Nurses' perspectives on feeding decisions for nursing home residents with advanced dementia.
To develop a broad understanding of nursing beliefs, knowledge and roles in feeding decisions for nursing home residents with advanced dementia. Concern is growing about the common use of feeding tubes in nursing home residents with advanced dementia. Nurses can play an important role in providing information and guiding family members through difficult feeding decisions. Little is known about nurses' perspectives on feeding decisions. Qualitative descriptive. In-depth semi-structured interviews of 11 licensed nurses who were experienced in caring for nursing home residents with dementia. Analysis of the interview transcripts revealed three themes: insufficient empirical information, ambiguous role in feeding decisions and uncertainty about moral agency in decisions about the placement of feeding tubes. Despite views that family members would benefit from guidance in decisions regarding the placement of feeding tubes, nurses were, nevertheless, reluctant to become involved in these difficult decisions. If nurses are to guide family members in decisions about the use of feeding tubes, they need more education about evidence-based practice as well as support in exercising their nursing responsibilities.


Small changes in gene expression of targeted osmoregulatory genes when exposing marine and freshwater threespine stickleback (Gasterosteus aculeatus) to abrupt salinity transfers.
Salinity is one of the key factors that affects metabolism, survival and distribution of fish species, as all fish osmoregulate and euryhaline fish maintain osmotic differences between their extracellular fluid and either freshwater or seawater. The threespine stickleback (Gasterosteus aculeatus) is a euryhaline species with populations in both marine and freshwater environments, where the physiological and genomic basis for salinity tolerance adaptation is not fully understood. Therefore, our main objective in this study was to investigate gene expression of three targeted osmoregulatory genes (Na+/K+-ATPase (ATPA13), cystic fibrosis transmembrane regulator (CFTR) and a voltage gated potassium channel gene (KCNH4) and one stress related heat shock protein gene (HSP70)) in gill tissue from marine and freshwater populations when exposed to non-native salinity for periods ranging from five minutes to three weeks. Overall, the targeted genes showed highly plastic expression profiles, in addition the expression of ATP1A3 was slightly higher in saltwater adapted fish and KCNH4 and HSP70 had slightly higher expression in freshwater. As no pronounced changes were observed in the expression profiles of the targeted genes, this indicates that the osmoregulatory apparatuses of both the marine and landlocked freshwater stickleback population have not been environmentally canalized, but are able to respond plastically to abrupt salinity challenges.


Elevated cerebellar cyclic GMP levels during the deltamethrin-induced motor syndrome.
Adult male Porton albino rats received deltamethrin (0.5--40.0 mg/kg IP) or glycerol formal solvent IP. Their behaviour was observed during the subsequent 110 minutes and the incidence and latency of salivation, tremor and incoordination and spontaneous choreiform episodes were noted. Cyclic GMP levels in the cerebellum were determined by radioimmunoassay at various times after deltamethrin administration. The development of the motor syndrome was dose-dependent and followed a specific time course. The threshold dose for profuse salivation and tremor and incoordination was 2.5 mg/kg IP, and for spontaneous choreiform episodes, 5.0 mg/kg IP. The latency of tremor and incoordination decreased significantly as the deltamethrin dose was increased. The first significant increase in cyclic GMP levels in the cerebellum was at 70 minutes, which was 10 minutes after the mean latency of tremor and incoordination. The levels increased further at 100 minutes which was approximately 20 minutes after the mean latency of spontaneous choreiform episodes. Deltamethrin did not have a dose-dependent effect on cyclic GMP levels. The results suggest that deltamethrin changes cerebellar cyclic GMP levels indirectly.


