol(-1). The average vibrational energy of CO is estimated to be 26+/-4 kJ mol(-1) according to observed vibrational populations of v=1-6 and that of v=0 predicted with a surprisal analysis. Combining the average internal energy of CO determined in this work and average translational energies of photofragments Cl and CO determined previously by Hemmi and Suits, we propose a four-body dissociation mechanism producing one pair of translationally rapid and internally excited CO and one pair of translationally rapid Cl, each with similar energies, to account for the energy balance. Formation of translationally slow ClCO, Cl, and CO reported previously by Hemmi and Suits might be rationalized with a second channel involving emission of electronically excited intermediates. We observed no emission of ClCO near 1880 cm(-1), indicating that surviving ClCO has little vibrational excitation in the C-O stretching mode.


[Investigation of diabetic men with erectile dysfunction to determine coronary flow reserve (CFR) and cardiac risk under medication with sildenafil (Viagra)].
Since Sildenafil (Viagra) has become available, there have been reports of death and cardiac risks associated with its use. As large doses of Sildenafil medication is often prescribed particularly in diabetic patients with erectile dysfunction (ED), our study was designed to evaluate the coronary flow reserve (CFR) and possible resulting cardiac risk specifically in diabetic men. Because these men often suffer from clinically significant ischaemic heart problems without their knowledge and without symptoms, all of our patients were examined by treadmill ECG and CFR. In 44 men (35 - 74 years) with type I and II diabetes also suffering from ED objectified by FCDS measurement of the penile vessels, a surprisingly high rate of objective cardiac problems were found, which were then verified by coronary angiography. These patients are at risk for ischaemic problems during Sildenafil-assisted intercourse and were excluded from further study. Interestingly, only 3 of theses 11 men would have been detected by conventional examinations. Patients free of coronary stenosis who received 50 mg Sildenafil (20 patients) showed no cardiac problems during treadmill exercise and CFR measurement. Coronary flow reserve in diabetic men lies at the lower end of the normal range, but is not further decreased by Sildenafil. However, diabetics with ED frequently showed coronary artery stenosis that was not clinically symptomatic. Furthermore, conventional cardiological examinations often fail to detect these patients, although they are at ischaemic risk during medically assisted intercourse. Furthermore, although 5 of 20 men who received Sildenafil had an increase in penile blood flow without sexual stimulation, only 7 of 20 were responders to Sildenafil after take home medication. Thus, Sildenafil medication is not a suitable test medication for organic erectile dysfunction.


Swelling of the breast following augmentation mammaplasty and minimally invasive cardiac surgery.
Complications following breast augmentation procedures occur in the acute setting, usually in the form of hematoma, seroma, wound breakdown or infection. Late complications of augmentation mammaplasty usually manifest as either a failure of the prosthesis (eg, leak, rupture) or capsular contracture. We present an interesting case of a hematoma following augmentation mammaplasty that occurred 7 years postoperatively. What makes this case particularly intriguing is that in the time period between the augmentation mammaplasty and the late hematoma, the patient underwent minimally invasive cardiac surgery to treat a malfunctioning mitral valve. Ultimately, the breast implant was salvaged and the patient obtained a very satisfactory result. This case is important to report because as more women choose to have breast augmentation procedures and as more people have minimally invasive cardiac surgery, this clinical scenario will be encountered with greater frequency. We also make several suggestions that we feel may help avoid the problems seen with this patient in the future.


Muscle abnormalities in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research.


Informant Discrepancies in the Assessment of Adaptive Behavior of Children with Autism Spectrum Disorder.
This study examined informant discrepancies for parent and teacher adaptive behavior ratings of 103 children, ages 6-12 years, with ASD (without intellectual disability). Scores on the Adaptive Behavior Assessment System, third edition (Harrison and Oakland, Western Psychological Services, Los Angeles, 2015) General Adaptive Composite (GAC) and practical, social, and conceptual domains were examined for mean differences, level of agreement, and moderators of difference scores between informant groups. Teacher scores were significantly higher (indicating better functioning) than parents for the GAC and practical domain. Parent and teacher scores were moderately correlated and Bland-Altman plots and regression analyses revealed no systematic differences in parent-teacher agreement across the range of scores. None of the tested variables moderated the parent-teacher difference scores. Implications for clinical practice are discussed.


Laboratory and field measurements of dry deposition of sulfur dioxide onto Chinese loess surfaces.
Laboratory and field measurements were conducted to examine dry deposition of SO2 onto Chinese loess surfaces using native soil sampled in the loess plateau, China. The field tests were employed in Beijing and Lanzhou, China, by directly measuring the dry deposition of SO2 on soil, which uses soil put on a collector as an SO2 passive sampling medium. In the laboratory, a high rate of uptake to SO2 deposition for Chinese soil surfaces due to the highly alkalinity was found. The uptake of SO2 deposition was dependent on the pH soil and relative humidity. Furthermore, we evaluated some factors that affect the measurement precision: response of SO2 uptake, repeatability, recovery factor, and variability associated with the weight and the surface coverage on the collectors. As a result, it was shown that the measurement precision was primarily related to the ratio of the SO2 deposition amount relative to the sulfur content of the original soil. This result was consistent with the field observations. The laboratory and field results indicated an excellent agreement on the SO2 uptake inherent in the results from the soil surfaces in different regions.


Psychiatric comorbidity in juvenile myoclonic epilepsy.
To assess the prevalence of psychiatric disturbances among patients with juvenile myoclonic epilepsy (JME). Forty-three patients with JME (22 female, 21 male, mean age 32.4+/-13, range 15-63) were assessed by means of the Structured Clinical Interviews for DSM-IV (SCID-I and SCID-II). Current and lifetime psychiatric diagnoses were assigned. Thirty-five percent of the JME patients suffered from one or more psychiatric disorders (Axis I and Axis II). Personality disorders were present in 23% and Axis I disorders in 19%. Altogether, 47% had a psychiatric disorder at any time of their life. Psychiatric diagnoses are slightly higher than in representative community samples. The substantially increased number of personality disorders in JME patients might be attributed to frontal lobe deficits.


