Dynamic Evaluation of Intensive Land Use Based on Objective Empowerment by Entropy Method and Neural Network Algorithm.
In the past, the extreme value standardization of indicators, the traditional weighting method, and the multifactor comprehensive model of land intensive use inevitably linearly correlate the evaluation indicators with the evaluation objects, ignoring the direction differences of different indicators in different intervals. At the same time, these methods are also difficult to meet the change of evaluation index weight value with land use type, and cannot adapt to the actual situation of land use environment level and dynamic change. Considering the objectivity of nonlinear correlation moderate index and weight assignment, based on the standardization of quadratic function index and entropy assignment, this paper studies the intensive and dynamic use of land in development zones by different regions to improve the realistic fit of the evaluation model. The results show that the overall level of land intensive use in Chongqing center district and western Chongqing is better than that in northeast Chongqing and southeast Chongqing, roughly showing the state of "high in west and low in east."


Structure-activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators.
Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter and functions to remove glutamate from synapses. A thiopyridazine derivative has been found to increase EAAT2 protein levels in astrocytes. A structure-activity relationship study revealed that several components of the molecule were required for activity, such as the thioether and pyridazine. Modification of the benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that enhanced EAAT2 levels by >6-fold at concentrations < 5 μM after 24h. In addition, one of the derivatives (7-22) enhanced EAAT2 levels 3.5-3.9-fold after 24h with an EC(50) of 0.5 μM.


Effects of Antihypertensive Drugs Use on Risk and Prognosis of Colorectal Cancer: A Meta-Analysis of 37 Observational Studies.
Background: Antihypertensive drugs might play a key role in the risk and poor prognosis of colorectal cancer. However, current epidemiologic evidence remains inconsistent. The aim of this study is to quantify the association between antihypertensive drugs and colorectal cancer. Methods: To identify available studies, we systematically searched electronic databases: PubMed, Web of Science, Embase, Cochrane Library. The risk estimates and their corresponding 95% confidence intervals (CIs) were collected and analyzed by using random-effects models. Heterogeneity test and sensitivity analysis were also performed. Results: Overall, 37 observational studies were included in this analysis (26 studies with cohort design, three studies with nested case-control design, and 8 studies with case-control design). Antihypertensive drugs did not present a significant effect on the risk or overall survival of patients with colorectal cancer [Risk ratio (RR) = 1.00, 95% CI: 0.95-1.04; Hazard ratio (HR) = 0.93, 95% CI: 0.84-1.02]. In the subgroup analysis, diuretics use was significantly associated with a worse overall survival of patients with colorectal cancer (HR = 1.27; 95% CI: 1.14-1.40). However, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was associated with improved progression-free survival of patients who suffered from colorectal cancer (HR = 0.83; 95% CI: 0.72-0.95). Conclusion: Antihypertensive drug usage did not influence the risk and overall survival of patients with colorectal cancer in general. Further investigation reminded us that diuretics use might reduce the overall survival time in colorectal cancer patients, whereas those who took Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had a longer progression-free survival.


Expanding the Scope of Biocatalysis: Oxidative Biotransformations on Solid-Supported Substrates.
Oxidative biocatalytic reactions were performed on solid-supported substrates, thus expanding the repertoire of biotransformations that can be carried out on the solid phase. Various phenylacetic and benzoic acid analogs were attached to controlled pore glass beads via an enzyme-cleavable linker. Reactions catalyzed by peroxidases (soybean and chloro), tyrosinase, and alcohol oxidase/dehydrogenase gave a range of products, including oligophenols, halogenated aromatics, catechols, and aryl aldehydes. The resulting products were recovered following cleavage from the beads using α-chymotrypsin to selectively hydrolyze a chemically non-labile amide linkage. Controlled pore glass (CPG) modified with a polyethylene glycol (PEG) linker afforded substantially higher product yields than non-PEGylated CPG or non-swellable polymeric resins. This work represents the first attempt to combine solid-phase oxidative biotransformations with subsequent protease-catalyzed cleavage, and serves to further expand the use of biocatalysis in synthetic and medicinal chemistry.


Complete fatty degeneration of thymus associates with male sex, obesity and loss of circulating naïve CD8+ T cells in a Swedish middle-aged population.
Fatty degeneration of thymus (or thymus involution) has long been considered a normal ageing process. However, there is emerging evidence that thymic involution is linked to T cell aging, chronic inflammation and increased morbidity. Other factors, aside from chronological age, have been proposed to affect the involution rate. In the present study, we investigated the imaging characteristics of thymus on computed tomography (CT) in a Swedish middle-aged population. The major aims were to establish the prevalence of fatty degeneration of thymus and to determine its associations with demographic, lifestyle and clinical factors, as well as inflammation, T cell differentiation and thymic output. In total, 1 048 randomly invited individuals (aged 50-64 years, 49% females) were included and thoroughly characterized. CT evaluation of thymus included measurements of attenuation, size and a 4-point scoring system, with scale 0-3 based on the ratio of fat and soft tissue. A majority, 615 (59%) showed complete fatty degeneration, 259 (25%) predominantly fatty attenuation, 105 (10%) half fatty and half soft-tissue attenuation, while 69 (6.6%) presented with a solid thymic gland with predominantly soft-tissue attenuation. Age, male sex, high BMI, abdominal obesity and low dietary intake of fiber were independently associated with complete fatty degeneration of thymus. Also, fatty degeneration of thymus as well as low CT attenuation values were independently related to lower proportion of naïve CD8+ T cells, which in turn was related to lower thymic output, assessed by T-cell receptor excision circle (TREC) levels. Among Swedish middle-aged subjects, nearly two-thirds showed complete fatty degeneration of thymus on CT. This was linked to depletion of naïve CD8+ T cells indicating that CT scans of thymus might be used to estimate immunological aging. Furthermore, our findings support the intriguing concept that obesity as well as low fiber intake contribute to immunological aging, thereby raising the possibility of preventive strategies.


Clinical features and differential diagnoses in laryngeal mucoepidermoid carcinoma.
Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands. However, it is a rare entity in larynx. Laryngeal cases are frequently misdiagnosed with other malignancies and they are under-reported. So, recognizing the clinical and histological features of this tumor is essential. Laryngeal mucoepidermoid carcinoma can arise in supraglottis, glottis and subglottis. Generally, it presents as a submucosal mass; therefore, progressive symptoms without any identifiable lesion in laryngoscopy must be well considered. The prognosis is somehow dependent on the histological features. In high-grade tumors, recurrence is more common and radical surgery with radiotherapy is recommended. In this paper, we provide a thorough literature review on mucoepidermoid carcinoma in the larynx. The most important distinguishing features of mucoepidermoid carcinoma and its two major differential diagnoses (squamous cell carcinoma and adenosquamous carcinoma) are clearly stated and pitfalls in true diagnosis of this tumor are discussed.


Should the lateral chest radiograph be routine in the diagnosis of pneumonia in children? A review of the literature.
To assess the evidence of the additive diagnostic value of the lateral chest radiograph to the frontal chest radiograph in children (zero to 18 years) with suspected pneumonia in the emergency department. The MEDLINE database (1966 to 2001) was searched to identify the highest level of evidence available in support of the lateral. The key words used included chest radiograph, pneumonia and chest x-ray. Only four controlled studies were identified that assessed the role of the lateral chest x-ray. Three of these studies were retrospective. In the first study, the addition of the lateral to the frontal chest x-ray in 414 children would have detected an additional nine patients (2.3%) with pneumonia. In the second study, involving 179 patients, a high level of agreement was found between the interpretations based on the frontal chest x-ray alone and those based on both views. A third study of 359 children assessed the criterion validity of a frontal chest x-ray alone. Based upon a radiologist's interpretation of both views as the gold standard, the sensitivity of the frontal view alone was 86%. A fourth study of 158 children with suspected pneumonia revealed that the frontal view alone was diagnostic of pneumonia in 106 of 109 (97%) patients. There is no randomized controlled trial evidence to support the additive value of the lateral to the frontal chest x-ray in the diagnosis of children with pneumonia. Further prospective studies are required to determine if the addition of the lateral chest x-ray will modify therapy, prevent complications or whether it is cost-efficient.


Development and Use of an Enzyme-Linked Immunosorbent Assay to Determine Temporal Exposure Patterns to Putative Agents of Nocardioform Placentitis.
Cases of nocardioform placentitis are characterized by focal, mucoid placentitis resulting in late-term abortion, premature birth, or small, full-term foals, occur sporadically, and are most commonly associated with Crossiella equi and Amycolatopsis spp. infection. The goal of this project was to develop an enzyme-linked immunosorbent assay (ELISA) for quantifying antibodies against Crossiella equi and Amycolatopsis spp. and utilize the ELISA to determine when exposure occurs. Serum samples collected during the 2020 foaling season from Crossiella equi (n = 8) and Amycolatopsis spp. (n = 32) infected mares, as well as nonaffected mares (n = 51 mares), were used to develop and optimize bacteria-specific ELISAs. Following development of the ELISAs, banked serum samples from a single, central Kentucky Thoroughbred farm collected during 2012 to 2013 (n = 104 mares) and 2013-14 (n = 82 mares) were analyzed. Differences in various groups were analyzed using one-way analysis of variance (ANOVA). Crossiella equi-infected mares had significantly higher ELISA unit (EU) values on the Crossiella equi ELISA near parturition when compared to the other two groups (P < .001). Using the Amycolatopsis spp. ELISA, EU values were not significantly different between Amycolatopsis spp. infected and non-affected mares, suggesting this ELISA is not specific for Amycolatopsis spp. During 2013 to 2014, there were significant increases in EU values between June and late September for the Crossiella equi ELISA, suggesting exposure in the summer and early fall months. Data from the Crossiella equi ELISA may help provide a better understanding of the epidemiology of nocardioform placentitis, guide the development of a successful experimental challenge model, and allow for further refinement of these ELISAs.