Hydrogen peroxide generation from hydrated protein drink mixes.
Generation of oxygen radicals upon hydration of powdered protein products was examined using luminol-enhanced chemiluminescence. Among individual proteins powders examined oxidative bursts occurred almost immediately, and then rapidly declined in the 1st 5 min. Commercially available powdered protein drink mixes behaved differently, with an initial lag phase followed by a sustained increase in luminol-enhanced luminescence, lasting for an hour or beyond. The drink mix that produced the highest level of luminol-enhanced luminescence also contained 379 nM ascorbate radical when hydrated (28 nmole/g of powdered drink mix). The entire ascorbic acid content of this drink mix was oxidized to nondetectable levels (using HPLC-diode array detection) within 60 min of being hydrated. Treatment of the hydrated drink mixes with the enzyme catalase almost completely inhibited the luminol-enhanced luminescence from the hydrated drink mix demonstrating that hydrogen peroxide generated via a chemical reaction among the drink mixes' ingredients was a primary reactive oxygen species (ROS). This is the strongest oxidative capacity demonstrated in a food product as consumed (without any manipulation to increase ROS) and the 1st time that the ascrobate radical in a food product as been quantified. Generation of hydrogen peroxide in the hydrated drink mixes from metal catalyzed reactions involving oxygen and reducing equivalents from ascorbic acid is proposed.


The Discriminative Power of Different Olfactory Domains in Parkinson's Disease.
Background and Purpose: Olfactory dysfunction is one of the most common non-motor symptoms in Parkinson's disease (PD) preceding the motor symptoms for years. This study aimed to evaluate different olfactory domains in PD patients in comparison with healthy controls and to explore the relationships among olfactory deficit and other clinical manifestations in patients with PD. Methods: Sniffin' Sticks test, which detects olfactory threshold, discrimination, and identification (TDI), were conducted in 500 PD patients and 115 controls. Furthermore, demographic and clinical data including motor and other non-motor symptoms were collected. Results: In the single olfactory model, the identification test showed the area under the receiver operating characteristic (ROC) curve (AUC = 0.818), followed by threshold test (AUC = 0.731) and discrimination test (AUC = 0.723). Specifically, the identification test has a similar discriminative power as the TDI score (0.818 and 0.828, respectively, p = 0.481). In the integrated olfactory model involved with other non-motor manifestations, identification test scores performed as good as the TDI score in differentiating PD patients from controls (0.916 and 0.918, respectively, p = 0.797). In PD patients, age and cognition together explained 7.5% of the variance of the threshold score, while age, cognition, and gender accounted for the 15.2% explained variance of the discrimination score, while cognition, age, the ability of daily living, and gender together interpreted 11.1% of the variance of the identification score. Conclusion: Our results indicated that the identification domain was the most practical olfactory factor in differentiating PD patients, and the combination of several different manifestations was better than a single symptom. Furthermore, the olfactory identification score may be associated with the ability of daily living.


The Caenorhabditis elegans Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status.
Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm.


Interindividual Variations in the Adenosine-Induced Hemodynamics During Fractional Flow Reserve Evaluation: Implications for the Use of Quantitative Flow Ratio in Assessing Intermediate Coronary Stenoses.
Background Quantitative flow ratio (QFR), a novel functional angiography technique, computes fractional flow reserve (FFR) without pressure wires or adenosine. We investigated interindividual variations in the adenosine-induced hemodynamics during FFR assessment and their influence on QFR diagnostic performance. Methods and Results Patients with coronary stenoses who underwent intracoronary pressure and flow assessment were analyzed. Adenosine-induced hemodynamics during FFR measurement were determined by the percentage change in mean aortic pressure (%ΔPa) and the resistive reserve ratio (RRR). The diagnostic performance of QFR was evaluated and compared in each tertile of %ΔPa and RRR using FFR as reference. A total of 294 vessels (245 patients) were analyzed. Mean FFR was 0.80±0.11. Individuals showed a wide variation in the adenosine response in terms of %ΔPa (ranging from -75% to 43%; median, -9% [interquartile range, -3% to -17%]) and the RRR (ranging from 0.45 to 20.15; median, 3.1 [interquartile range, 2.1-4.9]). No significant differences for diagnostic efficiency of QFR were found between tertiles of %ΔPa (area under the curve for the receiver-operating characteristic analysis, 0.950 in tertile 1, 0.929 in tertile 2, and 0.910 in tertile 3; P=0.270) or between tertiles of the RRR (area under the curve for the receiver-operating characteristic analysis, 0.909 in tertile 1, 0.923 in tertile 2, and 0.959 in tertile 3; P=0.167). The classification agreement between QFR and FFR was not significantly modified by %ΔPa (tertile 1, 89%; tertile 2, 87%; and tertile 3, 86%; P=0.827) or by the RRR (tertile 1, 86%; tertile 2, 85%; and tertile 3, 91%; P=0.398). Conclusions Patients undergoing FFR assessment show large interindividual variations in the magnitude of adenosine-induced hemodynamics. However, such variations do not affect the diagnostic performance of QFR in assessing the functional relevance of observed stenoses.