Immunohistochemical study of the local humoral immune system of the equine respiratory mucosa.
An indirect immunoperoxidase technique was used to demonstrate both free immunoglobulin and immunoglobulin-containing plasma cells of IgG, IgA, and IgM classes in the mucosa of the equine respiratory tract. IgA-producing plasma cells predominated in the upper airways, whereas IgG-producing cells predominated in the lower respiratory tract. IgM-secreting cells were uncommon, but present in their highest numbers in the nasopharynx. Plasma cells specific for all of the immunoglobulin classes were identified in the surface epithelium, lamina propria connective tissue, glandular tissue and organised lymphoid tissue. The surface epithelium stained strongly for free IgA and IgM, but weakly for IgG, whereas glandular cells and the lamina propria connective tissue stained most strongly for IgG.


Structure, dynamics and solvation of HIV-1 protease/saquinavir complex in aqueous solution and their contributions to drug resistance: molecular dynamic simulations.
As it is known that the understanding of the basic properties of the enzyme/inhibitor complex leads directly to enhancing the capability in drug designing and drug discovery. Molecular dynamics simulations have been performed to examine detailed information on the structure and dynamical properties of the HIV-1 PR complexed with saquinavir in the three protonated states, monoprotonates at Asp25 (Mono-25) and Asp25'(Mono-25') and diprotonate (Di-Pro) at both Asp25 and Asp25'. The obtained results support clinical data which reveal that Ile84 and Gly48 are two of the most frequent residues where mutation toward a protease inhibitor takes place. In contrast to the Ile84 mutation due to high displacement of Ile84 in the presence of saquinavir, source of the Gly48 mutation was observed to be due to the limited space in the HIV-1 PR pocket. The Gly48 was, on one side, found to form strong hydrogen bonds with saquinavir, while on the other side this residue was repelled by the hydrophobic Phe53 residue. In terms of inhibitor/enzyme binding, interactions between saquinavir and a catalytic triad of the HIV-1 PR were calculated using the ab initio method. The results show an order of the binding energy of Mono25<Di-pro<<Mono-25', suggesting that the active site in the HIV-1 PR complexed with saquinavir is monoprotonated states on Asp25. In contrast to the binding energy, 3, 6 and 12 hydrogen bonds between saquinavir and HIV-1 PR were found for the Mono-25, Mono-25' and Di-pro states, respectively. Discrepancy between the two trends suggests us to conclude that interaction between inhibitor and catalytic residues should be used as a criteria to enhance capability in drug designing and drug screening instead of using the total inhibitor/enzyme interaction which is normally reported in the literature. In addition, the distribution and binding of water molecules, in terms of hydrogen bonding, to the donor atoms of saquinavir were investigated and discussed, referring to that which was reported experimentally.


Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events.
Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil-dependent hyperalgesia in the rat. The purpose of the present study was to examine the pathological consequence of NGF injected intradermally into mature rat skin and to examine further the role of neutrophils. Standard histopathology techniques (H & E) were employed to determine inflammatory cell counts. Circulating neutrophils were depleted using an anti-rat neutrophil antiserum and results were compared to treatment with vehicle controls. Saline-pretreated rats exhibited normal circulating neutrophil numbers and the dorsal skin showed a significant increase of neutrophil and macrophages at 3 and 5 h and lymphocytes at 5 h after NGF treatment. By comparison, skin sites from neutrophil-depleted rats did not demonstrate a significant increase in neutrophil and macrophage accumulation after NGF administration. All NGF-treated sites, independent of pretreatment, demonstrated abnormal muscle fibre morphology and proliferation of the muscle sarcolemmal nuclei after NGF injection, indicative of tissue injury. In addition, oedema and some fibroplasia were also noted. Furthermore, fibrin production was increased at 3 and 5 h after NGF administration. It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF-induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil-depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration.


Correlation between P300 and EEG rhythm in schizophrenia.
We hypothesized that cognitive deficits reflected by P300 abnormality and distorted EEG rhythm in schizophrenia, which might share the subcortical generation system, could be closely associated with each other. Our goal is to assess the relationship between P300 and EEG rhythm generation in schizophrenics. Quantitative EEG (QEEG) in resting condition and P300 during auditory oddball paradigm were recorded with 25 unmedicated patients. Additionally, lateral ventricular-brain ratio (LV-BR), which partially reflects thalamic volume, was measured using CT scan. Brief Psychotic Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS) were also rated. P300 amplitudes at Pz positively correlated with theta and slow alpha power before pharmacotherapy, however, the correlation tended to be confined to fast alpha after pharmacotherapy. BPRS and SANS showed no significant correlation with QEEG. High frequency bands such as fast alpha and beta showed trends to correlate negatively to LV-BR. The lack of correlation between P300 amplitudes and fast alpha power before pharmacotherapy, which was restored after pharmacotherapy, might indicate thalamocortical dysfunction in schizophrenia.


ROTS: An R package for reproducibility-optimized statistical testing.
Differential expression analysis is one of the most common types of analyses performed on various biological data (e.g. RNA-seq or mass spectrometry proteomics). It is the process that detects features, such as genes or proteins, showing statistically significant differences between the sample groups under comparison. A major challenge in the analysis is the choice of an appropriate test statistic, as different statistics have been shown to perform well in different datasets. To this end, the reproducibility-optimized test statistic (ROTS) adjusts a modified t-statistic according to the inherent properties of the data and provides a ranking of the features based on their statistical evidence for differential expression between two groups. ROTS has already been successfully applied in a range of different studies from transcriptomics to proteomics, showing competitive performance against other state-of-the-art methods. To promote its widespread use, we introduce here a Bioconductor R package for performing ROTS analysis conveniently on different types of omics data. To illustrate the benefits of ROTS in various applications, we present three case studies, involving proteomics and RNA-seq data from public repositories, including both bulk and single cell data. The package is freely available from Bioconductor (https://www.bioconductor.org/packages/ROTS).


