Subfailure damage in ligament: a structural and cellular evaluation.
Subfailure damage in ligaments was evaluated macroscopically from a structural perspective (referring to the entire ligament as a structure) and microscopically from a cellular perspective. Freshly harvested rat medial collateral ligaments (MCLs) were used as a model in ex vivo experiments. Ligaments were preloaded with 0.1 N to establish a consistent point of reference for length (and strain) measurements. Ligament structural damage was characterized by nonrecoverable difference in tissue length after a subfailure stretch. The tissue's mechanical properties (via stress vs. strain curves measured from a preloaded state) after a single subfailure stretch were also evaluated (n = 6 pairs with a different stretch magnitude applied to each stretched ligament). Regions containing necrotic cells were used to characterize cellular damage after a single stretch. It should be noted that the number of damaged cells was not quantified and the difference between cellular area and area of fluorescence is not known. Structural and cellular damage were represented and compared as functions of subfailure MCL strains. Statistical analysis indicated that the onset of structural damage occurs at 5.14% strain (referenced from a preloaded length). Subfailure strains above the damage threshold changed the shape of the MCL stress-strain curve by elongating the toe region (i.e., increasing laxity) as well as decreasing the tangential modulus and ultimate stress. Cellular damage was induced at ligament strains significantly below the structural damage threshold. This cellular damage is likely to be part of the natural healing process in mildly sprained ligaments.


Epidemiology of neonatal pneumothorax developed spontaneously and during respiratory supports in neonatal intensive care units.
Information on incidence and risk factors associated with different types of neonatal pneumothorax were lacking globally. To determine incidences of pneumothorax developed spontaneously and during different modes of respiratory support, and risk factors associated with each type of pneumothorax. Retrospective observational study of neonates in the Malaysian National Neonatal Registry. 44 Malaysian neonatal intensive care units (NICUs). All neonates born in 2015-2020 and admitted to NICUs. Pneumothorax developed in 3265 neonates: 37.5% occurred spontaneously, 62.5% during respiratory support. The incidence of all types of pneumothorax was 1.75 per 1000 livebirths, and of spontaneous pneumothorax was 0.58 per 1000 livebirths. Pneumothorax developed in 0.6% (450/70512) of neonates during continuous positive air way pressure therapy (nCPAPt), 1.8% (990/54994) of neonates during conventional mechanical ventilation (CMV), and 7.0% (599/8557) of neonates during high frequency ventilation (HFV). Term neonates had significantly higher pneumothorax rate than preterms (p<0.001). Multiple logistic regression analyses show that exposure to intermittent positive pressure ventilation and chest compression at birth were significant independent factors associated with increased risk of spontaneous pneumothorax and CMV, and persistent pulmonary hypertension was associated with increased risk of spontaneous pneumothorax and pneumothorax during CMV and HFV. The most common type of pneumothorax was spontaneous in-onset. Neonates on HFV had the highest and those on nCPAPt the lowest rate of pneumothorax. Improving training of resuscitation techniques at birth and strategies of use of invasive modes of respiratory support may reduce incidences of all types of pneumothorax.


Rape: medical and legal information.
The author explores the topic of rape in order to help security directors and rape victims better understand the medical and legal procedures a victim might experience. He describes how a rape case might be handled and what to expect.


Protein abundance is key to distinguish promiscuous from functional phosphorylation based on evolutionary information.
In eukaryotic cells, protein phosphorylation is an important and widespread mechanism used to regulate protein function. Yet, of the thousands of phosphosites identified to date, only a few hundred at best have a characterized function. It was recently shown that these functional sites are significantly more conserved than phosphosites of unknown function, stressing the importance of considering evolutionary conservation in assessing the global functional landscape of phosphosites. This leads us to review studies that examined the impact of phosphorylation on evolutionary conservation. While all these studies have shown that conservation is greater among phosphorylated sites compared with non-phosphorylated ones, the magnitude of this difference varies greatly. Further, not all studies have considered key factors that may influence the rate of phosphosite evolution. Such key factors are their localization in ordered or disordered regions, their stoichiometry or the abundance of their corresponding protein. Here we take into account all of these factors simultaneously, which reveals remarkable evolutionary patterns. First, while it is well established that protein conservation increases with abundance, we show that phosphosites partly follow an opposite trend. More precisely, Saccharomyces cerevisiae phosphosites present among abundant proteins are 1.5 times more likely to diverge in the closely related species Saccharomyces bayanus when compared with phosphosites present in the 5 per cent least abundant proteins. Second, we show that conservation is coupled to stoichiometry, whereby sites frequently phosphorylated are more conserved than those rarely phosphorylated. Finally, we provide a model of functional and noisy or 'accidental' phosphorylation that explains these observations.


Sequential chemotherapy and myeloablative allogeneic hematopoietic stem cell transplantation for refractory acute lymphoblastic leukemia.
The prognosis of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for refractory acute lymphoblastic leukemia (ALL) is very poor. To improve survival rates, we attempted to intensify the conditioning regimen with daunorubicin, vincristine, prednisolone, medium-dose etoposide, cyclophosphamide, and total body irradiation (DNR/VCR/PSL plus medium-dose VP/CY/TBI). Four patients in relapse or induction failure of B-precursor ALL without other complications underwent allogeneic HSCT. Initially, chemotherapy comprising DNR 60 mg/m(2) for 3 days, VCR 1.4 mg/m(2) for 1 day, and PSL 60 mg/m(2) for 3 days was administered, which was followed by medium-dose VP/CY/TBI; some modifications were made for individual patients. All patients achieved engraftment and complete remission after HSCT. Regimen-related toxicities were tolerable and no patient died within 100 days. Two patients were alive without disease on days 563 and 1,055. The third patient relapsed on day 951, while the fourth died on day 179 without disease. Our results indicate that intensified myeloablative HSCT should be considered for patients with refractory ALL.


A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis.
A mouse immunoglobulin G3 monoclonal antibody specific for the core oligosaccharide moiety of the lipooligosaccharide (LOS) of Bordetella pertussis has been shown to have complement-dependent bactericidal activity. This monoclonal antibody exhibits bactericidal activity against strains of B. pertussis that express the LOS A phenotype. In addition this monoclonal antibody was effective in reducing colonization by B. pertussis in both the lungs and tracheas of mice after aerosol infection.


Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.
Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ≤ 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ∩ PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.


A NEW METHOD OF POLARIZATION MICROSCOPIC ANALYSIS. I. SCANNING WITH A BIREFRINGENCE DETECTION SYSTEM.
A new method of polarized light analysis is described in which a highly sensitive electronic detector specific for birefringence is used to identify the crystalline axes of an object and then measure its phase retardation due to birefringence. The microscopic system employed in the method consists of an electronic birefringence detection system (BDS), a microscope with strain-free lenses, and a driven stage for passing the specimen at appropriate velocities across the image of an aperture placed at the field stop and imaged in the specimen plane by the condenser. The detector registers retardations directly as voltage at a constant deflection sensitivity of ca. 1.1 v per angstrom unit over a range of 120 angstrom units. The basal rms noise level is 0.002 A for a spot 36 micro in diameter formed by a 95 x, N. A. 1.25 objective pair, and increases in proportion to the reciprocal of the diameter of the scanning spot. The increase in noise with high resolution scanning can be offset by increasing the instrumental time constant, which is adjustable in decades between 0.004 and 0.4 seconds. A number of difficult problems in high extinction polarization microscopy are avoided by the use of modulated light and a rapid electronic detector. For example: (a) The measured distribution of birefringence is unaffected by the usual diffraction anomaly; therefore polarization rectifiers are not required. (b) The detector is selective for birefringence, so that there is no problem in separating contrast due to different optical properties (e.g. dichroism, light scattering). (c) The speed and sensitivity are both increased by between one and two orders of magnitude over that attainable by visual or photographic methods, thereby rendering a vast number of weakly birefringent, light-scattering, and motile objects readily analyzable for the first time with polarized light.


Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.
A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS.