[Diagnosis and therapeutic guidance of diastolic heart failure].
Despite diastolic dysfunction is recognized to play a major role in the pathophysiology of heart failure, the importance of an accurate diagnosis and treatment of this syndrome in clinical practice is poorly established. Recent publications suggest that diastolic dysfunction is the primary cause of heart failure in 30-50% of patients. Several studies also show that, in a significant number of patients with systolic dysfunction, diastolic function is the major determinant of their symptomatic status, their response to treatment and their outcome. Other preliminary data suggest that diastolic dysfunction is an important cause of exercise intolerance in patients with chronic hypertension. This paper discusses the most recent concepts related to the mechanisms, the diagnosis and the treatment of diastolic dysfunction based on diagnostic imaging techniques.


Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function.
Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found Melissa officinalis leaf extract. Rosmarinic acid, a component of Melissa officinalis leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50-60-year-old adult females (n = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions.


An approach to establish the uncertainty budget of catalytic activity concentration measurements in a reference laboratory.
Reference laboratories providing reference services recognized by the Joint Committee for Traceability in Laboratory Medicine (JCTLM) must be accredited as calibration laboratories according to ISO 17025 and ISO 15195. These standards require laboratories to establish an uncertainty budget, in which the uncertainty contributions of the relevant uncertainty components are specified. We present a model to estimate the measurement uncertainty of creatine kinase catalytic activity concentration results obtained by IFCC primary reference measurement procedure. The measurement uncertainty has been estimated by following the next steps: 1) specification of the measurand; 2) identification of the most relevant uncertainty sources; 3) estimation of standard uncertainties by either type A or type B evaluation; 4) estimation of combined uncertainty while taking into account sensitivity coefficients, as well as existence of correlated uncertainty sources; and 5) estimation of expanded uncertainty with a defined coverage probability. The estimated expanded uncertainty was 2.2% (k=2). Uncertainty sources with a significant contribution to the measurement uncertainty were the following: pH adjustment (0.68%), absorbance accuracy (0.48%), wavelength adjustment (0.20%), reaction temperature (0.19%), volume fraction of sample (0.15%) and absorbance linearity (0.06%). The present model is an approach to establish the uncertainty budget of primary reference procedures for the measurement of the catalytic activity concentration of enzymes, and aims at being an example to be followed by other reference laboratories, as well as by laboratories that carry out primary reference measurement procedures.


