Uniformity of carbohydrate chains within molecular variants of rat alpha 1-fetoprotein with distinct affinity for concanavalin A.
Three rat alpha 1-fetoprotein fractions were obtained by chromatography on concanavalin-A--Sepharose: one non-reactive, one weakly reactive and one reactive to concanavalin A. The non-reactive and reactive variants were found to vary in the structure of their carbohydrate chains while the conformation of the weakly reactive form may modulate the accessibility of these chains to the lectin. N-Glycosidically linked glycans from unfractionated alpha 1-fetoprotein were isolated and chemically characterized. Particular attention was paid to develop sensitive methods based upon hydrazinolysis, quantitative re-N-acetylation of glycans with [14C]acetic anhydride and thin-layer chromatography of labeled compounds. With the aid of these methods two main kinds of glycans (1a and 2a) were obtained and fractionated on concanavalin-A--Sepharose into non-reactive (1a) and reactive (2a) molecules. Moreover it was demonstrated that each alpha 1-fetoprotein variant contained either two glycans 1a or two glycans 2a, not randomly, but a pair of the identical carbohydrate chains at the two glycosylation sites.


Intrinsic Bond Energies from a Bonds-in-Molecules Neural Network.
Neural networks are being used to make new types of empirical chemical models as inexpensive as force fields, but with accuracy similar to the ab initio methods used to build them. In this work, we present a neural network that predicts the energies of molecules as a sum of intrinsic bond energies. The network learns the total energies of the popular GDB9 database to a competitive MAE of 0.94 kcal/mol on molecules outside of its training set, is naturally linearly scaling, and applicable to molecules consisting of thousands of bonds. More importantly, it gives chemical insight into the relative strengths of bonds as a function of their molecular environment, despite only being trained on total energy information. We show that the network makes predictions of relative bond strengths in good agreement with measured trends and human predictions. A Bonds-in-Molecules Neural Network (BIM-NN) learns heuristic relative bond strengths like expert synthetic chemists, and compares well with ab initio bond order measures such as NBO analysis.


Use of oral antidiabetic agents and risk of community-acquired pneumonia: a nested case-control study.
To evaluate the association between use of different oral antidiabetic agents (OAD) and the risk of community-acquired pneumonia (CAP) in patients with type-2 diabetes (T2DM). Case-control study nested in a cohort of patients with T2DM and use of OAD between 2002 and 2013, based in a Spanish general practice research database. Cases were people diagnosed with T2DM, aged >18 years and with a validated diagnosis of CAP between 2002 and 2013. Ten controls were matched on age, sex and calendar year. Odds ratio (OR) of CAP was estimated comparing patients treated with: (1) metformin vs. other monotherapies or no antidiabetic treatment; (2) metformin + sulfonylureas vs. other antidiabetic combinations. OR of CAP was also assessed according to antidiabetic treatment duration. From a cohort of 76 009 T2DM patients, we identified 1803 cases of CAP. No difference in the incidence of CAP was observed when comparing any OAD in monotherapy with metformin. Compared with current use of metformin + sulfonylurea, thiazolidinediones + metformin was associated with an increased risk of CAP (adjusted OR = 2.48, 95% CI 1.40-4.38). The use of any combination with thiazolidinediones was also associated with higher risk of CAP (adjusted OR = 2.00, 95% CI 1.22-3.28). Current use of DPP-4 inhibitors was not associated with an increased risk of CAP. No differences in the incidence of CAP were observed between the use of OAD in monotherapy vs. metformin. Thiazolidinedione use in combination was associated with an increase in the risk of CAP when compared to metformin + sulfonylureas. The use of DPP-4 inhibitors was not associated with an increased risk of CAP.


Effectiveness of Fertility Awareness-Based Methods for Pregnancy Prevention: A Systematic Review.
To summarize best available prospective data on typical and perfect use effectiveness of fertility awareness-based methods for avoiding pregnancy. We conducted a systematic review of studies published in English, Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. We reviewed 8,755 unique citations and included 53 studies that contained 50 or greater women using a specific fertility awareness-based method to avoid pregnancy, calculated life table pregnancy probabilities or Pearl rates, and prospectively measured pregnancy intentions and outcomes. We systematically evaluated study quality. Of 53 included studies, we ranked 0 high quality, 21 moderate quality, and 32 low quality for our question of interest. Among moderate-quality studies, first-year typical use pregnancy rates or probabilities per 100 woman-years varied widely: 11.2-14.1 for the Standard Days Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method, 4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double-check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus Method. First-year perfect use pregnancy rates or probabilities among moderate-quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method, 1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method, 0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor. Studies on the effectiveness of each fertility awareness-based method are few and of low to moderate quality. Pregnancy rates or probabilities varied widely across different fertility awareness-based methods (and in some cases, within method types), even after excluding low-quality studies. Variability across populations studied precludes comparisons across methods.


Payment for deliveries in Sierra Leone.
The type and amount of payment for deliveries were investigated in 1982 during a survey on health status in two districts. Data on the payments made for 83.5% of the 2591 deliveries in 535 randomly selected study villages showed that the most common method of payment was in cash only. Payments in kind were mostly given to trained traditional birth attendants (TBAs) (for 38.1% of their deliveries) and rare for professional staff (2.9% of deliveries). The total amount paid for a delivery differed significantly with the type of birth attendant (P less than 0.00001) and the place of delivery (hospital, peripheral health unit or home) (P less than 0.00001). The total average payment for a delivery was highest for professional birth attendants (Le 16.60) and lowest for untrained TBAs (Le 4.85) (Le 2 = approx. US+ 1 at the time of the study). The outcome of a delivery had a significant effect on the amount paid. Payments were significantly higher for stillbirths than for live births among professional and auxiliary birth attendants (P less than 0.0001). However, the trained and untrained TBAs received less payment for stillbirths (Le 2.25) than for live births (Le 4.89) (P = 0.0146). The results show that there are several levels of financial disincentives for pregnant women requiring the services of trained auxiliary or professional health workers at the time of delivery.


Avidin-like domain in an epidermal growth factor homolog from a sea urchin.
We have found that a protein from the purple sea urchin has a carboxyl-terminal domain with striking sequence similarity to chicken avidin and bacterial streptavidin. All our evidence supports the homology of these sequences. Tetramers of avidin and streptavidin bind biotin strongly; the biotin binding site involves two to four tryptophans and probably an adjacent lysine in each chain. The presence of four tryptophans at equivalent positions in the sea urchin protein domain suggests that it may also be able to bind biotin and inhibit cell growth, as do the two other proteins. Alternatively, this domain may have acquired a new role as part of a multidomain protein.


Development of a large-scale continuous substrate feed process for the biotransformation of simvastatin by Nocardia s.p.
This article describes a process for microbial hydroxylation of simvastatin by a Nocardia sp. Simvastatin (Zocor) belongs to the family of HMGCoA reductase inhibitors used as cholesterol-lowering drugs. Studies at 14 L scale showed that high substrate (simvastatin) concentrations inhibited product formation; consequently, continuous slow feeding of the substrate was introduced to maintain low residual simvastatin concentrations. Dissolved oxygen levels above 50% air saturation were desirable for the biotransformation. The process was scaled up to 19,000-L fermentors using an on-line filter sterilization system for substrate feeding. The feed rate was regulated by off-line high-pressure liquid chromatography (HPLC) assays to keep the substrate concentration below 20 mg/L. Intermittent addition of nutrients helped to boost the bioconversion rate to give final titers of 400 mg/L 6-beta-hydroxymethyl simvastatin. Enrichment of the nutrient medium led to bioconversion titers of 800 mg/L 6-beta-hydroxymethyl simvastatin. Bioconversion efficiencies (desired product/substrate) of 22-25% with a ratio of desired product/side products of 0.7 were obtained by this process.


Differentiation margins of ovarian tumor pathology: first incidences of epithelial ovarian tumors monitored by marker antibodies.
The first incidence of ovarian tumors in The Netherlands was analyzed during the PALGA data. The first incidences of benign epithelial ovarian tumors reach a plateau, at a level of 60 to 65 cases per 100,000 women beyond the age of 40 years. The borderline malignant epithelial ovarian tumors account for 10 per 100,000 women aged 30 to 85, while the ovarian carcinomas reach a plateau level of 25 to 35 per 100,000 women after the age of 50. Despite the long lag period (+/- 10 years) between benign and malignant ovarian tumors, the question of whether or not all epithelial ovarian cancers develop via an intermediate step of cystadenomas is still unanswered. Therefore, we examined whether the expression pattern of intermediate filaments and tumor antigens in normal, benign, and malignant ovarian tissues might contribute to this question. The following changes in expression pattern were observed: generally, all tumor cells retained the keratin profile of the corresponding original cell type. However, in a limited number of tumor samples ectopic keratin types, such as nos. 4, 10, 13, and 14, became expressed additionally. Most epithelial ovarian tumors and mesothelial cells coexpressed vimentin. The panepithelial marker BW495/36 clearly distinguished between negatively stained normal ovarian surface mesothelium and the positively stained (inclusion) cystic epithelium. TAG-72 as well as OV-632 marked a subsequent tumor stage by discriminating between negative serous adenomas and positive serious carcinomas. TAG-72, however, stained both mucinous adenomas and carcinomas. The ovarian tumor markers (OC125, OV-TL 33, OV-TL16, MOv18), all showed an increasing expression level in the sequence order from normal cells to benign and malignant ovarian tumors. Both our epidemiological and our immunohistochemical data have shown that in the Dutch population there is a lag period of at least 10 years between the plateau levels of benign and malignant ovarian tumors. The early transformation of mesothelial cells to benign and/or malignant tumors is clearly marked by a switch on of the BW495/36 marker. Although no general transformation or progression marker from adenomas to carcinomas emerged from this study, TAG-72 might be considered a (progression) marker between the subgroup of benign and malignant serous ovarian tumors.