Rapid method for detection of Vibrio cholerae from drinking water with nanomaterials enhancing electrochemical biosensor.
Cholera is a potentially fatal diarrheal disease caused by Vibrio cholerae and is spread to humans from contaminated food and water. In order to prevent spread of epidemic chlorea, the development of novel sensitive, selective, user-friendly, cost-effective and rapid detection systems to detect of V. cholerae are necessary. Therefore, in this study, it was aimed to develop a specific, electrochemical immunoassay with high selectivitiy and sensitivity for detection of V. cholerae from drinking water using in house synthesized Gold Nanoparticles (AuNPs). The synthesized AuNPs were characterized by UV/Vis spectroscopy, Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM) and electrochemical techniques were applied to confirm the succesful fabrication of the immunosensor. Also, this study focuses on the development of an antibody sensor for V. cholerae detection using a standard immunoassay without using nanoparticle. To accomplish that, in house spherical synthesized AuNPs at various sizes were synthesized, conjugated with secondary antibody-horseradish peroxidase enzyme (HRP) complex and their possible effect on the lowest detection limit of V. cholerae was investigated in comparison to commercially available AuNPs. The AuNPs-immunosensor on the results enabled the quantification of V. cholerae in a wide concentration range with a high sensitivity limit of detection (1 Colony-Forming Units/Milliliter) and specificity. Although the effect of 33 and 54 nm AuNPs on the process is close to each other, it has been observed that there is a 34% loss of efficiency when the size of the nanoparticle increases. With this study, a novel V. cholerae specific immunosensor was developed and the effects of in house synthesized AuNPs with various diameter on this developed biosensor were investigated in detail.


Influence of Renal Function on Treatment Results after Stroke Thrombectomy.
Renal dysfunction (RD) may be associated with poor outcome in ischemic stroke patients treated with mechanical thrombectomy (MT), but data concerning this important and emerging comorbidity do not exist so far. Here, we investigated the influence of RD on postprocedural intracerebral hemorrhage (ICH), clinical outcome, and mortality in a large prospectively collected cohort of acute ischemic stroke patients treated with MT. Consecutive patients with anterior-circulation stroke treated with MT between October 2010 and January 2016 were included. RD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m2. In a prospective database, clinical characteristics were recorded and brain images were analyzed for the presence of ICH after treatment in all patients. Clinical outcome was assessed by the modified Rankin Scale (mRS) after 3 months. To evaluate associations between clinical factors and outcomes uni- and multivariate regression analyses were conducted. In total, 505 patients fulfilled all inclusion criteria (female: 49.7%, mean age: 71.0 years). RD at admission was present in 20.2%. RD patients were older and had cardiovascular risk factors more often. Multivariate regression analysis after adjustment for age, stroke severity, diabetes, hypertension, GFR, previous stroke, MT alone, or additional thrombolysis and recanalization results revealed that lower GFR was not independently associated with poor outcome (mRS 3-6; OR 1.13, 95% CI 0.99-1.28; p = 0.072) or ICH. However, lower GFR at admission was associated with a higher risk of mortality (OR 1.15, 95% CI 1.01-1.31; p = 0.038). Compared to admission, GFR values were higher at discharge (mean: 77.9 vs. 80.8 mL/min/1.73 m2; p = 0.046). We did not find evidence for an association of lower GFR with an increased risk of poor outcome and ICH, but lower GFR was a determinant of 90-day mortality after endovascular stroke treatment. Our findings encourage also performing MT in this relevant subgroup of acute ischemic stroke patients.


Two-photon polymerization with variable repetition rate bursts of femtosecond laser pulses.
We describe fabrication of microstructures by two-photon polymerization using bursts of femtosecond laser pulses. With the aid of an acousto-optic modulator driven by a function generator, two-photon polymerization is performed at variable burst repetition rates. We investigate how the time between the bursts of laser pulses influences the ultimate dimensions of lines written in a photosensitive resin. We observe that when using the same laser fluence, polymer lines fabricated at different burst repetition rates have different dimensions. In particular, the widths of two-photon polymerized lines become smaller with decreasing burst repetition rates. Based on the thermal properties of the resin and experimental writing conditions, we attribute this effect to localized heat accumulation.


[On the dose-effect relation of allopurinol (author's transl)].
The hypuricemic action(y) of 1H-pyrazolo(3,4-d)pyrimidin-4-ol (allopurinol) is dependent on the serum concentration of uric acid (x). After treatment with allopurinol at doses of 300 mg daily for 8 days there exists a highly significant correlation corresponding the equation y = 0.875x + 3.950. At a level of 8 mg/dl without any therapy serum uric acid concentration is expected to decrease by an average of 3 mg/dl if allopurinol is applied at daily doses of 300 mg in a preparation with or without any retarding effect. Following a dose reduction to 150 mg allopurinol daily over a period of 8 days, too, the mean diminution of the hypuricemic action amounts only to 0.43 +/- 0.26 mg/dl (S.D.). In some cases, however, long-term therapy with allopurinol at daily doses of 150 mg is insufficient to guarantee a normuricemic state.


Towards Control of a Transhumeral Prosthesis with EEG Signals.
Robotic prostheses are expected to allow amputees greater freedom and mobility. However, available options to control transhumeral prostheses are reduced with increasing amputation level. In addition, for electromyography-based control of prostheses, the residual muscles alone cannot generate sufficiently different signals for accurate distal arm function. Thus, controlling a multi-degree of freedom (DoF) transhumeral prosthesis is challenging with currently available techniques. In this paper, an electroencephalogram (EEG)-based hierarchical two-stage approach is proposed to achieve multi-DoF control of a transhumeral prosthesis. In the proposed method, the motion intention for arm reaching or hand lifting is identified using classifiers trained with motion-related EEG features. For this purpose, neural network and k-nearest neighbor classifiers are used. Then, elbow motion and hand endpoint motion is estimated using a different set of neural-network-based classifiers, which are trained with motion information recorded using healthy subjects. The predictions from the classifiers are compared with residual limb motion to generate a final prediction of motion intention. This can then be used to realize multi-DoF control of a prosthesis. The experimental results show the feasibility of the proposed method for multi-DoF control of a transhumeral prosthesis. This proof of concept study was performed with healthy subjects.


Headspace gas chromatography with flame ionization detection (HS-GC-FID) for the determination of dissolved methane in wastewater.
There is currently a need for a simple, accurate and reproducible method that quantifies the amount of dissolved methane in wastewater in order to realize the potential methane that can be recovered and account for any emissions. This paper presents such a method, using gas chromatography with flame ionization detection fitted with a GS-Gas PRO column coupled with a headspace auto sampler. A practical limit of detection for methane of 0.9 mg L(-1), with a retention time of 1.24 min, was obtained. It was found that the reproducibility and accuracy of the method increased significantly when samples were collected using an in-house constructed bailer sampling device and with the addition of 100 μL hydrochloric acid (HCl) and 25% sodium chloride (NaCl) and sonication for 30 min prior to analysis. Analysis of wastewater samples and wastewater sludge collected from a treatment facility were observed to range from 12.51 to 15.79 mg L(-1) (relative standard deviation (RSD) 8.1%) and 17.56 to 18.67 mg L(-1) (RSD 3.4%) respectively. The performance of this method was validated by repeatedly measuring a mid-level standard (n=8; 10 mg L(-1)), with an observed RSD of 4.6%.


Average crop yield (2001-2017) in Ethiopia: Trends at national, regional and zonal levels.
This article presents average agricultural yield data per hectare for key cereal, legume and root crops from 2001 until 2017. Data was obtained from the annual Agricultural Sample Surveys of the Central Statistics Agency (CSA) of Ethiopia. We present data at national, regional (SNNPRS) and zonal (Wolaita) levels. The data shows that average yields for all crops, at all levels, show increasing trends during the time period. Data for the main cereal crops is consistent and aligns with literature relatively well, however we raise questions about the root crop data in an effort to encourage greater critical reflection of components of data from the CSA.


A Tensionable Suture-based Cerclage Is an Alternative to Stainless Steel Cerclage Fixation for Stabilization of a Humeral Osteotomy During Shoulder Arthroplasty.
Fixation of periprosthetic humeral fractures is most commonly obtained with steel-based wires or cables; however, disadvantages with these constructs are numerous. Suture-based cerclages offer the advantage of easy handling, less radiographic interference, and risk of metallosis, as well as decreased risk of cutting into the soft humeral bone. Therefore, the purpose of this study was to compare a suture-based cerclage to a stainless steel wire cerclage (SSWC) for stabilization of the humerus during shoulder arthroplasty. In part I of the study, SSWC fixation was compared with single-looped tape cerclage and a double-looped tape cerclage (DLTC) fixation. In part II, a subsidence test was performed on 12 cadaveric humeri. After an osteotomy, the humeri were secured with either a SSWC or DLTC. Subsequently, a metal wedge was introduced into the humerus to simulate the stem of a shoulder arthroplasty. In part I, load to 2-mm displacement was significantly higher for the DLTC construct compared with the SSWC construct (2,401 ± 483 N versus 750 ± 33 N; P < 0.0001). Load to failure was 935 ± 143 N with the SSWC, 1,737 ± 113 N with the single-looped tape cerclage, and 4,360 ± 463 N with the DLTC constructs, and all differences were statistically significant (P < 0.05). In part II, load at 20-mm subsidence was higher for the DLTC (320 ± 274 N) compared with the SSWC (247 ± 137 N), but no significant difference was observed (P > 0.05). However, gap displacement at 20 mm subsidence was significantly lower with the DLTC construct (0.33 ± 0.31 mm versus 0.77 ± 0.23 mm; P = 0.009). Load to failure was higher with the DLTC construct compared with the SSWC construct (4,447 ± 2,325 N versus 1,880 ± 1,089 N; P = 0.032), but the final gap displacement did not differ significantly (DLTC 5.23 ± 6.63 mm versus SSWC 6.03 ± 8.82 mm; P > 0.05). A DLTC has higher load to failure and trends toward lower gap displacement compared with a SSWC. The DLTC construct may therefore be a viable alternative for fixation of periprosthetic fractures or osteotomies of the humeral shaft during shoulder arthroplasty.