[The results of internal fixation of proximal humeral fractures with the PHILOS locking plate].
Proximal and diaphyseal humeral fractures are common especially in the elderly, presenting as a challenging problem due to their high complication rates following surgical treatment. In this prospective study, we evaluated the results of patients treated with the PHILOS (Proximal Humeral Internal Locking System) locking plate, a new technique recently developed by the AO/ASIF. Forty-one patients who were treated with the PHILOS plate for proximal humeral fractures were evaluated in two age groups. Group A included 24 patients (12 males, 12 females; mean age 47 years; range 24 to 64 years) younger than 65 years, and group B involved 17 patients (4 males, 13 females; mean age 78 years; range 67 to 90 years) at or above 65 years. Radiographically, all fractures were classified according to the AO/ASIF system. Surgery was performed with the deltopectoral approach in 10 and two patients, and with a deltoid split in 14 and 15 patients in group A and B, respectively. Functional and radiographic results were evaluated after a mean follow-up of 15 months (range 6 to 28 months). The mean Constant scores were 95.0 (range 74 to 100) and 92.8 (range 72 to 100) in group A and B, respectively (p>0.05). After six months of surgery, Constant scores and functional outcomes were similar in patients operated on with the deltopectoral approach or deltoid split. There was neither nonunion nor implant failure. Complications included intra-articular screw penetration (n=1), displacement of the greater tuberculum (n=1) with oblique placement of the plate (n=1), insufficient reduction (n=4), and varus displacement of the humeral head (n=3). No avascular necrosis was seen. Locking plate system is superior over other means of fixation methods, particularly in osteoporotic fractures, because it allows early rehabilitation and does not result in implant failure.


Depth-Dependent Segmental Melting of the Sphingomyelin Alkyl Chain in Lipid Bilayers.
The chain melting of lipid bilayers has often been investigated in detail using calorimetric methods, such as differential scanning calorimetry (DSC), and the resultant main transition temperature is regarded as one of the most important parameters in model membrane experiments. However, it is not always clear whether the hydrocarbon chains of lipids are gradually melting along the depth of the lipid bilayer or whether they all melt concurrently in a very narrow temperature range, as implied by DSC. In this study, we focused on stearoyl-d-sphingomyelin (SSM) as an example of raft-forming lipids. We synthesized deuterium-labeled SSMs at the 4', 10', and 16' positions, and their depth-dependent melting was measured using solid-state deuterium NMR by changing the temperature by 1.0 °C, and comparing with that observed from a saturated lipid, palmitoylstearoylphosphatidylcholine (PSPC). The results showed that SSM exhibited a characteristic depth-dependent melting, which was not observed for PSPC. The strong intermolecular hydrogen bonds between the sphingomyelin amide moiety probably caused the chain melting to start from the chain terminus through the middle part and end in the upper part. This depth-dependent melting implies that the small gel-like domains of SSM remain at temperatures slightly above the main transition temperature. These sphingomyelin features may be responsible for the biological properties of SM-based lipid rafts.


Superior liver sparing by combined coplanar/noncoplanar volumetric-modulated arc therapy for hepatocellular carcinoma: a planning and feasibility study.
Compared with step-and-shoot intensity-modulated radiotherapy (sIMRT) and tomotherapy, volumetric-modulated arc therapy (VMAT) allows additional arc configurations in treatment planning and noncoplanar (NC) delivery. This study was first to compare VMAT planning with sIMRT planning, and the second to evaluate the toxicity of coplanar (C)/NC-VMAT treatment in patients with hepatocellular carcinoma (HCC). Fifteen patients with HCC (7 with left-lobe and 8 with right-lobe tumors) were planned with C-VMAT, C/NC-VMAT, and sIMRT. The median total dose was 49Gy (range: 40 to 56Gy), whereas the median fractional dose was 3.5Gy (range: 3 to 8Gy). Different doses/fractionations were converted to normalized doses of 2Gy per fraction using an α/β ratio of 2.5. The mean liver dose, volume fraction receiving more than 10Gy (V10), 20Gy (V20), 30Gy (V30), effective volume (Veff), and equivalent uniform dose (EUD) were compared. C/NC-VMAT in 6 patients was evaluated for delivery accuracy and treatment-related toxicity. Compared with sIMRT, both C-VMAT (p = 0.001) and C/NC-VMAT (p = 0.03) had significantly improved target conformity index. Compared with C-VMAT and sIMRT, C/NC-VMAT for treating left-lobe tumors provided significantly better liver sparing as evidenced by differences in mean liver dose (p = 0.03 and p = 0.007), V10 (p = 0.003 and p = 0.009), V20 (p = 0.006 and p = 0.01), V30 (p = 0.02 and p = 0.002), Veff (p = 0.006 and p = 0.001), and EUD (p = 0.04 and p = 0.003), respectively. For right-lobe tumors, there was no difference in liver sparing between C/NC-VMAT, C-VMAT, and sIMRT. In all patients, dose to more than 95% of target points met the 3%/3mm criteria. All 6 patients tolerated C/NC-VMAT and none of them had treatment-related ≥ grade 2 toxicity. The C/NC-VMAT can be used clinically for HCC and provides significantly better liver sparing in patients with left-lobe tumors.