Influence of stubble burning on air quality of Northern India: a case study of Indo-Gangetic plains of India.
Stubble burning is an emerging environmental issue in Northern India, which has severe implications for the air quality of the region. Although stubble burning occurs twice during a year, first during April-May and again in October-November due to paddy burning, the effects are severe during October-November months. This is exacerbated by the role of meteorological parameters and presence of inversion conditions in the atmosphere. The deterioration in the atmospheric quality can be attributed to the emissions from stubble burning which can be perceived from the changes observed in land use land cover (LULC) pattern, fire events, and sources of aerosol and gaseous pollutants. In addition, wind speed and wind direction also play a role in changing the concentration of pollutants and particulate matter over a specified area. The present study has been carried out for the states of Punjab, Haryana, Delhi, and western Uttar Pradesh to study the influence of stubble burning on the aerosol load of this region of Indo-Gangetic Plains (IGP). In this study, the aerosol level, smoke plume characteristics, long-range transport of pollutants, and affected areas during October-November from year 2016 to 2020 were examined over the Indo-Gangetic Plains (Northern India) region by the satellite observations. By MODIS-FIRMS (Moderate Resolution Imaging Spectroradiometer-Fire Information for Resource Management System) observations, it was revealed that there was an increase in stubble burning events with the highest number of events being observed during the year 2016 and then a decrease in the number of events in subsequent years from 2017 to 2020. MODIS observations revealed a strong AOD gradient from west to east. The prevailing north-westerly winds assist the spread of smoke plumes over Northern India during the peak burning season of October to November. The findings of this study might be used to expand on the atmospheric processes that occur over northern India during the post-monsoon season. The pollutant, smoke plume features, and impacted regions of biomass-burning aerosols in this region are critical for weather and climate research, especially given the rising trend in agricultural burning over the previous two decades.


Soft materials deformation, flow, and lubrication between compliant substrates: impact on flow behavior, mouthfeel, stability, and flavor.
Foods are rationally designed to be semifluids or soft solids for optimal stabilization of the multiple phases they contain and to provide favorable textural properties. Although rheology provides a guide to physical stability and initial texture perception, measurements on intact foods do not enable predictions of the organoleptic properties experienced during oral processing. Oral processing includes lubrication between compliant oral substrates, and studies into soft lubrication/tribology are providing new insights into the physical processes experienced by soft foods in the mouth. We provide a review of the key rheological considerations for food product stability and texture, and we delve into how rheology and soft tribology, with consideration for oral physiology and saliva, are providing new insights into texture, mouthfeel, taste, and aroma.


The search for mechanisms of change in behavioral treatments for alcohol use disorders: a commentary.
Definitive results from efforts to identify mechanisms of change in behavioral treatments for alcohol use disorders have been elusive. The working hypothesis guiding this paper is that one of the reasons for this elusiveness is that the models we hypothesize to account for treatments effectiveness are unnecessarily restricted and too simple. This paper aims to accomplish 3 things. First, a typography for locating potential mediators of change will be presented. In the course of doing so, a nomenclature will be proposed with the hope that this will facilitate communications among alcohol treatment researchers studying mechanisms of change. Second, alternatives to the classic test of mediation of alcohol treatment effects will be considered and one such alternative described. Third, alternative ways of conceptualizing, constructing and analyzing variables to measure mediators will be suggested. It is hoped that this commentary will facilitate research on mechanisms of change in behavioral treatments for alcohol use disorders. Behavioral change is a complex process, and the models that we develop to account for this process need to reflect this complexity. Advances in statistical approaches for testing mediation, along with a better understanding as to how to use these tools should help in moving toward this goal.


[Humeroradial plica: frequency and visualization on MRI].
To determine frequency and size of a humeroradial plica and correlate it with degenerative changes, and to determine frequency of the visualization of a synovial fold on MR-Images (T1-weighted spin-echo and STIR sequences) and correlate it with degenerative changes. Forty-two elbow specimens were dissected and studied for humeroradial synovial folds (small, medium, large) and degenerative changes (absent, medium, strong), and 88 elbow MR-images were analyzed for a synovial fold (not visible, small, large) and degenerative changes (absent, medium, strong). Comparison was performed using the chi (2) test. Dissections revealed a synovial fold in all cases. The sizes were small in n = 13 (31 %), medium in n = 24 (57 %), and large in n = 5 (12 %). Degenerative changes were absent in n = 9 (21.4 %), medium in n = 29 (69 %), and strong in n = 4 (9.6 %). On MRI the synovial fold was not visible in n = 67 (76 %), small in n = 12 (14 %), and large in n = 9 (10 %). Degenerative changes on MRI were absent in n = 65 (74 %), medium in n = 15 (17 %), and strong in n = 8 (9 %). The size of the fold correlated positively with degenerative changes in the specimen but not with degenerative changes on MRI. The T1-SE sequence was superior to the STIR sequence in revealing the synovial fold. A humeroradial plica is a regular finding, but visualized by MRI in only approximately 20 %, probably due to its variable size. Its visualization succeeds best with T1-spin-echo sequences.


Risk of contralateral breast cancer associated with common variants in BRCA1 and BRCA2: potential modifying effect of BRCA1/BRCA2 mutation carrier status.
Rare deleterious mutations in BRCA1 and BRCA2 are associated with an elevated risk of breast and ovarian cancer. Whether or not common variants in these genes are independently associated with risk of breast cancer remains unclear. In this study, we included 632 Caucasian women with asynchronous contralateral breast cancer (CBC, cases) and 1,221 women with unilateral breast cancer (UBC, controls) from the WECARE (Women's Environment, Cancer and Radiation Epidemiology) Study. BRCA1 and BRCA2 deleterious mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing, yielding including 88 BRCA1 and 60 BRCA2 deleterious mutation carriers. We also genotyped samples on the Illumina Omni1-Quad platform. We assessed the association between CBC risk and common (minor allele frequency (MAF) > 0.05) single-nucleotide polymorphisms (SNPs) in BRCA1 (n SNPs = 22) and BRCA2 (n SNPs = 30) and haplotypes using conditional logistic regression accounting for BRCA1/BRCA2 mutation status. We found no significant associations between any single-SNPs or haplotypes of BRCA1 or BRCA2 and risk of CBC among all women. When we stratified by BRCA1 and BRCA2 mutation carrier status, we found suggestive evidence that risk estimates for selected SNPs in BRCA1 (rs8176318, rs1060915, and rs16940) and BRCA2 (rs11571686, rs206115, and rs206117) may differ in non-carriers and carriers of deleterious mutations in BRCA1 and BRCA2. One common haplotype on BRCA1 was inversely significantly associated with risk only among non-BRCA1 and BRCA2 carriers. The association between common variants in BRCA1 and BRCA2 and risk of CBC may differ depending on BRCA1 and BRCA2 mutation carrier status.