Electrocatalytic oxidation of hydroxylamine on glassy carbon electrodes modified by hybrid copper-cobalt hexacyanoferrate films.
An electrochemical sensor for amperometric detection of hydroxylamine was developed by electrodeposition of hybrid copper-cobalt hexacyanoferrate films on a glassy carbon electrode. The modified electrode could reduce the overpotential of the hydroxylamine oxidation by about 400 mV. This sensor exhibited a linear relationship between the response current and the hydroxylamine concentration in the range of 1.8 x 10(3) M to 4.6 x 10(-6) M with a detection limit of 2.1 x 10(-7) M. Good agreement was obtained between results from the present method and conventional UV-visible spectrophotometry results. The sensor had good recovery, stability and anti-interference ability.


Nursing students experience during the COVID-19 pandemic: a qualitative research.
To describe the professional practice experiences of fifth year nursing students during the COVID-19 pandemic. Qualitative research design with content analysis. Participant sampling was purposive. 13 fifth-year nursing students participated. All of them completed their professional clinical practice in public hospitals and private clinics who cared for COVID-19 patients in Chile. The data were obtained through guided online written self-reflections. Three main themes were inductively identified: (1) Facing with a very difficult and stressful situation, due to the permanent use of personal protection elements, multiple emotions, and physical fatigue, as well as facing ethical-clinical dilemmas in daily tasks; (2) Recognising different coping styles in difficult moments, highlighting contact with significant people and combination form of support and harmful ways of coping with stress; and (3) Experiences disciplinary learning and personal growth, such as: nursing care management, interpersonal skills in times of crisis and having contributed to the country in this adverse context. The clinical experience of the students in times of COVID-19, was an opportunity to learn how to perform nursing care in times of crisis, humanize care and support health teams in some of the country's hospitals.


Enucleation after argon laser photocoagulation for choroidal melanoma.
We report the case of a choroidal melanoma 3 disc-diameter in size and 1 mm in thickness located superiorly at 2 disc-diameters from the optic disc. Argon laser photocoagulation was done in 1977. No recurrence was observed for eight years. In 1985, the melanoma suddenly reappeared, invading the posterior pole and causing secondary retinal detachment. The histologic examination after enucleation revealed a spindle-cell melanoma. Considering the fluorescein angiographic findings, we question the effectiveness of argon laser photocoagulation of choroidal melanoma.


Metastatic Breast Cancer with BRCA Mutation Discovered By Next-Generation Sequencing Responding to Olaparib.
Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) mutations are associated with hereditary breast and ovarian cancer syndromes (HBOC). However, certain individuals with breast cancer do not meet high-risk factors for hereditary breast cancer screening based on age, family history, and biology of malignancy. We present a patient with relapsed breast cancer who developed progressive disease with significant tumor burden causing a recurrent pleural effusion. Next-generation sequencing (NGS) done on a tumor biopsy was positive for the BRCA2 mutation. Olaparib was initiated with a resolution of the pleural effusion and a significant decrease in the size of the malignant lymphadenopathy and pulmonary lesions. There are numerous reports of comprehensive molecular profiling improving access to therapy, most notably for lung cancer, as well as melanoma. However, this has not been widely utilized for breast cancer. However, in our case, NGS provided our patient with an effective therapy and should be considered for the future management of metastatic breast cancer.


Understanding generalized inversions of nuclear magnetic resonance transverse relaxation time in porous media.
The nuclear magnetic resonance transverse relaxation time T2, measured using the Carr-Purcell-Meiboom-Gill (CPMG) experiment, is a powerful method for obtaining unique information on liquids confined in porous media. Furthermore, T2 provides structural information on the porous material itself and has many applications in petrophysics, biophysics, and chemical engineering. Robust interpretation of T2 distributions demands appropriate processing of the measured data since T2 is influenced by diffusion through magnetic field inhomogeneities occurring at the pore scale, caused by the liquid/solid susceptibility contrast. Previously, we introduced a generic model for the diffusion exponent of the form -ante(k) (where n is the number and te the temporal separation of spin echoes, and a is a composite diffusion parameter) in order to distinguish the influence of relaxation and diffusion in CPMG data. Here, we improve the analysis by introducing an automatic search for the optimum power k that best describes the diffusion behavior. This automated method is more efficient than the manual trial-and-error grid search adopted previously, and avoids variability through subjective judgments of experimentalists. Although our method does not avoid the inherent assumption that the diffusion exponent depends on a single k value, we show through simulation and experiment that it is robust in measurements of heterogeneous systems that violate this assumption. In this way, we obtain quantitative T2 distributions from complicated porous structures and demonstrate the analysis with examples of ceramics used for filtration and catalysis, and limestone of relevance to the construction and petroleum industries.


Hyperthymic affective temperament and hypertension are independent determinants of serum brain-derived neurotrophic factor level.
Brain-derived neurotrophic factor (BDNF) has neuroprotective, proangiogenic and myogenic effects and, therefore, possibly acts as a psychosomatic mediator. Here, we measured serum BDNF (seBDNF) level in hypertensive patients (HT) and healthy controls (CONT) and its relation to affective temperaments, depression and anxiety scales, and arterial stiffness parameters. In this cross-sectional study, affective temperaments, anxiety, and depression were studied with questionnaires (TEMPS-A, HAM-A, and BDI, respectively). SeBDNF level and routine laboratory parameters were measured as well. Arterial stiffness was evaluated with a tonometric method. Allover, 151 HT, and 32 CONT subjects were involved in the study. SeBDNF level was significantly higher in HT compared to CONT (24880 ± 8279 vs 21202.6 ± 6045.5 pg/mL, p < 0.05). In the final model of regression analysis, hyperthymic temperament score (Beta = 405.8, p = 0.004) and the presence of hypertension (Beta = 6121.2, p = 0.001) were independent determinants of seBDNF. In interaction analysis, it was found that in HT, a unit increase in hyperthymic score was associated with a 533.3 (95 %CI 241.3-825.3) pg/mL higher seBDNF. This interaction was missing in CONT. Our results suggest a complex psychosomatic involvement of BDNF in the pathophysiology of hypertension, where hyperthymic affective temperament may have a protective role. BDNF is not likely to have an effect on large arteries.


Modulation of CFTR gating by permeant ions.
Cystic fibrosis transmembrane conductance regulator (CFTR) is unique among ion channels in that after its phosphorylation by protein kinase A (PKA), its ATP-dependent gating violates microscopic reversibility caused by the intimate involvement of ATP hydrolysis in controlling channel closure. Recent studies suggest a gating model featuring an energetic coupling between opening and closing of the gate in CFTR's transmembrane domains and association and dissociation of its two nucleotide-binding domains (NBDs). We found that permeant ions such as nitrate can increase the open probability (Po) of wild-type (WT) CFTR by increasing the opening rate and decreasing the closing rate. Nearly identical effects were seen with a construct in which activity does not require phosphorylation of the regulatory domain, indicating that nitrate primarily affects ATP-dependent gating steps rather than PKA-dependent phosphorylation. Surprisingly, the effects of nitrate on CFTR gating are remarkably similar to those of VX-770 (N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide), a potent CFTR potentiator used in clinics. These include effects on single-channel kinetics of WT CFTR, deceleration of the nonhydrolytic closing rate, and potentiation of the Po of the disease-associated mutant G551D. In addition, both VX-770 and nitrate increased the activity of a CFTR construct lacking NBD2 (ΔNBD2), indicating that these gating effects are independent of NBD dimerization. Nonetheless, whereas VX-770 is equally effective when applied from either side of the membrane, nitrate potentiates gating mainly from the cytoplasmic side, implicating a common mechanism for gating modulation mediated through two separate sites of action.


Total uterine volume: a new graph and its clinical applications.
The prolate ellipse formula has been shown to be inaccurate and inconsistent in the calculation of total uterine volume. The stepped area-to-volume technique has proven to be both accurate and consistent and provides a value equal to the true uterine volume. When these true volumes were plotted on previously published graphs of total uterine volume derived from the prolate ellipse formula, the graphs were found to be inaccurate. New graphs based on normal values have been constructed, comparing total uterine volume with both biparietal diameter and average gestational age. When 26 abnormal values were plotted on the total uterine volume versus biparietal diameter graph, almost all fell outside the 90 per cent confidence limits. Seven of the abnormal value were from fetuses found to have growth retardation. Six of these cases, including two not appreciated either clinically or ultrasonographically, were detected by this method. The stepped area-to-volume technique should allow reconsideration of the total uterine volume concept and aid in the detection of the subtle changes in uterine size.


Benefit of adjuvant radiotherapy following narrow-margin hepatectomy in patients with intrahepatic cholangiocarcinoma that adhere to major vessels.
To evaluate the role of adjuvant radiotherapy after narrow-margin (<1.0 cm) resection in patients with intrahepatic cholangiocarcinoma (ICC) adherent to major vessels. This retrospective study included 70 ICC patients. Forty-nine patients received narrow-margin (<1.0 cm) hepatectomy and 21 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Twenty-six of 49 were treated with postoperative radiotherapy (Group A), while the remaining 23 did not receive radiotherapy (Group B). Clinical outcomes were compared in the 3 groups. Toxicities of radiotherapy were evaluated. With a median follow-up time of 42 months, the 3-year overall survival (OS) and disease-free survival rates were 55% and 44% for Group A, 20% and 10% for Group B, and 65% and 33% for Group C, respectively. The OS and disease-free survival in Groups A and C were comparable and improved compared to Group B (Group A vs B, P=0.011 and P=0.031; and Group C vs B, P=0.031 and P=0.105). Multivariate analysis showed that receiving narrow-margin resection only (adjusted hazard ratio: 3.73; 95% CI: 1.36-10.25; P=0.001) was a significant poor prognostic risk factor of OS. Group B experienced more intrahepatic recurrence and extrahepatic recurrence than Groups A and C. For Groups A and B, the 3-year intrahepatic recurrence rates were 36% vs 67% (P=0.133) and extrahepatic recurrence rates were 43% vs 65% (P=0.007). Only 2 patients in Group A suffered from grade 3 toxicities. No patient developed classic or nonclassic radiation-induced liver disease. Postoperative radiotherapy following narrow-margin hepatectomy seems to be efficacious and well-tolerated in patients with ICC adjacent to major vessels.