Revisiting the "enigma" of musicians with dyslexia: Auditory sequencing and speech abilities.
Previous research has suggested a link between musical training and auditory processing skills. Musicians have shown enhanced perception of auditory features critical to both music and speech, suggesting that this link extends beyond basic auditory processing. It remains unclear to what extent musicians who also have dyslexia show these specialized abilities, considering often-observed persistent deficits that coincide with reading impairments. The present study evaluated auditory sequencing and speech discrimination in 52 adults comprised of musicians with dyslexia, nonmusicians with dyslexia, and typical musicians. An auditory sequencing task measuring perceptual acuity for tone sequences of increasing length was administered. Furthermore, subjects were asked to discriminate synthesized syllable continua varying in acoustic components of speech necessary for intraphonemic discrimination, which included spectral (formant frequency) and temporal (voice onset time [VOT] and amplitude envelope) features. Results indicate that musicians with dyslexia did not significantly differ from typical musicians and performed better than nonmusicians with dyslexia for auditory sequencing as well as discrimination of spectral and VOT cues within syllable continua. However, typical musicians demonstrated superior performance relative to both groups with dyslexia for discrimination of syllables varying in amplitude information. These findings suggest a distinct profile of speech processing abilities in musicians with dyslexia, with specific weaknesses in discerning amplitude cues within speech. Because these difficulties seem to remain persistent in adults with dyslexia despite musical training, this study only partly supports the potential for musical training to enhance the auditory processing skills known to be crucial for literacy in individuals with dyslexia. (PsycINFO Database Record


Catalysis and Mechanism of H2 Release from Amine-Boranes by Diiron Complexes.
Studies focused on the dehydrogenation of amine-borane by diiron complexes that serve as well-characterized rudimentary models of the diiron subsite in [FeFe]-hydrogenase are reported. Complexes of formulation (μ-SCH2XCH2S)[Fe(CO)3]2, with X = CH2, CMe2, CEt2, NMe, NtBu, and NPh, 1-CO through 6-CO, respectively, were determined to be photocatalysts for release of H2 gas from a solution of H3B ← NHMe2 (B:A(s)), dissolved in THF. The thermal displacement of the tertiary amine-borane, H3B ← NEt3 (B:A(t)) from photochemically generated (μ-SCH2XCH2S)[Fe(CO)3][Fe(CO)2(μ-H)(BH2-NEt3)], 1-B:A(t) through 6-B:A(t), by P(OEt)3 was monitored by time-resolved FTIR spectroscopy. Rates and activation barriers for this substitution reaction were consistent with a dissociative mechanism for the alkylated bridgehead species 2-CO through 6-CO, and associative or interchange for 1-CO. DFT calculations supported an intermediate [I] for the dissociative process featuring a coordinatively unsaturated diiron complex stabilized by an agostic interaction between the metal center and the C-H bond of an alkyl group on the central bridgehead atom of the SRS linker. The rate of H2 production from the initially formed 1-B:A(s) through 6-B:A(s) complexes was inversely correlated with the lifetime of the analogous 1-B:A(t) through 6-B:A(t) adducts. Possible mechanisms are presented which feature involvement of the pendent nitrogen base as well as a separate mechanism for the all carbon bridgeheads.


