Evaluation of gamma-enolase as a tumor marker for lung cancer.
The alpha-enolase and gamma-enolase in tumor tissues and sera of patients with lung cancer were determined with an enzyme immunoassay system. Tissue gamma-enolase in small cell carcinoma of the lung (SCCL, n = 11), large cell carcinoma (n = 11), and non-SCCL (except for large cell carcinoma) (n = 34) were enhanced approximately 35-fold, ninefold, and fourfold, respectively; tissue gamma/alpha + gamma value of SCCL was significantly higher than that of normal lung tissue (P less than 0.01). Serum gamma-enolase level was elevated (greater than 6.0 ng/ml) in 14/18, 3/10, and 15/60 patients with SCCL, large cell carcinoma, and non-SCCL (except for large cell carcinoma), respectively, and serum gamma/alpha + gamma value of SCCL was significantly higher than that of healthy subjects (P less than 0.01). Immunohistochemically, the gamma-enolase was positive in 29/31 of the lung cancers. Serum gamma-enolase value is a useful tumor marker for staging and monitoring treatment of patients with lung cancer, and serum gamma/alpha + gamma value may be useful for differential diagnosis of SCCL from non-SCCL or in differentiating lung cancers possessing neuroendocrine features from other lung cancers.


[Modern diagnosis and postoperative monitoring of acromegaly patients at a neurosurgical clinic].
Acromegaly is a severe disease associated with chronic overproduction of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1), which is caused in most cases by pituitary adenoma. The main causes of mortality in acromegaly are cardiovascular diseases, respiratory diseases, and cancers. At present, the most effective treatment for acromegaly is surgical pituitary adenomectomy. Complete resection of pituitary tumors leads to the normalization of GH and IGF-1 levels, regression of symptoms, and a reduction in the risk of death. The article discusses the current criteria for diagnosis and remission of acromegaly after surgical adenomectomy as well as postoperative monitoring issues aligned with the recent guidelines of the Russian and international endocrinology associations.


A Physiological Sensor-Based Android Application Synchronized with a Driving Simulator for Driver Monitoring.
In this paper, we present an Android application to control and monitor the physiological sensors from the Shimmer platform and its synchronized working with a driving simulator. The Android app can monitor drivers and their parameters can be used to analyze the relation between their physiological states and driving performance. The app can configure, select, receive, process, represent graphically, and store the signals from electrocardiogram (ECG), electromyogram (EMG) and galvanic skin response (GSR) modules and accelerometers, a magnetometer and a gyroscope. The Android app is synchronized in two steps with a driving simulator that we previously developed using the Unity game engine to analyze driving security and efficiency. The Android app was tested with different sensors working simultaneously at various sampling rates and in different Android devices. We also tested the synchronized working of the driving simulator and the Android app with 25 people and analyzed the relation between data from the ECG, EMG, GSR, and gyroscope sensors and from the simulator. Among others, some significant correlations between a gyroscope-based feature calculated by the Android app and vehicle data and particular traffic offences were found. The Android app can be applied with minor adaptations to other different users such as patients with chronic diseases or athletes.


Thermally-actuated, phase change flow control for microfluidic systems.
An easy to implement, thermally-actuated, noninvasive method for flow control in microfluidic devices is described. This technique takes advantage of the phase change of the working liquid itself-the freezing and melting of a portion of a liquid slug-to noninvasively close and open flow passages (referred to as a phase change valve). The valve was designed for use in a miniature diagnostic system for detecting pathogens in oral fluids at the point of care. The paper describes the modeling, construction, and characteristics of the valve. The experimental results favorably agree with theoretical predictions. In addition, the paper demonstrates the use of the phase change valves for flow control, sample metering and distribution into multiple analysis paths, sealing of a polymerase chain reaction (PCR) chamber, and sample introduction into and withdrawal from a closed loop. The phase change valve is electronically addressable, does not require any moving parts, introduces only minimal dead volume, is leakage and contamination free, and is biocompatible.


Modulation of hepatitis B infection by intravenous application of an immunoglobulin preparation that contains antibodies to hepatitis B e and core antigens but not to hepatitis B surface antigen.
Repeated administration of an intravenous immunoglobulin containing antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc) but free of antibody to hepatitis B surface antigen (anti-HBs) before and after the inoculation of 10(4.9) 50% chimpanzee infective doses of hepatitis B virus (HBV) markedly prolonged the incubation period of HBV in experimentally infected chimpanzees. Similar administration of an immunoglobulin preparation containing anti-HBc but free of anti-HBe and anti-HBs or intramuscular administration of a single dose of immunoglobulin containing anti-HBe and anti-HBc 3 days before or after inoculation with HBV did not appear to modulate HBV infection. These observations suggested that anti-HBe, or an unidentified antibody associated with it, may have biological activity in the modulation of HBV replication.


Osteogenic Sarcoma of Mandible.
Osteosarcoma (OS) is a malignant neoplasm characterised by the formation of osteoid matrix by neoplastic cells. It is the most common primary malignant bone tumor accounting for 20% of all sarcomas, although its occurrence in the jaw is rare. It shows typical clinical behaviour but varied radiological and histopathological features. It presents various histological aspects. We report a case of 30-year male presented with a painful swelling of mandible, diagnosed as OS after histopathological evaluation.


Endogenous Collagenases Regulate Osteoclast Fusion.
The precise regulation of osteoclast differentiation and function is crucial for the maintenance of healthy bone. Despite several reports of collagenase expression in bone tissues, the precise isoform expression as well as the role in osteoclasts are still unclear. In the present report, the expression of matrix metalloprotease (MMP)8 and MMP13 was confirmed in mouse bone marrow macrophage osteoclast precursors. The mRNA and protein expressions of both collagenases were significantly reduced by receptor activator of nuclear factor κB ligand (RANKL) stimulation. Notably, either inhibition of MMP expression by siRNA or treatment of cells with collagenase inhibitor Ro 32-3555 significantly augmented osteoclast fusion and resorption activity without affecting the osteoclast number. The inhibition of collagenase by Ro 32-3555 increased the expression of osteoclast fusion genes, Atp6v0d2 and Dcstamp, without affecting nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) protein expression. The enhanced osteoclast fusion by collagenase inhibition appears to be mediated through an extracellular signal regulated kinase (ERK)-dependent pathway. Collectively, these data provide novel information on the regulation of osteoclast fusion process.


Acquired External Auditory Canal Atresia: A Comparison of Acellular Dermal Matrix and Split-thickness Skin Grafting Techniques.
To describe the use of acellular dermal matrix (ADM) in the repair of acquired external auditory canal atresia (AEACA), and compare surgical results to AEACA repair by split-thickness skin grafting (STSG). Retrospective chart review. Neurotology clinical practice. From 2007 to 2015, 25 AEACA surgeries (8 ADM and 17 STSG) were identified meeting inclusion and exclusion criteria. Pre- and postoperative audiometric data with clinical follow-up were examined. Rate of external auditory canal restenosis, improvement of conductive hearing loss, and resolution of otorrhea. Both surgical groups had similar preoperative air bone gaps (ABG). Mean follow-up was 24 months. There was no significant difference in restenosis rates between the ADM (13%, n = 1/8) and STSG (12%, n = 2/17) groups. ABG improved from 28 dB to 11 dB in the ADM group and from 24 dB to 9 dB in the STSG group. ABG closure with surgery was statistically significant (p < 0.05), but there was no difference between the two groups. There was no significant reduction of otorrhea. Acellular dermal matrix grafting has not been previously reported for use in AEACA repair, and is a reasonable alternative to STSG with similar hearing, restenosis, and otorrhea outcomes.


Association between chlorhexidine gluconate concentrations and resistant bacterial bioburden on skin.
We studied the association between chlorhexidine gluconate (CHG) concentration on skin and resistant bacterial bioburden. CHG was almost always detected on the skin, and detection of methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant Enterococcus on skin sites was infrequent. However, we found no correlation between CHG concentration and bacterial bioburden.


Cathepsin L gene expression and promoter activation in rodent granulosa cells.
The cysteine protease cathepsin L exhibits hormone-regulated expression during ovulation. In situ hybridization analyses of immature and pregnant mare serum gonadotropin-treated mouse and rat ovaries showed that cathepsin L expression in granulosa cells of small, growing follicles increased in periovulatory follicles after human chorionic gonadotropin stimulation. In the rat ovary, cathepsin L was also expressed in follicles with signs of atresia. To determine the molecular mechanisms that mediate the diverse regulation of this gene in granulosa cells, rat cathepsin L promoter-reporter constructs were analyzed by transient transfection assays in rat granulosa cells and EMSAs. A construct containing the transcriptional start site and -244 bp of upstream promoter sequence (-244/+33 bp) exhibited inducibility by forskolin, the phorbol ester phorbol myristate acetate, and an additive effect of both. Within this region, three functional specificity protein 1 (Sp1) sites, an overlapping early growth response protein-1 site, and a cAMP regulatory element-binding protein site were identified. Single or double mutants of the above-mentioned sites did not alter forskolin/phorbol myristate acetate inducibility of the promoter. Mutation of all three Sp1/specificity protein 3 (Sp3) sites, which also mutated the early growth response protein-1 site, reduced the promoter activation. Mutation of the cAMP regulatory element-binding protein site in the triple Sp1 mutant construct completely blocked the inducibility of the promoter. When these same constructs were transfected into MCF-7 human breast cancer cells or were cotransfected with an Sp1 expression vector in Drosophila SL2 cells, similar results were obtained. Collectively, the data document that three Sp1/specificity protein 3 binding GC-rich regions and a functional cAMP regulatory element constitute an important transcriptional regulatory complex for expression of the cathepsin L gene in rat granulosa cells.