Thickness-modulated passivation properties of PEDOT:PSS layers over crystalline silicon wafers in back junction organic/silicon solar cells.
PSS/silicon heterojunction solar cell has recently attracted much attention due to the fact that it can be simply and cost-effectively fabricated. It is crucial to suppress the interfacial recombination rate between silicon (Si) and organic film for improving device efficiency. In this study, we demonstrated a thickness-dependent passivation effect, i.e. the passivation quality over Si substrate was promoted dramatically with increasing the thickness of PEDOT:PSS layer. The effective minority carrier lifetime increased from 32 μs for 50 nm to 360 μs for 200 nm, which corresponds to a change in implied open circuit voltage (V oc-implied) from 545 to 635 mV. Back-junction hybrid solar cells featuring PEDOT:PSS films at rear side were designed to enable adoption of thick PEDOT:PSS layers without having to worry about parasitic absorption, showing a power conversion efficiency (PCE) of 16.3%. Combined with a proper pre-condition on the Si substrate, the back-junction hybrid solar cell with 200 nm PEDOT:PSS layer received an enhanced PCE of 16.8%. In addition, the improved long-term stability for the back-junction device was also observed. The PCE remained 90% (unsealed) after being stored in ambient atmosphere for 30 days and over 80% (sealed) after 150 days.


[The effect of dorsal cortical comminution on radiographic results of unstable distal radius fractures treated with closed reduction and K-wire fixation].
The purpose of this study was to evaluate the effect of dorsal cortical comminution on radiographic outcome of unstable distal radius fractures after treatment with closed reduction and K-wire fixation. Forty-two patients were treated with closed reduction and K-wire fixation for unstable, extra-articular distal radius fractures with dorsal angulation. The patients were evaluated in two groups depending on the presence or absence of dorsal metaphyseal cortical comminution observed as a radiopacity on lateral radiographs. Thus, 30 patients (13 males, 17 females; mean age 56 years; range 22 to 77 years) did not have dorsal cortical comminution, whereas 12 patients (8 males, 4 females; mean age 48 years; range 18 to 76 years) did. The mean follow-up period was 8.8 months (range 3 to 106 months) in the former, and 5.5 months (range 3 to 131 months) in the latter groups. Radiographic parameters were compared including palmar tilt measured on lateral, radial inclination and radial length on posteroanterior radiographs obtained before treatment and after union. Radial inclination, palmar tilt, and radial length showed significant improvements in both groups (p<0.05). The results were acceptable in all the patients with achievement of standard reference values. The presence of dorsal cortical comminution did not have any significant effect on radiographic parameters (p>0.05). No significant complications were encountered during the follow-up period. Dorsal cortical metaphyseal comminution does not have an adverse effect on radiographic results. Treatment with closed reduction and K-wire fixation is safe and effective even in the presence of dorsal cortical comminution.


Frequent expression of bcl-2 protein in solitary fibrous tumors.
The distinction of solitary fibrous tumors from histologically similar neoplasms is often difficult because they rarely occur at a variety of extrapleural sites. CD34 immunoreactivity has recently been recognized to be an adjunct for the diagnosis of solitary fibrous tumors. However, it is now known that CD34 staining is not entirely specific for this entity. We evaluated 23 solitary fibrous tumors and 54 other spindle cell tumors often considered in the differential diagnosis for immunoreactivity using monoclonal antibodies directed against bcl-2 protein, which protects cells from apoptosis and CD34. The patients with solitary fibrous tumors comprised 11 men and 12 women, ranging in age from 35 to 85 years (mean, 57.6 years). Fourteen tumors arose in the pleura, four in the retroperitoneum, three in the superficial soft tissue and one each in the mediastinum and uterine cervix. Nineteen of 23 solitary fibrous tumors (83%), irrespective of tumor site, demonstrated diffuse cytoplasmic staining for bcl-2 protein. bcl-2 immunoreactivity was also observed in five of seven neurofibromas (71%), eight of 10 synovial sarcomas (80%) and one of three spindle cell lipomas (33%). CD34 immunoreactivity was present in all but one solitary fibrous tumor (96%), seven of seven neurofibromas (100%), three of three spindle cell lipomas (100%), five of five dermatofibrosarcomas (100%), three of three hemangiopericytomas (100%) and two of seven malignant fibrous histiocytomas (29%). To date, most of the pleural and extrapleural cases have not shown aggressive features. We suggest that bcl-2 protein can be used together with CD34 in the diagnosis of solitary fibrous tumor to distinguish this entity from other spindle cell neoplasms.


The self determinants recognized by human virus-immune T cells can be distinguished from the serologically defined HLA antigens.
The self specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to clarify the relationship between the self antigens that they recognize and the serologically defined HLA-A and -B antigens. Virus-immune effectors from HLA-A2-positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for HLA-A2. Virus-immune T cells from 11 out of 11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cells consistently failed to lyse virus-infected target cells from one A2-positive donor (designated M7). Although the A2 specificity of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serologic analyses. These results indicate that there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity.


Cytokine mediators of renal inflammation.
This review focuses on the role of two cytokines, platelet-derived growth factor and transforming growth factor-beta, in glomerular injury. The most recent in vitro and in vivo evidence for the role of platelet-derived growth factor and transforming growth factor-beta in glomerular hypercellularity and matrix expansion is summarized. In vitro studies utilizing cultured glomerular cells continue to provide valuable information as to the mechanism by which these cytokines result in glomerular injury. Upregulation of both cytokines and their receptors have been demonstrated during the course of experimental proliferative glomerulonephritis. Neutralization studies using specific antibodies in vivo established a causative role in glomerular pathology. Studies should be extended to humans and other animal models of renal disease. Practical approaches to modify biologic effects of cytokines in vivo should also be sought.


Delayed response toward activation stimuli in pancreatic stellate cells.
Pancreatic stellate cells (PSCs) are known to be crucially involved in the development of pancreatic fibrosis, a characteristic feature of chronic pancreatitis and pancreatic cancer. The key event in the pathogenesis of fibrosis represents a transition process of quiescent PSCs into a myofibroblastlike phenotype associated with cell activation in terms of proliferation and synthesis of profibrogenic substances. There is little information available regarding the dynamics of the complex processes initiated by an activating stimulus in quiescent stellate cells. Using microarray analysis, we characterized the expression profiles during PSC activation caused by in vitro cultivation on days 2, 4, 7, and 14 after cell isolation. Activation status has been identified by the expression of the activation marker alpha-smooth muscle actin. Genes of interest were subjected to reverse transcription-polymerase chain reaction. To test biologic functions, the responsiveness of stellate cells toward the activators activin A and transforming growth factor-beta1 was investigated in dependence on the cell transition status. Our results revealed that freshly isolated (=quiescent) PSCs were refractory to stimuli for several days, a phenomenon that we referred to as delay phase. The retarded response could be considered a protection mechanism to prevent inappropriate stellate cell activation.


Exclusions and attributions of paternity: practical experiences of forensic genetics and statistics.
The Swedish State Institute for Blood Group Serology is a central government laboratory handling all blood typing in paternity cases in Sweden, each year testing 1,500-2,000 cases using about 13 polymorphisms. Of the accused men, 35%-40% are nonfathers, but in one-man cases (about 78% of all cases), approximately 75% are the true fathers. Exclusions appear to be distributed as expected from allele frequencies, and the paternity probability of nonexcluded men is assessed with a Bayesian approach. Some cases are retested in extended investigations which raise theoretical exclusion capability from about 87% to about 99%. Both the results of extended investigations and the theoretical consideration of the distribution of paternity probabilities support the use of such positive statistical evidence for the attribution of paternity.


Interspecies introgressive hybridization in spiny frogs Quasipaa (Family Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.
Introgression may lead to discordant patterns of variation among loci and traits. For example, previous phylogeographic studies on the genus Quasipaa detected signs of genetic introgression from genetically and morphologically divergent Quasipaa shini or Quasipaa spinosa. In this study, we used mitochondrial and nuclear DNA sequence data to verify the widespread introgressive hybridization in the closely related species of the genus Quasipaa, evaluate the level of genetic diversity, and reveal the formation mechanism of introgressive hybridization. In Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were detected between Quasipaa boulengeri and Q. shini. Unidirectional mitochondrial introgression was revealed from Q. spinosa to Q. shini. By contrast, bidirectional mitochondrial gene introgression was detected between Q. spinosa and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang Province. Analyses on mitochondrial and nuclear genes verified three candidate cryptic species in Q. spinosa, and a cryptic species may also exist in Q. boulengeri. However, no evidence of introgressive hybridization was found between Q. spinosa and Q. boulengeri. Quasipaa exilispinosa from all the sampling localities appeared to be deeply divergent from other communities. Our results suggest widespread introgressive hybridization in closely related species of Quasipaa and provide a fundamental basis for illumination of the forming mechanism of introgressive hybridization, classification of species, and biodiversity assessment in Quasipaa.