Near field communication: getting in touch with mobile users.
Near field communication is a method for sending and receiving small amounts of data across very short distances wirelessly. This technology is already available in a number of mobile devices and has many possible uses, including electronic payment, access control, and information exchange. This article will explain the basic principles of near field communication, discuss some of the ways it can be used in libraries, and explore some possible concerns with the technology. A list of resources for additional information is also included.


Hydroxybutyl Chitosan Polymer-Mediated CD133 Antibody Coating of Metallic Stents to Reduce Restenosis in a Porcine Model of Atherosclerosis.
Antibody-coated stents to capture circulating endothelial progenitor cells (EPCs) for re-endothelialization appear to be a novel therapeutic option for the treatment of atherosclerotic disease. Hydroxybutyl chitosan (HBC), a linear polysaccharide made from shrimps and other crustacean shells, is biocompatible, nontoxic, and hydrophilic, making it ideal for biomedical applications. In this study, HBC was explored for the immobilization of anti-CD133 antibodies. We demonstrated that CD133 antibodies mediated by HBC were successfully coated on cobalt-chromium alloy discs and metal stents. The coating was homogeneous and smooth as shown by electronic microscopy analysis. Balloon expansion of coated stents did not cause cracking or peeling. The HBC discs promoted CD133+ EPCs and human umbilical vein endothelial cell growth in vitro. The CD133 antibody-coated but not bare discs bound CD133+ EPCs in vitro. Implantation of CD133 antibody-coated stents significantly inhibited intimal hyperplasia and reduced restenosis compared with implantation of bare stents in a porcine model of atherosclerosis. These findings suggest HBC is a valuable anchoring agent that can be applied for bioactive coating of stents and that CD133 antibody-coated stents might be a potential therapeutic alternative for the treatment of atherosclerotic disease.


Exposure therapy for substance abusers with PTSD: translating research to practice.
Epidemiological research indicates that there is substantial comorbidity between posttraumatic stress disorder (PTSD) and substance use disorder (SUD). Moreover, there is growing evidence that having a comorbid PTSD diagnosis is associated with greater substance use problem severity and poorer outcomes from SUD treatment. In an attempt to improve the treatment outcome for individuals with PTSD-SUD, recently developed treatments combine exposure therapy for PTSD with an empirically supported treatment for SUD. This article describes one of the treatments and discusses treatment modifications that have been incorporated when translating this research-based therapy to practice in an inner-city community mental health center.


AUDIT (Alcohol Use Disorders Identification Test) to Estimate the Pattern and Correlates of Alcohol Consumption among the Adult Population of West Bengal, India: A Community Based Cross-sectional Study.
Pattern of alcohol consumption substantially changed in India with in last 20 to 25 years. Excessive alcohol consumption is a major risk factor for various morbidity and mortality. So, scientific study to identify alcohol consumption patterns and its correlates will be helpful to formulate preventive strategies. To estimate the pattern of alcohol consumption and to determine its correlates, among the adult population of the state of West Bengal in India. A community based cross-sectional study was conducted among the adult population of the state of West Bengal at Gram Panchayat (GP) level. Ninety-nine (n=99) adult (≥ 18 years) men and women of Guchati GP at Paschim Medinipur district, was selected using Lot Quality Assurance Sampling (LQAS) technique. The study participants were interviewed using a pre-designed and pre-tested schedule. It was estimated that the prevalence of low risk drinking or abstinence (Zone I) was 65.5% (95% CI 55.5% to 75.5%) and the prevalence of alcohol use in excess of low-risk (Zone II) was 17.6% (95% CI 7.6% to 27.6%), and the prevalence of harmful and hazardous drinking (Zone III) was 8.5% (95% CI 0% to 18.5%) and the prevalence alcohol dependence (Zone-IV) was 8.4% (0% to 18.4%). Logistic regression model shows that "gender" (p = 0.00) and "employment status" (p = 0.01) added significantly to the model with adjusted odds ratio of 82.27 (95% CI 18.17-372.58) and 0.13 (0.03-0.66). There is a need for comprehensive screening and treatment programme to deal with the problems of Alcohol Use Disorders among adults to achieve good health and well being for sustainable development.


Distinction in the mode of receptor-mediated endocytosis between high density lipoprotein and acetylated high density lipoprotein: evidence for high density lipoprotein receptor-mediated cholesterol transfer.
The interactions of high density lipoprotein (HDL) and acetylated high density lipoprotein (acetyl-HDL) with isolated rat sinusoidal liver cells have been investigated. Cellular binding of 125I-acetyl-HDL at 0 degrees C demonstrated the presence of a specific, saturable membrane-associated receptor. This receptor was affected neither by formaldehyde-treated albumin nor by low density lipoprotein modified either by acetylation or malondialdehyde, ligands known to undergo receptor-mediated endocytosis by the cells, indicating that the receptor for acetyl-HDL constitutes a distinct class among the scavenger receptors for chemically modified proteins. Parallel binding experiments using 125I-HDL also revealed the presence on these cells of a receptor for unmodified HDL. The ligand specificities of these two receptors were similar to each other except that the acetyl-HDL receptor was sensitive to polyanions such as dextran sulfate and fucoidin. Interaction of HDL with the cells at 37 degrees C was totally different from that of acetyl-HDL. Cellular binding of HDL was not accompanied by subsequent intracellular degradation of its apoprotein moiety, whereas its cholesterol moiety was significantly transferred to the cells. In contrast, acetyl-HDL was endocytosed and underwent lysosomal degradation as a holoparticle. This shift in receptor-recognition from the HDL receptor to the acetyl-HDL receptor was accomplished by acetylation of approximately 8% of the total lysine residues of HDL apoprotein. This unique difference in endocytic behavior between HDL and acetyl-HDL suggests a potential link of the HDL receptor to HDL-mediated cholesterol transfer in sinusoidal liver cells.


Controlled growth of filamentous fatty acid vesicles under flow.
The earliest forms of cellular life would have required a membrane compartment capable of growth and division. Fatty acid vesicles are an attractive model of protocell membranes, as they can grow into filamentous vesicles that readily divide while retaining their contents. In order to study vesicle growth, we have developed a method for immobilizing multilamellar fatty acid vesicles on modified glass surfaces and inducing filamentous membrane growth under flow. Filament formation strictly depended on the presence of freshly neutralized fatty acid micelles in the flow chamber. Using light microscopy, we observed a strong dependence of initial growth velocity on initial vesicle size, suggesting that new fatty acid molecules were incorporated into the membrane over the entire external surface of the vesicle. We examined the influences of flow rate, fatty acid concentration, and salt concentration on filamentous growth and observed drastic shape changes, including membrane pearling, of preexisting membrane tubules in response to osmotic stress. These results illustrate the versatility of flow studies for exploring the process of fatty acid vesicle growth following exposure to free fatty acids.