A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots.
Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93; P < 0.0001). The mean difference between DBS and plasma VL values was -1.06 log10 copies/ml (95% confidence interval [CI], -1.17, -0.97; P < 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system.


Worth the weight: using inverse probability weighted Cox models in AIDS research.
In an observational study with a time-to-event outcome, the standard analytical approach is the Cox proportional hazards regression model. As an alternative to the standard Cox model, in this article we present a method that uses inverse probability (IP) weights to estimate the effect of a baseline exposure on a time-to-event outcome. IP weighting can be used to adjust for multiple measured confounders of a baseline exposure in order to estimate marginal effects, which compare the distribution of outcomes when the entire population is exposed versus when the entire population is unexposed. For example, IP-weighted Cox models allow for estimation of the marginal hazard ratio and marginal survival curves. IP weights can also be employed to adjust for selection bias due to loss to follow-up. This approach is illustrated using an example that estimates the effect of injection drug use on time until AIDS or death among HIV-infected women.


Qualitative study to elicit patients' and primary care physicians' perspectives on the use of a self-management mobile health application for knee osteoarthritis.
To elicit perspectives of family physicians and patients with knee osteoarthritis (KOA) on KOA, its treatment/management and the use of a mobile health application (app) to help patients self-manage their KOA. A qualitative study using Cognitive Task Analysis for physician interviews and peer-to-peer semistructured interviews for patients according to the Patient and Community Engagement Research (PaCER) method. Primary care practices and patient researchers at an academic centre in Southern Alberta. Intentional sampling of family physicians (n=4; 75% women) and patients with KOA who had taken part in previous PaCER studies and had experienced knee pain on most days of the month at any time in the past (n=5; 60% women). Physician and patient views about KOA were starkly contrasting. Patient participants expressed that KOA seriously impacted their lives and lifestyles, and they wanted their knee pain to be considered as important as other health problems. In contrast, physicians uniformly conceptualised KOA as a relatively minor health problem, although they still recognised it as a painful condition that often limits patients' activities. Consequently, physicians did not regard KOA as a condition to be proactively and aggressively managed. The gap between physicians' and patients' conceptualisation of KOA and its treatment extended to the use of an app for self-management. While patients were supportive of the app, physicians were sceptical of its use and focused more on accountability and patient resources. The clear discord between physicians' mental models and patients' lived experience and perceived needs around KOA emphasised a gap in understanding and communication about treatment and management of KOA. As such, this preliminary and formative research will inform a codesign approach to develop an app that will act as a communications tool between patients and physicians, enabling patient-physician discussions regarding modifiable self-management options based on a patient's perspectives and needs.


Distribution of the alpha 1-alpha 6 integrin subunits in human developing and term placenta.
The distribution of the alpha 1-alpha 6 as well as alpha v, beta 1, beta 3 and beta 4 integrin subunits in human first and second trimester and term placentas was studied by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (mAbs). In first and second trimester villi, the alpha 1 and beta 1 integrin subunits were detected in the stromal cells, that were mostly also immunoreactive for desmin. Desmin-positive stromal cells were also found in villi of term placentas, but the stroma was negative for anti-alpha 1 and -beta 1. In the villous trophoblast, anti-alpha 6 and -beta 4 revealed a distinct basal immunoreactivity during all stages of development, whereas immunoreactivity for the alpha 3 and beta 1 subunits emerged during the second and third trimesters. Throughout placental development, endothelia of villous capillaries reacted prominently with anti-alpha 1 and -beta 1. Intermediate trophoblastic cells displayed a somewhat heterogenous immunoreactivity for the beta 1, alpha 1, alpha 3 and alpha 5 integrin subunits, and differed from villous trophoblast also in their lack of expression of the alpha 6 and beta 4 subunits. While nondecidualized endometrial cells displayed weak reactivity for the alpha 1 and beta 1 integrin subunits, the individual decidual cells presented both a basement membrane and a cell surface-confined immunoreactivity for anti-alpha 1, -alpha 3, and -beta 1. The results suggest a role for integrins in placental development, and show that expression of integrins is modulated during the differentiation of trophoblast, villous stroma, and decidual cells. Furthermore, the basal localization of alpha 6 beta 4 and alpha 3 beta 1 integrins suggests that they are employed as basement membrane receptors in the villous trophoblast, and the emergence of the alpha 3 beta 1 complex may reflect that the cytotrophoblast and syncytiotrophoblast recognize the basement membrane differently.


Dual origin of the vertebral artery mimicking dissection.
Vertebral artery injury may occur at the time of cervical fracture or dislocation. Congenital vertebral artery variations, especially a double vertebral artery origin, may be responsible for angiographic findings that mimic vertebral artery dissection. Two cases of cervical spine fracture with ipsilateral double vertebral artery are presented. Conventional cerebral angiography is the easiest and best way to make this diagnosis and to exclude vertebral artery dissection.


[Hepatorotective activity of honeysuckle fruit extract in carbon tetrachloride intoxicated rats].
We have studied the effects of the extract from the dry pomace of honeysuckle fruits Lonicera edulis Turcz. and commercial reference preparation Legalon on weight and biochemical liver indexes in rats upon carbon tetrachloride intoxication. The extract of honeysuckle fruits favored a decrease in the total lipid content, reduced specific liver weight, and facilitated restoration of the activity of serum alanine aminotransferase and liver lysosomal enzymes. It the blood of rats, the extract increased superoxide dismutase activity, decreased glutathione level, enhanced antiradical activity, and reduced the level of malonic dialdehyde. The effect of administration of honeysuckle fruits pomace extract on restoration of the liver function was more pronounced than the effect of Legalon.


Evaluation of the application of veterinary judgement in the pre-emptive cull of contiguous premises during the epidemic of foot-and-mouth disease in Cumbria in 2001.
This paper presents a detailed analysis of the application of contiguous culling in Cumbria between May 1 and September 30, during the outbreak of foot-and-mouth disease in 2001. The analysis shows that the application of veterinary risk assessment and judgement identified and removed groups of susceptible stock which were at risk of direct transmission of infection and avoided infected animals being left that might have spread the disease. When compared with an automatic contiguous cull, fewer culls were made and some of these were reduced in scale, providing economies in the use of resources. The data suggest that farms contiguous to an infected premises faced a 5 per cent risk of infection by direct transmission and a 12 per cent risk of infection by indirect transmission.


GSK-3beta down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress.
Oxidant injury activates the neuroprotective pathway represented by phosphatidylinositol 3 kinase (PI3K) and Akt. However, the final outcome of oxidant exposure is often associated with neuronal death. This study was aimed to identify the molecular mechanism responsible for loss of tolerance to an oxidative environment. In N2A neuroblasts, serum and H2O2 exhibited different kinetics of regulation for the Ser/Thr kinases Akt and glycogen synthase kinase 3beta (GSK-3beta) and for the transcription factor Nrf2, which governs redox homeostasis. Thus, H2O2 rapidly activated Akt, inhibited GSK-3beta, and directed the transcription factor Nrf2 to the nucleus, but after 4 h Akt was inactive, GSK-3beta was active and Nrf2 was more cytosolic than nuclear. Inhibition of the PI3K/Akt pathway by LY294002, impeded the short-term effect of H2O2 on nuclear translocation of Nrf2. GSK-3beta activation (inhibiting PI3K/Akt) or direct GSK-3beta inhibition in cerebellar granule neurons resulted in respective nuclear exclusion and nuclear accumulation of Nrf2. Moreover, in these neurons, nuclear accumulation of Nrf2 correlated with increased heme oxygenase-1 expression. Over-expression of the kinase active GSK-3beta (Delta9) mutant, induced Nrf2 cytoplasmic localization and inhibited Nrf2 transcriptional activity towards an antioxidant-response-element luciferase reporter. Moreover, GSK-3beta (Delta9) sensitized N2A neuroblasts to H2O2-induced oxidative stress and cell death. This study identifies GSK-3beta, a kinase known to participate in neurodegeneration, as a fundamental element in the down-regulation of the antioxidant cell defense elicited by Nrf2 after oxidant injury and provides a mechanism to explain the loss of oxidant tolerance that happens under persistent oxidant exposure such as those found in several neuropathologies.