Lance-Adams syndrome: a report of two cases.
Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS), is a rare complication of successful cardiopulmanry resuscitation often accompanied by action myoclonus and cerebellar ataxia. It is seen in patients who have undergone a cardiorespiratory arrest, regained consciousness afterwards, and then developed myoclonus days or weeks after the event. Worldwide, 122 cases have been reported in the literature so far, including 1 case of Chinese. Here we report 2 Chinese LAS patients with detailed neuroimagings. Cranial single photon emission computed tomography (SPECT) of patient 1, a 52-year-old woman, showed a mild hypoperfusion in her left temporal lobe, whereas patient 2, a 54-year-old woman, manifested a mild bilateral decrease of glucose metabolism in the frontal lobes and a mild to moderate decrease of the N-acetyl aspartate (NAA) peak in the bilateral hippocampi by cranial [(18)F]-fluorodeoxyglucose positron emission tomographic (PET) scan and cranial magnetic resonance spectroscopy (MRS), respectively. We also review the literature on the neuroimaging, pathogenesis, and treatment of LAS.


Associations of the estrogen receptors 1 and 2 gene polymorphisms with the metabolic syndrome in women.
Genetic variation of the estrogen receptor alpha (ESR1) and beta (ESR2) has been associated with components of the metabolic syndrome. The relationships of two ESR1 (rs2234693 and rs9340799) and three ESR2 (rs1271572, rs1256049, and rs4986938) polymorphisms with the metabolic syndrome were examined in 532 Caucasian female participants (median age 63.1 years) in the Women's Health Study. Most women (99.1%) were postmenopausal. The associations between ESR1 and ESR2 genotypes and haplotypes with the metabolic syndrome were evaluated. Effect modification by hormone therapy was also assessed. Genotype and haplotype distributions were similar between women with and without metabolic syndrome. We found no consistent associations between the genotypes and haplotypes tested and the metabolic syndrome, or its components, in logistic regression models. No effect modification by hormone therapy use was noted. No association between these genetic variants in ESR1 and ESR2 and the metabolic syndrome was observed among these Caucasian women. Further investigation regarding the potential involvement of estrogen receptor genes and the metabolic syndrome may be warranted in other ethnic groups.


[The genetic polymorphism of the grape studied by RAPD analysis].
Genetic polymorphism in plant of 3 genera of Vitaceae family, 11 species of Vitis genera, 10 cultivars of Vitis vinifera and 4 cultivars that obtained from distant hybridization was studied. According to date of RAPD analysis genetic distances were determined and phylogenetic dendrogram was constructed. The possibility of using PCR for evaluation of breeding material by the levels of genetic relations was shown.


Diabetes mellitus in pregnancy and the assessment of umbilical artery waveforms using pulsed Doppler ultrasonography.
The utility of Doppler ultrasonography as a means of assessing potential alterations of vascular resistance prior to fetal or maternal compromise is very attractive. We investigated this relationship by prospectively performing Doppler studies of the fetal umbilical artery in 56 diabetic patients, 14 of whom had varying degrees of vascular complications. When regression curves were established for the S/D ratio, the Pourcelot index, and the resistance index of the fetal umbilical artery, the mean Doppler values were higher in diabetic patients with vasculopathy than in nondiabetic control patients or in diabetic patients without vasculopathy. The third trimester S/D ratio was greater than 3.0 in almost 50% of patients with vasculopathy. A tendency toward adverse outcomes was observed at S/D ratios approaching 4.0. Statistically significant correlations were found between elevated Doppler indices and maternal vasculopathy associated with hypertension and worsening renal insufficiency. Intrauterine growth retardation and neonatal metabolic complications were also significantly correlated with elevated Doppler indices. There was, however, no correlation between Doppler indices and glucose values, although most were within a euglycemic range. The aforementioned data indicate an increased resistance circuit among diabetics with vasculopathy, which may reflect a relative reduction in basal uteroplacental blood flow and the need for cautious interpretation of Doppler indices in these patients.


Further studies of the mineralocorticoid activity of 19-oxo-deoxycorticosterone.
Antinatriuretic and kaliuretic activities of 19-oxo-deoxycorticosterone (19-oxo-DOC) were measured in male adrenalectomized rats and compared with those of aldosterone. No significant effects of 19-oxo-DOC or aldosterone were observed in the lag period (i.e. the first hour post injection). In the subsequent 2 h, rats injected with 25 micrograms 19-oxo-DOC excreted less than half the sodium and more than twice the potassium compared to rats injected with vehicle alone. Overall mineralocorticoid activity (based on changes in urinary Na+/K+), antinatriuretic activity (based on changes in urinary Na+/creatinine) and kaliuretic activity (based on changes in urinary K+/creatinine) of 19-oxo-DOC were all in the range of 1:100th-1:200th that of aldosterone. These results are not in agreement with a recent report suggesting that 19-oxo-DOC possesses antinatriuretic activity but no kaliuretic activity.


Simultaneous early adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach associated with Helicobacter pylori infection.
The simultaneous association of gastric carcinoma with gastric lymphoma is a rare event. Recent studies have suggested that not only gastric cancer but also primary gastric lymphomas, especially those of mucosa-associated lymphoid tissue (MALT) type, are associated with Helicobacter pylori infection. We report on a 51-year-old woman who was referred to our hospital for the evaluation of abnormal shadows revealed by an upper gastrointestinal radiography series. Endoscopy of the upper gastrointestinal tract revealed early cancer in the middle body of the stomach. Biopsy of the lesion subsequently proved it to be a signet-ring cell carcinoma. Total gastrectomy was performed, under a diagnosis of early gastric carcinoma. The resected specimen revealed two grossly separate lesions. Histological examination confirmed that the gastric body lesion was compatible with early moderately differentiated tubular adenocarcinoma of type 0-IIc, while the lesion of the fundus corresponded to MALT lymphoma. H. pylori was detected, and chronic gastritis was also present in the resected gastric specimen. H. pylori infection may have played a major role in the development of both the MALT lymphoma and the adenocarcinoma of the stomach in this patient.


Identification of sex hormone-binding globulin in the human hypothalamus.
Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin (SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin.


STING1 in Different Organelles: Location Dictates Function.
Stimulator of interferon response cGAMP interactor 1 (STING1), also known as TMEM173, is an immune adaptor protein that governs signal crosstalk that is implicated in many physiological and pathological processes. Although it has been established that STING1 traffics from the endoplasmic reticulum (ER) to Golgi apparatus (Golgi) upon DNA-triggered activation, emerging evidence reveals that STING1 can be transported to different organelles, which dictate its immune-dependent (e.g., the production of type I interferons and pro-inflammatory cytokines) and -independent (e.g., the activation of autophagy and cell death) functions. In this brief review, we outline the roles of STING1 in different organelles (including the ER, ER-Golgi intermediate compartment, Golgi, mitochondria, endosomes, lysosomes, and nucleus) and discuss the potential relevance of these roles to diseases and pharmacological interventions.


Oncology social worker competencies and implications for education and training.
A mailed and online survey of 622 members of the Association of Oncology Social Workers (AOSW) indicated their proportion of time committed to certain aspects of practice and to certain population groups, and the extent to which they feel competent in various practice areas. Respondents indicated high levels of competence in 17 topic areas, including promotion of patient coping skills, end-of-life issues, and group work. Topic areas in which at least one third of respondents indicated little to no competence included pain assessment and management, cognitive behavioral therapy, complementary and alternative practices, and political advocacy. Although respondents indicated that they spend approximately 10% of their time with non-English-speaking populations, 50% of the sample indicated that they have little to no competence working with this population. Differences in levels of competence by years of experience and work setting were noted across many areas. Findings from this survey may be useful in the development of curriculum for preparing oncology social workers for practice in today's changing health care environment.


Puberty in children with intrauterine growth retardation.
There is a remarkable scarcity of data concerning puberty in children born with intrauterine growth retardation (IUGR). What little there is suggests that puberty occurs at a normal age compared with the general population, but a little early compared with other short children. The pattern of puberty is quite normal in children born with IUGR, with normal inter-relationships between the various events, although the growth spurt is, on average, a little less intense than in the normal population. In general, adult height is significantly compromised, partly because of the rather attenuated pubertal growth spurt.


Rotational isomerism of acetic acid isolated in rare-gas matrices: Effect of medium and isotopic substitution on IR-induced isomerization quantum yield and cis-->trans tunneling rate.
Rotational isomerization of acetic acid (CH3COOH) is studied in Ar, Kr, and Xe matrices. The light-induced trans-->cis reaction is promoted using resonant excitation of a number of modes in the 3500-7000 cm(-1) region, and the quantum yields for this process are measured for various acetic acid isotopologues and matrix materials. For excitation of acetic acid at energies above the predicted isomerization energy barrier (> or =4400 cm(-1)), the measured quantum yields are in average 2%-3%, and this is one order of magnitude smaller than the corresponding values known for formic acid (HCOOH). This difference is interpreted in terms of the presence of the methyl group in acetic acid, which enhances energy relaxation channels competing with the rotational isomerization. This picture is supported by the observed large effect of deuteration of the methyl group on the photoisomerization quantum yield. The trans-->cis reaction quantum yields are found to be similar for Ar, Kr, and Xe matrices, suggesting similar energy relaxation processes for this molecule in the various matrices. The IR-induced cis-->trans process, studied for acetic acid deuterated in the hydroxyl group, shows reliably larger quantum yields as compared with the trans-->cis process. For pumping of acetic acid at energies below the predicted isomerization barrier, the trans-->cis reaction quantum yields decrease strongly when the photon energy decreases, and tunneling is the most probable mechanism for this process. For the cis-->trans dark reaction, the observed temperature and medium effects indicate the participation of the lattice phonons in the tunneling-induced process.