PAM variants in patients with thyrotrophinomas, cyclical Cushing's disease and prolactinomas.
Germline loss-of-function variants in PAM, encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological pituitary hypersecretion, specifically: somatotrophinoma, corticotrophinoma, and prolactinoma. PAM is the sole enzyme responsible for C-terminal amidation of peptides, and plays a role in the biosynthesis and regulation of multiple hormones, including proopiomelanocortin (POMC). We performed exome sequencing of germline and tumour DNA from 29 individuals with functioning pituitary adenomas (12 prolactinomas, 10 thyrotrophinomas, 7 cyclical Cushing's disease). An unfiltered analysis was undertaken of all PAM variants with population prevalence <5%. We identified five coding, non-synonymous PAM variants of interest amongst seven individuals (six germline, one somatic). The five variants comprised four missense variants and one truncating variant, all heterozygous. Each variant had some evidence of pathogenicity based on population prevalence, conservation scores, in silico predictions and/or prior functional studies. The yield of predicted deleterious PAM variants was thus 7/29 (24%). The variants predominated in individuals with thyrotrophinomas (4/10, 40%) and cyclical Cushing's disease (2/7, 29%), compared to prolactinomas (1/12, 8%). This is the second study to demonstrate a high yield of suspected loss-of-function, predominantly germline, PAM variants in individuals with pathological pituitary hypersecretion. We have extended the association with corticotrophinoma to include the specific clinical entity of cyclical Cushing's disease and demonstrated a novel association between PAM variants and thyrotrophinoma. PAM variants might act as risk alleles for pituitary adenoma formation, with a possible genotype-phenotype relationship between truncating variants and altered temporal secretion of cortisol.


Aspiration Pneumonia in Children with Cerebral Palsy after Videofluoroscopic Swallowing Study.
Introduction Dysphagia is a common symptom in children with cerebral palsy, either in oral or pharyngeal phases. Children who face such difficulties tend to show health problems such as food aspiration, malnutrition and respiratory infections. Videofluoroscopic swallowing study is the most recommended for these cases, as it reveals the real situation during swallowing. Objective The study aimed to verify the occurrence of aspiration pneumonia in children with cerebral palsy after videofluoroscopy. Methods The population for this prospective cross-sectional study involved 103 children with cerebral palsy, referred for videofluoroscopic who had returned for medical examination after a week to search for signs and symptoms of pneumonia. Results The study involved 46 girls (44.66%) and 57 boys (55.34%), aged between 0 and 14 years of age. Of the total, 84 (81.5%) had dysphagia, of which 24 (23.3%) were severe, 8 (7.7%) were moderate and 52 (50.4%) were mild dysphagia. None of the children presented aspiration pneumonia or infectious complications during the course of videofluoroscopy or after the procedure. Conclusion In the population studied, the authors found no cases of aspiration pneumonia, even with tracheal aspiration present in 32 (31.07%) cases.


Transpancreatic precut papillotomy versus double-guidewire technique in difficult biliary cannulation: prospective randomized study.
Difficult biliary cannulation and unintentional pancreatic duct cannulation are thought to be important contributors to pancreatitis occurring after endoscopic retrograde cholangiopancreatography. Our aim was to compare and evaluate the rates of success and complications of transpancreatic precut papillotomy (TPPP) and the double-guidewire technique (DGT), both with prophylactic pancreatic stenting. From April 2011 to March 2014, patients with difficult biliary cannulation, in whom we planned to first position a guidewire in the pancreatic duct, were enrolled, and 68 patients were prospectively randomly allocated to two groups (TPPP 34, DGT 34). We evaluated the rates of success and complications for each group. TPPP had a significantly higher success rate (94.1 %) than DGT (58.8 %). The rate of post-ERCP pancreatitis was 2.9 % in both groups. There was no significant difference between the two groups in the overall rate of complications related to cannulation. CONCLUSION : If biliary cannulation cannot be achieved, TPPP should be selected first after unintentional pancreatic duct cannulation.