Effect of varying physicochemistry of European surface waters on the copper toxicity to the green alga Pseudokirchneriella subcapitata.
Most standard toxicity test results, used in present environmental risk assessment and water quality criteria (WQC) setting procedures are obtained with standard test media that are not representative for natural surface waters when metal toxicity modifying factors like pH, water hardness and dissolved organic carbon (DOC) are considered. The aim of this study was, using the green alga Pseudokirchneriella subcapitata, (1) to investigate the individual effects of Ca, Mg (the hardness cations) and pH on the toxicity of copper in reconstituted artificial test waters and (2) to study the copper toxicity in 13 spiked surface waters originating from different European eco-regions. Surface waters were selected such that a broad range of DOC (1.55-20.4 mg/l), pH (5.52-8.30) and water hardness (7-238 mg CaCO(3)/l) was covered. Tests in reconstituted artificial waters demonstrated that the 72 h-E(b)C50 (expressed as dissolved Cu) increased by about a factor of 3 when the Ca and Mg concentrations increased from 0.25 to 2.5 mM. When pH was increased from 5.8 to 8.0, dissolved 72 h-E(b)C50 decreased by a factor of 3. It is suggested that competition between Cu2+, Ca2+, Mg2+ and H+ ions at the cell surface are the most likely explanation for these observations. Dissolved 72 h-E(b)C50s in the natural surface waters varied between 32.0 and 245 mug Cu/l and were up to a factor 15 higher than the 72 h-E(b)C50 in standard artificial medium (16.5+/-4.8 mug Cu/l). Consequently, Water Effect Ratio's (WER, the ratio between the EC50 in natural water to the EC50 in standard test water) ranged from 1.9 to 14.8. Linear regression analysis revealed that higher E(b)C50 were significantly related to higher DOC-concentration of the natural waters (R2 = 0.69), but that water hardness and pH did not show a significant relation with copper toxicity in these surface waters. In European surface waters, a positive correlation is observed between water hardness and pH. As a result, hardness and pH effects on copper toxicity are counteractive in European surface waters, resulting in the highly significant relation between the 72 h-E(b)C50 and DOC-concentration. Normalisation of the obtained effect concentrations using a Biotic Ligand based predictive Cu-toxicity model revealed that variation in DOC and pH are mainly responsible for the observed differences of Cu-toxicity in natural waters.


Perioperative use of gabapentinoids in France. Mismatch between clinical practice and scientific evidence.
Gabapentinoids have governmental health agency approval for "chronic neuropathic pain." Over the last decade, however, the perioperative prescription of gabapentinoids has become more popular among anaesthesiologists due to their anxiolytic and antihyperalgesic proprieties, despite weak scientific evidence supporting the risk/benefit ratio for this indication. Our aim was to extensively describe the use of perioperative gabapentinoids by French anaesthesiologists. An online questionnaire was sent to the French Society of Anaesthesiology members. The questionnaire, focusing on gabapentinoid prescriptions, included questions on demographic data, patient conditions and types of surgeries, mode of prescription, motives and presumed side effects (dizziness, confusion, desaturation and visual disorders). Five hundred and eight questionnaires were analysed, among which 70% reported gabapentinoid use. Twenty-five percent of prescribers stated using gabapentinoids in all types of surgeries, 30% in outpatient surgeries and 46% in combination with regional anaesthesia. In 66% of the cases, preoperative and postoperative prescriptions were combined. Sedation, dizziness and visual disturbance were expected side effects according to 68%, 45% and 20% of anaesthesiologists, respectively. Reported reasons in favor of gabapentinoid prescription were prevention of chronic pain (93%), expected high postoperative acute pain, i.e. painful surgeries (91%), a history of chronic pain (72%) and patient opioid dependence (72%). French anaesthesiologists have recently included gabapentinoids in the multimodal management of postoperative pain but they are unaware of certain frequent side effects. Moreover, their expectations about the prevention of chronic pain are not validated. Our survey is a call to moderate the systematic prescription of these drugs in the perioperative period.


Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery.
The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application. The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application.


Homogeneous luminescence decay time-based assay using energy transfer from nanospheres.
Following a study on the feasibility of resonance energy transfer (RET) from carboxylated nanospheres with an incorporated phosphorescent donor to a cationic polyelectrolyte/acceptor aggregate on their surface, a novel scheme for homogeneous assays is presented that is based on RET from phosphorescent biotinylated nanospheres to fluorescently labeled streptavidin (SA). The phosphorescent nanospheres, with a diameter of well below 50 nm, are made from carboxylated polyacrylonitrile and dyed with ruthenium(II)-tris-4,7-diphenyl-1,10-phenanthroline dichloride (Ru(dpp)). Due to the small size of the nanospheres and the complete extraction of the ruthenium dye into the nanospheres during the precipitation process, RET occurs from Ru(dpp) to the label if labeled SA binds to the surface of the nanospheres. Luminescence quenching by oxygen or other species present in the sample can be neglected due to the shielding effect of the polymer matrix. Based on this finding, a competitive binding assay was established, where avidin and labeled SA compete for the biotin binding sites on the nanosphere. The process of binding to the surface can be detected by measurement of the luminescence intensity or the apparent decay time which is in the order of 2.5-4.5 micros.


Cortical metabolic activity matches the pattern of visual suppression in strabismus.
When an eye becomes deviated in early childhood, a person does not experience double vision, although the globes are aimed at different targets. The extra image is prevented from reaching perception in subjects with alternating exotropia by suppression of each eye's peripheral temporal retina. To test the impact of visual suppression on neuronal activity in primary (striate) visual cortex, the pattern of cytochrome oxidase (CO) staining was examined in four macaques raised with exotropia by disinserting the medial rectus muscles shortly following birth. No ocular dominance columns were visible in opercular cortex, where the central visual field is represented, indicating that signals coming from the central retina in each eye were perceived. However, the border strips at the edges of ocular dominance columns appeared pale, reflecting a loss of activity in binocular cells from disruption of fusion. In calcarine cortex, where the peripheral visual field is represented, there were alternating pale and dark bands resembling ocular dominance columns. To interpret the CO staining pattern, [(3)H]proline was injected into the right eye in two monkeys. In the right calcarine cortex, the pale CO columns matched the labeled proline columns of the right eye. In the left calcarine cortex, the pale CO columns overlapped the unlabeled columns of the left eye in the autoradiograph. Therefore, metabolic activity was reduced in the ipsilateral eye's ocular dominance columns which serve peripheral temporal retina, in a fashion consistent with the topographic organization of suppression scotomas in humans with exotropia.


ICeE an interface for C. elegans experiments.
An increasing number of laboratories are using the COPAS Biosort™ to implement high-throughput approaches to tackle diverse biological problems. While providing a powerful tool for generating quantitative data, the utility of the Biosort is currently limited by the absence of resources for data management. We describe a simple electronic database designed to allow easy storage and retrieval of Biosort data for C. elegans, but that has a wide potential application for organizing electronic files and data sets. ICeE is an Open Source application. The code and accompanying documentation are freely available via the web at http://www.ciml.univ-mrs.fr/EWBANK_jonathan/software.html.


Biphasic alteration of renin release by calcium.
The effects of calcium reintroduction on renin release were examined. Calcium reintroduction to calcium-deprived rat renal cortical slices caused an initial stimulation of renin release (30-40 min) followed by a period of suppression of release (4.5 hr). With ouabain present the initial stimulation was enhanced but the subsequent fall in release was more pronounced. Our results suggest that although renin release from juxtaglomerular cells can be both stimulated and inhibited by raising intracellular calcium, it is the inhibition of release that is the more persistent effect.


Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza.
The efficacy of TCN-032, a human monoclonal antibody targeting a conserved epitope on M2e, was explored in experimental human influenza. Healthy volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2) and received a single dose of the study drug, TCN-032, or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation. Although the primary objective of reducing the proportion of subjects developing any grade ≥2 influenza symptom or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (P = .047) in median total symptom area under the curve (days 1-7) and 2.2 log reduction in median viral load area under the curve (days 2-7) by quantitative polymerase chain reaction (P = .09) compared with placebo-treated subjects. TCN-032 was safe and well tolerated with no additional safety signals after administration of oseltamivir. Serum cytokine levels (interferon γ, tumor necrosis factor α, and interleukin 8 and 10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain. These data indicate that TCN-032 may provide immediate immunity and therapeutic benefit in influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression. Clinicaltrials.gov registry number. NCT01719874.


[Do nurses utilize the scientific method?].
The authors wanted to discover the utilization of the Process of Nursing Attention and the NANDA Diagnoses, as well as the main reasons why these methods are or are not put to use. The authors conclude that the non-use of these methods is due to their difficult and complicated language.