Nonfusion method in thoracolumbar and lumbar spinal fractures.
a retrospective study of surgically managed patients. to evaluate the results of posterior stabilization of thoracolumbar fracture using nonfusion method followed by the removal of metal implants within an appropriate period. Changes in the sagittal alignment and the restoration of segmental motion were also investigated. posterior fusion using a transpedicular screw system remains the treatment of choice for the management of thoracolumbar and lumbar fractures. However, fusion methods result in the permanent loss of segmental motion. If both stability and motion could be achieved, functional results would improve considerably. twenty-three patients under 40 years of age (mean, 28.0 years) with thoracolumbar or lumbar spine fractures were managed by this nonfusion method. Implants were removed at a mean 9.7 months after initial fracture fixation, and patients were observed for more than 18 months. Sagittal alignments of metal fixed segments, heights of vertebral bodies, recovered motion ranges in flexion/extension, right-left bending view were measured radiologically. Clinical aspects, such as gross deformities and functional abilities, were also investigated. heights of fractured bodies were well maintained at final follow-up. Initial mean sagittal angle was 17.2° kyphosis, which became 2.8° lordosis after fixation of fractures. This angle was 1.7° kyphosis just before implant removal, 2.4° kyphosis just after implant removal, and showed 5.9° kyphosis at final follow-up. Mean segmental motion was 14.2° in the sagittal plane and 13.1° in the coronal plane at final follow-up. Most patients were satisfied with final gross appearance and functional outcome. the described nonfusion method appears to be effective in achieving favorable sagittal alignment and regaining motions of fixed segments. The present study suggests that the nonfusion method is one of the most effective methods for managing thoracolumbar fractures, especially in young active people.


Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads.
Dystrophic neurites in senile plaque (SP) coronas and neuropil threads (NTs) massively accumulate in Alzheimer's disease (AD) cortex. Hence, they may contribute to the cognitive deficits in AD. However, the composition of these neuritic lesions is poorly understood, and it is not known if they derive from axons, dendrites or both. To gain insights into the composition and derivation of SP neurites and NTs in AD, we undertook an in situ epitope mapping study wherein we probed these lesions using 278 monoclonal antibodies specific for spatially distinct epitopes in each neurofilament (NF) subunit, or in microtubule-associated proteins, i.e., tau and microtubule-associated protein 2. The middle molecular weight NF subunit (NF-M) and tau were extensively represented in SP neurites, i.e., epitopes extending from the NH2 to COOH domains of NF-M and tau were present. In contrast, microtubule-associated protein 2 was not present in any SPs, and only epitopes in the core domain of the low (NF-L), and in the tail piece of the high molecular weight subunit were detected in SP neurites. SP cores never stained with these antibodies. NTs were similar to SP neurites in that they contained the same complement of tau epitopes, and were devoid of any microtubule-associated protein 2 immunoreactivity, but they were also distinct because they rarely contained any NF determinants. These antigenic dissimilarities between SP neurites and NTs suggest that NTs and SP neurites are distinctly separate lesions that reflect widespread disruption of the neuronal cytoskeleton in AD.


The use of positive pressure devices by physiotherapists.
The aim of this paper is to review the indications for use by physiotherapists, such as physiological rationale and the comparative efficacy of intermittent positive pressure breathing (IPPB) and continuous positive airway pressure (CPAP). A brief discussion of nasal intermittent positive airway pressure is also included. The use of IPPB for post operative prophylaxis has not been supported in the literature. In patients with low lung volumes resulting from neuromuscular disease or spinal injury, IPPB may be useful in the acute phase to improve tidal volume and cough effectiveness. The physiological benefits of CPAP to improve lung volumes are well documented in the literature. Physiotherapists use CPAP as an intermittent application in patients with low lung volumes following surgery. It is predominantly used as a second line intervention in the presence of refractory atelectasis and poor gas exchange. It may also be indicated in other patient groups with similar physiological problems. Nasal intermittent positive airway pressure combines the beneficial effects of intermittent positive pressure breathing and continuous positive airway pressure. There have been many studies evaluating its effectiveness. These have been supportive for patients with neuromuscular disease and sleep disordered breathing, but more research is needed in patients with acute respiratory failure.


Electrogenic transport properties of growing Arabidopsis root hairs : the plasma membrane proton pump and potassium channels.
Ion transport, measured using double-barreled micropipettes to obtain current-voltage relations, was examined in Arabidopsis thaliana root hairs that continued tip growth and cytoplasmic streaming after impalement with the micropipette. To do this required in situ measurements with no handling of the seedlings to avoid wounding responses, and conditions allowing good resolution microscopy in tandem with the electrophysiological measurements. Two ion transport processes were demonstrated. One was a tetraethylammonium-sensitive potassium ion current, inward at hyperpolarized potentials and outward at depolarized potentials. The addition of tetraethylammonium (a potassium channel blocker) caused the potential to hyperpolarize, indicating the presence of a net inward potassium current through the ion channels at the resting potential. The potassium influx was sufficient to "drive" cellular expansion based upon growth rates. Indeed, tetraethylammonium caused transient inhibition of tip growth. The other electrogenic process was the plasma membrane proton pump, measured by indirect inhibition with cyanide or direct inhibition by vanadate. The proton pump was the dominant contribution to the resting potential, with a very high current density of about 250 microamperes per square centimeter (seen only in young growing root hairs). The membrane potential generated by the proton pump presumably drives the potassium influx required for cellular expansion. The pump appears to be a constant current source over the voltage range -200 to 0 millivolts. With this system, it is now possible to study the physiology of a higher plant cell in dynamic living state using a broad range of cell biological and electrophysiological techniques.


Federated learning: a collaborative effort to achieve better medical imaging models for individual sites that have small labelled datasets.
Despite the overall success of using artificial intelligence (AI) to assist radiologists in performing computer-aided patient diagnosis, it remains challenging to build good models with small datasets at individual sites. Because many medical images do not come with proper labelling for training, this requires radiologists to perform strenuous labelling work and to prepare the dataset for training. Placing such demands on radiologists is unsustainable, given the ever-increasing number of medical images taken each year. We propose an alternative solution using a relatively new learning framework. This framework, called federated learning, allows individual sites to train a global model in a collaborative effort. Federated learning involves aggregating training results from multiple sites to create a global model without directly sharing datasets. This ensures that patient privacy is maintained across sites. Furthermore, the added supervision obtained from the results of partnering sites improves the global model's overall detection abilities. This alleviates the issue of insufficient supervision when training AI models with small datasets. Lastly, we also address the major challenges of adopting federated learning.


Insulin-like growth factor II in the pathogenesis of human neuroblastoma.
Insulin-like growth factor II (IGF-II) acts as an autocrine growth factor for many in vitro tumor cell lines including neuroblastoma. To examine the role of IGF-II in tumor biology we have analyzed a total of 56 primary neuroblastoma tumor samples for the presence of IGF-II using a combination of mRNA and protein analysis. A group of 21 samples was examined for the presence of IGF-II mRNA by slot blot and a separate group of 37 samples was examined for IGF-II immunoreactivity. IGF-II was detected in 48% of the total tumor specimens analyzed. IGF-II immunoreactivity was observed in cells resembling developing neuroblasts and was confined to the cytoplasm and proximal neurites. The appearance of IGF-II mRNA and protein did not correlate with tumor prognostic features including stage, histology, or N-myc amplification. These data suggest that the expression of IGF-II is not confined to a specific stage of the disease but may have a broader role in the pathogenesis of neuroblastoma.


Influence of stenosis on hemodynamic parameters in the realistic left coronary artery under hyperemic conditions.
The current study investigates the hyperemic flow effects on heamodynamics parameters such as velocity, wall shear stress in 3D coronary artery models with and without stenosis. The hyperemic flow is used to evaluate the functional significance of stenosis in the current era. Patients CT scan data of having healthy and coronary artery disease was chosen for the reconstruction of 3D coronary artery models. The diseased 3D models of coronary artery shows a narrowing of >50% lumen area. Computational fluid dynamics was performed to simulate the hyperemic flow condition. The results showed that the recirculation zone was observed immediate to the stenosis and highest wall shear stress was observed across the stenosis. The decrease in pressure was found downstream to the stenosis as compared to the coronary artery without stenosis. Our analysis provides an insight into the distribution of wall shear stress and pressure drop, thus improving our understanding of hyperemic flow effect under both conditions.


Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes.
Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing. Although immensely powerful, current implementations of calling cards in bulk experiments on populations of cells are technically cumbersome and require many replicates to identify independent insertions into the same genomic locus. Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself. An additional barcode incorporated during reverse transcription enables simultaneous transcriptome measurement in a facile and affordable protocol. We demonstrate that barcoded self-reporting transposons recover in vitro binding sites for four basic helix-loop-helix transcription factors with important roles in cell fate specification: ASCL1, MYOD1, NEUROD2 and NGN1. Further, simultaneous calling cards and transcriptional profiling during transcription factor overexpression identified both binding sites and gene expression changes for two of these factors. Lastly, we demonstrated barcoded calling cards can record binding in vivo in the mouse brain. In sum, RNA-based identification of transcription factor binding sites and gene expression through barcoded self-reporting transposon calling cards and transcriptomes is an efficient and powerful method to infer gene regulatory networks in a population of cells.