Transcriptome analysis of the phytopathogenic fungus Rhizoctonia solani AG1-IB 7/3/14 applying high-throughput sequencing of expressed sequence tags (ESTs).
Rhizoctonia solani is a soil-borne plant pathogenic fungus of the phylum Basidiomycota. It affects a wide range of agriculturally important crops and hence is responsible for economically relevant crop losses. Transcriptome analysis of the bottom rot pathogen R. solani AG1-1B (isolate 7/3/14) by applying high-throughput sequencing and bioinformatics methods addressing Expressed Sequence Tag (EST) data interpretation provided new insights in expressed genes of this fungus. Two normalized cDNA libraries representing different cultivation conditions of the fungus were sequenced on the 454 FLX (Roche) system. Subsequent to cDNA sequence assembly and quality control, ESTs were analysed applying advanced bioinformatics methods. More than 14 000 transcript isoforms originating from approximately 10 000 predictable R. solani AG1-IB 7/3/14 genes are represented in each dataset. Comparative analyses revealed several differentially expressed genes depending on the growth conditions applied. Determinants with predicted functions in recognition processes between the fungus and the host plant were identified. Moreover, many R. solani AG1-IB ESTs were predicted to encode putative cellulose, pectin, and lignin degrading enzymes. Furthermore, genes playing a possible role in mitogen-activated protein (MAP) kinase cascades, 4-aminobutyric acid (GABA) metabolism, melanin synthesis, plant defence antagonism, phytotoxin, and mycotoxin synthesis were detected.


Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding.
β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia result from mutations in the adult HBB (β-globin) gene. Reactivating the developmentally silenced fetal HBG1 and HBG2 (γ-globin) genes is a therapeutic goal for treating SCD and β-thalassemia 1 . Some forms of hereditary persistence of fetal hemoglobin (HPFH), a rare benign condition in which individuals express the γ-globin gene throughout adulthood, are caused by point mutations in the γ-globin gene promoter at regions residing ~115 and 200 bp upstream of the transcription start site. We found that the major fetal globin gene repressors BCL11A and ZBTB7A (also known as LRF) directly bound to the sites at -115 and -200 bp, respectively. Furthermore, introduction of naturally occurring HPFH-associated mutations into erythroid cells by CRISPR-Cas9 disrupted repressor binding and raised γ-globin gene expression. These findings clarify how these HPFH-associated mutations operate and demonstrate that BCL11A and ZBTB7A are major direct repressors of the fetal globin gene.


Modification of the existing maximum residue levels for tau-fluvalinate in tomatoes and watermelons.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant ADAMA Agriculture BV on behalf of ADAMA Makhteshim Ltd submitted a request to the competent national authority in Denmark to modify the existing maximum residue levels (MRL) for the active substance tau-fluvalinate in tomatoes and watermelons. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for tomatoes. For watermelons, a change of the MRL recently set in the EU legislation is not required. Adequate analytical methods for enforcement are available to control the residues of tau-fluvalinate in the commodities under consideration. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the intended uses of tau-fluvalinate according to the reported agricultural practices is unlikely to present a risk to consumer health. The risk assessment shall be regarded as indicative.


Socio-economic circumstances and food habits in Eastern, Central and Western European populations.
To assess the relationship between several socio-economic indicators and frequency of consumption of seven predefined healthy foods (consumption of fruit, vegetables, wholegrain bread, vegetable-fat spread, vegetable cooking fat, low-fat milk and low-fat cheese) in populations from Eastern, Central and Western Europe. Analysis of baseline data collected in two cross-sectional cohort studies between 2000 and 2005: the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study and the Finnish Helsinki Health Study (HHS). Urban populations in the Czech Republic, Russia, Poland and Finland. In the HAPIEE study, random samples of men and women aged 45-69 years were drawn from population registers and electoral lists of selected cities. In the HHS, men and women aged 40-60 years employed by the City of Helsinki were recruited. Data on 21,326 working subjects from both cohorts were analysed. Healthy food habits were, in general, positively associated with higher education, occupational position and fewer economic difficulties, but there were differences in the strength of the gradient by food and country. Fruit consumption showed the most consistent gradients, especially in relation to socio-economic status among men (country-specific relative index of inequality (RII)=2.02-5.17) and women (RII=2.09-3.57). The associations between socio-economic indicators and healthy food habits showed heterogeneity between countries. Future studies of dietary behaviours should consider multiple measures of socio-economic position.


Food security in an era of economic volatility.
This article analyzes international commodity price movements, assesses food policies in response to price fluctuations, and explores the food security implications of price volatility on low-income groups. It focuses specifically on measurements, causes, and consequences of recent food price trends, variability around those trends, and price spikes. Combining these three components of price dynamics shows that the variation in real prices post-2000 was substantially greater than that in the 1980s and 1990s, and was approximately equal to the extreme volatility in commodity prices that was experienced in the 1970s. Macro policy, exchange rates, and petroleum prices were important determinants of price variability over 2005–2010, highlighting the new linkages between the agriculture-energy and agriculture-finance markets that affect the world food economy today. These linkages contributed in large part to misguided expectations and uncertainty that drove prices to their peak in 2008. The article also argues that there is a long-lasting effect of price spikes on food policy around the world, often resulting in self-sufficiency policies that create even more volatility in international markets. The efforts by governments to stabilize prices frequently contribute to even greater food insecurity among poor households, most of which are in rural areas and survive on the margin of net consumption and net production. Events of 2008—and more recently in 2010—underscore the impact of price variability for food security and the need for refocused policy approaches to prevent and mitigate price spikes.


[Pernicious anemia. A study of initial forms of the disease and diagnostic significance of determination of the intrinsic factor antibody and parietal cell antibody].
In a prospective study of thirty five consecutive patients with decreased plasma cobalamine (P-Cbl), twenty-two (63%) were diagnosed as having pernicious anaemia (PA) (no age or sex differences) on basis of the B12-absorption test and/or megaloblastic changes in the bone marrow. In this group ten patients were anaemic (six of whom were characterized as macrocytic), sixteen of nineteen examined had megaloblastic changes in the bone marrow, and all of thirteen examined had achlorhydria with positive correlation to Parietal Cell Antibodies (PCA). Two patients with PA had normal Cbl-absorption and two had malabsorption at the time of diagnosis. Twenty-one patients (95%) had PCA and thirteen (59%) were Intrinsic Factor Antibody (IFAb) positive. Three patients IFAb-seroconverted within a year. Among the remaining thirteen patients (37%), one had PCA but not IFAb and three were IFAb-positive all of whom had normal Cbl-absorption. Of the three patients with IFAb one had also PCA, one IFAb-seroconverted within three months, and one had microcytic anaemia with iron depleted bone marrow due to coecal cancer. Among twenty two healthy adult controls four (18%) had PCA while none had IFAb. This investigation shows that at the debut half of PA patients (55%) do not have anaemia, some have normal Cbl-absorption and some have malabsorption. 95% have PCA and 59% have IFAb. So, IFAb-negative PA is often seen (41%) and seroconversion can take place. Diagnosis is even more reliable, when achlorhydria is present in PCA-positive persons. Healthy PCA-positive persons are probably predisposed to develop PA. Patients with cbl-deficiency, IFAb and/or PCA must be considered as having latent PA even if they have normal haemoglobin and normal Cbl-absorption. These patients should be followed and, in case of anaemia or signs of neuropathia, treated.(ABSTRACT TRUNCATED AT 250 WORDS)


Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).
Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials. To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people. We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022. We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile. We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome. We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I2 = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I2 = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates. In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.


Multi-purpose, multi-level feature modeling of large-scale industrial software systems.
Feature models are frequently used to capture the knowledge about configurable software systems and product lines. However, feature modeling of large-scale systems is challenging as models are needed for diverse purposes. For instance, feature models can be used to reflect the perspectives of product management, technical solution architecture, or product configuration. Furthermore, models are required at different levels of granularity. Although numerous approaches and tools are available, it remains hard to define the purpose, scope, and granularity of feature models. This paper first reports results and experiences of an exploratory case study on developing feature models for two large-scale industrial automation software systems. We report results on the characteristics and modularity of the feature models, including metrics about model dependencies. Based on the findings from the study, we developed FORCE, a modeling language, and tool environment that extends an existing feature modeling approach to support models for different purposes and at multiple levels, including mappings to the code base. We demonstrate the expressiveness and extensibility of our approach by applying it to the well-known Pick and Place Unit example and an injection molding subsystem of an industrial product line. We further show how our approach supports consistency between different feature models. Our results and experiences show that considering the purpose and level of features is useful for modeling large-scale systems and that modeling dependencies between feature models is essential for developing a system-wide perspective.