Hyperthermia equipment evaluation.
This article looks briefly at the advances over the past 2 decades in the development of equipment for administering clinical hyperthermia, and observes that while there has been much progress, the equipment available today still does not meet the design criteria articulated 20 years ago. The assertation is made that the testing of hyperthermia equipment in animals has not addressed the questions most of interest in the clinic, and a suggestion is made for a more rigorous way to evaluate clinical equipment. Finally some areas where significant progress in equipment development seems possible are mentioned.


Epidermal growth factor outperforms placebo in the treatment of diabetic foot ulcer: a meta-analysis.
Background: Diabetic foot ulcers (DFUs) are a life-threatening ailment caused by diabetes. Several growth factors, as well as their various combinations, have shown promising effect in aiding diabetic foot ulcer healing. However, contradictory or paradoxical results are often available, and debates about this issue are ongoing. Therefore, a comprehensive meta-analysis was performed to compare the efficacy and safety of epidermal growth factor (EGF) and placebo in healing diabetic foot ulcers. Methods: The database search included relevant English literature from Cochrane Library, PubMed, Google Scholar, Elsevier, and EMBASE that was published between 2009 and 2021. Inclusion criteria included type 1 and 2 diabetic patients with foot wounds focusing on complete healing rate. Exclusion criteria included combined therapy, non-human studies, reviews, and protocols. To assess the quality of each study, biases regarding random sequence generation, allocation concealment, participant and personnel blinding, outcome assessment blinding and incomplete outcome data were thoroughly identified. Results: Eight randomized control trials comprising 620 patients (337 in EGF group, 283 in placebo group), were included in this meta-analysis. EGF achieved a significantly higher complete healing rate than placebo after four weeks of treatment, with relative risk (RR): 3.04 (0.50, 18.44) and heterogeneity (Chi 2 = 6.46, df = 2 (P = 0.04) I 2 = 69 %). Notably, the healing frequency in the placebo group was 17%, whereas the healing frequency in the epidermal growth factor group was 34%. Likewise, after eight weeks of treatment, the relative risk and heterogeneity were RR: 2.59 (1.42, 4.72) and (Chi 2 =7.92, df= 4 (p= 0.09): I 2= 49%), respectively. Moreover, the risk ratio at 12 weeks was RR: 1.01 (0.42, 2.46), and heterogeneity was (Chi 2 =8.55, df= 2 (p= 0.01): I 2= 77%). Conclusions: Our findings indicate that EGF significantly promotes wound healing, and could be recommended as an effective and safe treatment for DFUs.


A high frequency builder software for arbitrary radio frequency signals.
While the frequencies accessible by signal generators steadily rise, the synthesization of complex and arbitrary waveforms with high frequency components remains challenging, especially when restricted by an external reference clock. In this article, we present a comprehensive software package combined with state-of-the-art hardware as a solution for the generation of highly sampled, arbitrary radio frequency waveforms. The software can be used to conduct both synchronous and heterodyne pump-probe experiments due to a variety of different synchronization modules. While both kinds of modules allow for standard waveforms, such as sines, pulses, and bursts, as well as any arbitrary signal, the heterodyne modules additionally are not restricted by the reference clock frequency. Both the output and the synchronization module can be adapted to support additional measurement devices. Due to the modular software structure, individual classes can be exchanged while maintaining all functionalities. The software provides a user friendly graphical interface that allows us to compose, save, and load complex arbitrary waveforms within only a few steps. The frequency selectivity provided by the software-hardware combination allows us to directly target specific excitation states of physical systems. Conducting a heterodyne scanning transmission x-ray microscopy experiment, we are able to demonstrate the capabilities of the software when paired with a high sample rate arbitrary waveform generator. The heterodyne synchronization modules allow for unlimited flexibility leveraging arbitrary waveform generation to their full power. By solving the challenges of synthesizing highly complex electromagnetic waves, the software enables a large variety of experiments to be performed more conveniently.


Testing for high-risk HPV in cervical and tonsillar paraffin-embedded tissue using a cartridge-based assay.
This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin-fixed paraffin-embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.


Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation.
Activation of dendritic cells (DCs) enhances their ability to prime naïve T cells. How activation renders them immunogenic rather than tolerogenic is unclear. Here, we show, using temporally regulated expression of a transgene-encoded neoself antigen in DCs, that either prolonged antigen presentation or DC activation could elicit full expansion, effector cytokine production, and memory-cell differentiation. Microarray analysis of gene expression in T cells showed that all changes linked to DC activation through CD40 could be reproduced by persistent antigen delivery, suggesting that stabilization of antigen presentation is an important consequence of DC activation in vivo. In this system, DC activation by CD40 engagement indeed extended their ability to present antigen to CD4(+) T cells in vivo, although different results were obtained with antigen delivered to DCs by means of endocytosis from the cell surface. These results suggest that antigen persistence may be an important discriminator of immunogenic and tolerogenic antigen exposure.


Aerobic and Anaerobic Swimming Force Evaluation in One Single Test Session for Young Swimmers.
This study aims to propose and validate the tethered swimming lactate minimum test (TSLacmin) estimating aerobic and anaerobic capacity in one single test session, using force as measurement parameter. 6 male and 6 female young swimmers (age=15.7±1.1 years; height=173.3±9.5 cm; weight=66.1±9.5 kg) performed 4 sessions comprising i) an all-out 30 s test and incremental test (TSLacmin); ii) 30 min of tethered swimming at constant intensity (2 sessions); iii) free-swimming time trials used to calculate critical velocity. Tethered swimming sessions used an acquisition system enabling maximum (Fmax) and mean (Fmean) force measurement and intensity variation. The tethered all-out test lasting 30 s resulted in hyperlactatemia of 7.9±2.0 mmol·l-1. TSLacmin presented a 100% success applicability rate, which is equivalent to aerobic capacity in 75% of cases. TSLacmin intensity was 37.7±7.3 N, while maximum force in the all-out test was 105±27 N. Aerobic and anaerobic TSLacmin parameters were significantly related to free-swimming performance (r=-0.67 for 100 m and r=-0.80 for 200 m) and critical velocity (r=0.80). TSLacmin estimates aerobic capacity in most cases, and both aerobic and anaerobic force parameters are well related to critical velocity and free swimming performance.


Elicitors of Host Plant Defenses Partially Suppress Cacopsylla pyricola (Hemiptera: Psyllidae) Populations Under Field Conditions.
Defense elicitors are products that activate acquired defense responses in plants, thus rendering the plants less susceptible to attack by a broad range of pests. We demonstrated previously under laboratory conditions that foliar applications of the defense elicitors Actigard (acibenzolar-S-methyl), Employ (harpin protein), or ODC (chitosan) to potted pear trees (Pyrus communis L.) each caused an increase in mortality of Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) nymphs and altered the settling and oviposition behavior of the adults. In this study, we monitored C. pyricola populations over a 3-yr period on orchard-grown trees treated with water (untreated control), Actigard, Employ, or ODC. Fewer nymphs were observed on trees treated with elicitors compared with untreated trees in both 2014 and 2016. A similar but statistically nonsignificant pattern was observed in 2015 when nearly 30% fewer nymphs were observed on trees treated with elicitors versus untreated controls. Observed reductions in psyllid numbers by defense elicitors were modest and do not warrant the use of these products alone for managing C. pyricola. However, these products are often used for management of fire blight, and our observations that elicitors also reduce C. pyricola populations may be useful for system-wide integrated pest management approaches.


[Optimal possibilities in pediatric radiology].
The feasibility of compliance with the WHO guidelines on safe and economical use of pediatric radiology is discussed. The easiest way of reducing risks and costs is to dispense with unnecessary investigations; this is possible without harm in many diagnostic fields. Replacement of more invasive techniques, especially by ultrasonography, has made an outstanding contribution to pediatric radiology.


A goal attainment pain management program for older adults with arthritis.
The purpose of this study was to test a pain management intervention that integrates goal setting with older adults (age > or =65) living independently in residential settings. This preliminary testing of the Goal Attainment Pain Management Program (GAPMAP) included a sample of 17 adults (mean age 79.29 years) with self-reported pain related to arthritis. Specific study aims were to: 1) explore the use of individual goal setting; 2) determine participants' levels of goal attainment; 3) determine whether changes occurred in the pain management methods used and found to be helpful by GAPMAP participants; and 4) determine whether changes occurred in selected pain-related variables (i.e., experience of living with persistent pain, the expected outcomes of pain management, pain management barriers, and global ratings of perceived pain intensity and success of pain management). Because of the small sample size, both parametric (t test) and nonparametric (Wilcoxon signed rank test) analyses were used to examine differences from pretest to posttest. Results showed that older individuals could successfully participate in setting and attaining individual goals. Thirteen of the 17 participants (76%) met their goals at the expected level or above. Two management methods (exercise and using a heated pool, tub, or shower) were used significantly more often after the intervention, and two methods (exercise and distraction) were identified as significantly more helpful. Two pain-related variables (experience of living with persistent pain and expected outcomes of pain management) revealed significant change, and all of those tested showed overall improvement.