MicroRNA-214 inhibits angiogenesis by targeting Quaking and reducing angiogenic growth factor release.
Angiogenesis is a critical component of many pathological conditions in adult tissues and is essential for embryonic development. MicroRNAs are indispensable for normal vascular development, but their exact role in regulating angiogenesis remains unresolved. Previously, we have observed that miR-214 is differentially expressed in compensatory arteriogenesis. Here, we investigated the potential role of miR-214 in the process of angiogenesis. miR-214 is expressed in all major vascular cell types, and modulation of miR-214 levels in endothelial cells significantly affected tubular sprouting. In vivo silencing of miR-214 enhanced the formation of a perfused vascular network in implanted Matrigel plugs and retinal developmental angiogenesis in mice. miR-214 directly targets Quaking, a protein critical for vascular development. Quaking knockdown reduced pro-angiogenic growth factor expression and inhibited endothelial cell sprouting similar to miR-214 overexpression. In accordance, silencing of miR-214 increased the secretion of pro-angiogenic growth factors, including vascular endothelial growth factor, and enhanced the pro-angiogenic action of the endothelial cell-derived conditioned medium, whereas miR-214 overexpression had the opposite effect. Here, we report a novel role for miR-214 in regulating angiogenesis and identify Quaking as a direct target of miR-214. The anti-angiogenic effect of miR-214 is mediated through the down-regulation of Quaking and pro-angiogenic growth factor expression. This study presents miR-214 as a potential important target for pro- or anti-angiogenic therapies.


[Prophylaxis of early radiation injuries to intact tissues following exposure to combined photon-neutron radiotherapy for malignant head and neck tumors].
Our data are presented on comparison of early- and late-response and complications in 320 patients with head and neck tumors after combined photon-neutron radiotherapy (CPNT) alone or in conjunction with cisplatin. Laser therapy via the LGN-222 quartz installation alternating with irradiation sessions was used to prevent and palliate radiation injuries. As a result, the incidence of acute (grade I-II) reactions was significantly lowered and severe fast-neutron-induced complications were avoided. Grade I (RTOG) skin and mucous membrane injuries were rarer in the main group receiving laser therapy (2.47%) as compared with controls (8.93%) (p < or = 0.02). Grade II injuries totaled 11.6% as compared with 5.57% in control (p < or = 0.02). No damage to skin and mucous membranes in grade III-IV (RTOG) was reported. Use of cisplatin was followed by a rise in frequency of both focal (90%) and diffuse (10%) film-coated membrane epithelite (p < or = 0.02). However, radiation-related response was aborted within 10-14 days after treatment in all cases. Our procedure may be used as a method of choice in prophylaxis of severe tissue damage and CPNT-induced complications.


Analgesic effects of interpleural bupivacaine with fentanyl for post-thoracotomy pain.
The analgesic effect of bupivacaine/fentanyl with epinephrine given interpleurally after thoracotomy was investigated in a randomized placebo and intravenous controlled study. Prospective clinical study. University teaching hospital. Sixty American Society of Anesthesiologists physical status II and III patients scheduled for posterolateral thoracotomy with general anesthesia. Patients were randomly divided into 4 groups to receive either 0.5% bupivacaine/1.5 microg/kg of fentanyl with 5 microg/mL of epinephrine (n = 15, group IPBF), 0.5 % bupivacaine with 5 microg/mL of epinephrine (n = 15, group IPB), or saline (n = 15, group IPS) in a total volume of 15 to 20 mL in 60 seconds by an interpleural catheter placed at the end of surgery by direct vision. The same volume of bupivacaine 0.25% and 1.5 microg/kg of fentanyl with 5 microg/mL of epinephrine to group IPBF, bupivacaine 0.25% with 5 microg/mL of epinephrine to group IPB or saline to group IPS was injected through the interpleural catheter every 6 hours for 48 hours postoperatively. Intravenous fentanyl (n = 15, group IVF) and interpleural saline groups received 1.5 microg/kg of fentanyl intravenously at the first complaint of pain. All patients also received patient-controlled analgesia (PCA) with fentanyl for 48 hours postoperatively. Metamizol sodium was used as a rescue analgesic. Adequacy of pain relief was evaluated with the "Prince Henry Pain Scale" and visual analog pain scale. Fentanyl consumption via PCA and complications were evaluated for 48 hours. Visual analog scale scores were significantly higher in the interpleural saline group at 4 and 12 hours (6.6 +/- 1.2 and 5.0 +/- 2.1, respectively) postoperatively. Significantly more patients in the IPBF group had lower pain scores during coughing and deep breathing. Fentanyl consumption via PCA device was significantly higher in the intravenous fentanyl group (1,069 +/- 96.9 microg) than the interpleural groups (577.3 +/- 72.2 microg, 651.1 +/- 61.9 microg, and 601.0 +/- 22.6 microg in IPBF, IPB, and IPS groups, respectively). It is concluded that total fentanyl consumption via PCA decreased in all interpleural groups, but pain during coughing and deep breathing was significantly reduced in only the interpleural bupivacaine/fentanyl with epinephrine group.


Clinical effectiveness and cost-effectiveness of nurse-led care in Chinese patients with rheumatoid arthritis: A randomized trial comparing with rheumatologist-led care.
The concept of nurse-led care (NLC) was not familiar in China. This study was designed to evaluate the clinical effectiveness and cost-effectiveness of NLC versus rheumatologist-led care (RLC) in Chinese patients with rheumatoid arthritis (RA). Patients of either gender (aged ≥18 years) with RA were enrolled at Wenhai Central Hospital, China (January 2015 to December 2015). The participants were then randomized to NLC or RLC. Outcomes of both the groups were compared in terms of effectiveness by measuring the Disease Activity Score 28, visual analogue scores pertaining to pain and fatigue, and duration of morning stiffness. Costs associated with resource use for RA were assessed and compared between both groups. A total of 214 RA patients in 2 groups (n = 107 in each group) were enrolled and analysed. Improvements in clinical outcomes (disease activity, pain, fatigue, and morning stiffness) over 12 months were significantly greater in the NLC group compared to RLC (P < 0.001). Overall, costs associated with resource use were higher in the RLC group compared to the NLC group (P < 0.05). Our preliminary finding suggested that RA patients managed by NLC compared to RLC may have better clinical outcomes and more cost-effective care in China.


The economic impact of insomnia in managed care: a clearer picture emerges.
An important question for managed care organizations is whether insomnia is associated with increased consumption of healthcare resources. Even though a large number of adults complain of insomnia, few actually receive a diagnostic code for the condition. Consequently, it has been challenging to consistently measure both direct medical costs and indirect costs attributable to insomnia. Recent data have provided a clearer picture showing that insomnia is a costly medical condition. This paper summarizes current understanding of the prevalence of insomnia and explores its impact on health-related quality of life, workplace productivity, and healthcare resource utilization.


Exposure assessment of food preservatives (sulphites, benzoic and sorbic acid) in Austria.
An exposure assessment was performed to estimate the potential intake of preservatives in the Austrian population. Food consumption data of different population groups, such as preschool children aged 3-6 years, female and male adults aged 19-65 years were used for calculation. Levels of the preservatives in food were derived from analyses conducted from January 2007 to August 2010. Dietary intakes of the preservatives were estimated and compared to the respective acceptable daily intakes (ADIs). In the average-intake scenario, assuming that consumers randomly consume food products that do or do not contain food additives, estimated dietary intakes of all studied preservatives are well below the ADI for all population groups. Sulphite exposure accounted for 34%, 84% and 89% of the ADI in preschool children, females and males, respectively. The mean estimated daily intake of benzoic acid was 32% (preschool children), 31% (males) and 36% (females) of the ADI. Sorbic acid intakes correspond to 7% of the ADI in preschool children and 6% of the ADI in adults. In the high-intake scenario assuming that consumers always consume food products that contain additives and considering a kind of brand loyalty of consumers, the ADI is exceeded for sulphites among adults (119 and 124%, respectively). Major contributors to the total intake of sulphites were wine and dried fruits for adults. Mean estimated dietary intakes of benzoic acid exceeded the ADI in all population groups, 135% in preschool children, 124% in females and 118% of the ADI in males, respectively. Dietary intakes of sorbic acid are well below the ADI, accounting for a maximum of 30% of the ADI in preschool children. The highest contributors to benzoic and sorbic acid exposure were fish and fish products mainly caused by high consumption data of this large food group, including also mayonnaise-containing fish salads. Other important sources of sorbic acid were bread, buns and toast bread and fruit and vegetable juices.


Diagnosis and management of giant cell arteritis: a review.
This article aims to provide a review of giant cell arteritis (GCA) clinical features, differential diagnosis, treatment options, and recent literature. GCA, first described by Horton et al., is a systemic immune-mediated vasculitis affecting medium-sized and large-sized arteries. Characteristic findings include headache, jaw claudication, visual loss, and constitutional symptoms (malaise, fever, weight loss, loss of appetite). Localized GCA symptoms are the end-result of vascular insufficiency and tissue ischemia. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. Additional diagnostic tests include blood tests (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; platelets) and imaging modalities (ultrasound of the arteries; fluorescein angiography, FA; MRI; and positron emission tomography, PET). The mainstay of management includes high-dose corticosteroids, and additional cytotoxic drugs, antitumor necrosis factor monoclonal antibody, and antiplatelet aggregation therapy may be used. The goal of treatment is to prevent ischemic damage and halt progression of visual loss in the affected eye and prevent involvement of the fellow eye. Further research is warranted concerning the immunogenetics of GCA. Further treatment trials are also needed to develop more specific and sensitive diagnostic tests and new corticosteroid-sparing treatment modalities.


Maternal employment effects on family and preterm infants at three months.
The purpose of this study was to investigate the effects of maternal employment status and the mother's degree of choice and satisfaction regarding her employment status on family functioning and on the preterm infant's development at three months chronologic age. Families with preterm infants (N = 110) were categorized as employed, nonemployed, and on leave of absence based on the mother's employment status at three months postpartum. There were no significant differences across employment groups on family functioning and child development. The infant's motor development was positively correlated with number of hours employed per week and degree of choice for the employed mother families, but negatively correlated with choice for the nonemployed mother families. These results suggest that maternal employment may not be detrimental for infants born prior to term. Indeed, it may be beneficial, especially if the mother has a choice in the matter.