Cerebral ischemia due to congenital malformations of brachiocephalic arteries--case reports.
Seven cases of congenital anomalies of brachiocephalic arteries are presented; malformations include unilateral absence of the internal carotid artery (ICA) (n = 3), unilateral hypoplasia of the ICA (n = 2), agenesis of the innominate artery (n = 1), and atresia of the subclavian artery (n = 1). All patients but 1 exhibited symptoms of cerebrovascular insufficiency at the time of radiologic investigation; they were not affected by other cardiovascular malformations, except right aortic arch in 2 cases and left cervical arch in another case. Two patients suffering from congenital subclavian steal syndrome underwent surgery to correct the vascular malformations. Embryogenesis and natural history of such malformations are briefly discussed.


Levamisole-Induced Vasculitis: A Characteristic Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine.
Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically present with a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis involving the extremities, trunk, nasal tip, digits, cheeks, and/or ears. A history of cocaine abuse can be elicited. Histologic features include microvascular thrombi and/or leukocytoclastic vasculitis involving small vessels of the superficial and deep dermis. Epidermal involvement is variably seen. Laboratory findings include leukopenia, neutropenia (including agranulocytosis), elevated erythrocyte sedimentation rate, normal coagulation studies, and positive autoantibodies including perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibody, and lupus anticoagulant. Differential diagnosis includes other microscopic vasculitides, and clinical and laboratory correlation with histologic findings is essential. Lesions typically resolve with the cessation of cocaine use. Because of the treatment implications and rising incidence of this entity, rapid and accurate diagnosis is essential.


Rearrangements of intranuclear structures involved in RNA processing in response to adenovirus infection.
We have studied in HeLa cells at the electron microscope level the response to adenovirus infection of the RNA processing machinery. Components of the spliceosomes were localized by in situ hybridization with biotinylated U1 and U2 DNA probes and by immunolabeling with Y12 anti-Sm monoclonal antibody, whereas poly(A)+ RNAs were localized by specific binding of biotinylated poly(dT) probe. At early stages of nuclear transformation, the distribution of small nuclear RNPs was similar to that previously described in non-infected nuclei (Visa, N., Puvion-Dutilleul, F., Bachellerie, J.P. and Puvion, E., Eur. J. Cell Biol. 60, 308-321, 1993; Visa, N., Puvion-Dutilleul, F., Harper, F., Bachellerie, J. P. and Puvion, E., Exp. Cell Res. 208, 19-34, 1993). As the infection progresses, the large virus-induced inclusion body consists of a central storage site of functionally inactive viral genomes surrounded by a peripheral shell formed by clusters of interchromatin granules, compact rings and a fibrillogranular network in which are embedded the viral single-stranded DNA accumulation sites. Spliceosome components and poly(A)+ RNAs were then exclusively detected over the clusters of interchromatin granules and the fibrillogranular network whereas the viral single-stranded DNA accumulation sites and compact rings remained unlabeled, thus appearing to not be directly involved in splicing. Our data, therefore, suggest that the fibrillogranular network, in addition to being the site of viral transcription, is also a major site of viral RNA splicing. Like the clusters of interchromatin granules, which had been already involved in spliceosome assembly, they could also have a role in the sorting of viral spliced polyadenylated mRNAs before export to the cytoplasm. The compact rings, which contain non-polyadenylated viral RNA, might accumulate the non-used portions of the viral transcripts resulting from differential poly(A)+ site selection.


Interference with renal organic cation transport by (-)- and (+)-nicotine at concentrations documented in plasma of habitual tobacco smokers.
Nicotine is the principal psychoactive Nicotiana alkaloid in tobacco. In the present study, we used amantadine as a marker and investigated the potential ability of nicotine and cotinine to interfere with renal organic cation transport in vitro. [3H]Amantadine is concentrated actively by isolated proximal tubules, distal tubules and cortical slices. In proximal tubules, the addition of (-)- or (+)-nicotine (0.1-100 microM) facilitated amantadine (10 microM) accumulation. Apparent Km for amantadine uptake was decreased by a clinically relevant concentration of (-)- and (+)-nicotine (0.4 microM), from 78 +/- 2 to 52 +/- 2 and 61 +/- 5 microM, respectively (mean +/- S.E.M., P less than .05), whereas Vmax was not altered (6.6 +/- 0.1 to 6.3 +/- 0.1 and 6.5 +/- 0.2 nmol/mg/min). The addition of (-)-cotinine (0.4-100 microM) also facilitated amantadine uptake, but with lesser efficacy. Possible mechanisms underlying the present enhancement of uptake include facilitation of amantadine influx and/or attenuation of efflux. Efflux data indicate a prominent hindrance of amantadine egress from preloaded tubules in the presence of 0.4 microM (-)- and (+)-nicotine (51 +/- 4 to 32 +/- 8 and 27 +/- 4 pmol/mg/30 sec, P less than .05) and are supportive of the latter notion. In distal tubules, (-)- or (+)-nicotine produced inhibition only a high concentrations (greater than or equal to 100 microM). Km was increased by 400 microM (-)- and (+)-nicotine from 76 +/- 5 to 124 +/- 9 and 116 +/- 17 microM, and Vmax was moderately decreased from 3.4 +/- 0.5 to 3.0 +/- 0.4 and 3.0 +/- 0.4 nmol/mg/min (P less than .05). The incorporation of (-)-cotinine did not alter amantadine uptake. Enhancement of uptake by (-)- or (+)-nicotine was absent in cortical slices, in which tubular luminal transport has ben proposed to be insignificant, and only low affinity inhibition was apparent. The present data indicate potent interference of renal proximal tubular transport of amantadine by nicotine at concentrations equivalent to those documented in plasma of habitual tobacco smokers and suggest potential alterations in renal organic cationic drug elimination in these subjects.


Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients.
There is evidence suggesting that patients infected with human immunodeficiency virus (HIV) are under chronic oxidative stress. In the present study, the level of oxidatively modified bases in lymphocyte DNA and some other parameters of oxidative stress were measured in HIV-infected patients (n = 30), as well as in control groups (10 healthy volunteers and 15 HIV-seronegative injected drug users). Additional experiments were conducted using lymphocyte DNA samples from asymptomatic seropositive, HIV-infected patients who were supplemented with antioxidant vitamins A, C, and E or received placebo. Significant increases in the amount of the modified DNA bases were observed in HIV-infected patients when compared with the control group. The concentration of thiobarbituric acid reactive substances (TBARS) was higher and activities of antioxidant enzymes (superoxide dismutase and catalase) were lower in the group of HIV-infected patients in comparison to the control group. Vitamin supplementation resulted in the significant decrease in the levels of all modified DNA bases when compared to the patients who received placebo. The reduction of TBARS and the restoration of the activity of the enzymes were also observed. Our data suggest that people infected with HIV can benefit from treatment with antioxidant vitamins.


Determination of ABO Blood Groups and Rh Typing from Dry Salivary Samples.
A unique blood group is a characteristic every individual possesses. Blood group antigens like A, B, D, H, etc., are found to be present on the cell surfaces of red blood cells (RBCs). Besides blood, these are also secreted in various body secretions like semen, sweat, amniotic fluid, and saliva. Blood grouping has several applications in forensic sciences and is also a major part of routine medical investigations. Presence of these antigens in saliva is dependent on the secretor status of an individual. Saliva samples at the crime scene are very crucial, as they help in deoxyribonucleic acid typing, sex determination, bite mark analysis, and blood grouping. Dried salivary samples are often obtained in more number of cases as compared with the wet form, due to the variable time lapse between the occurrence of the crime and the start of the investigation. Blood grouping from these samples proves to be very efficient. Thus, the present study aims at evaluating the accuracy of ABO blood group determination and Rh typing from dried salivary samples. Also, the study would establish the use of saliva as a noninvasive technique in routine blood examinations, especially in children who have needle phobia. Blood grouping and Rh typing were performed on the dry salivary samples obtained from the 47 subjects using the absorption-inhibition technique. This was then compared with the results obtained using extraction socket blood and evaluated. The present study showed a 100% positive correlation for ABO blood grouping, but a mere 14.81% positive correlation for Rh typing between the dried salivary samples and the extraction socket blood. Dried salivary samples can thus be put to immense use in several areas of forensic investigations. It could also help in developing alternate methods for routine blood investigations in children and adults.How to cite this article: Velani PR, Shah P, Lakade L. Determination of ABO Blood Groups and Rh Typing from Dry Salivary Samples. Int J Clin Pediatr Dent 2018;11(2):100-104.