Neutralising ability of Terminalia fagifolia extract (Combretaceae) against the in vitro neuromuscular effects of Bothrops jararacussu venom.
The ability of Terminalia fagifolia hydroalcoholic extract (Tf-HE) to neutralise the paralysis and myotoxicity induced by Bothrops jararacussu venom was assayed using mouse phrenic nerve-diaphragm (PND) preparation and two varieties of chick biventer cervicis (BC) preparations. Tf-HE 100 μg/mL and 500 μg/mL were tested against 40 and 200 μg of venom/mL in PND and BC preparations, respectively, using pre- and post-venom incubation treatments. The effects of Tf-HE against the myotoxicity caused by venom were evaluated via histological analysis (PND) and creatine kinase (CK) release (BC). Tf-HE was able to reverse the venom paralysis in both preparation types. The contractures to exogenous ACh in BC preparations showed that Tf-HE may act on extrinsic, preserving those intrinsic postsynaptic receptors. There was a positive correlation between CK and morphological changes. The high non-hemolytic saponin content can explain the Tf-HE efficacy against the toxic effects of B. jararacussu venom in vertebrate neuromuscular preparations.


Distinct functional roles of peroxiredoxin isozymes and glutathione peroxidase from fission yeast, Schizosaccharomyces pombe.
To investigate the differences in the functional roles of peroxiredoxins (Prxs) and glutathione peroxidase (GPx) of Schizosaccharomyces pombe, we examined the peroxidase and molecular chaperone properties of the recombinant proteins. TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction with the thioredoxin system. GPx also showed thioreoxin-dependent peroxidase activity rather than GPx activity. The peroxidase activity of BCP (bacterioferritin comigratory protein) was similar to that of TPx. However, peroxidase activity was not observed for PMP20 (peroxisomal membrane protein 20). TPx, PMP20, and GPx inhibited thermal aggregation of citrate synthase at 43(o)C, but BCP failed to inhibit the aggregation. The chaperone activities of PMP20 and GPx were weaker than that of TPx. The peroxidase and chaperone properties of TPx, BCP, and GPx of the fission yeast are similar to those of Saccharomyces cerevisiae. The fission yeast PMP20 without thioredoxin-dependent peroxidase activity may act as a molecular chaperone.


Predictive value of device-derived activity level for short-term outcomes in MADIT-CRT.
There are limited data on the prognostic importance of declining activity level in patients with heart failure. We aimed to assess the association of reduced activity level with adverse cardiovascular outcomes in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Final device interrogations from patients enrolled in the MADIT-CRT with cardiac resynchronization devices capable of recording percent daily activity level were assessed. To determine temporal change, standardized activity levels (SALs) comparing each week to the monthly activity 3 months prior were obtained. Death, heart failure events (HFEs)/death, and ventricular tachyarrhythmias (VTAs)/death were the primary end points of this study. The average absolute activity level and SAL of the final week prior to death or end of study were significantly lower in patients who died compared with those in patients who did not. The total cohort (N = 1008) was further randomized into 2 subgroups to identify (group 1) and validate an optimal threshold (group 2). Patients with >40% reduced SAL had a significantly increased 77-day short-term cumulative incidence of death (P = .0006), HFE/death (P < .0001), or VTA/death (P = .0248). After adjustment for clinical covariates, these patients remained at an increased risk for death (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .001), HFE/death (HR, 2.7; 95% CI, 1.8-3.9; P ≤ .001) and VTA/death (HR, 1.9; 95% CI, 1.31-2.6; P = .001). A decline in SAL following a nonfatal VTA and HFE was also associated with an increased probability of death. Decline in activity level is a short-term predictor for adverse cardiovascular events in patients with mild to moderate heart failure undergoing cardiac resynchronization.


Arsenic Exposure and Haematological Derangement in Cervical Cancer Cases in India.
Cervical cancer is the second most common gynecological malignancy worldwide. According to HPV Information Centre, Spain (Aug'2014), in India approximately 1,22,844 women are diagnosed with the disease every year and of them 67,477 die due to the disease. CaCx is said to be mediated by HPV but recent data published reveal the role of Oxidative Stress in different Cancers. Arsenic is also one of the agents for causing Oxidative Stress. Arsenic has been linked with different types of cancer. Arsenic is considered responsible for generation of free radicals and eventually for apoptosis. Early diagnosis of CaCx is presently a matter of concern and clinical presentation in advanced stages become difficult for complete clinical response. For determination of oxidative stress, Malondialdehyde (MDA) was taken as an identifier and arsenic estimation was performed with the help of Atomic Absorption Spectrometer (AAS). RBC count and Haemoglobin levels were performed according to standard protocol. MDA was in direct proportion with arsenic concentration and inversely proportional to RBC and Haemoglobin in CaCx patients. Arsenic is one of the major causative agents for oxidative stress and hence may be a risk factor leading to cancer including CaCx.


Characterization of herpes simplex virus persistence in a human T lymphoblastoid cell line.
Persistent, dynamic-state infection with herpes simplex virus (HSV) type 1 has been maintained in human T lymphoblastoid (CEM) cells for many months after initial infection with the wild-type virus (HSV0) (input virus/cell multiplicity of 1.0). Persistently infected cells grew as well as uninfected cells, except during occasional periods of crisis (increased viral replication and cytopathic effect). Cells could survive the crisis when they were maintained for twice the usual time interval (8 to 10 rather than 4 to 5 days) before subculture. Interferon was not detectable in the cultures. HSV0 was compared with HSVp1, a small plaque-forming isolate from persistently infected CEM cells. Primary infection of CEM cells with HSV0 at a low input multiplicity (0.01) led to abortive replication, whereas infection with HSVp1 at the same multiplicity resulted in either rapidly lytic or persistent infection depending upon the time interval of subculture. Approximately 55% of plaque-purified clones of HSVp1, as compared with only 5% of HSV0 clones, displayed temperature-sensitive growth in Vero cells. Defective interfering virus was not detectable in uncloned HSVp1 by interference assay. Persistently infected cultures "cured" by treatment with HSV antiserum or incubation at 39 degrees C were resistant to reinfection with HSV but permissive for vesicular stomatitis virus replication, suggesting that these treatments modulated a shift from the dynamic-state of the static-state, latent infection. These studies provide a model for characterization of HSV persistence and latency in a highly differentiated human cell line.


Neonatal pain: What's age got to do with it?
The neurobiology of neonatal pain processing, especially in preterm infants, differs significantly from older infants, children, adolescence, and adults. Research suggests that strong painful procedures or repeated mild procedures may permanently modify individual pain processing. Acute injuries at critical developmental periods are risk factors for persistent altered neurodevelopment. The purpose of this narrative review is to present the seminal and current literature describing the unique physiological aspects of neonatal pain processing. Articles describing the structures and physiological processes that influence neonatal pain were identified from electronic databases Medline, PubMed, and CINAHL. The representation of neonatal pain physiology is described in three processes: Local peripheral nervous system processes, referred to as transduction; spinal cord processing, referred to as transmission and modulation; and supraspinal processing and integration or perception of pain. The consequences of undermanaged pain in preterm infants and neonates are discussed. Although the process and pain responses in neonates bear some similarity to processes and pain responses in older infants, children, adolescence, and adults; there are some pain processes and responses that are unique to neonates rendering them at risk for inadequate pain treatment. Moreover, exposure to repeated painful stimuli contributes to adverse long-term physiologic and behavioral sequelae. With the emergence of studies showing that painful experiences are capable of rewiring the adult brain, it is imperative that we treat neonatal pain effectively.


Assessing Ulcerative Pododermatitis of Breeding Rabbits.
Rabbits in conventional farms are housed in wire net cages with mesh floors to separate them from droppings. In time, lacerations appear on the legs of adult rabbits causing ulcerative pododermatitis or sore hocks, a severe health and welfare problem. Pain causes behavioral changes; productivity is reduced and the most seriously affected animals die or are culled. In this study we evaluated the attention producers have given to this problem and its prevention by installing footrests in cages. We made 2,331 visits to 664 commercial farms in Spain and Portugal between 2001 and 2012, and evaluated morbidity by examining 105,009 females and 10,722 males. The study highlights that the rate of farms with footrests increased from 27.8% in 2001 to 75.2% in 2012. Prevalence of sore hocks in does in 2001 was 11.4%, decreasing to 6.3% in 2012; prevention of ulcerative pododermatitis was associated (P < 0.001) with the presence of footrests. Overall, prevalence was 4.87 ± 0.26 on farms with footrests and 13.71 ± 0.32 without (P < 0.01).


A serological study on human Trypanosoma rhodesiense infections using a micro-scale enzyme linked immunosorbent assay.
A micro-scale enzyme linked immunosorbent assay for African trypanosomiasis is described. The test uses very small quantities of sera and with T. brucei antigen is sensitive in detecting T. rhodesiense infections in man. Cross reactions occur with antisera to, and antigens of, Leishmania donovani and Trypanosoma cruzi.