Children and television tipovers: a significant and preventable cause of long-term neurological deficits.
Television tipover has recently been recognized as a significant cause of injury in children, and head injury accounts for most of the associated deaths. The authors reviewed their experience with children who sustained head injury from falling televisions. Children admitted with the diagnosis of head injury related to falling televisions since 1992 were identified from the authors' trauma database, and a retrospective review of the medical records was performed. Eighteen patients were identified: 13 boys and five girls whose ages ranged from 12 months to 10 years (mean 44 months). The admission Glasgow Coma Scale (GCS) score was 15 in 10 patients. Only three patients had a GCS score of 8 or less (one patient had a score of 4). Neurological examinations were normal in 10 patients; three had cranial nerve deficits and three had otorrhea, otorrhagia, or hemotympanum. Radiological abnormalities included 16 skull fractures, three epidural hematomas, three small subdural hematomas, one intracranial hemorrhage, and three venous obstructions of the transverse-sigmoid sinus. The mean hospital stay was 8.9 days (range 2-39 days). Follow up at 0.2 to 68 months (mean 13.4 months) revealed severe neurological deficits in one patient and cranial nerve deficits of cranial nerves six, seven, or eight in six patients. Falling televisions result in significant head injuries in children, with substantial short- and long-term sequelae. This injury is easily preventable through simple measures taken by both the manufacturers and caregivers.


AAV Vectorization of DSB-mediated Gene Editing Technologies.
Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs), CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes are enhanced substrates for homology-directed repair in the presence or absence of targeted DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies. This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight into its trending applications for the treatment of genetic diseases.


Protective effect of Japanese green tea extract on gnotobiotic mice infected with an Escherichia coli O157:H7 strain.
We examined the effect of Japanese green tea extract (JGTE) on enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection in a gnotobiotic mouse model. Gnotobiotic mice inoculated with an EHEC strain developed neurologic and systemic symptoms, usually culminating in death. In contrast, none of mice receiving dietary JGTE showed clinical signs or death. This report describes the effect of JGTE, which includes the inhibition of bacterial growth in vivo. The Shiga-like toxin (SLT) level in the feces of the JGTE diet group was significantly lower than that of the control group.


Intracoronary ultrasound and angioscopic imaging facilitating the understanding and treatment of post-infarction angina.
We report on the use of intravascular ultrasound, coronary angioscopy and on-line quantitative angiography in an unstable patient soon after myocardial infarction. Combined intracoronary imaging made it possible to solve the therapeutic problem posed by an unusual angiographic appearance secondary to intracoronary thrombolysis during coronary recanalization. The pathological validation of the observations performed with angioscopy and intravascular ultrasound was made possible with the concomitant use of directional atherectomy.


A prospective longitudinal study of early cognitive development in tuberous sclerosis - a clinic based study.
We report a prospective longitudinal study of cognitive development in a series of 20 clinic-referred infants with Tuberous Sclerosis. The infants were seen between the ages of 11 and 37 months and were assessed regularly at 6-month periods using a within-subjects repeated measures design. Assessment using the Mullen Scales of Early Learning, a measure of cognitive and motor showed that with the exception of one child, all children had composite developmental quotients that fell into the mentally retarded range of intellectual functioning. In general, the infants' developmental quotients changed little between 12 and 36 months of age. Developmental progress was evident; however, with small incremental changes in raw scores for subjects over the course of the study. In three children, the developmental quotient changed by more than 20 points during the course of the study. The findings are considered in relation to the neurobiological risk factors for cognitive development in Tuberous Sclerosis.


Porous and nonporous silk fibroin (SF) membranes wrapping for Achilles tendon (AT) repair: Which one is a better choice?
Two types of silk fibroin (SF) membranes were developed for tendon repair: porous and nonporous SF membranes. The objective of this study was to compare the efficiency of these two films according to the ability of tendon regeneration using a rat Achilles tendon (AT) rupture suture wrapping model. The in vitro tests were conducted, and theSF membranes were proved to be with ultimate-biodegradability, good-biocompatibility and without toxicity. In vivo, 12 Sprague Dawley rats were used to create a rat AT rupture suture model wrapped by SF membranes. They were randomly divided into six groups. The results revealed that the nonporous SF membrane wrapping group was shown to reduce the inflammatory effect and induce the proliferation of fibroblast-like cells at one week and four weeks post-operatively. After four weeks, the nonporous SF membrane wrapping group exhibited more organized collagen structures and had increased expression of tendon repair proteins. Hence, our nonporous SF membrane improved the efficacy of tendon regeneration by decreasing inflammatory cells, growing fibroblast-like cells, and promoting extracellular matrix production. Nonporous SF membrane can, therefore, be regarded as a better functional membrane for tendon repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 733-740, 2019.


A Comparative Study of the Validity and Reliability of Two Wireless Telemetry Electrocardiogram Devices in the Emergency Medicine Department.
BACKGROUND This study aimed to compare the clinical validity and reliability of two wireless telemetry electrocardiogram (ECG) devices in the Emergency Medicine Department. MATERIAL AND METHODS Patients who attended the Emergency Medicine Department underwent wireless telemetry ECG testing (N=245) using the Infron Micro Cor and the Nihon Kohden Cardiofax M 1350 K devices. ECG recordings included heart rate, P-wave amplitude, PR segment length, QRS duration, QT and QTc intervals, ST depression and elevation, the number of ECG artifacts, the ECG diagnosis, and duration. Statistical analysis of reliability included the use of Cohen's kappa (κ) values. RESULTS One hundred women (40.8%) and 145 men (59.2%) were included in the study. The duration for the Infron Micro Cor ECG readings (57.5±0.93 seconds) was significantly shorter compared with the Nihon Kohden Cardiofax M ECG readings (65.2±9.72 seconds) (p=0.0001). The Infron Micro Cor ECG readings contained significantly more lead artifacts (93 or 37.9%) compared with the Nihon Kohden ECG readings (71 or 28.9%) (p=0.01). There was no difference between the two devices in terms of the other ECG parameters. The compatibility of ST-segment elevation detection was found to be almost in complete agreement between the Infron Micro Cor and Nihon Kohden Cardiofax M ECG devices, as determined by the k-values for ST elevation and ST depression. CONCLUSIONS Two wireless telemetry ECG devices were found to be reliable for use in the Emergency Medicine Department. The Infron Micro Cor wireless telemetry ECG device provided more rapid results.