Halogen bonding properties of 4-iodopyrazole and 4-bromopyrazole explored by rotational spectroscopy and ab initio calculations.
The combination of halogen- and hydrogen-bonding capabilities possessed by 4-bromopyrazole and 4-iodopyrazole has led to them being described as "magic bullets" for biochemical structure determination. Laser vaporisation was used to introduce each of these 4-halopyrazoles into an argon gas sample undergoing supersonic expansion prior to the recording of the rotational spectra of these molecules by chirped-pulse Fourier transform microwave spectroscopy. Data were obtained for four isotopologues of 4-bromopyrazole and two isotopologues of 4-iodopyrazole. Isotopic substitutions were achieved at the hydrogens attached to the pyrrolic nitrogen atoms of both 4-halopyrazoles and at the bromine atom of 4-bromopyrazole. The experimentally determined nuclear quadrupole coupling constants, χaa(X) and χbb(X)-χcc(X), of the halogen atoms (where X is the halogen atom) of each molecule are compared with the results of the ab initio calculations and those for a range of other halogen-containing molecules. It is concluded that each of 4-bromopyrazole and 4-iodopyrazole will form halogen bonds that are broadly comparable in strength to those formed by CH3X and CF3X.


Rheumatoid nodules of the lung in a patient with palindromic rheumatism.
We report a case of rheumatoid nodules of the lung seen in a patient with palindromic rheumatism. A 54-year-old man with palindromic rheumatism was admitted for evaluation of three nodules in the right upper lobe on chest roentgenogram. Wedge resection was performed for the purpose of confirmative diagnosis and treatment. Histology of these lung lesions revealed palisaded histiocytic cells surrounding a layer of central necrosis, which were considered to be characteristic findings of rheumatoid nodule. Such a case is extremely rare. To our knowledge, only one other case has been reported before in the literature.


Cerebrospinal fluid prohormone processing and neuropeptides stimulating feed intake of dairy cows during early lactation.
After parturition, feed intake of dairy cows increases within the first weeks of lactation, but the molecular mechanisms stimulating or delaying the slope of increase are poorly understood. Some of the molecules controlling feed intake are neuropeptides that are synthesized as propeptides and subsequently processed before they bind to specific receptors in feeding centers of the brain. Cerebrospinal fluid surrounds most of the feed intake regulatory centers and contains numerous neuropeptides. In the present study, we used a proteomic approach to analyze the neuropeptide concentrations in cerebrospinal fluid taken from dairy cows between day -18 and -10, and between day +10 and +20 relative to parturition. We found 13 proteins which were only present in samples taken before parturition, 13 proteins which were only present in samples taken after parturition, and 25 proteins which were commonly present, before and after parturition. Among them, differences in pro-neuropeptide Y, proenkephalin-A, neuroendocrine convertase-2, neurosecretory protein VGF, chromogranin-A, and secretogranin-1 and -3 concentrations relative to parturition highlight propeptides and prohormone processings involved in the control of feed intake and energy homeostasis. Scaffold analysis further emphasized an increased tone of endogenous opioids associated with the postparturient increase of feed intake.


Observation of short range order driven large refrigerant capacity in chemically disordered single phase compound Dy2Ni0.87Si2.95.
In this work, we report the successful synthesis of a new intermetallic compound Dy2Ni0.87Si2.95 forming in single phase only with a chemically disordered structure. The random distribution of Ni/Si and crystal defects create a variation in the local electronic environment between the magnetic Dy ions. In the presence of both disorder and competing exchange interactions driven magnetic frustration, originating due to c/a ∼ 1, the compound undergoes spin freezing behaviour below 5.6 K. In the non-equilibrium state below the spin freezing behaviour, the compound exhibits aging phenomena and magnetic memory effects. In the magnetically short-range ordered region, much above the freezing temperature, an unusual occurrence of considerable magnetic entropy change, -ΔSmaxM ∼ 21 J kg-1 K-1 with large cooling power RCP ∼ 531 J kg-1 and adiabatic temperature change, ΔTad ∼ 10 K for a field change of 70 kOe, is observed for this short range ordered cluster-glass compound without any magnetic hysteresis loss.


Integrated analysis identifies a class of androgen-responsive genes regulated by short combinatorial long-range mechanism facilitated by CTCF.
Recently, much attention has been given to elucidate how long-range gene regulation comes into play and how histone modifications and distal transcription factor binding contribute toward this mechanism. Androgen receptor (AR), a key regulator of prostate cancer, has been shown to regulate its target genes via distal enhancers, leading to the hypothesis of global long-range gene regulation. However, despite numerous flows of newly generated data, the precise mechanism with respect to AR-mediated long-range gene regulation is still largely unknown. In this study, we carried out an integrated analysis combining several types of high-throughput data, including genome-wide distribution data of H3K4 di-methylation (H3K4me2), CCCTC binding factor (CTCF), AR and FoxA1 cistrome data as well as androgen-regulated gene expression data. We found that a subset of androgen-responsive genes was significantly enriched near AR/H3K4me2 overlapping regions and FoxA1 binding sites within the same CTCF block. Importantly, genes in this class were enriched in cancer-related pathways and were downregulated in clinical metastatic versus localized prostate cancer. Our results suggest a relatively short combinatorial long-range regulation mechanism facilitated by CTCF blocking. Under such a mechanism, H3K4me2, AR and FoxA1 within the same CTCF block combinatorially regulate a subset of distally located androgen-responsive genes involved in prostate carcinogenesis.


Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.
Epidemiological and experimental evidence suggests that high levels of vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis. There are no prospective studies addressing this hypothesis. To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis. Prospective, nested case-control study among more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial multiple sclerosis symptoms. Odds ratios of multiple sclerosis associated with continuous or categorical levels (quantiles or a priori-defined categories) of serum 25-hydroxyvitamin D within each racial/ethnic group. Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found. The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.


Galectin-1, a beta-galactoside-binding lectin in Chinese hamster ovary cells. I. Physical and chemical characterization.
We report our studies on the characterization of an approximately 14-kDa lectin, termed galectin-1 that we have found to be expressed by Chinese hamster ovary (CHO) cells. cDNA for galectin-1 from CHO cells was prepared and sequenced, and a recombinant form (rGal-1) was expressed in Escherichia coli. A mutated form of the protein that fully retained activity was also constructed (termed C2SrGal-1) in which Cys-2 was changed to Ser-2. rGal-1 was stable in the presence of reducing agent, but it quickly lost all activity in the absence of reducing agent. In contrast, glycoprotein ligands, such as basement membrane laminin, stabilized the activity of rGal-1 in the absence of reducing agent (t1/2 = 2 weeks). C2SrGal-1 was stable in the presence or absence of either ligand or reducing agent. Unexpectedly, galectin-1 was found to exist in a reversible and active monomer-dimer equilibrium with a Kd approximately 7 microM and an equilibration time of t1/2 approximately 10 h. Addition of haptenic sugars did not affect this equilibrium. Galectin-1 isolated from the cytosol of CHO cells was found to exist as monomers and dimers. These studies demonstrate that galectin-1 binding to a biological ligand stabilizes its activity and that the monomer/dimer state of the protein is regulated by lectin concentration.


Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product in neural crest delamination.
During neural crest ontogeny, an epithelial to mesenchymal transition is necessary for cell emigration from the dorsal neural tube. This process is likely to involve a network of gene activities, which remain largely unexplored. We demonstrate that N-cadherin inhibits the onset of crest delamination both by a cell adhesion-dependent mechanism and by repressing canonical Wnt signaling previously found to be necessary for crest delamination by acting downstream of BMP4. Furthermore, N-cadherin protein, but not mRNA, is normally downregulated along the dorsal tube in association with the onset of crest delamination, and we find that this process is triggered by BMP4. BMP4 stimulates cleavage of N-cadherin into a soluble cytoplasmic fragment via an ADAM10-dependent mechanism. Intriguingly, when overexpressed, the cytoplasmic N-cadherin fragment translocates into the nucleus, stimulates cyclin D1 transcription and crest delamination, while enhancing transcription of beta-catenin. CTF2 also rescues the mesenchymal phenotype of crest cells in ADAM10-inhibited neural primordia. Hence, by promoting its cleavage, BMP4 converts N-cadherin inhibition into an activity that is likely to participate, along with canonical Wnt signaling, in the stimulation of neural crest emigration.