Effectiveness of formalin-killed vaccines containing CpG oligodeoxynucleotide 1668 adjuvants against Vibrio harveyi in orange-spotted grouper.
Vibrio harveyi is a major bacterial pathogen that causes serious vibriosis in cultured groupers, leading to massive deaths. In this study, we evaluated the immune responses and protective efficacy of vaccines containing V. harveyi formalin-killed cells (FKC) formulated with CpG ODN 1668-enriched plasmids (p30CpG and p60CpG) in the orange-spotted grouper. Results indicated that antibody titres were remarkably increased in vaccinated fish 2 weeks post-immunisation. Expression level of major histocompatibility complex (MHC) class II, CD 8, and toll-like receptor 9 was significantly upregulated in the spleen of fish immunised with CpG ODN 1668-adjuvanted vaccines, as recorded at 6 weeks after immunisation. Additionally, the FKC + p60CpG-vaccinated fish displayed greater mRNA levels of MHC I and tumor necrosis factor-alpha. Of note, the relative percent survival after V. harveyi challenge was significantly higher in FKC + p60CpG-vaccinated fish (96.2%) than in FKC + p30CpG-vaccinated (79.8%) and FKC-vaccinated fish (59.9%). These results demonstrate that the FKC + CpG ODN 1668 vaccines are promising candidates that could enhance both innate and adaptive immune responses, conferred remarkable protection, and CpG ODN 1668 is a potential adjuvant for vaccines against V. harveyi.


Combined use of geochemistry and compound-specific stable isotopes for sediment fingerprinting and tracing.
Sediment fingerprinting has emerged as a valuable tool for elucidating soil erosion processes and assessing the sources of sediment and particle-bound chemicals. Due to its upward trend in popularity and the parallel advances in analytical methods, different types of tracers such as Compound-Specific Stable Isotopes (CSSIs) have been incorporated to identify the potential sources. However, the physical processes of CSSIs, usually characterised by the ratio of two stable isotopes, also depends on the isotopic content requiring specific fingerprinting models. For this reason, isotopic tracers have not been combined with classical tracers such as the elemental composition. In this context, we i) propose a simple physical model describing the mixing of isotopic tracers, ii) derive the conservative balance (CB) governing the isotopic ratio of the mixture, iii) demonstrate that previous models for isotopic tracers are approximations of the proposed formulation, and iv) obtain an exact transformation combining the isotopic ratio and the isotopic content into a virtual elemental tracer. The CB model was successfully validated and tested in three fingerprint datasets from published isotopic tracer studies, demonstrating the equivalence of the proposed transformation. Compared to previously reported methods, the CB has two advantages: the model enables the analysis of isotopic tracers using classical unmixing models and, at the same time, allows the combined use of isotopic and elemental tracers. Within the CB framework the Consensus and the Consistent Tracer Selection (CTS) methods can also be applied to isotopic tracers, which is critical for a correct fingerprinting analysis. The effect of combining both types of tracers is illustrated in a dataset composed of elemental and CSSI tracers. The results support its compatibility and reveal an increase in the discriminant capacity and better-defined results for the channel bank source when combining elemental and CSSI tracers.


A case of cellulitis that complicated lymphedema of the lower limb and produced systemic inflammatory response syndrome (SIRS).
This is the first report describing lymphedema of the lower limb after surgery for ovarian cancer complicated by severe cellulitis with systemic inflammatory response syndrome (SIRS). Debridement of the lesion and a split-thickness graft were required for a complete cure. Although lymphedema as a complication after surgery for gynecologic malignancies is prone to be considered less serious on the medical side, it is considered necessary to treat lymphedema of the lower limbs while it is still in a mild state since severe cellulitis may accompany lymphedema, as in the present case.


Recent immigrants show improved clinical outcomes at a tertiary care HIV clinic.
In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically. Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared. In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status. Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants. In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically. Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared. In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status. Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants.


Transposon excision from an atypical site: a mechanism of evolution of novel transposable elements.
The role of transposable elements in sculpting the genome is well appreciated but remains poorly understood. Some organisms, such as humans, do not have active transposons; however, transposable elements were presumably active in their ancestral genomes. Of specific interest is whether the DNA surrounding the sites of transposon excision become recombinogenic, thus bringing about homologous recombination. Previous studies in maize and Drosophila have provided conflicting evidence on whether transposon excision is correlated with homologous recombination. Here we take advantage of an atypical Dissociation (Ds) element, a maize transposon that can be mobilized by the Ac transposase gene in Arabidopsis thaliana, to address questions on the mechanism of Ds excision. This atypical Ds element contains an adjacent 598 base pairs (bp) inverted repeat; the element was allowed to excise by the introduction of an unlinked Ac transposase source through mating. Footprints at the excision site suggest a micro-homology mediated non-homologous end joining reminiscent of V(D)J recombination involving the formation of intra-helix 3' to 5' trans-esterification as an intermediate, a mechanism consistent with previous observations in maize, Antirrhinum and in certain insects. The proposed mechanism suggests that the broken chromosome at the excision site should not allow recombinational interaction with the homologous chromosome, and that the linked inverted repeat should also be mobilizable. To test the first prediction, we measured recombination of flanking chromosomal arms selected for the excision of Ds. In congruence with the model, Ds excision did not influence crossover recombination. Furthermore, evidence for correlated movement of the adjacent inverted repeat sequence is presented; its origin and movement suggest a novel mechanism for the evolution of repeated elements. Taken together these results suggest that the movement of transposable elements themselves may not directly influence linkage. Possibility remains, however, for novel repeated DNA sequences produced as a consequence of transposon movement to influence crossover in subsequent generations.


Magnetic resonance imaging abnormalities in the corpus callosum of a patient with neuropsychiatric lupus.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder which can present with a variety of neurologic and psychiatric complications. Currently, there are no consensus neuroimaging findings associated with neuropsychiatric SLE. We describe the unusual neuroimaging findings in a patient with SLE and a history of epilepsy who presented to a tertiary care emergency department with features of neuropsychiatric lupus, as well as recent seizures. Magnetic resonance imaging of the brain revealed an isolated lesion with T2 signal hyperintensity and restricted diffusion in the midline splenium of the corpus callosum. While establishing the precise etiology underlying the clinical and radiographic observations in this case is difficult, several possibilities are discussed, including acute ischemia and epileptic sequelae. The location of the patient's lesion in a region potentially associated with pure psychotic disorders raises the possibility that such a lesion may be sufficient to produce acute behavior changes and psychotic features in certain patients.


An improved wet digestion procedure for the analysis of total arsenic in biological samples by direct hydride atomic absorption spectrophotometry.
The presence of dimethylarsinic acid (DMAA) in biological samples can cause an underestimation of total arsenic content when analyzed relative to an inorganic arsenic standard by direct hydride flame atomic absorption spectrophotometry. An acid digestion procedure is described that quantitatively recovers DMAA as well as monomethylarsonic acid, inorganic arsenic(III), and arsenic(V) from aqueous and biological samples. Methylated arsenicals are converted to inorganic arsenic by wet digestion with HNO3, H2SO4, and K2Cr2O7 and subsequently reduced to arsenic(III) with Nal. Arsine is generated with NaBH4 and converted to atomic arsenic following immediate introduction into a nitrogen-entrained air-hydrogen flame. This method produces a linear relationship to absorbance within a mass range of 50 to 300 ng arsenic/arsine reaction. A sensitivity of 2 ng arsenic and a detection limit of 7 ng arsenic/arsine reaction were also obtained. Recovery of DMAA from water, urine, feces, or whole blood ranged from 92 to 105% with a coefficient of variation of 5 to 10%.


Prospective associations between adolescent mental health problems and positive mental wellbeing in early old age.
Mental health problems in adolescence are predictive of future mental distress and psychopathology; however, few studies investigated adolescent mental health problems in relation to future mental wellbeing and none with follow-up to older age. To test prospective associations between adolescent mental health problems and mental wellbeing and life satisfaction in early old age. A total of 1561 men and women were drawn from the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). Teachers had previously completed rating scales to assess emotional adjustment and behaviours, which allowed us to extract factors of mental health problems measuring self-organisation, behavioural problems, and emotional problems during adolescence. Between the ages of 60-64 years, mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and life satisfaction was self-reported using the Satisfaction with Life Scale (SWLS). After controlling for gender, social class of origin, childhood cognitive ability, and educational attainment, adolescent emotional problems were independently inversely associated with mental wellbeing and with life satisfaction. Symptoms of anxiety/depression at 60-64 years explained the association with life satisfaction but not with mental wellbeing. Associations between adolescent self-organisation and conduct problems and mental wellbeing and life satisfaction were of negligible magnitude, but higher childhood cognitive ability significantly predicted poor life satisfaction in early old age. Adolescent self-organisation and conduct problems may not be predictive of future mental wellbeing and life satisfaction. Adolescent emotional problems may be inversely associated with future wellbeing, and may be associated with lower levels of future life satisfaction through symptoms of anxiety/depression in early old age. Initiatives to prevent and treat emotional problems in adolescence may have long-term benefits which extend into older age.