[Switzerland changes from U-40 to U-100 insulin].
At present over 95% of the insulin used in Switzerland is sold in a concentration of 40 units per ml (U-40 insulin). Only recently a small but increasing amount of more concentrated insulin has been introduced through the use of "pen" injectors which are all designed for U-100 (= 100 units per ml) insulin. Experience in other countries has shown that when different insulin concentrations are available on the market the risk of dosage errors with potentially severe consequences is high. The Swiss Diabetes Association has therefore taken the initiative in standardizing the concentrations available in Switzerland. A change from U-40 and U-100 to exclusively U-100 insulin is planned for the period from October 1988 to March 1989. A survey among 82 Swiss doctors and 243 IDDM patients has shown that about 60% of doctors and patients are in favour of the change while the remaining 40% are either neutral or opposed to it. Advantages, disadvantages and logistic problems of the change to exclusive use of U-100 insulin, and the possibility of pharmacological differences between insulins of different concentrations, are discussed. It is stressed that the change to U-100 must be medically supervised in every patient. An intensive information campaign providing detailed advice for patients, doctors and pharmacists is essential for the prevention of accidents.


[Acute organophosphorus intoxications in pregnant women].
Acute organophosphorus pesticides (OPs) poisoning during pregnancy are rare events, not well documented in the literature. We conducted a retrospective analysis of outcomes in seven cases of suicidal ingestion of OP in pregnant women. This intoxication was most often serious. Indeed, five of seven parturients had an initial Glasgow score < 9 and the POP score was ≥ 3 in all parturients. Five patients required mechanical ventilation for a mean duration of 3,4 days. All patients reported favorable outcomes but in more than half of the cases fetuses had unfavorable outcomes (fetal death in utero). Two mechanisms can explain these fetal complications. The first mechanism is fetal hypoxia, associated or not with a state of shock, which can be reflected in the Fetal Heart Rate (FHR) by tachycardia or decelerations and result in intrauterine fetal death. The second mechanism is the passage of these pesticides through the placental barrier representing a potential risk to the fetus due to the alteration of the microsomal enzyme systems.


Cytosolic malate dehydrogenase activity helps support glycolysis in actively proliferating cells and cancer.
Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal glycolytic enzyme, lactate dehydrogenase (LDH). However, loss of glucose carbons to biosynthetic pathways early in glycolysis reduces the carbon supply to LDH. Thus, alternative routes for NAD regeneration must exist to support the increased glycolytic rate while allowing for the diversion of glucose to generate biomass and support proliferation. Here we demonstrate, using a variety of cancer cell lines as well as activated primary T cells, that cytosolic malate dehydrogenase 1 (MDH1) is an alternative to LDH as a supplier of NAD. Moreover, our results indicate that MDH1 generates malate with carbons derived from glutamine, thus enabling utilization of glucose carbons for glycolysis and for biomass. Amplification of MDH1 occurs at an impressive frequency in human tumors and correlates with poor prognosis. Together, our findings suggest that proliferating cells rely on both MDH1 and LDH to replenish cytosolic NAD, and that therapies designed at targeting glycolysis must consider both dehydrogenases.


The genomic landscape of metastatic breast cancer: Insights from 11,000 tumors.
Metastatic breast cancer is the leading cause of cancer death in women, but the genomics of metastasis in breast cancer are poorly studied. We explored a set of 11,616 breast tumors, including 5,034 metastases, which had undergone targeted sequencing during standard clinical care. Besides the known hotspot mutations in ESR1, we observed a metastatic enrichment of previously unreported, lower-prevalence mutations in the ligand-binding domain, implying that these mutations may also be functional. Furthermore, individual ESR1 hotspots are significantly enriched in specific metastatic tissues and histologies, suggesting functional differences between these mutations. Other alterations enriched across all metastases include loss of function of the CDK4 regulator CDKN1B, and mutations in the transcription factor CTCF. Mutations enriched at specific metastatic sites generally reflect biology of the target tissue and may be adaptations to growth in the local environment. These include PTEN and ASXL1 alterations in brain metastases and NOTCH1 alterations in skin. We observed an enrichment of KRAS, KEAP1, STK11 and EGFR mutations in lung metastases. However, the patterns of other mutations in these tumors indicate that these are misdiagnosed lung primaries rather than breast metastases. An order-of-magnitude increase in samples relative to previous studies allowed us to detect novel genomic characteristics of metastatic cancer and to expand and clarify previous findings.


Electrochemical Oxidation of Para-Aminophenol With Rare Earth Doped Lead Dioxide Electrodes: Kinetics Modeling and Mechanism.
In this study, La and Ce doped PbO2 electrodes were prepared and the characteristic of the electrodes were discussed with the help of structure analysis. The catalytic effects of the doped electrodes were explored through the degradation of para-aminophenol wastewater. The results showed that the para-aminophenol removal was 96.96%, 89.34%, and 77.55% after 180 min treatment with Ce-PbO2, La-PbO2, and PbO2, respectively. The para-aminophenol enhanced degradation mechanism was discussed with rare earth element doping electrodes and a kinetic model was established based on radical reactions mechanism with genetic algorithm (GA) calculation. The reaction constants of these electrodes were calculated and the results showed that the reaction constant of Ce-PbO2 electrode was the highest, which indicated that Ce-PbO2 electrode could have a better treatment effect. The EE/O was used as the index of energy consumption efficiency and the results were calculated and compared. This paper could provide basic data and technique reference of the prediction the oxidation reaction process of different electrodes for the electrochemical oxidation application in wastewater treatment.