Nuclear interactions of retinoic acid-binding protein in chemically induced mammary adenocarcinoma.
Cellular retinoic acid-binding protein (CRABP) was detected in the nuclear fraction of N-methyl-N-nitrosourea-induced mammary cancers after the incubation of cytosol containing [3H]retinoic acid (RA)-bound CRABP with isolated nuclei. CRABP extracted from the nuclei in buffer containing 0.4 M-KCl sedimented as a 2 S component when subjected to sucrose-density-gradient analysis. [3H]RA-CRABP was found to be a prerequisite for the detection of nuclear binding, since the incubation of isolated nuclei or 0.4 M-KCl extract of the nuclei with [3H]RA did not result in any significant binding. Incubation of [3H]RA-CRABP at 25 or 30 degrees C before incubation with the nuclei neither altered the sedimentation coefficient nor enhanced the nuclear binding compared with 0 degrees C incubation. The tumour nuclei contained a saturable number of binding sites with a dissociation constant of 1.6 x 10(-9) M. These results indicate that the action of retinoic acid in the target organ may be mediated by its interaction with the nuclei.


Structural and regulatory characterization of the placental epigenome at its maternal interface.
Epigenetics can be loosely defined as the study of cellular "traits" that influence biological phenotype in a fashion that is not dependent on the underlying primary DNA sequence. One setting in which epigenetics is likely to have a profound influence on biological phenotype is during intrauterine development. In this context there is a defined and critical window during which balanced homeostasis is essential for normal fetal growth and development. We have carried out a detailed structural and functional analysis of the placental epigenome at its maternal interface. Specifically, we performed genome wide analysis of DNA methylation in samples of chorionic villus (CVS) and maternal blood cells (MBC) using both commercially available and custom designed microarrays. We then compared these data with genome wide transcription data for the same tissues. In addition to the discovery that CVS genomes are significantly more hypomethylated than their MBC counterparts, we identified numerous tissue-specific differentially methylated regions (T-DMRs). We further discovered that these T-DMRs are clustered spatially along the genome and are enriched for genes with tissue-specific biological functions. We identified unique patterns of DNA methylation associated with distinct genomic structures such as gene bodies, promoters and CpG islands and identified both direct and inverse relationships between DNA methylation levels and gene expression levels in gene bodies and promoters respectively. Furthermore, we found that these relationships were significantly associated with CpG content. We conclude that the early gestational placental DNA methylome is highly organized and is significantly and globally associated with transcription. These data provide a unique insight into the structural and regulatory characteristics of the placental epigenome at its maternal interface and will drive future analyses of the role of placental dysfunction in gestational disease.


[In-vitro susceptibilites to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004].
A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.


Cerebral palsy. Evaluation and management of equinus and equinovarus deformities.
Walking function may be enhanced by correcting equinus and equinovarus deformities in CP. Nonoperative management should be used in young children. Muscle balancing procedures, such as gastrocnemius aponeurosis lengthening, Achilles' tendon lengthening, and SPLATT, are particularly useful in correcting these deformities.


Elevated and Sustained Intracellular Calcium Signalling Is Necessary for Efficacious Induction of the Human Sperm Acrosome Reaction.
Progesterone and prostaglandin E1 are postulated to trigger the human sperm acrosome reaction (AR). However, their reported efficacy is very variable which likely, in part, reflects the plethora of experimental conditions and methodologies used to detect this physiologically relevant event. The purpose of this study was to develop an assay for the robust induction and objective measurement of the complete AR. Sperm from healthy volunteers or patients undertaking IVF were treated with a variety of ligands (progesterone, prostaglandin E1 or NH4Cl, alone or in combinations). AR, motility and intracellular calcium measurements were measured using flow cytometry, computer-assisted sperm analysis (CASA) and fluorimetry, respectively. The AR was significantly increased by the simultaneous application of progesterone, prostaglandin E1 and NH4Cl, following an elevated and sustained intracellular calcium concentration. However, we observed notable inter- and intra-donor sample heterogeneity of the AR induction. When studying the patient samples, we found no relationship between the IVF fertilization rate and the AR. We conclude that progesterone and prostaglandin E1 alone do not significantly increase the percentage of live acrosome-reacted sperm. This assay has utility for drug discovery and sperm toxicology studies but is not predictive for IVF success.