In vitro characteristics of Lactobacillus spp. strains isolated from the chicken digestive tract and their role in the inhibition of Campylobacter colonization.
Campylobacter jejuni/coli infections are the leading cause of bacterial diarrheal illnesses in humans. Many epidemiological studies indicate that improperly prepared meat from chickens that carry a high load of Campylobacter in their intestinal tracts is the key source of human infections. LAB, mainly members of the Lactococcus and Lactobacillus genera, increasingly have been tested as vehicles for the delivery of heterologous bacterial or viral antigens to animal mucosal immune systems. Thus, the objective of this study was to isolate, identify, and characterize Lactobacillus spp. strains isolated from chickens bred in Poland. Their ability to decrease the level of bird gut colonization by C. jejuni strain was also analyzed. First, the influence of the different chicken rearing systems was evaluated, especially the effect of diets on the Lactobacillus species that colonize the gut of chickens. Next, selected strains were analyzed in terms of their anti-Campylobacter activity in vitro; potential probiotic traits such as adhesion properties, bile and low pH tolerance; and their ability to grow on a defined carbon source. Given that improperly prepared chicken meat is the main source of human infection by Campylobacter, the selected strains were also assessed for their ability to inhibit Campylobacter colonization in the bird's intestine. These experiments revealed enormous physiological diversity among the Lactobacillus genus strains. Altogether, our results showed that L. plantarum strains isolated from the digestive tracts of chickens bred in Poland displayed some probiotic attributes in vitro and were able to decrease the level of bird gut colonization by C. jejuni strain. This suggests that they can be employed as vectors to deliver Campylobacter immunodominant proteins to the bird's immune system to strengthen the efficacy of in ovo vaccination.


Costs associated with ambulatory care and education.
The adoption of an ambulatory care classification system by the Health Care Financing Administration in 1991 may have significant implications for medical education programs in the Department of Veterans Affairs (VA) ambulatory care setting. Presently there is not adequate methodology in the VA to determine costs in ambulatory care and education. (Experience with the VA allocation model suggests that selected characteristics of reimbursement systems are incompatible with educational goals.) Barriers that inhibit the cost-effective delivery of ambulatory care in many VA hospitals must be eliminated so that effective patient care and training care can take place. These barriers include inadequacies of information systems, physical layouts, and staffing. Despite the perception that outpatient care is less costly than inpatient care, the transition from an inpatient-based education model to an ambulatory care model will require an infusion of resources to improve the ambulatory care environment in the VA.


Preclinical anti-tumor activity of XR5944 in combination with carboplatin or doxorubicin in non-small-cell lung carcinoma.
XR5944 (MLN944) is a novel bis-phenazine currently in phase I clinical trials that has demonstrated potent cytotoxic activity against a variety of tumor models. The combinations of XR5944 with carboplatin or doxorubicin were investigated in COR-L23/P human non-small-cell lung carcinoma (NSCLC) cells in vitro and the corresponding xenografts in vivo. In vitro cytotoxicity was evaluated by the sulforhodamine B assay and the drug interactions following simultaneous or sequential exposure were determined using median-effect analysis to calculate combination indices (CIs). XR5944 demonstrated potent cytotoxicity compared to either carboplatin or doxorubicin in COR-L23/P cells. Simultaneous or sequential exposure of XR5944 followed by carboplatin led to a synergistic response (CI<1), whereas the reverse order of addition showed an additive or antagonistic response (CI< or =1). Sequential administration of doxorubicin followed by XR5944 demonstrated marginally improved cytotoxicity (CI=1.31-0.77) than other schedules (CI=1.50-1.22) relative to individual drugs. Anti-tumor activity against COR-L23/P xenografts in nude mice was enhanced by administration of XR5944 (2 or 5 mg/kg) immediately before carboplatin (50 mg/kg) compared to single-agent treatment at the same doses. Improved efficacy was also observed by sequential administration of 7 mg/kg doxorubicin 48 h before 2.5 or 5 mg/kg XR5944. No additional toxicity was observed with combinations compared to single-agent treatment alone as determined by body weights. These data suggest that combinations of XR5944 with carboplatin or doxorubicin are of significant interest for clinical use, and that the schedule of administration may be important for achieving clinical efficacy over single-agent therapy.


Shelterin Complex at Telomeres: Implications in Ageing.
Different factors influence the development and control of ageing. It is well known that progressive telomere shorting is one of the molecular mechanisms underlying ageing. The shelterin complex consists of six telomere-specific proteins which are involved in the protection of chromosome ends. More particularly, this vital complex protects the telomeres from degradation, prevents from activation of unwanted repair systems, regulates the activity of telomerase, and has a crucial role in cellular senescent and ageing-related pathologies. This review explores the organization and function of telomeric DNA along with the mechanism of telomeres during ageing, followed by a discussion of the critical role of shelterin components and their changes during ageing.


Preoperative spinal canal investigation in adolescent idiopathic scoliosis curves > or = 70 degrees.
This is a prospective evaluation of a consecutive series of patients with adolescent idiopathic scoliosis (AIS) with curves > or = 70 degrees. The authors investigated the possibility that large curve size may constitute an atypical presentation of idiopathic scoliosis suggestive of underlying neurologic pathology, which would warrant preoperative investigation. The potential for intraspinal pathology to cause scoliosis is well accepted. The incidence of spinal canal abnormalities in congenital or atypical scoliosis may be as high as 30-60%. Identification of clinical neurologic deficits, congenital abnormalities, or atypical features of scoliosis are often helpful in identifying the subpopulation of scoliosis patients at risk for spinal canal pathology. Thirty-three consecutive patients with large (> or = 70 degrees) adolescent idiopathic scoliosis (AIS) and without evidence of neurologic or congenital abnormalities, were evaluated with either computed tomography/myelogram (n = 3) or magnetic resonance imaging (n = 30) to assess the entire spinal canal. None of the studies revealed any pathology of the neuraxis, and all 33 patients were treated with surgery without any neurologic sequelae. Preoperative investigation of the central neuraxis is not mandatory in large (> or = 70 degrees) but otherwise typical AIS curves. These large curves do not appear to suggest associated spinal canal anomalies.


Clinicopathologic study of 208 patients with early gastric cancer in Taiwan: a comparison between Eastern and Western countries.
To investigate whether there are any differences between the clinicopathologic characteristics of early gastric cancer (EGC) patients in Eastern and Western countries, 208 Taiwanese patients with EGC were reviewed between 1964 and 1992. The incidence of cancer has increased slightly over the 29-year period. Men were diagnosed with EGC frequently than women, and their mean age was 56 years. Epigastralgia (58.2%) was the most common symptom, whereas 5.8% of cancers were incidentally detected by endoscopy. Physical signs and laboratory tests were of limited value in making the diagnosis. Endoscopy was a better diagnostic aid than radiology. Tumours were frequently located in the lower third (53.2%) and middle third (43.3%) of the stomach. Cancers of the elevated type (17.8%) were less frequent than the depressed type (82.2%). Type IIc (31.2%) was the most common macroscopic type. The frequency of mucosal carcinoma (51.0%) was similar to submucosal carcinoma (49.0%). Mucosal carcinoma had less lymph node metastases (3.1%) than submucosal carcinoma (12.2%; P < 0.05), with an overall frequency of metastases of 7.5% (14/186). The 5-year survival rate was 90.8%. The clinicopathologic characteristics of EGC in Taiwan were similar to those of Western countries and other Eastern countries. Improvement of diagnostic examinations and endoscopic surveillance of asymptomatic subjects may lead to early diagnosis and thus ensure a more favourable outcome.


[Management of recurrent stress urinary incontinence after anti-incontinence surgery].
The review article describes the possibilities of procedures for failed anti-incontinence surgery - sling procedure or "bulking agent"? Review article. Department of Obstetrics and Gynecology, General Faculty Hospital and 1st Medical Faculty, Charles University, Prague. The correct choice of procedure type to treat persistent SUI (Stress Urinary Incontinence) which persists or soon reoccurs after anti-incontinence surgery is often problematic. The procedures that treat SUI decrease excessive mobility of the urethra by partially compressing it. If the excessive mobility of the urethra and BN (bladder neck) persist and MUCP (Maximal Urethral Closure Pressure) is within normal range, then we choose a new sling operation to treat the persistent SUI. What type of sling procedure is preferable in this situatitons: transobturator, retropubic or possibly SISs (Single Incision Slings)? SISs are not adequately fixed to the surrounding structures after implantation and are often not of the correct size - especially regarding length - with poor compliance (elasticity). For mentioned reasons we do not use them in reoperations. In this cases we choose such a sling which is properly fixed to the surrounding structures, is of sufficient length, and of appropriate elasticity. When choosing the right type of procedure we also have to consider previous operations: for example, whether reconstructive surgery of pelvic floor defects using mesh has been carried out, where the mesh has been placed, and whether it might be an obstacle to the newly implanted sling. If there is a low urethral mobility after the unsuccessful incontinence operation and a low MUCP is observed on urodynamic examination, then we prefer either a retropubic sling or the application of a bulking agent. The decision of which method to choose also depends on other circumstances, such as whether the patient has undergone radiation treatment or more than on previous surgery to treat SUI. The results of urodynamic, ultrasound and other examinations are very important. The choice of the right type of surgery to treat SUI after a previous failed procedure depends on information and findings from complex examination of the patient. Case history, examination results, imaging and the experience of the surgeon in individual procedures are therefore most important.


[Safety and efficacy of yellow zebra guide wire exchange system in the treatment of complete upper digestive stenosis].
To investigate the efficacy and safety of yellow zebra guide wire exchange system in the treatment of complete upper digestive stenosis. To analyze the success rate and adverse events, a retrospective analysis was conducted on patients with complete digestive stenosis in Zhongda Hospital Affiliated to Southeast University from May 2019 to April 2023 and the First Affiliated Hospital of Nanjing Medical University from August 2011 to March 2015. A total of 41 patients were included, including 25 males and 16 females, aged (65±12) years (28-94 years). Among them, 40 patients were successfully inserted with yellow zebra guide wire and underwent endoscopic treatment using the outer tube replacement with hard steel wire, with 97.6% (40/41) effective rate. Eleven patients (27.5%) were accompanied by varying degrees of retrosternal pain, without complications such as bleeding or perforation.