Quantitative Label-Free Imaging of Lipid Domains in Single Bilayers by Hyperspectral Coherent Raman Scattering.
Lipid phase separation in cellular membranes is thought to play an important role in many biological functions. This has prompted the development of synthetic membranes to study lipid-lipid interactions in vitro, alongside optical microscopy techniques aimed at directly visualizing phase partitioning. In this context, there is a need to overcome the limitations of fluorescence microscopy, where added fluorophores can significantly perturb lipid packing. Raman-based optical imaging is a promising analytical tool for label-free chemically specific microscopy of lipid bilayers. In this work, we demonstrate the application of hyperspectral coherent Raman scattering microscopy combined with a quantitative unsupervised data analysis methodology developed in-house to visualize lipid partitioning in single planar membrane bilayers exhibiting liquid-ordered and liquid-disordered domains. Two home-built instruments were utilized, featuring coherent anti-Stokes Raman scattering and stimulated Raman scattering modalities. Ternary mixtures of dioleoylphosphatidylcholine, sphingomyelin, and cholesterol were used to form phase-separated domains. We show that domains are consistently resolved, both chemically and spatially, in a completely label-free manner. Quantitative Raman susceptibility spectra of the domains are provided alongside their spatially resolved concentration maps.


[Diagnostics and treatment of esophageal cancers].
The incidence of esophageal cancer has increased markedly during the past 3 decades, especially due to an increase of the incidence of adenocarcinoma. The prognosis for patients with esophageal cancer is poor, with a 5-year survival rate of 10-25%. The important risk factors for esophageal squamous cell carcinoma are smoking and alcohol intake. Esophageal adenocarcinomas are related to gastro-esophageal reflux disease. The diagnostic procedures are not only focused on obtaining diagnoses, but also on determining how advanced the tumor is. If a patient is fit enough to undergo surgery and no evidence is found that the tumor has spread to adjacent organs or that there are distant metastases, a surgical resection is the primary treatment. In case surgical resection is not an option, palliative treatment is generally needed to reduce the complaints of dysphagia. The improvement or maintenance of the quality of life and symptom-control are important goals of both curative and palliative treatment of esophageal cancer.


Hyperbaric oxygen therapy for trauma: crush injury, compartment syndrome, and other acute traumatic peripheral ischemias.
In the future, the indications for HBO therapy in acute peripheral ischemic injuries will likely be based on objective criteria rather than, as at present, on clinical diagnoses alone. This chapter offers objective criteria for using HBO in crush injuries and compartment syndromes. The pathophysiology of ATPI are well defined. Hyperbaric oxygen mediates the effects of ATPI through four mechanisms: hyperoxygenation, vasoconstriction, reperfusion, and host factors. The cost benefits of using HBO will be substantial, since complications from ATPI are very expensive. As objective criteria replace the presently used subjective criteria, hyperbaric oxygen therapy will become an integral part of trauma management of these injuries.


[Treatment of aspirin resistance patients at transient ischemic attack by buyang huanwu decoction combination with aspirin: a randomized control observation].
To investigate the curative effect and safety of buyang huanwu decoction (BHD) combined aspirin (ASP) in treatment of aspirin resistance (AR) patients at transient ischemic attack (TIA). Recruited were 86 AR patients at TIA who took ASP as the secondary prevention. Two cases were rejected due to poor compliance. The rest 84 patients were randomly assigned to the treatment group and the control group. Those in the treatment group were treated with BHD and ASP, while those in the control group took Clopidogrel and ASP. After 30-, 60-, and 90-day of treatment, arachidonic acid (AA) and adenosine diphosphate (ADP) induced platelet aggregation rate (PAG) were detected using turbidimetry. After treatment of 90 days, the case numbers of TIA recurrence or of progressing to cerebral infarction were counted. The incidence of adverse events was also observed. The ADP-and AA-induced PAG showed similar decreasing tendency in the treatment group and the control group at each time point (P >0.05). There was no statistical difference in the risk control of end point events (including ischemic cerebrovascular diseases, TIA recurrence, cerebral infarction) between the two groups (P >0.05). One patient suffered from bleeding (mild gastrointestinal bleeding) in the treatment group, while 4 patients suffered from bleeding (3 due to skin and mucous membrane bleeding and 1 to stool bleeding). The bleeding risk was lowered by 76.29% in the treatment group when compared with the control group. BHD combined ASP showed similar efficacy in treating AR and controlling endpoint events. Besides, they lowered bleeding risk.


COVID-19 Vaccination in those with mental health difficulties: A guide to assist decision-making in England, Scotland, and Wales.
There is currently no specific guidance addressing vaccine hesitancy in those with mental health difficulties in the United Kingdom. This is particularly problematic when one considers that individuals with serious mental illnesses are at greater risk of infection and have poorer health outcomes for a range of reasons. There are also many individual and system level barriers to vaccination in this group. When an affected adult lacks the capacity to make a decision for themselves, it often falls to healthcare professionals to make a decision on that person's behalf and in their best interests. This article explores this matter with regard to the law in practice in the English and Welsh, and Scottish, jurisdictions and consider this with relevance to the safest approach that doctors and other healthcare professionals should take in working with patients for whom mental disorder may impact on decision-making capacity. The article focuses on psychiatric inpatients, including those who are detained involuntarily, to consider whether, and in what circumstances, COVID-19 vaccination should be given to individuals who cannot or do not consent.


Application of bromoacetate-substituted beta-CD-bonded silica particles as chiral stationary phase for HPLC.
Bromoacetate-substituted [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (BACD-HPS), an important and useful synthetic intermediate for preparation of novel types of macrocycles-capped beta-CD-bonded silica particles including crown ether/cyclam/calix[4]arene-capped beta-CD-bonded silica particles, have been prepared and used as chiral stationary phase for HPLC. This synthetic stationary phase is characterized by means of elemental analysis. For the first time, the chromatographic behavior of BACD-HPS was systematically evaluated with several disubstituted benzenes and some chiral drug compounds under both normal and RP conditions in HPLC. The results show that BACD-HPS has excellent selectivity for the separation of aromatic positional isomers and chiral isomers of some drug compounds when used as stationary phase in HPLC.


Characterization of Kinase Expression Related to Increased Migration of PC-3M Cells Using Global Comparative Phosphoproteome Analysis.
Prostate cancer (PCa) is the second-most commonly occurring cancer among men, worldwide. Although the mechanisms associated with the progression of castration-resistant prostate cancer (CRPC) have been widely studied, the mechanism associated with more distant metastases from the bone remains unknown. This study aimed to characterize potential pathogenic kinases associated with highly metastatic PCa, that may regulate phosphorylation in extensively involved and diverse signaling pathways that are associated with the development of various cancers. A mass spectrometry (MS)-based comparative phosphoproteome strategy was utilized to identify differentially expressed kinases between the highly aggressive PCa cell-lines PC-3 and PC-3M. Among 2,968 phosphorylation sites in PCa cells, 151 differently expressed phosphoproteins were identified. Seven motifs: -SP-, -SxxE-, -PxS-, -PxSP-, -SxxK-, -SPxK-, and -SxxxxxP- were found to be highly expressed in PC-3M cells. Based on these motifs, the kinases p21-activated kinase (PAK)2, Ste20-like kinase (SLK), mammalian Ste20-like kinase (MST)4, mitogen-activated kinase kinase (MAP2K)2, and A-Raf proto-oncogene serine/threonine kinase (ARAF) were up-regulated in PC-3M cells. PAK2, SLK, MST4, MAP2K2, and ARAF are kinases that are potentially associated with the progression of increased migration in PC-3M cells and may represent molecule regulators or drug targets for highly metastatic PCa therapy.


Do you know this syndrome?
The hyperimmunoglobulin E syndrome, or Job's syndrome is a rare primary immunodeficiency characterized by recurrent skin abscesses, recurrent respiratory tract infections, and high levels of IgE, eosinophilia, bone and dental changes. We report the case of a fourteen-year-old male patient presenting this disease, with both typical and also some relatively sporadic manifestations. We performed a literature review on the syndrome and its associated clinical findings.


The Influence of Residents' Resilience on the Recovery in the Torrential Rain in Western Japan in 2018.
In 2018 torrential rain caused serious human suffering and damage to property in western Japan. Following such disasters, the investigation of residents' subsequent recovery process is important to determine the support required in affected areas and disaster risk management. This study examines the effects of psychological resilience on residents' life recovery following the torrential rain. We conducted a web survey with 1,000 residents in 13 districts of Hiroshima prefecture and 6 districts of Okayama prefecture that suffered the most damage caused by the torrential rain. The survey used the "recovery calendar" approach to assess residents' life recovery from the disaster. Results indicated that residents who had suffered relatively little damage began to recover during the "disaster utopia" phase up to 2 months after the disaster. However, residents who had suffered serious damage began to recover during the "reentry to everyday life" phase up to 6 months after the disaster. Moreover, older residents or residents with strong psychological resilience who suffered serious damage were likely to recover sooner than those with weaker psychological resilience. Therefore, this study indicates the importance of an approach to disaster recovery according to the level of damage, phased time period, and psychological resilience.


Importance of b value in diffusion weighted imaging for the diagnosis of pancreatic cancer.
To investigate the use of multi-b-value diffusion-weighted imaging in diagnosing pancreatic cancer. We retrospectively analyzed 33 cases of pancreatic cancer and 12 cases of benign pancreatic tumors at the Second Affiliated Hospital of Kunming Medical University from December 2008 to January 2011. The demographic characteristics, clinical presentation, routine magnetic resonance imaging and diffusion weighted imaging (DWI) features with different b values were reviewed. Continuous data were expressed as mean ± SD. Comparisons between pancreatic cancer and benign pancreatic tumors were performed using the Student's t test. A probability of P < 0.05 was considered statistically significant. Thirty-three patients with pancreatic cancer were identified. The mean age at diagnosis was 60 ± 5.6 years. The male: female ratio was 21:12. Twenty cases were confirmed by surgical resection and 13 by biopsy of metastases. T1 weighted images demonstrated a pancreatic head mass in 16 patients, a pancreatic body mass in 10 cases, and a pancreatic tail mass with pancreatic atrophy in 7 cases. Eight patients had hepatic metastases, 13 had invasion or envelopment of mesenteric vessels, 4 had bone metastases, and 8 had lymph node metastases. DWI demonstrated an irregular intense mass with unclear margins. Necrotic tissue demonstrated an uneven low signal. A b of 1100 s/mm² was associated with a high intensity signal with poor anatomical delineation. A b of 700 s/mm² was associated with apparent diffusion coefficients (ADCs) that were useful in distinguishing benign and malignant pancreatic tumors (P < 0.05). b values of 50, 350, 400, 450 and 1100 s/mm² were associated with ADCs that did not differentiate the two tumors. Low b value images demonstrated superior anatomical details when compared to high b value images. Tumor tissue definition was high and contrast with the surrounding tissues was good. DWI was useful in diagnosing pancreatic cancer.