Expression of organic cation transporter SLC22A16 in human endometria.
SLC22A16 is one of newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is one of the key drugs for treatment of endometrial cancer. Therefore, we examined expression of SLC22A16 in human endometrium and its disorders. Protein and mRNA expression levels of SLC22A16 were examined in 124 endometrial cancer specimens, 25 normal endometrial tissue samples (15 in proliferative phase, 10 in secretory phase), and 7 endometrial cancer cell lines using immunohistochemical analysis and reverse transcription-polymerase chain reaction. Changes in SLC22A16 mRNA expression level after progesterone exposure were also examined. Immunohistochemical analysis showed that SLC22A16 protein was highly expressed in endometrium during the normal secretory phase, but its level was significantly reduced in the proliferative phase. SLC22A16 protein was detected in 59 of 124 (48%) endometrial cancer specimens and 3 of 7 (43%) endometrial cancer cell lines. The mRNA levels measured by quantitative reverse transcription-polymerase chain reaction were comparable with levels of protein expression. Furthermore, SLC22A16 mRNA levels were increased in endometrial cancer cell lines in the presence of progesterone. In conclusion, SLC22A16 is expressed in various endometrial tissues. Its expression level is high during the secretory phase and may be regulated by progesterone. Our findings also suggest that it may be possible to use progestins to increase the response of endometrioid endometrial carcinoma with SLC22A16 expression to adriamycin-based chemotherapeutic regimens.


An Integrative Clustering Approach to tDCS Individual Response Variability in Cognitive Performance: Beyond a Null Effect on Working Memory.
Despite the growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of human cognitive function, there are contradictory findings regarding the cognitive benefits of this technique. Inter-individual response variability to tDCS may play a significant role. We explored the effects of anodal versus sham tDCS over the left prefrontal cortex (LPFC) on working memory performance, taking into account the inter-individual variability. Twenty-nine healthy volunteers received an 'offline' anodal tDCS (1.5 mA, 15 min) to the left prefrontal cortex (F3 electrode site) in an intra-individual, cross-over, sham-controlled experimental design. n-back and Sternberg task performance was assessed before (baseline), immediately after tDCS administration (T1) and 5 min post-T1 (T2). We applied an integrative clustering approach to characterize both the group and individual responses to tDCS, as well as identifying naturally occurring subgroups that may be present within the total sample. Anodal tDCS failed to improve working memory performance in the total sample. Cluster analysis identified a subgroup of 'responders' who significantly improved their performance after anodal (vs. sham) stimulation, although not to a greater extent than the best baseline or sham condition. The proportion of 'responders' ranged from 15% to 59% across task conditions and behavioral outputs. Our findings show a high inter-individual variability of the tDCS response, suggesting that the use of tCDS may not be an effective tool to improve working memory performance in healthy subjects. We propose that the use of clustering methods is more suitable in identifying 'responders' and for evaluating the efficacy of this technique.


Determinants of vaccination after the Colombian health system reform.
To assess the effects of individual, household and healthcare system factors on poor children's use of vaccination after the reform of the Colombian health system. A household survey was carried out in a random sample of insured poor population in Bogota, in 1999. The conceptual and analytical framework was based on the Andersen's Behavioral Model of Health Services Utilization. It considers two units of analysis for studying vaccination use and its determinants: the insured poor population, including the children and their families characteristics; and the health care system. Statistical analysis were carried out by chi-square test with 95% confidence intervals, multivariate regression models and Cronbach's alpha coefficient. The logistic regression analysis showed that vaccination use was related not only to population characteristics such as family size (OR=4.3), living area (OR=1.7), child's age (OR=0.7) and head-of-household's years of schooling (OR=0.5), but also strongly related to health care system features, such as having a regular health provider (OR=6.0) and information on providers' schedules and requirements for obtaining care services (OR=2.1). The low vaccination use and the relevant relationships to health care delivery systems characteristics show that there are barriers in the healthcare system, which should be assessed and eliminated. Non-availability of regular healthcare and deficient information to the population are factors that can limit service utilization.


The development of the entire end-systolic pressure-volume and ejection fraction-afterload relations: a new concept of systolic myocardial stiffness.
In this study we introduce a new concept of systolic myocardial stiffness that extends the Suga-Sagawa maximum ventricular elastance concept to the myocardium. End-systole is defined as the time of maximum systolic myocardial stiffness (max Eav), which we examined for its load independence and sensitivity to changes in the inotropic state and to heart rate. Seven adult mongrel dogs were instrumented with ultrasonic crystals for measurements of long and short axes and left ventricular wall thickness, and a high-fidelity micromanometer was inserted for measurement of left ventricular pressures. Preload and afterload were altered by inferior vena cava occlusion, nitroprusside, angiotensin II, atropine, propranolol, and various combinations with propranolol. End-systolic stress-strain relations (slope: max Eav) were linear in all seven dogs, implying that end-systolic myocardial stiffness is independent of end-systolic stress. Changes in max Eav (for constant preload and afterload) reflected changes in the ejection fraction; max Eav was also insensitive to propranolol and to changes in heart rate over the range from 120 to 180 beats/min. End-systolic pressure-volume relations (ESPVRs), derived analytically from these stress-strain relations, were nonlinear, and estimates of volume at zero stress (Vom) were always positive. On the other hand, ESPVRs obtained on the basis of the Suga-Sagawa maximum ventricular elastance concept, were linear, and volume at zero pressure (Vop) estimated by linear extrapolation was negative in one case. Based on the concept of systolic myocardial stiffness, the slope of the ESPVR varies with end-systolic volume and attains its maximum value (Emax) at zero end-systolic pressure. Normalization of Emax with Vom demonstrated a close relationship to max Eav. Thus both max Eav and Vom and Emax are ideal variables for assessing changes in myocardial contractility when preload and afterload are constant. Furthermore, Vom and max Eav permit development of the entire ejection fraction-afterload relationship for a given preload, thus providing a method for comparing myocardial contractile states between ventricles.


The abbreviated form of the Brief Cognitive Battery in the diagnosis of dementia in Alzheimer's disease.
The Brief Cognitive Battery (BCB) developed by our group for cognitive assessment of low educated individuals has also shown to be highly accurate in diagnosing dementia of individuals with medium or high levels of education, making it a useful tool for populations with heterogeneous educational background. The application of BCB takes around eight minutes, a rather long period for a screening test. Our aim was to evaluate whether the exclusion of items of the BCB could reduce its application time without losing accuracy. Patients with Alzheimer's disease with mild or moderate dementia (N=20), and 30 control subjects were submitted to an abbreviated version of the BCB in which the clock drawing test was not included as an interference test for the delayed recall test. Data from another 22 control individuals who were submitted to the original BCB in another study were also included for comparison. A mathematical formula was employed to compare the two versions of the BCB. Descriptive statistics and ROC (receiver operator characteristic) curves were used (alpha=0.05). Using the abbreviated version, the delayed recall test also had high accuracy in diagnosing dementia and the mathematical formula results did not differ to those obtained using the original version, while mean time was reduced by 2 minutes and 37 seconds. This abbreviated form of the BCB is a potentially valuable tool for screening dementia in population studies as well as in busy clinical practices in countries with heterogeneous educational backgrounds.


Computer use, language, and literacy in safety net clinic communication.
Patients with limited health literacy (LHL) and limited English proficiency (LEP) experience suboptimal communication and health outcomes. Electronic health record implementation in safety net clinics may affect communication with LHL and LEP patients.We investigated the associations between safety net clinician computer use and patient-provider communication for patients with LEP and LHL. We video-recorded encounters at 5 academically affiliated US public hospital clinics between English- and Spanish-speaking patients with chronic conditions and their primary and specialty care clinicians. We analyzed changes in communication behaviors (coded with the Roter Interaction Analysis System) with each additional point on a clinician computer use score, controlling for clinician type and visit length and stratified by English proficiency and health literacy status. Greater clinician computer use was associated with more biomedical statements (+12.4, P = .03) and less positive affect (-0.6, P < .01) from LEP/LHL patients. In visits with patients with adequate English proficiency/health literacy, greater clinician computer use was associated with less positive patient affect (-0.9, P < .01), fewer clinician psychosocial statements (-3.5, P < .05), greater clinician verbal dominance (+0.09, P < .01), and lower ratings on quality of care and communication. Higher clinician computer use was associated with more biomedical focus with LEP/LHL patients, and clinician verbal dominance and lower ratings with patients with adequate English proficiency and health literacy. Implementation research should explore interventions to enhance relationship-centered communication for diverse patient populations in the computer era.


Diagnostic values of GHSR DNA methylation pattern in breast cancer.
DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p < 2.1 × 10(-4)) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p < 1.9 × 10(-7)). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.