[Management of infected vascular grafts. Are there any factors predictive of early clinical success?].
The aim of the study was to define mortality and limb loss rates and to identify factors predictive of early clinical success in the management of infected vascular grafts. Clinical data of 40 patients were reviewed, evaluating comorbidity factors, laboratory findings, ischaemic symptoms, graft material and time of onset of infections. Diabetes and chronic renal insufficiency were reported in 15% of cases, malignancy in 10%, pathological C-reactive protein in 77.5% and leukocytosis in 60%. 52.5% of the patients presented with a disabling claudication, and 77.5% with an infected alloplastic graft. Early infection had developed in 57.5%. A total graft excision was performed in 72.5% of cases. Early complications were recorded in 32.5% of the patients, with a limb loss rate of 22.5% and a mortality rate of 10%. Total graft excision is the treatment of first choice in patients with an infected vascular graft. Patients presenting with critical ischaemia and early septic complications will experience poor clinical results in terms of limb loss and mortality. Pathological blood levels of C-reactive protein could help in the choice of treatment in unclear cases.


[The results of epidemiological studies of dental caries in children of the Siberian region].
Thorough epidemiologic studies are the basis for the development of effective methods and means of primary prevention of dental caries in children. With this aim in view, we examined 21,035 children living in various rural and urban regions of west Siberia. The duration of their stay in the Extreme North was taken account of, as well as levels of fluoride, selenium, and other odontotropic substances in drinking water and other biogeographical factors over the recent one or two decades. The study demonstrated an increasing incidence and intensity of caries, particularly so in the rural regions, which is due to insufficient primary and secondary prophylactic measures. The highest incidence and intensity of the disease were observed in the residents of Tyumen Province. For improving the prevention of dental diseases it is necessary that epidemiological factors in the studied regions be taken into consideration.


Implementation of integrated circuit and design of SAR ADC for fully implantable hearing aids.
The hearing impaired population has been increasing; many people suffer from hearing problems. To deal with this difficulty, various types of hearing aids are being rapidly developed. In particular, fully implantable hearing aids are being actively studied to improve the performance of existing hearing aids and to reduce the stigma of hearing loss patients. It has to be of small size and low-power consumption for easy implantation and long-term use. The objective of the study was to implement a small size and low-power consumption successive approximation register analog-to-digital converter (SAR ADC) for fully implantable hearing aids. The ADC was selected as the SAR ADC because its analog circuit components are less required by the feedback circuit of the SAR ADC than the sigma-delta ADC which is conventionally used in hearing aids, and it has advantages in the area and power consumption. So, the circuit of SAR ADC is designed considering the speech region of humans because the objective is to deliver the speech signals of humans to hearing loss patients. If the switch of sample and hold works in the on/off positions, the charge injection and clock feedthrough are produced by a parasitic capacitor. These problems affect the linearity of the hold voltage, and as a result, an error of the bit conversion is generated. In order to solve the problem, a CMOS switch that consists of NMOS and PMOS was used, and it reduces the charge injection because the charge carriers in the NMOS and PMOS have inversed polarity. So, 16 bit conversion is performed before the occurrence of the Least Significant Bit (LSB) error. In order to minimize the offset voltage and power consumption of the designed comparator, we designed a preamplifier with current mirror. Therefore, the power consumption was reduced by the power control switch used in the comparator. The layout of the designed SAR ADC was performed by Virtuoso Layout Editor (Cadence, USA). In the layout result, the size of the designed SAR ADC occupied 124.9 μm × 152.1 μm. The circuit verification was performed by layout versus schematic (LVS) and design rule check (DRC) which are provided by Calibre (Mentor Graphics, USA), and it was confirmed that there was no error. The designed SAR ADC was implemented in SMIC 180 nm CMOS technology. The operation of the manufactured SAR ADC was confirmed by using an oscilloscope. The SAR ADC output was measured using a distortion meter (HM 8027), when applying pure tone sounds of 94 dB SPL at 500, 800, and 1600 Hz regions. As a result, the THD performance of the proposed chip was satisfied with the ANSI. s3. 22. 2003 standard. We proposed a low-power 16-bit 32 kHz SAR ADC for fully implantable hearing aids. The manufactured SAR ADC based on this design was confirmed to have advantages in power consumption and size through the comparison with the conventional ADC. Therefore, the manufactured SAR ADC is expected to be used in the implantable medical device field and speech signal processing field, which require small size and low power consumption.


[Clinical studies on tumor markers for monitoring prostate cancer patients; the evaluation of prostate-specific antigen and comparison with prostatic acid phosphatase and gamma-seminoprotein].
To evaluate the usefulness of tumor markers in monitoring the patients with prostate cancer, serial measurements of serum prostate-specific antigen (PA), prostatic acid phosphatase (PAP) and gamma-seminoprotein (gamma-Sm) were performed in 78 stage C or D patients. Positive rates of each marker prior to the treatment were as follows; PA; 75%, PAP; 56% and gamma-Sm; 62% in stage C, and PA; 95%, PAP; 79% and gamma-Sm; 91% in stage D. In most cases showing PR (partial response) and S (stable) in clinical responses, these three markers decreased their serum titers corresponding to clinical course if the markers were elevated at the start of the treatment. But the usefulness of PAP was lessened because of its lower positive rate than those of PA and gamma-Sm. In 33 PD (progressive disease) cases, positive rates of each marker at time of clinical diagnosis as PD were found to be 85% in PA, 55% in PAP and 76% in gamma-Sm. And with the combination assays of these three tumor markers, positive rate was elevated to 88%. Moreover, elevation of serum values of these three markers at 3 months before the progression event were observed in 50% of PA, 39% of PAP and 46% of gamma-Sm. Then the prognostic significance of each marker was examined. In PA and PAP, there were statistical differences in non-relapsing rates between patients whose reduction rates from the pretreatment value on 7th day were more than and less than 50%. But in gamma-Sm, a statistical difference between each group was firstly observed on 14th day. As a result, in monitoring patients with prostate cancer, PA and gamma-Sm are more useful than PAP and, in prediction of patients' prognosis, PA is more useful than gamma-Sm.


Global burden of hypertension among people living with HIV in the era of increased life expectancy: a systematic review and meta-analysis.
Although HIV infection and antiretroviral therapy (ART) increase the risk for hypertension in people living with HIV (PLHIV), the global and regional burden of hypertension in PLHIV is not well characterized. In this systematic review and meta-analysis, we searched multiple databases for studies reporting on hypertension in PLHIV and conducted between 2007 and 2018. Meta-analysis through random-effect models served to obtain the pooled prevalence estimates. Heterogeneity was assessed via the χ test on Cochran's Q statistic. We included 194 studies (396 776 PLHIV from 61 countries). The global prevalence of hypertension was 23.6% [95% confidence interval (95% CI: 21.6-25.5)] with substantial heterogeneity. The regional distribution was Western and Central Europe and North America [28.1% (95% CI: 24.5-31.9)], West and Central Africa [23.5% (16.6-31.0)], Latin America and the Caribbean [22.0% (17.8-26.5)], Eastern and Southern Africa [19.9% (17.2-22.8)], and Asia and Pacific [16.5% (12.5-21.0)]; P = 0.0007. No study originated from the Middle East and North Africa, and Eastern Europe and Central Asia regions. The prevalence was higher in high-income countries than others (P = 0.0003) and higher in PLHIV taking ART than those ART-naive (P = 0.0003). The prevalence increased over time (mainly driven by Eastern and Southern Africa) and with age. There was no difference between men and women. We estimated that in 2018, there were 8.9 (95% CI: 8.3-9.6) million cases of hypertension in PLHIV globally, among whom 59.2% were living in Sub-Saharan Africa. Cost-effective strategies to curb the dreadful burden of hypertension among PLHIV are needed.


Silencing of the FRO1 gene and its effects on iron partition in Nicotiana benthamiana.
To evaluate the dynamic role of the ferric-chelate reductase enzyme (FCR) and to identify possible pathways of regulation of its activity in different plant organs an investigation was conducted by virus-induced gene silencing (VIGS) using tobacco rattle virus (TRV) to silence the ferric reductase oxidase gene (FRO1) that encodes the FCR enzyme. Half of Nicotiana benthamiana plants received the VIGS vector and the rest remained as control. Four treatments were imposed: two levels of Fe in the nutrient solution (0 or 2.5 μM of Fe), each one with silenced or non-silenced (VIGS-0; VIGS-2.5) plants. Plants grown without iron (0; VIGS-0) developed typical symptoms of iron deficiency in the youngest leaves. To prove that FRO1 silencing had occurred, resupply of Fe (R) was done by adding 2.5 μM of Fe to the nutrient solution in a subset of chlorotic plants (0-R; VIGS-R). Twelve days after resupply, 0-R plants had recovered from Fe deficiency while plants containing the VIGS vector (VIGS-R) remained chlorotic and both FRO1 gene expression and FCR activity were considerably reduced, consequently preventing Fe uptake. With the VIGS technique we were able to silence the FRO1 gene in N. benthamiana and point out its importance in chlorophyll synthesis and Fe partition.