Executive functions and performance on high-stakes testing in children from urban schools.
High-stakes achievement testing is a centerpiece of education reform. Children from socially disadvantaged backgrounds typically perform more poorly than their more advantaged peers. The authors evaluated 91 fifth-grade children from low-income urban schools using clinical neuropsychological tests and behavioral questionnaires and obtained fourth-grade scores on state mandated standards-based testing. Goals were to determine whether executive functions are selectively diminished in children from poor urban environments and to evaluate to what extent integrity of executive functions is associated with test scores. Neuropsychological variables (particularly executive functions) accounted for 40% of the variance in English scores and 30% in mathematics. Efforts to improve children's academic achievement should consider developmental factors as well as curricular content.


Analysis of differences in oxygen sensitivity of Fe-S clusters.
Many but not all iron-sulphur clusters in metalloproteins are known to be sensitive to molecular oxygen with dramatic consequences for their biological function. We performed a systematic quantum chemical investigation that sheds light on the differences in oxygen sensitivity depending on charge and spin states of these clusters as well as on their spatial fixation by the enzyme's scaffold. We find that significant structural distortions are required to bind O2 exothermically to [Fe2S2] and [Fe3S4] clusters, while only small conformational changes allow for the thermodynamically favorable coordination of molecular oxygen to [Fe4S4] cubanes and [Fe4S3] clusters.


Species and genetic diversity in the genus Drosophila inhabiting the Indian subcontinent.
Biodiversity is the sum total of all living things on the earth with particular reference to the profound variety in structure,function and genetic constitution. It includes both number and frequency of species or genes in a given assemblage and the variety of resulting ecosystems in a region. It is usually considered at three different levels: genetic, species and ecological diversities. Genus Drosophila belongs to the family Drosophilidae (class Insecta, order Diptera), characterized by rich species diversity at global level and also in India, which is a megadiverse country. At global level, more than 1500 species have been described and several thousands estimated. Hawaiian Islands are particularly rich in species diversity with more than 500 species which provides a unique opportunity to study evolution in genus Drosophila. About 150 species of Drosophila have been reported from India. Certain species of Drosophila found in India have been investigated for genetic diversity within the species. In this regard, Drosophila ananassae is noteworthy. It is a cosmopolitan and domestic species with common occurrence in India and is endowed with many genetic peculiarities. Population genetics and evolutionary studies in this species have revealed as to how genetic diversity within a species play an important role in adaptation of populations to varying environments. In addition, the work carried on D. melanogaster, D. nasuta, D. bipectinata and certain other species in India has shown that these species vary in degree and pattern of genetic diversity, and have evolved different mechanisms for adjusting to their environments. The ecological adaptations to various kinds of stress studied in certain species of Drosophila inhabiting the Indian subcontinent are also discussed.


Safety of olanzapine versus conventional antipsychotics in the treatment of patients with acute schizophrenia. A naturalistic study.
Conventional antipsychotics although effective in treating acute psychotic and behavioural symptoms are subject to certain limitations due to the high incidence of side effects associated, mainly extrapyramidal symptoms (EPS), and insufficient response shown in some cases. EPS are a major factor in neuroleptic non compliance and high relapse rates among patients. This study was designed to assess the safety and effectiveness of olanzapine compared to typical antipsychotics drugs in the treatment of schizophrenic inpatients at acute psychiatric in-patient units. Data from 904 patients schizophrenic patients (F20 of ICD10, WHO) were collected in this prospective, comparative, non-randomized, open and observational study. Patients were followed during their entire hospital stay. Safety was assessed through the collection of spontaneous adverse events and a specific extrapyramidal symptoms questionnaire (EPS). Clinical status was measured through the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Improvement (PGI) and the Nursing Observational Scale for In-patient Evaluation (NOSIE). A total of 483 patients received olanzapine (olanzapine group, OG), and 421 received typical antipsychotics (control group, CG). Treatment emergent EPS, or worsening of previous EPS were statistically significantly higher in the CG (P=0.001). Responder rate was statistically greater in the OG (P<0.001). Mean change in BPRS-total, BPRS-negative, BPRS-agitation subscales and PGI was significantly higher in the OG (P<0.001). Mean decrease in CGI, BPRS positive and BPRS depression sub-scales was also significantly lower (P< or =0.05). Mean change in the NOSIE scale was similar between both groups. Olanzapine has been shown to be better tolerated in comparison with conventional antipsychotics in a large unselected sample of acutely psychotic schizophrenic in-patients. Its effectiveness may be greater than that of conventional antipsychotics.


Vitamin A fortification in Uganda: comparing the feasibility, coverage, costs, and cost-effectiveness of fortifying vegetable oil and sugar.
Twenty-eight percent of Ugandan preschool children suffer from vitamin A deficiency. With vitamin A supplementation covering only a third of children under 5 years of age, fortification is essential to reduce their vitamin A deficiency-related disease burden. At present, the only widely consumed food in Uganda that is fortified with vitamin A is vegetable oil. To compare the feasibility, coverage, costs, and cost-effectiveness of fortifying vegetable oil and sugar with vitamin A in order to assess, from a public health policy perspective, whether sugar should also be fortified. The 2005/6 Uganda Household Budget Survey was used to analyze households' apparent consumption levels of sugar and vegetable oil and to model the additional intake of vitamin A, assuming the sugar and oil fortification levels are those set by the Uganda Bureau of Standards. The annual incremental private sector cost of vitamin fortification is US $555,668 for oil and US $2,644,765 for sugar. Assuming that oil and sugar fortification are both effective in reducing vitamin A deficiency by 30% among those who consume these foods, the estimated cost per disability-adjusted life year (DALY) averted is US $82 for sugar and US $18 for oil. Vitamin Afortification of vegetable oil is 4.6 times more cost-effective than vitamin A fortification of sugar. If sugar were to be fortified, the 17% of Ugandans who purchase sugar but do not purchase oil would become new beneficiaries of vitamin A fortification. This would increase the coverage of vitamin A-fortified foods by 31% and reduce the percentage of Ugandans without any coverage to 25%. Those most at risk for vitamin A deficiency-members of rural, poor households-would benefit disproportionately from the introduction of sugar fortification. Although the lack of information on the vitamin A deficiency status of consumers of oil and sugar precludes making definitive conclusions, the increased coverage and cost per DALY averted due to sugar fortification suggests-based on World Health Organization guidelines-that the Government of Uganda should pursue sugar fortification.


The Radiologic Features of Non-Neoplastic Tumors of Soft Tissue.
Neoplasms of the soft tissues cause localized swelling and a variable degree of tissue response on the part of the host; these features they share with many non-neoplastic disorders. A spectrum of lesions that may simulate soft tissue neoplasms are described, with their radiologic appearances. The cellular nature of the matrix of a lesion cannot be identified absolutely as neoplastic by current imaging methods. Although sonography and magnetic resonance imaging can each produce valuable diagnostic information hitherto not provided by imaging the soft tissues, they do not per se show evidence of neoplasia. The differentiation of the two types of tumor, neoplastic and non-neoplastic, can only be achieved by a combination of clinical, radiologic and histologic information. Ultimately, biopsy with histologic examination may be required for the definitive diagnosis.


Molecular biological approaches to studying trace minerals: why should clinicians care?
The approaches and tools of molecular biology have been enormously valuable to all branches of biological science over the last decade. Nutrition is no exception, where studies on the influence of nutrients on gene expression and of gene products on nutrient metabolism have resulted in a much more sophisticated and detailed understanding of nutritional biochemistry. An example of this as applied to trace minerals research can be seen in the area of thyroidology. Until recently, the sole link between thyroid hormones and trace minerals was iodide. Then the thyroid hormone receptor was cloned and analysis of the protein coding sequence showed it to be a member of a large family of gene activating receptor proteins. These all possess a region containing two clusters of cysteine residues, thought to chelate zinc, which is required for binding of the receptors to their target genes. Zinc appears to be necessary for the biological functioning of not only the thyroid hormone receptor but also many other nuclear proteins which regulate gene expression. The principal product of the thyroid gland is thyroxine from which the more active form of the hormone, triiodothyronine, is derived by peripheral monodeiodination. One of the two enzymes responsible, type I 5'-iodothyronine deiodinase, was recently cloned and shown to contain selenocysteine. Thus production of the active thyroid hormone is dependent on selenium status. These advances made with molecular biology have important implications for clinicians. The possibilities for understanding the clinical picture are immediately enhanced, improving both diagnosis and treatment. Molecular biology also provides the opportunity for developing more specific and sensitive tools for assessing nutritional status. Diseases with a genetic basis can be unequivocally diagnosed and perhaps even treated. A strength of nutrition is that it encompasses molecular biology and clinical practice and practitioners of each can benefit from an understanding of the complementary area.