Molecular Dynamics Simulation of Amorphous SiO2, B2O3, Na2O-SiO2, Na2O-B2O3, and Na2O-B2O3-SiO2 Glasses with Variable Compositions and with Cs2O and SrO Dopants.
Selection of suitable glass composition for vitrification of high-level radioactive wastes (HLWs) is one of the major challenges in nuclear waste reprocessing. Atomic and molecular level understanding of various structural, thermodynamical, and dynamical properties of a glass matrix can help in preliminary screening and thus reduce the dependency to some extent on tedious experimental procedures. In that context, extensive molecular dynamics (MD) simulations have been performed to calculate various microscopic properties of the glass matrix. The present article demonstrates that the "Buckingham potential-included long-ranged Coulomb interaction" can be utilized to simulate the glasses of varied compositions. The proposed simulation model has been validated for a wide range of glass compositions: pure glass matrix-SiO2 and B2O3; binary glass mixtures-SiO2-B2O3, Na2O-SiO2, and Na2O-B2O3; ternary glass-Na2O-SiO2-B2O3; and also the Cs2O- and SrO-doped matrix of sodium borosilicate. Most importantly, the MD results have been validated with those of in-house synthesized glasses. The effect of alkali addition on the density and network connectivity of the glass matrix has been explored. The results capture well the boron anomalies for varied concentrations of network formers and network modifiers. The intermediate structural ordering in glasses has been explored by calculating the partial and total structure factors. Further, the characteristic vibration density of states of constituent atoms in the glass matrix is determined. In addition, the glass structures with the addition of dopant oxides Cs2O and SrO have been examined as they are known to be prime heat-generating agents in HLWs. The results establish the structure and dynamics of the doped glass matrix to be a complex nature of the dopant's mass, concentration, charge, and ionic radius. The present MD results might be of great academic and technological significance for further studies in the field of vitrification and prediction of effects associated with the dopant's nature and concentration.


Characterization of plant virus-encoded gene silencing suppressors.
Agroinfiltration assay using green fluorescent protein (GFP)-expressing Nicotiana benthamiana line 16c is a powerful method for screening of putative plant virus-encoded gene silencing suppressors. This method allows the investigator to know whether the putative viral suppressor inhibits silencing in a cell (local silencing) and/or spreading of silencing throughout a plant (systemic silencing). Additionally, grafting experiments using transgenic plants expressing the suppressor and the GFP will indicate whether the suppressor blocks systemic silencing steps, which include the production of a silencing signal in a silenced cell, and the cell-to-cell and long-distance movement of a silencing signal throughout a plant. Here, we describe methods and techniques of an agroinfiltration assay and grafting experiments, which were used for the characterization of Apple chlorotic leaf spot virus 50 kDa movement protein as a gene silencing suppressor. This protocol should allow the investigator to characterize putative plant virus-encoded gene silencing suppressors.


The implication of gut microbiota in recovery from gastrointestinal surgery.
Recovery from gastrointestinal (GI) surgery is often interrupted by the unpredictable occurrence of postoperative complications, including infections, anastomotic leak, GI dysmotility, malabsorption, cancer development, and cancer recurrence, in which the implication of gut microbiota is beginning to emerge. Gut microbiota can be imbalanced before surgery due to the underlying disease and its treatment. The immediate preparations for GI surgery, including fasting, mechanical bowel cleaning, and antibiotic intervention, disrupt gut microbiota. Surgical removal of GI segments also perturbs gut microbiota due to GI tract reconstruction and epithelial barrier destruction. In return, the altered gut microbiota contributes to the occurrence of postoperative complications. Therefore, understanding how to balance the gut microbiota during the perioperative period is important for surgeons. We aim to overview the current knowledge to investigate the role of gut microbiota in recovery from GI surgery, focusing on the crosstalk between gut microbiota and host in the pathogenesis of postoperative complications. A comprehensive understanding of the postoperative response of the GI tract to the altered gut microbiota provides valuable cues for surgeons to preserve the beneficial functions and suppress the adverse effects of gut microbiota, which will help to enhance recovery from GI surgery.


A new look at population health through the lenses of cognitive, functional and social disability clustering in eastern DR Congo: a community-based cross-sectional study.
The importance of viewing health from a broader perspective than the mere presence or absence of disease is critical at primary healthcare level. However, there is scanty evidence-based stratification of population health using other criteria than morbidity-related indicators in developing countries. We propose a novel stratification of population health based on cognitive, functional and social disability and its covariates at primary healthcare level in DR Congo. We conducted a community-based cross-sectional study in adults with diabetes or hypertension, mother-infant pairs with child malnutrition, their informal caregivers and randomly selected neighbours in rural and sub-urban health zones in South-Kivu Province, DR Congo. We used the WHO Disability Assessment Schedule 2.0 (WHODAS) to measure functional, cognitive and social disability. The study outcome was health status clustering derived from a principal component analysis with hierarchical clustering around the WHODAS domains scores. We calculated adjusted odds ratios (AOR) using mixed-effects ordinal logistic regression. Of the 1609 respondents, 1266 had WHODAS data and an average age of 48.3 (SD: 18.7) years. Three hierarchical clusters were identified: 9.2% of the respondents were in cluster 3 of high dependency, 21.1% in cluster 2 of moderate dependency and 69.7% in cluster 1 of minor dependency. Associated factors with higher disability clustering were being a patient compared to being a neighbour (AOR: 3.44; 95% CI: 1.93-6.15), residency in rural Walungu health zone compared to semi-urban Bagira health zone (4.67; 2.07-10.58), female (2.1; 1.25-2.94), older (1.05; 1.04-1.07), poorest (2.60; 1.22-5.56), having had an acute illness 30 days prior to the interview (2.11; 1.24-3.58), and presenting with either diabetes or hypertension (2.73; 1.64-4.53) or both (6.37; 2.67-15.17). Factors associated with lower disability clustering were being informally employed (0.36; 0.17-0.78) or a petty trader/farmer (0.44; 0.22-0.85). Health clustering derived from WHODAS domains has the potential to suitably classify individuals based on the level of health needs and dependency. It may be a powerful lever for targeting appropriate healthcare service provision and setting priorities based on vulnerability rather than solely presence of disease.


Comparative macromolecular composition of filaments and rods of a Bacillus megaterium thermoconditional morphological mutant.
Filaments of a thermosensitive Bacillus megaterium mutant showed an altered macromolecular composition compared with salt-cured mutant cells and parental cells. Filaments contained more peptidoglycan, polyglucose, poly-beta-hydroxy-butyrate, and deoxyribonucleic acid per unit of protein. The ribonucleic acid-to-protein ratio of filaments was similar to that of rods or salt-cured cells. Filament formation seemed to be due to defective protein or ribonucleic acid metabolism.


Evaluation of the clonality of multilobar bronchioloalveolar carcinoma of the lung: case report.
A case of multilobar bronchioloalveolar carcinoma (BAC) is reported. To investigate the clonality of BAC, immunohistochemical staining as well as genetic analysis were performed. To investigate point mutations of the p53 gene, we used the polymerase chain reaction and fluorescence-based single strand conformation polymorphism analysis method. The BAC tissues of the right upper lobe, right lower lobe, and the other lobes were considered to be multiclonal. This case suggests that multilobar BAC might occur with multiclonality.


Decoding the consecutive lysosomal degradation of 3-O-sulfate containing heparan sulfate by Arylsulfatase G (ARSG).
The lysosomal degradation of heparan sulfate is mediated by the concerted action of nine different enzymes. Within this degradation pathway, Arylsulfatase G (ARSG) is critical for removing 3-O-sulfate from glucosamine, and mutations in ARSG are causative for Usher syndrome type IV. We developed a specific ARSG enzyme assay using sulfated monosaccharide substrates, which reflect derivatives of its natural substrates. These sulfated compounds were incubated with ARSG, and resulting products were analyzed by reversed-phase HPLC after chemical addition of the fluorescent dyes 2-aminoacridone or 2-aminobenzoic acid, respectively. We applied the assay to further characterize ARSG regarding its hydrolytic specificity against 3-O-sulfated monosaccharides containing additional sulfate-groups and N-acetylation. The application of recombinant ARSG and cells overexpressing ARSG as well as isolated lysosomes from wild-type and Arsg knockout mice validated the utility of our assay. We further exploited the assay to determine the sequential action of the different sulfatases involved in the lysosomal catabolism of 3-O-sulfated glucosamine residues of heparan sulfate. Our results confirm and extend the characterization of the substrate specificity of ARSG and help to determine the sequential order of the lysosomal catabolic breakdown of (3-O-)sulfated heparan sulfate.


Density-functional theory study of vibrational relaxation of CO stretching excitation on Si(100).
A first-principles theory is presented for calculating the lifetime of adsorbate vibrations on semiconductor or insulator surfaces, where dissipation of the vibrational energy to substrate phonons is the dominant relaxation mechanism. As an example, we study the stretching vibration of CO/Si(100), where a lifetime of 2.3 ns has been measured recently [K. Lass, X. Han, and E. Hasselbrink, J. Chem. Phys. 123, 051102 (2005)]. Density-functional theory (DFT) calculations for the local modes of the adsorbate, including their anharmonic coupling, are combined with force field calculations for the substrate phonons. Using the DFT-Perdew-Burke-Ernzerhof functional, we have determined the most stable adsorption site for CO on top of the lower Si atom of the Si surface dimer, the local normal modes of CO, and the multidimensional potential energy surface for the CO vibrations. The anharmonic stretching frequency of adsorbed CO obtained in DFT-PBE is 5% lower than the experimental value, while the B3LYP functional reproduces the CO stretching frequency with only 1.4% error. The coupling between the anharmonic vibrational modes and the phonon continuum is evaluated within first-order perturbation theory, and transition rates for the CO vibrational relaxation are calculated using Fermi's golden rule. The lifetime of 0.5 ns obtained with DFT-PBE is in qualitative agreement with experiment, while using vibrational frequencies from the B3LYP functional gives a much too long lifetime as compared to experiment. We find that the numerical value of the lifetime is very sensitive to the harmonic frequencies used as input to the calculation of the transition rate. An empirical adjustment of these frequencies yields excellent agreement between our theory and experiment. From these calculations we conclude that the most probable microscopic decay channel of the CO stretching mode is into four lateral shift/bending quanta and one phonon.