Validation and verification of the ICRP biokinetic model of 32P: the criticality accident at Tokai-Mura, Japan.
Regrettably, a criticality accident occurred at a uranium conversion facility in Tokai-mura, Ibaraki, Japan, on 30 September 1999. Radioactivities of 32P in urine, blood and bone samples of the victims, who were severely exposed to neutrons, were measured. 32P was induced in their whole bodies at the moment of the first nuclear release by the reaction 31P (n, gamma) 32P and 32S (n, p) 32P. A realistic biokinetic model was assumed, as the exchange of 32P between the extracellular fluid compartment and the soft tissue compartment occurs only through the intracellular compartment, and the model was used for preliminary calculations. Some acute excretion of 32P, caused by decomposition or elution of tissues which occurred at the time of the accident, may have happened in the victims' bodies in the first few days. The working hypotheses in the present work should initiate renewed discussion of 32P biokinetics.


The inhibitor protein of the F1F0-ATP synthase is associated to the external surface of endothelial cells.
The ATPase inhibitor protein (IP) of mitochondria was detected in the plasma membrane of living endothelial cells by flow cytometry, competition assays, and confocal microscopy of cells exposed to IP antibodies. The plasma membranes of endothelial cells also possess beta-subunits of the mitochondrial ATPase. Plasma membranes have the capacity to bind exogenous IP. TNF-alpha decreases the level of beta-subunits and increases the amount of IP, indicating that the ratio of IP to beta-subunit exhibits significant variations. Therefore, it is probable that the function of IP in the plasma membrane of endothelial cells is not limited to regulation of catalysis.


Function and control of human invasive trophoblast subtypes: Intrinsic vs. maternal control.
The establishment of a functional placenta is pivotal for normal fetal development and the maintenance of pregnancy. In the course of early placentation, trophoblast precursors differentiate into highly invasive trophoblast subtypes. These cells, referred to as extravillous trophoblasts (EVTs), penetrate the maternal uterus reaching as far as the inner third of the myometrium. One of the most fundamental functions of EVTs is the transformation of spiral arteries to establish the uteroplacental blood circulation assuring an adequate nutrient and gas supply to the developing fetus. To achieve this, specialized EVT subpopulations interact with maternal immune cells, provoke elastolysis in the arterial wall and replace the endothelial cells lining the spiral arteries to induce intraluminal vascular remodeling. These and other trophoblast-mediated processes are tightly controlled by paracrine signals from the maternal decidua and furthermore underlie an intrinsic cell-type specific program. Various severe pregnancy complications such as preeclampsia or intrauterine growth retardation are associated with abnormal EVT function, shallow invasion, and decreased blood flow to the placenta. Hence a better understanding of human trophoblast invasion seems mandatory to improve therapeutic intervention. This approach, however, requires a profound knowledge of the human placenta, its various trophoblast subtypes and in particular a better understanding of the regulatory network that controls the invasive phenotype of EVTs.


Recent Advances and Future Prospects of Aggregation-induced Emission Carbohydrate Polymers.
Aggregation-induced emission (AIE) is an abnormal phenomenon that has sparked great attention for diverse applications in different fields. In particular, the fabrication and biological imaging applications of AIE-active fluorescent organic nanoparticles (FONs) have become a focus in the emerging and promising fields. A large number of AIE-active polymeric nanoprobes have recently been fabricated through different strategies. The advances and progress in this direction have also recently been summarized by some groups. However, the fabrication and biomedical applications of AIE-active FONs based on carbohydrate polymers and AIE-active dyes are quite rare and limited. In this feature article, the recently reported AIE-active FONs with different structures and applications based on AIE-active dyes and carbohydrate polymers are highlighted, and the major current limitations and development tendencies are also discussed.


Formation and properties of stabilized aluminum nanoparticles.
The wet-chemical synthesis of aluminum nanoparticles was investigated systematically by using dimethylethylamine alane and 1-methylpyrrolidine alane as precursors and molecules with one or a pair of carboxylic acid groups as surface passivation agents. Dimethylethylamine alane was more reactive, capable of yielding well-defined and dispersed aluminum nanoparticles. 1-Methylpyrrolidine alane was less reactive and more complex in the catalytic decomposition reaction, for which various experimental parameters and conditions were used and evaluated. The results suggested that the passivation agent played dual roles of trapping aluminum particles to keep them nanoscale during the alane decomposition and protecting the aluminum nanoparticles postproduction from surface oxidation and that an appropriate balance between the rate of alane decomposition (depending more sensitively on the reaction temperature) and the timing in the introduction of the passivation agent into the reaction mixture was critical to the desired product mixes and/or morphologies. Some fundamental and technical issues on the alane decomposition and the protection of the resulting aluminum nanoparticles are discussed.


Efficacy of human serum butyrylcholinesterase against sarin vapor.
Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male Göttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.


Coherence analysis of EEG changes during olfactory stimulation.
In a pilot study, EEG changes during odor stimulation were evaluated by coherence analysis. Ten normal adults were studied. Simultaneous recordings of 16 EEG channels with and without odor stimulation were stored on magnetic tape for further processing. EEG signals were analyzed using a signal analyzer. Coherence spectra were calculated between all possible channel pairs on the scalp. The amount of data was reduced by extracting broad band coherence values for five frequency bands: delta (2-3.9 Hz), theta (4-7.9 Hz), alpha 1 (8-9.9 Hz), alpha 2 (10-12.9 Hz), and beta 1 (13-17.9 Hz). Coherence values extracted from the control EEG recordings and those during odor stimulation were compared to evaluate the presence of any significant differences. The results demonstrated significant changes in the EEG coherence between the two control recordings (before and after) in the theta and beta 1 bands. These frequency bands were therefore excluded from the examination. During odorant stimulation with methyl-cyclopentenolone, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the bilateral temporal region. During odorant stimulation with scatol, the coherence in the delta band decreased in the frontal region, while that in the alpha 1 and alpha 2 bands increased in the frontal, temporal and occipital regions. It is suggested that EEG coherence mapping may provide the basis for the development of an objective test of olfactory function in humans.