Neisseria mucosa Peritonitis in the Setting of a Migrated Intrauterine Device.
Peritonitis is a major complication in peritoneal dialysis (PD) patients, often requiring a switch to hemodialysis (HD). Common sources of bacterial peritonitis are touch contamination and PD catheter-related infection. Intra-abdominal pathology is a less common cause of peritonitis in PD patients, and rarely is Neisseria mucosa the causative organism.We present an uncommon case of N. mucosa peritonitis in a 30-year-old African American female patient treated with nocturnal intermittent PD. The infection occurred in the setting of a translocated intrauterine contraceptive device (IUCD) in the infrahepatic region because of transmural migration. Our patient underwent laparoscopic removal of the IUCD and received empiric intraperitoneal (IP) vancomycin and intravenous ceftriaxone. After the isolate was identified as N. mucosa, her regimen was changed to IP ceftriaxone for a total of 21 days. Cell count after completion of antibiotics showed resolution of the peritonitis. The PD catheter was salvaged and transition to HD was avoided.


Comparison of the Ca2+-binding properties of human recombinant calretinin-22k and calretinin.
Calretinin-22k (CR-22k) is a splice product of calretinin (CR) found specifically in cancer cells, and possesses four EF-hands and a differently processed C-terminal end. The Ca2+-binding properties of recombinant human calretinin CR-22k were investigated by flow dialysis and spectroscopic methods and compared with those of CR. CR possesses four Ca2+-binding sites with positive cooperativity (nH = 1.3) and a [Ca2+]0.5 of 1.5 microM, plus one low affinity site with an intrinsic dissociation constant (K'D) of 0.5 mM. CR-22k contains three Ca2+-binding sites with nH of 1.3 and [Ca2+]0.5 of 1.2 microM, plus a low affinity site with K'D of 1 mM. All the sites seem to be of the Ca2+-specific type. Limited proteolysis and thiol reactivity suggest that that the C terminus of full-length CR, but not of CR-22k, is in close proximity of site I leading to mutual shielding. Circular dichroism (CD) spectra predict that the content of alpha-helix in CR and CR-22k is similar and that Ca2+ binding leads to very small changes in the CD spectra of both proteins. The optical properties are very similar for CR-22k and CR, even though CR-22k possesses one additional Trp at the C-terminal end, and revealed that the Trp residues are organized into a hydrophobic core in the metal-free proteins and become even better shielded from the aqueous environment upon binding of Ca2+. The fluorescence of the hydrophobic probe 2-p-toluidinylnaphtalene-6-sulfonate is markedly enhanced by the two proteins already in the absence of Ca2+ and is further increased by binding of Ca2+. The trypsinolysis patterns of CR and CR-22k are markedly dependent on the presence or absence of Ca2+. Together, our data suggest the presence of an allosteric conformational unit encompassing sites I-III for CR-22k and I-IV for CR, with a very similar conformation and conformational changes for both proteins. In the allosteric unit of CR, site IV is fully active, whereas in CR-22k this site has a 80-fold decreased affinity, due to the decreased amphiphilic properties of the C-terminal helix of this site. Some very specific Ca2+-dependent conformational changes suggest that both CR and CR-22k belong to the "sensor"-type family of Ca2+-binding proteins.


Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades.
MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.


Intracellular degradation of newly synthesized apolipoprotein B.
Intracellular degradation of newly synthesized apolipoprotein (apo) B can occur at every stage of the secretory pathway, from the protein translation, polypeptide translocation across the membrane of endoplasmic reticulum (ER), to vesicular transport. The prevalence of apoB degradation at each stage varies in different hepatic cell systems examined. Proteolysis of nascent apoB can be catalyzed by the ubiquitin-proteasome system in the cytosol, and probably by unidentified ER resident proteases as well. Cytosolic and ER lumenal molecular chaperones that facilitate apoB translocation and folding may also assist in the degradation of misfolded apoB proteins. Factors affecting the synthesis and mobilization of lipids during lipoprotein assembly exert important regulatory effects on apoB degradation in trans, and specific hydrophobic amino acid sequence elements within the apoB-100 molecule may play roles in apoB degradation in cis. This review summarizes the current understanding of the cellular and molecular mechanisms responsible for intracellular degradation of apoB in hepatocytes. The emphasis centers primarily on the topology of apoB with respect to the ER membrane during and after apoB translation and its relationship to proteolytic mechanisms potentially involved in apoB degradation.


Determination of glucose in a biological matrix by multivariate analysis of multiple band-pass-filtered Fourier transform near-infrared interferograms.
A multivariate calibration method is described in which Fourier transform near-infrared interferogram data are used to determine clinically relevant levels of glucose in an aqueous matrix of bovine serum albumin (BSA) and triacetin. BSA and triacetin are used to model the protein and triglycerides in blood, respectively, and are present in levels spanning the normal human physiological range. A full factorial experimental design is constructed for the data collection, with glucose at 10 levels, BSA at 4 levels, and triacetin at 4 levels. Gaussian-shaped band-pass digital filters are applied to the interferogram data to extract frequencies associated with an absorption band of interest. Separate filters of various widths are positioned on the glucose band at 4400 cm-1, the BSA band at 4606 cm-1, and the triacetin band at 4446 cm-1. Each filter is applied to the raw interferogram, producing one, two, or three filtered interferograms, depending on the number of filters used. Segments of these filtered interferograms are used together in a partial least-squares regression analysis to build glucose calibration models. The optimal calibration model is realized by use of separate segments of interferograms filtered with three filters centered on the glucose, BSA, and triacetin bands. Over the physiological range of 1-20 mM glucose, this 17-term model exhibits values of R2, standard error of calibration, and standard error of prediction of 98.85%, 0.631 mM, and 0.677 mM, respectively. These results are comparable to those obtained in a conventional analysis of spectral data. The interferogram-based method operates without the use of a separate background measurement and employs only a short section of the interferogram.


Vacuolar Acid hydrolysis as a physiological mechanism for sucrose breakdown.
Sucrose breakdown in mature acidic ;Persian' limes (Citrus aurantifolia [Christm.] Swing.) occurred at a rate of 30.6 picomoles per milliliter per day during 9 weeks storage at 15 degrees C. Neither enzyme of sucrose catabolism (sucrose synthase or acid/alkaline invertase) was present in extracts of mature storage tissue. The average vacuolar pH, estimated by direct measurement of sap from isolated vacuoles and by the methylamine method, was about 2.0 to 2.2. In vitro acid hydrolysis of sucrose at physiological concentrations in a buffered solution (pH 2.2) occurred at identical rates as in matured limes. The results indicate that sucrose breakdown in stored mature acidic limes occurs by acid hydrolysis.


[Activation of T lymphocytes and severity of atopic bronchial asthma in children].
Recent studies point out to the role of activated T lymphocytes in the pathogenesis of bronchial asthma. We analyzed (1) T subpopulations and (2) expression of the cell surface activation markers (the light chain of interleukin-2 receptor (IL-2R) and HLA-DR antigen) in the peripheral blood of 36 children with stable atopic asthma and 10 non-atopic control subjects. Flow cytometry and double phenotyping with monoclonal antibodies conjugated with fluorescein and phycoerythrin were used. The results of these studies were correlated to the degree of asthma severity. We found no differences between the two evaluated subgroups (severe asthma--AC and moderate asthma--AU) in the percentage of T cells with CD3 and CD4 antigen. In the severe asthma subgroup there were the following differences as compared with those from control subjects: decrease of the percentage of CD8+ lymphocytes (p < 0.01) and the increase of activated cells expressing IL-2R (p < 0.001) and HLA-DR (p < 0.001). Differences in the expression of activation markers were more pronounced in the CD4+ subpopulation (CD4+/IL-2R, p < 0.001 and CD4+/HLA-DR+, p < 0.001), while they were less visible, but still significant, in the CD8+ cells (CD8+/IL-2R+, p < 0.01 and CD8+/HLA-DR+, p < 0.05). When comparing the results in severe asthma subgroup with those in moderate asthma, significant elevation was found in CD4+/IL-2R+ (p < 0.03), CD4+/HLA-DR+ (p < 0.05) and CD8+/IL-2R+ (p < 0.03) double positive cells. These observations may indicate a role of activated T lymphocytes, CD4+ and CD8+, in the pathogenesis of atopic bronchial asthma in children and existence of prolonged activation factors in chronic severe asthma.


The use of immunohistochemistry for biomarker assessment--can it compete with other technologies?
A morphology-based assay such as immunohistochemistry (IHC) should be a highly effective means to define the expression of a target molecule of interest, especially if the target is a protein. However, over the past decade, IHC as a platform for biomarkers has been challenged by more quantitative molecular assays with reference standards but that lack morphologic context. For IHC to be considered a "top-tier" biomarker assay, it must provide truly quantitative data on par with non-morphologic assays, which means it needs to be run with reference standards. However, creating such standards for IHC will require optimizing all aspects of tissue collection, fixation, section thickness, morphologic criteria for assessment, staining processes, digitization of images, and image analysis. This will also require anatomic pathology to evolve from a discipline that is descriptive to one that is quantitative. A major step in this transformation will be replacing traditional ocular microscopes with computer monitors and whole slide images, for without digitization, there can be no accurate quantitation; without quantitation, there can be no standardization; and without standardization, the value of morphology-based IHC assays will not be realized.


Laser-based patterning for transfected cell microarrays.
The spatial control over biomolecule- and cell-surface interactions is of great interest to a broad range of biomedical applications, including sensors, implantable devices and cell microarrays. Microarrays in particular require precise spatial control and the formation of patterns with microscale features. Here, we have developed an approach specifically designed for transfected cell microarray (TCM) applications that allows microscale spatial control over the location of both DNA and cells on highly doped p-type silicon substrates. This was achieved by surface modification, involving plasma polymerization of allylamine, grafting of poly(ethylene glycol) and subsequent excimer laser ablation. DNA could be delivered in a spatially defined manner using ink-jet printing. In addition, electroporation was investigated as an approach to transfect attached cells with adsorbed DNA and good transfection efficiencies of approximately 20% were observed. The ability of the microstructured surfaces to spatially direct both DNA adsorption and cell attachment was demonstrated in a functional TCM, making this system an exciting platform for chip-based functional genomics.