Outcomes of a 2-Portal Endoscopic Technique for Osseous Lesions Resulting in Posterior Ankle Impingement Syndrome.
Posterior ankle impingement syndrome is common in sporting populations and encompasses a range of disorders that cause posterior ankle pain during maximal forced plantarflexion. The aim of this study was to evaluate the short- and medium- to long-term outcomes of 2-portal endoscopic surgery for osseous lesions causing posterior ankle impingement syndrome. This was a retrospective case series analysis of all patients who underwent 2-portal endoscopic surgery at a single institution between 2005 and 2016. Visual analogue scales and selected components of the Short Form of the Revised Foot Function Index were used to assess ankle function, with the median follow-up time being 4.8 years. Of the 52 patients, 49 (94%) were able to return to their previous sport/physical activity, with the mean time taken being 5.8 months. At the completion of follow-up, the mean pain score during exercise had improved from 7.5 to 0.9 points. The mean work and sporting function scores also improved, from 5.9 to 9.6 points and 2.9 to 8.8 points, respectively. The mean score of the Short Form of the Revised Foot Function Index also improved by 77.7 points, from 84.4 to 6.7 at the completion of follow-up. There were no postoperative infections or any other major complications. This study provides strong supporting evidence for the use of hindfoot endoscopy in the treatment of posterior ankle impingement syndrome in athletes.


Antitumor agents 6. Synthesis, structure-activity relationships, and biological evaluation of spiro[imidazolidine-4,3'-thieno[2,3-g]quinoline]-tetraones and spiro[thieno[2,3-g]quinoline-3,5'-[1,2,4]triazinane]-tetraones with potent antiproliferative activity.
Two series of quinolinquinone derivatives, 2'H-spiro[imidazolidine-4,3'-thieno[2,3-g]quinoline]-2,4',5,9'-tetraones (2a-n) and 2H-spiro[thieno[2,3-g]quinoline-3,5'-[1,2,4]triazinane]-3',4,6',9-tetraones (3a-e), were designed and synthesized using the previously described ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3-g]quinoline-3-carboxylate (1) as a starting material. All compounds were evaluated for their antiproliferative activity against a panel of representative liquid and solid human tumor cell lines and exhibit IC(50) values in the micromolar/submicromolar range. Series 2 displayed higher cytotoxicity than did series 3. The nature of the substituents on both imidazoline and triazinane N1 nitrogen markedly affected the activity profile of these series. Spectrophotometric and fluorescence measurements as well as unwinding assays performed on the most cytotoxic compounds, 2c, 2g, and 2k, showed that they are nonintercalative DNA agents and inhibit the catalytic activity of Topo II in a concentration-dependent mode. 2g was the most active Topo II inhibitor with activity levels comparable to those of VP-16.


[Quality assurance for the assessment of postoperative pain: proposal of procedures and questionnaires].
This study presents a tool including survey questionnaires and a specific data-processing software for the data processing, allowing health care providers to assess the quality of postoperative pain management in surgical wards. Descriptive study. A committee including anesthesiologists, nurses and epidemiologists had elaborated and tested three survey questionnaires to assess patients, nurses and medical staff satisfaction respectively. Specific data processing software was issued out of the final questionnaires. It allowed a quick analysis of items possibly, explaining inadequate postoperative pain management. After this adjustment, this tool was used in three different surgical wards, named A, B, C. The rate of answer (of investigated persons) being over 50%, data resulting from the survey performed in the surgical wards A and B were considered valid. The items which could explain insufficient pain relief were classified into 4 levels: patients assertion (ex: more than 50% of patients experienced persistent postoperative pain); practices evaluation (ex: 42 to 72% health care providers declared being aware of analgesic procedures); behavior's evaluation (ex: 19 to 34% of health care providers considered persistent postoperative pain to be useful for monitoring); and surgical wards potential (ex: 21 to 61% of health care providers took a specific course on pain management). Pros and cons of this tool were carefully examined and subsequent strategies defined. This survey's device should allow health care providers to assess the quality of postoperative pain management in surgical wards. Its validation is currently developed to improve its use, and keep the most performing indicators, showing an adequate postoperative pain management.


Spinal cord ischemia secondary to transcatheter arterial chemoembolization for hepatocellular carcinoma.
Transcatheter arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma. Although considered relatively safe, TACE has been associated with several complications. Spinal cord ischemia secondary to TACE is an extremely rare but disastrous complication. We report a very rare case of spinal cord injuries after TACE, together with a literature review. During the procedure, the patient suddenly experienced sensory impairment below the T10 dermatome and bilateral lower extremity motor weakness. She was given high-dose steroids and supportive therapy. The sensory deficits nearly improved completely, but motor strength remained unchanged. Thereafter, a chest computed tomography scan showed tumor metastasis to the lungs. The patient is now receiving sorafenib and follow-up.


Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.
Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.


[Sharp's syndrome. Clinical, immunological and nosographic aspects].
LE cells, ds-DNA antibodies (radioimmunoassay), antinuclear antibodies (ANA) by indirect immunofluorescence (IFI) and anti-ENA antibodies have been sought in 150 clinical cases observed over a 5-year period in the Rheumatology Division of Bari University. For the latter, three parallel techniques were adopted on each serum, each completed by RNA-sensitivity assay for the demonstration of anti-RNP, i.e. IFI, passive haemoagglutination (PHA) and controimmunoelectrophoresis (CIE). The series included systemic lupus erythematodes (SLE), 30 cases; rheumatoid arthritis (RA), 30 cases; progressive systemic sclerosis (PSS), 12 cases; unclassified connective tissue disease (UCTD), 8 cases; mixed connective tissue disease (MCTD), 7 cases; Sjögren's syndrome (SS), 4 cases; dermatomyositis (DM), 3 cases; overlap syndromes (PSS-SLE, SS-SLE), 2 cases; rheumatological and internal miscellanea, 54 cases, LE cells and ds-DNA antibodies were found exclusively in SLE; the anti-ENA were found in various groups of diseases, while the anti-RNP were only demonstrated in the 7 MCTD and in some SLE. Of the three techniques for demonstrating anti-ENA, the PHA proved most sensitive and CIE most specific, whereas IFI was considered most suitable for clinical screening. The clinical aspects of the 7 MCTD faithfully followed the disease picture described by Sharp, but some overlap-syndromes and the unclassified connective tissue diseases did not present anti-RNP. It is also pointed out that nephropathy is not rare in MCTD and that the clinical course of the disease is not always benign. To conclude, it is considered that MCTD merits nosographic autonomy, but further investigations are recommended for more exact nosographical typing of connective tissue diseases.


Platelet Derived Vesicles Enhance the TGF-beta Signaling Pathway of M1 Macrophage.
Macrophages, mainly divided into M1 pro-inflammatory and M2 anti-inflammatory types, play a key role in the transition from inflammation to repair after trauma. In chronic inflammation, such as diabetes and complex bone injury, or the process of certain inflammatory specific emergencies, the ratio of M1/M2 cell populations is imbalanced so that M1-macrophages cannot be converted into M2 macrophages in time, resulting in delayed trauma repair. Early and timely transformation of macrophages from the pro-inflammatory M1-type into the pro-reparative M2-type is an effective strategy to guide trauma repair and establish the original homeostasis. We prepared purified nano-platelet vesicles (NPVs) and assessed their effects on macrophage phenotype switching through transcriptome analysis. The results elucidate that NPVs promote pathways related to angiogenesis, collagen synthesis, cell adhesion, and migration in macrophages, and we speculate that these advantages may promote healing in traumatic diseases.


HUNER: improving biomedical NER with pretraining.
Several recent studies showed that the application of deep neural networks advanced the state-of-the-art in named entity recognition (NER), including biomedical NER. However, the impact on performance and the robustness of improvements crucially depends on the availability of sufficiently large training corpora, which is a problem in the biomedical domain with its often rather small gold standard corpora. We evaluate different methods for alleviating the data sparsity problem by pretraining a deep neural network (LSTM-CRF), followed by a rather short fine-tuning phase focusing on a particular corpus. Experiments were performed using 34 different corpora covering five different biomedical entity types, yielding an average increase in F1-score of ∼2 pp compared to learning without pretraining. We experimented both with supervised and semi-supervised pretraining, leading to interesting insights into the precision/recall trade-off. Based on our results, we created the stand-alone NER tool HUNER incorporating fully trained models for five entity types. On the independent CRAFT corpus, which was not used for creating HUNER, it outperforms the state-of-the-art tools GNormPlus and tmChem by 5-13 pp on the entity types chemicals, species and genes. HUNER is freely available at https://hu-ner.github.io. HUNER comes in containers, making it easy to install and use, and it can be applied off-the-shelf to arbitrary texts. We also provide an integrated tool for obtaining and converting all 34 corpora used in our evaluation, including fixed training, development and test splits to enable fair comparisons in the future. Supplementary data are available at Bioinformatics online.


Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.
We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7-10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients. We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase-DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits. The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.