Person-Centered Interventions for Autistic Adults Ages 18+ (2013-2021).
Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence for a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adults aged 18+ years gathered from literature published between 2013 and 2021.


Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing mediastinal lymphadenopathy.
The diagnosis of mediastinal lymphadenopathy is always a challenge. There always a need of a technique that is highly accurate as well as safe for diagnosis the same. The aim of the study is to assess the clinical usefulness and safety profile of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing the patients with mediastinal lymphadenopathy. This was an observational prospective study. One hundred adult patients with mediastinal lymphadenopathy who underwent EBUS-TBNA with aspirate obtained from the most hypoechoic lymph node (with a 22 gauge needle) and its cytopathological analysis were included in the study. Patients were observed for postprocedure complications. Out of 100, 92 cases were reported as adequate (diagnostic yield = 92%). Among these 92, there were 71 granulomatous lymphadenitis (tuberculosis [TB] = 41 [44.5%], sarcoid-like granuloma = 30 [32.2%]). Malignancy was reported in 16 (17.3%) patients, and 5 (5.43%) were reported to have reactive lymphadenopathy. There was one case each of Mycobacterium avium complex and Mycobacterium abscessus. Out of 16 cases of malignancy, six cases were adenocarcinoma, four cases of squamous cell carcinoma, and two cases of small cell carcinoma. There were three cases of Hodgkin's lymphoma and one case of non-Hodgkin's lymphoma. No major complications were noted, except fever (26), nausea (20), mild bleeding (4), bronchospasm (3), and transient intraprocedural hypoxia (2). EBUS-TBNA is highly accurate (diagnostic yield 92%) and safe procedure for diagnosing mediastinal lymphadenopathy. In our experience, granulomatous lymphadenitis was most common with TB as the main etiology.


A new type of insulated molecular wire: a rotaxane derived from a metal-capped conjugated tetrayne.
The platinum butadiynyl complex trans-(C(6)F(5))(p-tol(3)P)(2)Pt(C≡C)(2)H and a CuI adduct of a 1,10-phenanthroline based 33-membered macrocycle react in the presence of K(2)CO(3) and I(2) or O(2) to give a rotaxane (ca. 9%) in which the macrocycle is threaded by the sp carbon chain of trans,trans-(C(6)F(5))(p-tol(3)P)(2)Pt(C≡C)(4)Pt(Pp-tol(3))(2)(C(6)F(5)). The crystal structure and macrocycle/axle electronic interactions are analyzed in detail.


Dark Self-Healing-Mediated Negative Photoconductivity of a Lead-Free Cs3Bi2Cl9 Perovskite Single Crystal.
Recently, halide perovskites have emerged as a promising material for device applications. Lead-based perovskites have been widely explored, while investigation of the optical properties of lead-free perovskites remains limited. Lead-halide perovskite single crystals have shown light-induced positive photoconductivity, and as lead-free perovskites are optically active, they are expected to demonstrate similar properties. However, we report here light-induced negative photoconductivity with slow recovery in lead-free Cs3Bi2Cl9 perovskite. Femtosecond transient reflectance (fs-TR) spectroscopy studies further reveal that these electronic transport properties are due to the formation of light-activated metastable trap states within the perovskite crystal. The figure of merits were calculated for Cs3Bi2Cl9 single-crystal detectors, including responsivity (17 mA/W), detectivity (6.23 × 1011 Jones), and the ratio of current in dark to light (∼7160). These observations for Cs3Bi2Cl9 single crystals, which were optically active but showed retroactive photocurrent on irradiation, remain unique for such materials.


Responses of root characteristics and nitrogen absorption and assimilation to different pH gradients of winter wheat at seedling stage.
Nitrogen (N) and rhizosphere pH are the two main factors restricting the growth of winter wheat (Triticum aestivum L.) in North China Plain. Soil nutrient availability is affected by soil acidity and alkalinity. In order to understand the effect of rhizosphere pH value on wheat nitrogen metabolism and the response of wheat growth to pH value at seedling stage, winter wheat varieties 'Aikang 58' (AK58) and 'Bainong 4199' (BN4199) were tested in hydroponics under three pH treatments (pH = 4.0, 6.5, and 9.0). The results showed that the accumulation of dry matter in root and above ground under pH 4.0 and pH 9.0 treatments was lower than that under pH 6.5 treatments, and the root/shoot ratio increased with the increase of pH value. Regardless of pH value, 'BN4199' had higher root dry weight, root length, root surface area, root activity and root tip than 'AK58'. Therefore, wheat that is tolerant to extreme pH is able to adapt to the acid-base environment by changing root characteristics. At pH 4.0, the net H+ outflow rate of wheat roots was significantly lower than that of the control group, and the net NO3- flux of wheat roots was also low. The net H+ outflow occurred at pH 6.5 and 9.0, and at the same time, the net NO3- flux of roots also increased, and both increased with the increase of pH. The activity of nitrate reductase (NR) in stem of pH 9.0 treatment was significantly higher than that of other treatments, while the activity of glutamine synthetase (GS) in root and stem of pH 6.5 treatment was significantly higher than that of other treatments. Under pH 4.0 and pH 9.0 treatments, the activities of NR and GS in 'BN4199' were higher than those in 'AK58', The root respiration of 'BN4199' was significantly higher than that of 'AK58' under pH 4.0 and pH 9.0 treatment, and 'BN4199' had higher NO3- net flux, key enzyme activity of root nitrogen metabolism and root respiration. Therefore, we believe that 'BN4199' has strong resistance ability to extreme pH stress, and high root/shoot ratio and strong root respiration can be used as important indicators for wheat variety screening adapted to the alkaline environment at the seedling stage.


Unrelated cord blood transplantation in patients with idiopathic refractory severe aplastic anemia: a nationwide phase 2 study.
Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.


Platelet factor 4: an inhibitor of collagenase.
Human platelet factor 4 (PF4) is known to bind to heparin and inhibit its anticoagulant effect. This factor also inhibits the enzyme collagenase derived from cultured human skin and collagenase extracted from human granulocytes. The addition of heparin to the PF4-collagenase assay system has no effect on the observed inhibition of collagenase. Thus PF4 inhibits collagenase, in addition to neutralizing heparin.


Safety and efficacy of ximelagatran: meta-analysis of the controlled randomized trials for the prophylaxis or treatment of venous thromboembolism.
Ximelagatran has been approved in Europe for VTE prophylaxis in orthopedic surgery at fixed doses and without laboratory monitoring. Aim of the study was to evaluate safety and efficacy of ximelagatran in a meta-analysis of prophylaxis and/or treatment randomized controlled trials. Absolute risk of events for ximelagatran and OR for its comparison with LMWH and coumarins were calculated. Subgroup analysis was performed for ximelagatran regimen, comparator agent, type of surgery, starting time of prophylaxis. Twelve studies and 16,992 patients were meta-analysed. Ximelagatran showed an absolute risk of major VTE of 4.04% and 1.69% and of major bleedings of 1.68% and 1.03% in prophylaxis and treatment trials, respectively. In prophylaxis trials, a significant excess mortality (OR: 2.5; 95% CI: 1.02 - 6.13) and an excess in major bleedings (OR: 1.41; 95% CI: 0.93 - 2.14) was found in the whole ximelagatran group. No evidence of treatment effect for major VTE was seen in the comparison with LMWH (OR: 1.01; 95% CI: 0.52 - 1.97). The cohort of patients treated with 24 mg b.i.d. showed similar results. An increase in the absolute risk of bleeding (from 1.04% to 3.03%) was found between post and preoperative administration of ximelagatran. Major VTE risk was increased when ximelagatran was compared to b.i.d. LMWH. Ximelagatran can be considered for its potential advantages for prevention and treatment of VTE. Future efforts are needed by researchers to prospectively investigate the best postoperatively starting time and by clinicians to monitor overall mortality in prophylactic use.


[Cefixim: clinical pharmacology and role in therapy of urogenital infections].
Cefixim belongs to oral cephalosporins of the third generation and has the longest half-life period among all oral cephalosporins and, therefore can be taken once a day. Moreover, cefixim presents in high concentrations in the urine, kidneys and urinary tract. In vitro, this drug has high activity against basic pathogens of urogenital infection. A randomized clinical trial has found that cefixim has higher clinical and microbiological efficacy than ciprofloxacin in patients with acute uncomplicated cystitis.


Decisions about dendritic cells: past, present, and future.
A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.


Synthesis of polyketide stereoarrays enabled by a traceless oxonia-Cope rearrangement.
Polyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4-promoted oxonia-Cope rearrangement of syn,syn-2-vinyl-1,3-diols was developed to forge an array of 1,5-pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5-stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross-aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti-conformation of the oxonium ion intermediate.