Interpersonal psychotherapy for postpartum depression : a treatment program.
Postpartum depression is a frequent complication of childbirth. Postpartum depression is associated with disruptions in interpersonal relationships, and the puerperium is a period of major role transition. In contrast to other subtypes of depression, however, postpartum depression often is not treated with medication, which is relatively contraindicated for women who are breastfeeding. Interpersonal psychotherapy (IPT) focuses specifically on the effects of depression on interpersonal functioning; this focus renders IPT a potentially useful psychosocial treatment for postpartum depression. The authors describe the use of IPT for the treatment of women with postpartum depression and present preliminary results from an open treatment trial of IPT.


Serum stromal-derived-factor-1 (CXCL12) and its alpha chemokine receptor (CXCR4) as biomarkers in neonatal sepsis.
Neonatal sepsis remains one of the leading causes of morbidity and mortality both among term and preterm infants. Advances in neonatal care improved survival and reduced complications in preterm infants. Chemokines are chemotactic cytokines that give directional guidance for leukocyte migration during inflammatory process. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in inflammatory states. However, its value as a biomarker in neonatal sepsis is unclear. To assess the value of measuring the serum levels of alpha-chemokine receptor type 4 (CXCR-4) and stromal-derived-factor-1 (CXCL12) in diagnosis of late onset neonatal sepsis. Serum levels of CXCL12 and CXCR4 were determined in 38 full term neonates, 23 cases of late onset sepsis (13 males and 10 female), and 15 healthy neonates as control (six males and nine females) by ELISA technique and flow-cytometry. Serum levels of CXCR4 and CXCL12 were significantly higher in neonates with late onset sepsis compared with the non-septic ones. The sensitivity, the specificity, and the overall accuracy of CXCL12 were 100%. The sensitivity of CXCR4 was 87%; the specificity was 80% and the overall accuracy was 84%. Serum CXCR4 and CXCL12 levels increase significantly in septic neonates and they are valuable marker in diagnosis of neonatal sepsis. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.


Hepatitis C virus coinfection does not affect CD4 restoration in HIV-infected patients after initiation of antiretroviral therapy.
There are conflicting data regarding the influence of hepatitis C virus (HCV) infection on the immune restoration experienced by HIV-infected patients who receive highly active antiretroviral therapy (HAART). In this multicenter, retrospective, longitudinal study, CD4 restoration was assessed according to HCV status in treatment-naive HIV-infected patients within 3 years of HAART. Only patients with persistent HIV suppression were included. Factors predicting CD4 gains were analyzed with multivariate linear regression. Out of 322 patients included 139 had positive HCV-RNA and 183 were only HIV infected. HCV-HIV-coinfected patients were older, more often ex-intravenous drug users (IVDU), and had less advanced HIV infection. Baseline CD4 count [OR -0.21 [95% CI (-0.34)-(-0.04)]; p = 0.01] and male sex [OR -0.19 [95% CI (-191.12)-(-10.87)]; p = 0.03] predicted smaller increments in absolute CD4 counts, and higher baseline CD4% [OR -0.38 [95% CI (-0.39)-(-0.21)]; p < 0.0001] and older age [OR -0.12 [95% CI (-0.23)-(-0.01)]; p = 0.03] predicted smaller gains in CD4% after 3 years of HAART. A history of IVDU was associated with smaller absolute CD4 count increases at 1 year of therapy [OR -0.20 [95% CI (-128.32)-(-16.24)]; p = 0.01]. Use of nucleoside reverse transcriptase inhibitor (NRTI)-only regimens and of zidovudine as part of the NRTI backbone was associated with smaller and greater gains in CD4%, respectively. HCV replication per se does not impair the CD4 restoration in HIV-infected patients successfully treated with antiretroviral therapy. Lower baseline CD4 counts are the strongest predictors of greater CD4 gains over a 3-year period, while a history of IVDU negatively affects CD4 restoration only early after the initiation of HAART.


Role of astrovirus in intussusception in Nigerian infants.
Intussusception (IS) is a form of intestinal obstruction in which a segment of the bowel prolapses into a more distal segment. Viral infections, mostly adenovirus, enteroviruses, human herpesvirus and Epstein-Barr virus are reported in 20-50% of childhood cases of IS. Between January and July 2004, six stool specimens collected from infants 0- to 8-months old diagnosed and admitted for IS were investigated for the presence of rotavirus, astrovirus and adenovirus antigens. Astrovirus antigen was detected in three of the six stool specimens by enzyme immune assay (EIA) and confirmed in two specimens by reverse transcription-polymerase chain reaction (RT-PCR). Rotavirus, non-enteric adenovirus and astrovirus were detected by EIA, as mixed infections in a single specimen. The rotavirus strain revealed a SGI+II, mixed G1G2G8P[6] genotype and had no visible electrophoretic profile. A larger study is needed to determine the extent of involvement of astroviruses in IS in infants and the virus should be included in studies investigating the aetiology of IS.


Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE.
Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. PROSPERO Identifier: CRD42021238486.


Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest.
Oxymatrine has been shown to exert an antitumor effect on several types of cancer cells. However, the role of oxymatrine in bladder cancer has not yet been evaluated. The present study was designed to investigate the potential anti-proliferative effect of oxymatrine on bladder cancer T24 cells and the possible mechanisms involved. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell growth, and the cell morphology was examined using hematoxylin and eosin staining, wrights' staining and electron microscopy. The caspase-3 and survivin mRNA and protein levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The expression of tumor protein p53 (p53), Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were analyzed using immunohistochemistry. Oxymatrine inhibited the proliferation of the T24 cells in a dose- and time-dependent manner. Oxymatrine also induced apoptosis and cell cycle arrest in the cells, in association with the upregulation of caspase-3 and Bax, and the downregulation of survivin, Bcl-2 and p53 expression. Overall, oxymatrine inhibits the proliferation of human bladder cancer cells by inducing apoptosis and cell cycle arrest via mechanisms that involve p53-Bax signaling and the downregulation of survivin expression.


Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies.
Acne vulgaris is a chronic inflammatory skin condition classified by the Global Burden of Disease Study as the eighth most prevalent disease worldwide. The pathophysiology of the condition has been extensively studied, with an increase in sebum production, abnormal keratinization of the pilosebaceous follicle, and an inflammatory immune response all implicated in its etiology. One of the most disputed points, however, is the role of the gram-positive anaerobic bacterium Propionibacterium acnes in the development of acne, particularly when this organism is also found in normal sebaceous follicles of healthy skin. Against this background, we now describe the different sampling strategies that have been adopted for qualitative and quantitative study of P acnes within intact hair follicles of the skin and discuss the strengths and weaknesses of such methodologies for investigating the role of P acnes in the development of acne.


Structural modeling for the open state of an NMDA receptor.
NMDA receptors are tetrameric ligand-gated ion channels that are crucial for neurodevelopment and higher order processes such as learning and memory, and have been implicated in numerous neurological disorders. The lack of a structure for the channel open state has greatly hampered the understanding of the normal gating process and mechanisms of disease-associated mutations. Here we report the structural modeling for the open state of an NMDA receptor. Staring from the crystal structure of the closed state, we repacked the pore-lining helices to generate an initial open model. This model was modified to ensure tight packing between subunits and then refined by a molecular dynamics simulation in explicit membrane. We identify Cα-H…O hydrogen bonds, between the Cα of a conserved glycine in one transmembrane helix and a carbonyl oxygen of a membrane-parallel helix, at the extracellular side of the transmembrane domain as important for stabilizing the open state. This observation explains why mutations of the glycine are associated with neurological diseases and lead to significant decrease in channel open probability.


Prolonged SARS-CoV-2 shedding in a person living with advanced HIV and diffuse large B-cell lymphoma: a case report.
The global spread of SARS-CoV-2 has necessitated case isolation, with recommended isolation times based on mean time to viral clearance. We present a 28-year-old female living with vertically acquired HIV, undergoing chemotherapy for lymphoma who tested SARS-CoV-2-PCR positive for 164 days. The patient had a history of difficulty taking ARVs, with detectable HIV-RNA and CD4 count below 200 × 106 for the 8 years prior to presentation with symptoms. She stopped ARVs 10 months prior to experiencing fevers, night sweats and loose stool, with a viral load of 354,000 copies/ml and CD4 count of 30 × 106. Following no yield on basic investigations, positron emission tomography scan showed diffuse colonic and oesophageal avidity and a caecal biopsy showed diffuse large B-cell lymphoma. She re-started ARVs and underwent five cycles of R-CHOP chemotherapy. Her first positive SARS-CoV-2 PCR test was detected through routine asymptomatic screening. She self-isolated due to repeated positive tests on a further 8 swabs for a total of 164 days until a negative PCR test. She reported feeling low in mood and frustrated by repeated positive tests and the associated lack of social contact or ability to work. Her positive tests prevented in-person review by her HIV team, which impacted her ARV adherence leading to an unplanned break in therapy. Our case highlights the challenges to physical and mental health faced by patients with prolonged SARS-CoV-2 shedding and the need to develop surrogate markers for infectivity to enable prompt medical and psychological support and accurate advice about the need for isolation.