Gas phase basicities of polyfunctional molecules. Part 5: Non-aromatic sp2 nitrogen containing compounds.
This paper constitutes the fifth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435, Part 4: Carbonyl as basic site, Mass Spectrom Rev 2015, 34:493-534). This part is devoted to non-aromatic molecules characterized by a lone pair located on a sp2 nitrogen atom, it embraces functional groups such as imines, amidines, guanidines, diazenes, hydrazines, oximes, and phosphazenes. Specific examples are examined under five major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) imines, hydrazones, and oximes are considered. A second chapter describes the protonation energetic of aliphatic, conjugated, or cyclic amidines. Guanidines, polyguanides, and biomolecules containing guanidine were examined in the third chapter. A fourth chapter describes the particular case of the phosphazene molecules. Finally, diazenes and azides were considered in the last chapter. Experimental data were re-evaluated according to the presently adopted basicity scale, i.e., PA(NH3 ) = 853.6 kJ/mol, GB (NH3 ) = 819 kJ/mol. Structural and energetic information given by G4MP2 quantum chemistry computations on typical systems are presented. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:139-170, 2018.


A longitudinal approach of lockdown effects on quality of life and the expression of anxiety-depressive disorders according to sensory processing sensitivity.
The COVID-19 health crisis is perceived as an anxiety-provoking situation. In some cases, policy measures such as containment can generate psychological distress. High sensory processing sensitivity is an innate component of temperament that characterises individuals with higher sensory sensitivity than their peers. It can be understood either as an individual's ability to adapt to specific situations, or as a factor of vulnerability to certain negative stimuli, which may impact upon quality of life, or manifest itself in the expression of anxiety-depressive symptoms. In this study, we investigated the effects of confinement from a longitudinal perspective on these aspects, according to the degree of sensitivity of individuals.Data collection was carried out longitudinally during the lockdown of the French population. The sample was composed of 493 adults who were asked to respond twice, anonymously, to a research protocol hosted online. We used a tool composed of the French version of the Highly Sensitive Person Scale, the Hospital Anxiety and Depression Scale, and the French short version of the World Health Organisation Quality Of Life scale.The results did not show a significant change in anxiety and depression disorders and quality of life in general between the beginning and the end of lockdown. Furthermore, notable disparities were observed according to the degrees of sensitivity in relation to the type of lifestyle during lockdown.The data from the literature, based on cross-cutting approaches, was clarified by the results, as they did not show any negative effects of lockdown on anxiety-depressive disorders during the lockdown period. Moreover, the latter even seemed to have improved one aspect of quality of life.


Incense burning smoke sensitizes lung cancer cells to EGFR TKI by inducing AREG expression.
Incense burning is common in Asian countries due to the religious beliefs. Environmental exposure to incense burning smoke is a potential risk factor for tumor development and progression of non-small cell lung cancer (NSCLC). Eastern Asia ethnic origin is strongly associated the clinical benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC patients. However, the impact of the oriental custom of incense burning on the cancer progression and the EGFR TKI-sensitivity of NSCLC remains unclear. Our results showed that long-term exposure to incense burning extract (IBE) increases the cellular proliferation with S phase accumulation and the motility activity of NSCLCs. Interestingly, IBE enhances EGFR signaling activity without affecting its genetic status, and increases the cellular sensitivity of NSCLC cell lines to EGFR TKIs. Auramine, a yellow dye for making incense sticks, was identified as a residual composition in the burning incense smoke, and showed similar EGFR TKI-sensitizing effects. Furthermore, IBE or auramine transcriptionally induce EGFR ligand amphiregulin (AREG) expression for the enhancement of EGFR activity. Neutralization of AREG reduced the viability of IBE-treated cells. These results indicated that exposure to incent smoke may enhance NSCLC progression and their sensitivity to EGFR TKIs through increasing their oncogenic addiction to AREG-induced EGFR signaling.


Two-generation analysis of pollen flow across a landscape. IV. Estimating the dispersal parameter.
The distance of pollen movement is an important determinant of the neighborhood area of plant populations. In earlier studies, we designed a method for estimating the distance of pollen dispersal, on the basis of the analysis of the differentiation among the pollen clouds of a sample of females, spaced across the landscape. The method was based solely on an estimate of the global level of differentiation among the pollen clouds of the total array of sampled females. Here, we develop novel estimators, on the basis of the divergence of pollen clouds for all pairs of females, assuming that an independent estimate of adult population density is available. A simulation study shows that the estimators are all slightly biased, but that most have enough precision to be useful, at least with adequate sample sizes. We show that one of the novel pairwise methods provides estimates that are slightly better than the best global estimate, especially when the markers used have low exclusion probability. The new method can also be generalized to the case where there is no prior information on the density of reproductive adults. In that case, we can jointly estimate the density itself and the pollen dispersal distance, given sufficient sample sizes. The bias of this last estimator is larger and the precision is lower than for those estimates based on independent estimates of density, but the estimate is of some interest, because a meaningful independent estimate of the density of reproducing individuals is difficult to obtain in most cases.


Intermittent Theta Burst Over M1 May Increase Peak Power of a Wingate Anaerobic Test and Prevent the Reduction of Voluntary Activation Measured with Transcranial Magnetic Stimulation.
Despite the potential of repetitive transcranial magnetic stimulation (rTMS) to improve performances in patients suffering from motor neuronal afflictions, its effect on motor performance enhancement in healthy subjects during a specific sport task is still unknown. We hypothesized that after an intermittent theta burst (iTBS) treatment, performance during the Wingate Anaerobic Test (WAnT) will increase and supraspinal fatigue following the exercise will be lower in comparison to a control treatment. Ten subjects participated in two randomized experiments consisting of a WAnT 5 min after either an iTBS or a control treatment. We determined voluntary activation (VA) of the right knee extensors with TMS (VATMS) and with peripheral nerve stimulation (VAPNS) of the femoral nerve, before and after the WAnT. T-tests were applied to the WAnT results and a two way within subject ANOVA was applied to VA results. The iTBS treatment increased the peak power and the maximum pedalling cadence and suppressed the reduction of VATMS following the WAnT compared to the control treatment. No behavioral changes related to fatigue (mean power and fatigue index) were observed. These results indicate for the first time that iTBS could be used as a potential intervention to improve anaerobic performance in a sport specific task.


Bromodeoxyuridine distribution patterns in L 929 fibroblasts and influence of tumor necrosis factor.
Incorporation of bromodeoxyuridine during the S phase of the cell cycle provides an appropriate method to study the replication of DNA in proliferating cells. We analyzed the distribution patterns of incorporated bromodeoxyuridine in L 929 cells and studied the influence of tumor necrosis factor-alpha in vitro by indirect immunofluorescence. Using conventional epifluorescent and confocal laser scanning microscopy, we defined three types of bromodeoxyuridine distribution patterns in synchronized L 929 cells which showed typical differences in their percentages during the time course of the S phase. Type I with small spots and unstained areas was typical for the early S phase. Type II was characterized by a texture of homogeneously distributed fluorescence and increased during middle and late S phase. Type III with a small number of larger clusters revealed its highest proportion in the late S phase. Incubation with tumor necrosis factor reduced the number of bromodeoxyuridine-positive cells. We found that the cytokine, when present in late S phase, provoked an increase in the percentage of type III distribution pattern. The results show that bromodeoxyuridine distribution pattern analysis can be used to detect influences on cell cycle kinetics induced by therapeutics.


Automated, fully computerized analysis of the clinical electroretinogram.
Being a relatively simply composed bioelectric signal, the ERG lends itself very well to computer analysis. This paper presents the results obtained by the employment of an automated, fully computerized ERG analysis system. It is concluded that programmable computing facilities have the effect of rendering diagnostic ERG evaluation more accurate and reliable as well as saving a lot of human effort.


A Case of Rathke's Cleft Cyst Associated with Transient Central Adrenal Insufficiency and Masked Diabetes Insipidus.
A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm. Transsphenoidal surgery revealed that the pituitary tumor was Rathke's cleft cyst. Following surgery, replacement with neither glucocorticoid nor desmopressin was needed any more. Therefore, it is suggested that Rathke's cleft cyst is responsible for the masked diabetes insipidus and the central insufficiency. Furthermore, it is speculated that thyrotoxicosis with painless thyroiditis might induce changes from subclinical adrenal insufficiency to transiently overt insufficiency.


Highly improved electroluminescence from a series of novel Eu(III) complexes with functional single-coordinate phosphine oxide ligands: tuning the intramolecular energy transfer, morphology, and carrier injection ability of the complexes.
The functional single-coordinate phosphine oxide ligands (4-diphenylaminophenyl)diphenylphosphine oxide (TAPO), (4-naphthalen-1-yl-phenylaminophenyl)diphenylphosphine oxide (NaDAPO), and 9-[4-(diphenylphosphinoyl)phenyl]-9H-carbazole (CPPO), as the direct combinations of hole-transporting moieties, and electron-transporting triphenylphosphine oxide (TPPO) were designed and synthesized (amines or carbazole), together with their Eu(III) complexes [Eu(tapo)(2)(tta)(3)] (1), [Eu(nadapo)(2)(tta)(3)] (2), and [Eu(cppo)(2)(tta)(3)] (3; TTA: 2-thenoyltrifluoroacetonate). The investigation indicated that by taking advantage of the modification inertia of the phosphine oxide ligands, the direct introduction of the hole-transport groups as chromophore made TAPO, NaDAPO, and CPPO obtain the most compact structure and mezzo S(1) and T(1) energy levels, which improved the intramolecular energy transfer in their Eu(III) complexes. The amorphous phase of 1-3 proved the weak intermolecular interaction, which resulted in extraordinarily low self-quenching of the complexes. The excellent double-carrier transport ability of the ligands was studied with Gaussian calculations, and the bipolar structure of TAPO and CPPO was proved. The great improvement of the double-carrier transport ability of 1-3 was shown by cyclic voltammetry. Their HOMO and LUMO energy levels of around 5.3 and 3.0 eV, respectively, are the best results for Eu(III) complexes reported so far. A single-layer organic light-emitting diode of 2 had the impressive brightness of 59 cd m(-2) which, to the best of our knowledge, is the highest reported so far. Both of the four-layer devices based on pure 1 and 2 had a maximum brightness of more than 1000 cd m(-2), turn-on voltages lower than 5 V, maximum external quantum yields of more than 3 % and excellent spectral stability.