Potential Role of Humoral IL-6 Cytokine in Mediating Pro-Inflammatory Endothelial Cell Response in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with limited therapeutic options. Numerous intrinsic and extrinsic factors are involved in ALS motor neuron degeneration. One possible effector accelerating motor neuron death in ALS is damage to the blood-Central Nervous System barrier (B-CNS-B), mainly due to endothelial cell (EC) degeneration. Although mechanisms of EC damage in ALS are still unknown, vascular impairment may be initiated by various humoral inflammatory factors and other mediators. Systemic IL-6-mediated inflammation is a possible early extrinsic effector leading to the EC death causing central nervous system (CNS) barrier damage. In this review, we discuss the potential role of humoral factors in triggering EC alterations in ALS. A specific focus was on humoral IL-6 cytokine mediating EC inflammation via the trans-signaling pathway. Our preliminary in vitro studies demonstrated a proof of principle that short term exposure of human bone marrow endothelial cells to plasma from ALS patient leads to cell morphological changes, significantly upregulated IL-6R immunoexpression, and pro-inflammatory cell response. Our in-depth understanding of specific molecular mechanisms of this humoral cytokine in EC degeneration may facilitate an endothelial-IL-6-targeting therapy for restoring cell homeostasis and eventually reestablishing B-CNS-B integrity in ALS.


Psychological disorders in adults with inherited cardiomyopathies and Takotsubo syndrome.
We performed a narrative review about psychological disorders in adults with Takotsubo syndrome and inherited cardiomyopathies. Through the electronic database PubMed and PsycINFO we searched all relevant related manuscripts published between 2000 and 2015. We found twelve studies that explore psychological disorders in Takotsubo syndrome and eight about inherited cardiomyopathies: five enrolled patients with hypertrophic cardiomyopathy, two dilated cardiomyopathy, and one arrhythmogenic right ventricular cardiomyopathy. All papers reported the presence of psychological disorders. In Takotsubo syndrome, depression fluctuates between 20.5 and 48% and anxiety was present among 26 and 56%. A study reported that anxiety increases the probability of developing Takotsubo syndrome. In dilated cardiomyopathy, anxiety was present in 50% and depression in 22%. In arrhythmogenic right ventricular cardiomyopathy, younger age, poorer functional capacity and having experienced at least one implantable cardioverter defibrillator shock, were significant independent predictors of both device-specific and generalized anxiety. In hypertrophic cardiomyopathy, anxiety and depression were present in 45.2% and 17.9%, respectively. Thirty seven percent met diagnostic criteria for anxiety disorders and 21% for mood disorders. Nearby half hypertrophic cardiomyopathy patients report triggering of chest pain, dyspnea, and dizziness by emotional stress. Due to the small number of studies, conclusions are limited. However, we discuss some results.


Hairy-cell leukemia with the appearance of mixed cryoglobulinemia and vasculitis.
Hairy-cell leukemia has been associated with a number of disorders of the immune system. At least 13 cases of vasculitis and hairy-cell leukemia have been reported. However, the occurrence of cryoglobulinemia and hairy-cell leukemia is rare. We report a case of a patient with the unusual combination of hairy-cell leukemia, vasculitis, and cryoglobulinemia. This case illustrates that hairy-cell leukemia should now be included in the differential diagnosis of patients with the appearance of vasculitis and cryoglobulinemia. The association presents a therapeutic challenge and emphasizes the need for individualized treatment in such patients.


Desmoid Tumors Respond to Sorafenib.
A recent clinical trial shows that sorafenib is effective against desmoid tumors. The study found that 33% of tumors shrank in patients who received the drug. The estimated 1-year progression-free survival for the sorafenib-treated patients was 89%, and the 2-year rate was 81%.


Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and molecular methods.
To evaluate neonatal screening for cystic fibrosis (CF), including study of the screening procedures and characteristics of false-positive infants, over the past 10 years in Wisconsin. An important objective evolving from the original design has been to compare use of a single-tier immunoreactive trypsinogen (IRT) screening method with that of a two-tier method using IRT and analyses of samples for the most common cystic fibrosis transmembrane regulator (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10 additional CFTR mutations in the screening protocol. From 1985 to 1994, using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates, respectively, were screened for CF. For the IRT protocol, neonates with an IRT >/=180 ng/mL were considered positive, and the standard sweat chloride test was administered to determine CF status. For the IRT/DNA protocol, samples from the original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110 ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA test revealed one or two DeltaF508 alleles, a sweat test was obtained. Both screening procedures had very high specificity. The sensitivity tended to be higher with the IRT/DNA protocol, but the differences were not statistically significant. The positive predictive value of the IRT/DNA screening protocol was 15.2% compared with 6.4% if the same samples had been screened by the IRT method. Assessment of the false-positive IRT/DNA population revealed that the two-tier method eliminates the disproportionate number of infants with low Apgar scores and also the high prevalence of African-Americans identified previously in our study of newborns with high IRT levels. We found that 55% of DNA-positive CF infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding analyses for 10 more CFTR mutations has only a small effect on the sensitivity but is likely to add significantly to the cost of screening. Advantages of the IRT/DNA protocol over IRT analysis include improved positive predictive value, reduction of false-positive infants, and more rapid diagnosis with elimination of recall specimens.


Validity of an Abbreviated, Clinically Feasible Test for Postprandial Lipemia in Healthy Adults: A Randomized Cross-Over Study.
A large post-meal triglyceride (TG) response is an independent risk factor for cardiovascular disease, but postprandial lipemia assessments are not clinically practical in their current form. Therefore, we assessed the validity of an abbreviated, clinically feasible protocol in measuring postprandial lipemia. Eighteen healthy adults (8 male and 10 female) completed 3 high-fat meal trials in random order: (1) a Standard in Lab (SL) protocol wherein blood draws (to determine TG) were made from a catheter at baseline and hourly for 6 h; (2) an Abbreviated in Lab (AL) protocol in which participants remained in the laboratory but blood draws were only made at baseline and 4 h post-meal; and (3) an Abbreviated with Freedom (AF) protocol in which participants vacated the laboratory between the meal and the 4-h blood draw. TG increase from baseline was very similar (p = 0.93) across the 3 trials (SL: 68.5 ± 62.7 mg/dL; AL: 71.1 ± 58.0 mg/dL; AF: 66.7 ± 46.4 mg/dL), as were 4-h TG levels (SL: 144.6 ± 84.2 mg/dL; AL: 171.4 ± 88.2 mg/dL; AF: 157.7 ± 76.7 mg/dL; p = 0.49). Similarly, total and incremental area under the curve (AUC) were not significantly different across the trials (p = 0.12 and 0.91, respectively). The TG results of the clinically feasible, abbreviated protocol were similar to those of the more exhaustive standard protocol. The AF protocol could be a valid and feasible clinical tool for measurement of postprandial lipemia and assessment of cardiovascular risk, although studies in larger and more diverse cohorts are needed.