Mesoporous Membrane Materials Based on Ultra-High-Molecular-Weight Polyethylene: From Synthesis to Applied Aspects.
The development of new porous polymeric materials with nanoscale pore dimensions and controlled morphology presents a challenging problem of modern materials and membrane science, which should be based on scientifically justified approaches with the emphasis on ecological issues. This work offers a facile and sustainable strategy allowing preparation of porous nanostructured materials based on ultra-high-molecular-weight polyethylene (UHMWPE) via the mechanism of environmental intercrystallite crazing and their detailed characterization by diverse physicochemical methods, including SEM, TEM, AFM, liquid and gas permeability, DSC, etc. The resultant porous UHMWPE materials are characterized by high porosity (up to ~45%), pore interconnectivity, nanoscale pore dimensions (below 10 nm), high water vapor permeability [1700 g/(m2 × day)] and high gas permeability (the Gurley number ~300 s), selectivity, and good mechanical properties. The applied benefits of the advanced UHMWPE mesoporous materials as efficient membranes, breathable, waterproof, and insulating materials, light-weight materials with reduced density, gas capture and storage systems, porous substrates and scaffolds are discussed.


Noninvasive assessment of bladder contractility in men.
Preoperative assessment of detrusor function by pressure flow study (PFS) improves outcome from prostatectomy but is invasive and uncomfortable for the patient. We report on a large scale validation of a novel noninvasive assessment of detrusor contractility. A flexible cuff placed around the penis was inflated automatically during voiding until flow interruption. Cuff pressure at interruption (pcuff.int) reflects isovolumetric bladder pressure (pves.isv), a measure of detrusor contractility. For comparison 151 symptomatic men performed the cuff test with simultaneous PFS monitoring. Test/retest agreement was assessed in 91 subjects who performed a cuff test without PFS on 2 occasions. For the 117 (77%) subjects with an acceptable cuff pressure flow trace, Bland Altman analysis showed that pcuff.int overestimated pves.isv by a mean (s.d.) of 16.4 (27.5) cm H2O, predominantly due to the cuff being positioned below the bladder. For test/retest analysis 52 (57%) of the men who were able to attend twice provided acceptable cuff data on both occasions with a mean (s.d.) difference in pcuff.int of -3.3 (32.0) cm H2O, improving to 0.0 (20.3) cm H2O in a subgroup of 39 subjects who voided more than 150 ml. On questionnaire assessment 121 (80%) subjects preferred the cuff test to PFS. The cuff test gives a valid and reproducible estimate of isovolumetric bladder pressure in a manner acceptable to patients, although test failure and variability of agreement require improvement. The test may be of value in the assessment of urinary symptoms and may aid in patient selection for prostatectomy.


[300 years of the first Russian resort. History of studies of Marcial Waters].
The article presents the main stages of studying the mineral ferruginous waters of the first Russian spa 'Marcial Waters', the beginning of the 300-year history of which is associated with the name of Peter I. It gives the results of studies of natural sources in the 18th and 19th centuries. Studies of the mineral waters during the exploration and exploitation of the field in the 20th century have shown that in the local area, wells open confined groundwater that has various mineralization and iron content and forms the characteristic hydrochemical type of mineral water called marcial. It is noted that the results of the long-term, but insufficiently regular and analytically comprehensive series of observations of the composition of an extremely unstable system of ferruginous waters do not allow one to unequivocally identify seasonal and long-term changes in the composition of the water. Regular isotope-chemical studies, which began in 2018, will make it possible to identify the patterns of formation of unique fresh high-iron waters.


Streptococcus pneumoniae and its bacteriophages: one long argument.
Infectious diseases currently kill more than 15 million people annually, and the WHO estimates that every year 1.6 million people die from pneumococcal diseases. Streptococcus pneumoniae (pneumococcus), a bacterium with a long biological pedigree, best illustrates the rapid evolution of antibiotic resistance, which has led to major public health concern. This article discusses the molecular basis of the two main virulence factors of pneumococcus, the capsule and cell-wall hydrolases, as well as new approaches to developing medicinal weapons for preventing pneumococcal infections. In addition, current knowledge regarding pneumococcal phages as potential contributors to virulence and the use of lytic enzymes encoded by these phages as therapeutic tools is reviewed.


Expression of ARVCF in the human ganglionic eminence during fetal development.
ARVCF (armadillo repeat gene deleted in velocardiofacial syndrome) is a recently characterized member of the catenin p120 (ctn) subfamily of the armadillo repeat proteins. It is involved in modulation of cell-cell adhesion essential to many developmental processes including cellular rearrangement and migration. In the present study, by using specific immunohistochemical methods, strongly ARVCF-immunoreactive cells in a high packing density were found in the human ganglionic eminence (GE), a telencephalic structure which gives rise to precursor neurons of the striatum, the amygdala and the basal nucleus of Meynert. From 20 to 25 weeks of gestation, stripes of immunoreactive cells were found to extend from both the superior part of the GE towards the intermediate zone of the neocortex and from the inferior part of the GE either towards the amygdaloid complex or more laterally towards the intermediate zone. Bands of ARVCF-positive cells were also identified in the gangliothalamic body, a transient target for the migrating neurons from the GE to the thalamus. Double immunolabelling with ARVCF and calretinin antibodies, which mark the GE neurons migrating towards the cerebral cortex, revealed that a majority of ARVCF-positive neurons at the periphery of the GE and the cellular extensions from the GE also expressed calretinin. Our results implicate a very close association of ARVCF with migrating neurons from the GE.


Safety of cangrelor and transition to oral P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: the ARCANGELO study.
Cangrelor is the only intravenous P2Y12 inhibitor available. Safety, efficacy, and transitioning from cangrelor to oral P2Y12 inhibitors were recorded in patients with acute coronary syndrome (ACS). The ARCANGELO study aims to assess the safety of cangrelor on bleeding and the effects of the transition to oral P2Y12 inhibitors in a real-world setting according to the European Medical Agency's requirement. Adult patients with ACS undergoing percutaneous coronary intervention (PCI) receiving cangrelor were included in the study. Patients were followed for 30 days. Incidence of bleeding events, major adverse cardiac events, and transition strategy to oral P2Y12 were recorded. Among 1004 ACS patients undergoing PCI, 995 (99.1%) were eligible for the analysis; 597 (60.0%) of them had ST-segment elevation myocardial infarction. A total of 925 (93.1%) patients underwent PCI by radial catheter access, and 972 (97.2%) received drug-eluting stents. All eligible patients received bolus and cangrelor infusion between 2 and 4 h in 95% of the cases. A total of 730 patients (73.4%) received ticagrelor, 127 (12.8%) prasugrel, and 138 (13.9%) clopidogrel as transition therapy. Bleeding, according to Bleeding Academic Research Consortium (BARC) criteria, within 30 days post-PCI occurred in 5.2% of patients (95% confidence interval: 3.9-6.8%); 0.5% experienced a moderate (BARC 3), and all others mild (BARC 1-2) bleeding events. Major adverse cardiac events occurred in 14 (1.4%) patients, principally all-cause mortality (n = 6 patients) and myocardial infarction (n = 7 patients). The use of cangrelor in ACS patients undergoing PCI and the transition strategy to P2Y12 inhibitors are confirmed as safe and effective in daily practice.


The fraction of RNA that folds into the correct branched secondary structure determines hepatitis delta virus type 3 RNA editing levels.
RNA editing by the host RNA adenosine deaminase ADAR1 at the amber/W site of hepatitis delta virus RNA plays a central role in the viral replication cycle by affecting the balance between viral RNA synthesis and packaging. Previously, we found that HDV genotype III (HDV-3) RNA can form two secondary structures following transcription: an unbranched rod structure, which is characteristic of HDV, and a metastable branched structure that serves as the substrate for editing. The unstable nature of the branched editing substrate structure raised the possibility that structural dynamics of the RNA following transcription could determine the rate at which editing occurs. Here, editing and its control are examined in two HDV-3 isolates, from Peru and Ecuador. Analysis of editing in vitro by ADAR1 indicated that the branched structure formed by RNA derived from the Peruvian isolate is edited more efficiently than that from the Ecuadorian isolate. In contrast, in the context of replication, Peruvian RNA is edited less efficiently than RNA containing Ecuadorian sequences. Computational analyses of RNA folding using the massively parallel genetic algorithm (MPGAfold) indicated that the Peruvian RNA is less likely to form the branched structure required for editing than the Ecuadorian isolate. This difference was confirmed by in vitro transcription of these RNAs. Overall, our data indicate that HDV-3 controls RNA editing levels via (1) the fraction of the RNA that folds, during transcription, into the metastable branched structure required for editing and (2) the efficiency with which ADAR1 edits this branched substrate RNA.


Metabolic and Epigenetic Regulation by Estrogen in Adipocytes.
Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.


Microvascular reconstruction of the foot: weight-bearing patterns, gait analysis, and long-term follow-up.
Between 1980 and 1989, 46 free-tissue transfers (32 skin flaps, 14 muscle flaps) were performed in 44 patients for foot reconstruction. Patient age averaged 25.8 years (range 2 to 74 years). Length of follow-up averaged 43 months. Flap survival rate was 96 percent. Debulking was done in 16 skin and 8 muscle flaps. The ulceration rate in 25 patients with weight-bearing flaps was 32 versus 11 percent in 19 patients with non-weight-bearing flaps. Time before ambulation averaged 6.4 months following weight-bearing reconstruction and 4.5 months following non-weight-bearing reconstruction. All patients with either abnormal foot-mat diagrams or major gait abnormalities had significant underlying radiologic foot abnormalities or nerve injuries. We conclude that both skin and muscle free flaps frequently need secondary debulking procedures to improve function. The ulceration rate tends to be higher in weight-bearing flaps than in non-weight-bearing flaps. Underlying bony architecture and nerve function affected weight-bearing patterns and gait more than type of wound coverage.


A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.