Palmitate induces insulin resistance in human HepG2 hepatocytes by enhancing ubiquitination and proteasomal degradation of key insulin signaling molecules.
Obesity-associated insulin resistance is a major pathogenesis of type 2 diabetes mellitus and is characterized by defects in insulin signaling. High concentrations of plasma free fatty acids (FFAs) are involved in the etiology of obesity-associated insulin resistance. However, the detailed mechanism by which FFAs contribute to the development of insulin resistance is not yet fully understood. We investigated the molecular basis of insulin resistance elicited by FFAs using the human hepatocyte cell line HepG2. Among major human FFAs, palmitate markedly inhibited insulin-stimulated phosphorylation of key insulin signaling molecules such as insulin receptor, insulin receptor substrate-1, and Akt, indicating that palmitate is the principal inducer of insulin resistance. We revealed that palmitate facilitates ubiquitination of the key insulin signaling molecules, and subsequently elicits their proteasomal degradation. Furthermore, we demonstrated that inhibition of ubiquitination by the ubiquitin-activating enzyme E1 inhibitor PYR41 significantly prevents palmitate-inducible insulin resistance but not by the proteasome inhibitor MG132, implying that ubiquitinated signaling molecules may be dysfunctional. In conclusion, inhibition of ubiquitination of the key insulin signaling molecules may be a potential strategy for preventing and treating obesity-associated insulin resistance.


Successful Treatment of Plantar Hyperkeratosis in the Form of Recurrent Corns With Split-Thickness Sole Skin Graft.
Plantar hyperkeratosis, such as corns and calluses, is common in older people and associated with pain, mobility impairment, and functional limitations. It usually develops on the palms, knees, or soles of feet, especially under the heels or balls. There are several treatment methods for plantar hyperkeratosis, such as salicylic acid plaster and scalpel debridement, and conservative modalities, such as using a shoe insert and properly fitting shoes. We present an effective method of reconstructing the wound after corn excision using a split-thickness sole skin graft (STSSG). We harvested the skin graft from the arch of the sole using the dermatome with a skin thickness of 14/1000th inches. Because the split-thickness skin graft, harvested from the sole arch near the distal sole, is much thicker than the split-thickness skin graft from the thigh, it is more resistant to weight and friction. The healed wound with STSSG coverage over the distal sole was intact, and the donor site over the sole arch had healed without complication during the outpatient follow-up, 3 months after surgery. The recovery time of STSSG for corn excision is shorter than that with traditional treatment. Therefore, STSSG can be a reliable alternative treatment for recurrent palmoplantar hyperkeratosis.


MDS overlap disorders and diagnostic boundaries.
Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). These disorders are characterized by hematopoietic dysplasia with increased proliferation of monocytes, neutrophils, or platelets. They may have mutational profiles that distinguish them from the disorders they resemble and reflect important differences in pathophysiology. MDS also shares diagnostic borders with other diseases. For example, aplastic anemia and hypoplastic MDS can be difficult to distinguish in patients with pancytopenia and bone marrow hypocellularity. Genetic features may help in this regard, because they can identify differences in prognosis and risk of progression. The boundary between MDS and secondary acute myeloid leukemia (sAML) is arbitrarily defined and has been redefined over the years. Genetic studies have demonstrated that sAML clones can precede clinical progression from MDS by many months, suggesting that MDS with excess blasts could be viewed as an overlap between a dysplastic bone marrow failure syndrome and an oligoblastic leukemia. This review will describe the diagnostic boundaries between MDS, MDS/MPNs, sAML, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, and aplastic anemia and how genetic approaches may help to better define them.


Direct generation of red and orange optical vortex beams from an off-axis diode-pumped Pr3+:YLF laser.
We demonstrate the direct generation of visible vortex beams at 640 nm and 607 nm by employing an off-axis pumping scheme in a diode end-pumped Pr3+:YLF laser. A detailed numerical analysis, based on the coherent superposition of Hermite-Gaussian modes with different amplitudes and phases, is perfectly consistent with the experimentally observed lasing modes. The maximum vortex output powers have been measured to be 808 mW and 211 mW at a pump power of 3.16 W, for the wavelengths of 640 nm and 607 nm, respectively. We also demonstrate the handedness control of the generated vortex beam. Such a visible vortex laser can potentially be applied in super-resolution fluorescent microscopes and micro-fabrication research.


Efficacy and safety of direct oral anticoagulants with and without Aspirin: A systematic review and Meta-analysis.
Various anticoagulant therapies are prescribed to patients under physicians' discretion and recently Direct Oral Anticoagulants(DOAC) have been under trials to evaluate their safety and efficacy. In addition to this, the regimen of DOACs and Aspirin is of keen interest as researchers continue to find an optimal regimen to treat blood clots in patients. This study is a systematic review and meta-analysis of randomized controlled trials and observational studies that asses the safety and efficacy of DOAC with and without Aspirin. We queried MEDLINE and Cochrane CENTRAL from their inception to April 2021, for published and randomized controlled trials and observational studies in any language that compared dual (DOAC + ASA) therapy or mono (DOAC alone) therapy in patients with AF. The results from the studies were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Endpoints of interest included major bleeding, myocardial infarction (MI), major adverse cardiovascular events (MACEs), hospitalizations, all-cause mortality, and stroke. The risk of major bleeding was significantly lower in the DOAC alone group compared with DOAC plus aspirin group. Non-significant results were obtained (P value greater than 0.05) for other outcomes establishing that DOAC monotherapy was not superior to the combined regimen in reducing the risk of MACE, Stroke, Hospitalization, Death. Among patients with NVAF (Non valvular Atrial Fibrillation) and VTE (Venous thromboembolism) receiving anticoagulation prophylaxis, in terms of safety profile our comparisons showed a statistically significant reduction in Major Bleeding in DOAC Alone group compared with DOAC Plus Aspirin.


Detection of Needle Dislodgement Using Extracorporeal Pressure Signals: A Feasibility Study.
Venous needle dislodgement (VND) during dialysis is a rarely occurring adverse event, which becomes life-threatening if not handled promptly. Because the standard venous pressure alarm, implemented in most dialysis machines, has low sensitivity, a novel approach using extracted cardiac information to detect needle dislodgement is proposed. Four features are extracted from the arterial and venous pressure signals of the dialysis machine, characterizing the mean venous pressure, the venous cardiac pulse pressure, the time delay, and the correlation between the two pressure signals. The features serve as input to a support vector machine (SVM), which determines whether dislodgement has occurred. The SVM is first trained on a set of laboratory data, and then tested on another set of laboratory data as well as on a small data set from clinical hemodialysis sessions. The results show that dislodgement can be detected after 12-17 s, corresponding to 24-143 ml blood loss. The standard venous pressure alarm used in clinical routine only detects 50% of the VNDs, whereas the novel method detects all VNDs and has a false alarm rate of 0.12 per hour, provided that the amplitude of the extracted cardiac pressure signal exceeds 1 mmHg. The results are promising; however, the method needs to be tested on a larger set of clinical data to better establish its performance.


Kaistia soli sp. nov., isolated from a wetland in Korea.
A bacterial strain, 5YN9-8(T), was isolated from a peat layer in Yongneup, Republic of Korea. It was strictly aerobic, Gram-negative, non-motile, short rod- or coccus-shaped and produced ivory-pigmented colonies. Results of 16S rRNA gene sequence analyses indicated a close relationship between this isolate and Kaistia granuli Ko04(T) (97.2 % similarity) and Kaistia adipata Chj404(T) (96.2 % similarity), members of the order Rhizobiales within the Alphaproteobacteria. Predominant cellular fatty acids of strain 5YN9-8(T) were C(18 : 1)omega7c, C(18 : 0), C(19 : 0)omega8c cyclo and C(16 : 0). The DNA G+C content was 67.0 mol%. Phylogenetic, phenotypic and chemotaxonomic data accumulated in this study revealed that the isolate represents a novel species of the genus Kaistia, for which the name Kaistia soli sp. nov. is proposed; strain 5YN9-8(T) (=KACC 12605(T) =DSM 19436(T)) is the type strain.


Ab initio study of the BiSe and BiTe electronic spectra: what happens with X2-X1 emission in the heavier Bi chalcogenides?
A series of spin-orbit configuration interaction calculations has been carried out for the BiSe and BiTe molecules and analyzed in comparison with data obtained earlier for the isovalent BiO and BiS systems. An avoided crossing caused by the spin-orbit interaction between the X2Pi and A4Pi electronic states is shown to have a decisive effect on the lower-energy spectrum in each case. Irregularities in the X2 3/2 state vibrational manifold occur as a consequence of this nonadiabatic interaction, and the v vibrational number for the onset of these perturbations is found to gradually decrease in going from BiO to BiSe, in agreement with experiment. In BiTe the shape of the X2 potential curve is so altered by the avoided crossing that its minimum becomes shifted to a significantly larger distance than for the X1 state, unlike the case for BiSe or the lighter Bi chalcogenides. This characteristic appears to be the root cause for the fact that the X2 state has not yet been found experimentally in the BiTe spectrum, despite careful searches in the expected energy range. Radiative lifetimes have also been calculated for the low-lying states of both the BiSe and BiTe molecules, and these results are found to be consistent with experimental observations.