Solid-density plasma nanochannel generated by a fast single ion in condensed matter.
A plasma model of relaxation of a medium in heavy-ion tracks in condensed matter is proposed. The model is based on three assumptions: the Maxwell distribution of plasma electrons, localization of plasma inside the track nanochannel, and constant values of the plasma electron density and temperature during the x-ray irradiation. The model of multiple ionization of target atoms by a fast projectile ion is used to determine the initial conditions. An analysis of the results of the calculations performed makes it possible to define when the atomic relaxation model is a very rough approximation and the plasma relaxation model must be used. It is demonstrated that the plasma relaxation model adequately describes the x-ray spectra observed upon interaction of a fast ion with condensed target. The comparison with the experimental data justifies the reliability of the plasma relaxation model. Preassumptions of plasma relaxation model are validated by the molecular-dynamics simulation. An x-ray spectral method based on the plasma relaxation model is proposed for diagnostics of the plasma in fast ion tracks. The results obtained can be useful in examining the initial stage of defect formation in solids under irradiation with single fast heavy ions.


[Therapeutic effect of vaccinia virus secreting granulocyte-macrophage colony-stimulating factor on pulmonary metastatic melanoma].
A recombinant vaccinia virus containing and expressing the gene of murine granulocyte-macrophage colony-stimulating factor (VVGM-CSF) was tested for its antitumor activity. Murine pulmonary metastasis was established by injecting 2 x 10(5) B16F10 melanoma cells into tail vein of C57BL/6 mouse. Three days after B16F10 inoculation, VVGM-CSF or VVTK, a thymidine kinase gene deficient vaccinia virus, was injected intraperitoneally twice weekly for 2 weeks. Two weeks later mice were sacrificed and pulmonary metastasis foci counted. The results showed that VVGM-CSF treatment significantly decreased the number of pulmonary metastasis and prolonged the survival time of tumor-bearing mice (P < 0.01). Cytotoxic and phagocytic activities of peritoneal macrophages were found to be markedly elevated in mice treated with VVGM-CSF. Nitric oxide released from macrophages was also found to be increased. Based on these data, together with our previous results, we may speculate that continuous secretion of GM-CSF and activation of macrophages might partially explain the antitumor effects of VVGM-CSF.


Memory dysfunction in clinical practice.
Extract: Complaints of impaired memory are amongst the most common symptoms voiced by patients to physicians in the fields of neurology, psychiatry, medicine, and surgery. Impairment of memory is one of the most disabling aspects of many neurological disorders, including neurodegenerative diseases, strokes, tumors, head trauma, hypoxia (reduced exposure of tissue to oxygen), cardiac surgery, malnutrition, attention deficit disorder, depression, anxiety, medication side-effects, and normal aging. This memory loss often impairs the patient's normal daily activities, profoundly affecting both the patients and their families. Research in memory began with neuropsychological studies of patients with focal brain lesions and now includes new methods such as PET (positron emission tomography, where the decay of an injected radioactive element or drug creates an image) and functional MRI (magnetic resonance imaging, where hydrogen atoms are polarized by a magnet and the summation of their spinning energy creates an image). Event-related methodologies have provided us with more refined and improved classification systems. Rather than conceptualizing memory as "short-term" and "long-term," we now think of memory as a collection of mental abilities that use different systems within the brain. In the present article we will summarize the four memory systems that are of clinical relevance: episodic memory, semantic memory, procedural memory, and working memory.


Vitamin D levels and markers of arterial dysfunction in HIV.
HIV-infected patients have low vitamin D levels as well as an increase in cardiovascular (CVD) risk. We examined the relationship between vitamin D and three markers of arterial dysfunction among HIV-infected individuals on stable antiretroviral (ARV) therapy. Levels of 25-hydroxyvitamin D [25(OH)D] were assessed by chemiluminescent immunoassay (DiaSorin) in 100 enrollees into the Hawaii Aging with HIV-Cardiovascular Cohort Study, a cohort of HIV-infected subjects age ≥ 40 years on stable (≥ 6 months) ARV therapy. The relationships between 25(OH)D levels and brachial artery flow-mediated dilation (FMD), right common carotid artery intima-media thickness (cIMT), and coronary artery calcium (CAC) were examined. Analytical methods included Pearson's correlations, Kruskal-Wallis tests, relative risks, and linear regression models. The cohort was 86% male and 60% white with a median age of 52 years and CD4 of 510 cells/mm(3). The median (Q1, Q3) level of 25(OH)D was 27.9 ng/ml (21.8, 38.3). There were 72 FMD, 50 cIMT, and 90 CAC measurements available for analyses. A significant correlation was observed between 25(OH)D levels and FMD (r=0.30, p=0.01) but not with cIMT (r=-0.05, p=0.76). In a linear regression model, Framingham risk score attenuated the relationship between FMD and 25(OH)D. Those with lower 25(OH)D levels were at slightly higher risk of having CAC (RR=1.02, p=0.04). Among those with CAC, lower 25(OH)D levels were not associated with higher CAC scores (p=0.36). Lower vitamin D levels are associated with evidence of subclinical arterial dysfunction in HIV-infected individuals. The significance of these findings warrants further investigation.


Change in PMI During Neoadjuvant Therapy Is a Predictive Prognostic Marker in Rectal Cancer.
Neoadjuvant therapy is often administered to patients with locally advanced rectal cancer (LARC). The aim of this study was to investigate the correlation between the change in the psoas muscle index (PMI) during neoadjuvant therapy and the prognosis of LARC patients. Forty-seven patients who underwent potentially curative surgery for LARC with neoadjuvant therapy were enrolled in this study. We evaluated the relationship between the prognosis and clinicopathological factors, including the prognostic value of a change in the PMI. A >10% decrease in the PMI value was observed in 15 of the 47 patients. A >10% decrease in the PMI value was associated with shorter OS and RFS compared to patients who did not show a >10% decrease in their PMI. The decrease in PMI after neoadjuvant therapy was an independent negative prognostic factor for patients undergoing neoadjuvant therapy for LARC. A decrease in PMI after neoadjuvant therapy might predict a poor prognosis in LARC patients undergoing neoadjuvant therapy.


A novel α-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of α-synuclein-GFP.
Compelling evidence suggests that accumulation and aggregation of alpha-synuclein (α-syn) contribute to the pathogenesis of Parkinson's disease (PD). Here, we describe a novel Bacterial Artificial Chromosome (BAC) transgenic model, in which we have expressed wild-type human α-syn fused to green fluorescent protein (GFP), under control of the mouse α-syn promoter. We observed a widespread and high expression of α-syn-GFP in multiple brain regions, including the dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the ventral tegmental area, the olfactory bulb as well as in neocortical neurons. With increasing age, transgenic mice exhibited reductions in amphetamine-induced locomotor activity in the open field, impaired rotarod performance and a reduced striatal dopamine release, as measured by amperometry. In addition, they progressively developed deficits in an odor discrimination test. Western blot analysis revealed that α-syn-GFP and phospho-α-syn levels increased in multiple brain regions, as the mice grew older. Further, we observed, by immunohistochemical staining for phospho-α-syn and in vivo by two-photon microscopy, the formation of α-syn aggregates as the mice aged. The latter illustrates that the model can be used to track α-syn aggregation in vivo. In summary, this novel BAC α-syn-GFP model mimics a unique set of aspects of PD progression combined with the possibility of tracking α-syn aggregation in neocortex of living mice. Therefore, this α-syn-GFP-mouse model can provide a powerful tool that will facilitate the study of α-syn biology and its involvement in PD pathogenesis.


Protease-mediated ligation of abiotic oligomers.
We demonstrate that proteases can catalyze the ligation of peptidomimetic oligomers. The enzyme clostripain was used to facilitate the native ligation of N-substituted glycine oligomers, or peptoids. In addition to mediating the efficient condensation of two peptoid fragments, iterative ligation events were also performed, giving rise to concatenation products with molecular weights up to 20 kDa. Efficient ligation of peptoid foldamers may enable the chemical synthesis of biomimetic macromolecules capable of forming complex tertiary structures.


Inference for survival prediction under the regularized Cox model.
When a moderate number of potential predictors are available and a survival model is fit with regularization to achieve variable selection, providing accurate inference on the predicted survival can be challenging. We investigate inference on the predicted survival estimated after fitting a Cox model under regularization guaranteeing the oracle property. We demonstrate that existing asymptotic formulas for the standard errors of the coefficients tend to underestimate the variability for some coefficients, while typical resampling such as the bootstrap tends to overestimate it; these approaches can both lead to inaccurate variance estimation for predicted survival functions. We propose a two-stage adaptation of a resampling approach that brings the estimated error in line with the truth. In stage 1, we estimate the coefficients in the observed data set and in [Formula: see text] resampled data sets, and allow the resampled coefficient estimates to vote on whether each coefficient should be 0. For those coefficients voted as zero, we set both the point and interval estimates to [Formula: see text] In stage 2, to make inference about coefficients not voted as zero in stage 1, we refit the penalized model in the observed data and in the [Formula: see text] resampled data sets with only variables corresponding to those coefficients. We demonstrate that ensemble voting-based point and interval estimators of the coefficients perform well in finite samples, and prove that the point estimator maintains the oracle property. We extend this approach to derive inference procedures for survival functions and demonstrate that our proposed interval estimation procedures substantially outperform estimators based on asymptotic inference or standard bootstrap. We further illustrate our proposed procedures to predict breast cancer survival in a gene expression study.


Isolated bilateral ostial coronary stenosis with proximal right coronary artery occlusion.
The incidence of coronary ostial stenosis in patients undergoing coronary arteriography has been found to range between 0.07 and 0.25%. A slightly higher incidence has been observed in patients with angiographically confirmed coronary artery disease: between 0.13 and 2.7%. Bilateral ostial stenosis is even less common. Although cardiovascular syphilis is no longer a prominent condition, it must be considered in the differential diagnosis since it carries a very high risk (50%) of cardiovascular complications if left untreated. Ostial coronary stenosis occurs in 26% of patients with syphilitic aortitis. This paper reports on a 41-year-old Wasserman (WR)-positive woman with progressive angina caused by bilateral ostial coronary stenosis.