Technology and Integration Roadmap for Optoelectronic Memristor.
Optoelectronic memristors (OMs) have emerged as a promising optoelectronic Neuromorphic computing paradigm, opening up new opportunities for neurosynaptic devices and optoelectronic systems. These OMs possess a range of desirable features including minimal crosstalk, high bandwidth, low power consumption, zero latency, and the ability to replicate crucial neurological functions such as vision and optical memory. By incorporating large-scale parallel synaptic structures, OMs are anticipated to greatly enhance high-performance and low-power in-memory computing, effectively overcoming the limitations of the von Neumann bottleneck. However, progress in this field necessitates a comprehensive understanding of suitable structures and techniques for integrating low-dimensional materials into optoelectronic integrated circuit platforms. This review aims to offer a comprehensive overview of the fundamental performance, mechanisms, design of structures, applications, and integration roadmap of optoelectronic synaptic memristors. By establishing connections between materials, multilayer optoelectronic memristor units, and monolithic optoelectronic integrated circuits, this review seeks to provide insights into emerging technologies and future prospects that are expected to drive innovation and widespread adoption in the near future.


Flashing superluminal components in the jet of the radio galaxy 3C120
A 16-month sequence of radio images of the active galaxy 3C120 with the Very Long Baseline Array reveals a region in the relativistic jet where superluminal components flash on and off over time scales of months, while the polarization angle rotates. This can be explained by interaction between the jet and an interstellar cloud located about 8 parsecs from the center of the galaxy. The cloud, which rotates the polarization direction and possibly eclipses a section of the jet, represents a "missing link" between the ultradense broad-emission-line clouds closer to the center and the lower density narrow-emission-line clouds seen on kiloparsec scales.


A randomized trial of librarian educational participation in clinical settings.
In order to evaluate the librarian's educational role in patient care settings, an information service was provided for health professionals, patients, and families by two part-time clinical librarians. Eight clinical areas were randomly selected from a pool of settings which met predetermined entry criteria. Four of these settings were randomly allocated to the experimental maneuver (that is, the clinical librarian service), and four were control settings. Results showed that the clinical librarians were accepted by health professionals and that services to all groups were viewed as successful. Significant differences in information-seeking patterns were found between study and control groups of health professionals. In particular, the study group was more likely to use the library for direct patient care and rated the librarian and library resources more highly as sources of information. This time-limited and education-oriented model would be useful for settings in which a full-time librarian program is not feasible.


[Effect of isonicotinic acid derivates on reproduction of Epstein-Barr virus].
Current approaches to the treatment of herpes infection, particularly Epstein-Barr virus (EBV), include the use of etiotropic medicines, as well as sensitizing therapy. This virus plays an important role in the etiology of nasopharyngeal carcinoma, adenocarcinoma of the parotid glands, gastric carcinoma, Burkitt's lymphoma and lymphoproliferative syndromes [1, 2, 3]. The spectrum of drugs active against EBV remains very limited, and gancyclovir and acyclovir are used in medical practice, so the search of new compounds active against EBV remains urgent. The purpose of this work was to study antiEBV activity of isonicotinic acid derivatives in the cultures of lymphoblastoid Raji cells, B95-8, Namalwa. The indices of cytotoxicity (CC50) which amounted to 840, 1250 and 3000 microg/ml and the concentration of drugs, which inhibit the virus (IC50) reproduction is 0.1, 2.5 and 50 microg/ml, respectively, in cell cultures were identified. It was detected, the drug 4-(n-benzyl)aminocarbonyl-1-methylpyridinium iodide (PV-1) had an ability to inhibit reproduction of the Epstein-Barr virus in all studied cells cultures. The compounds PV-2 and PV-10 were less toxic in respect of the initial preparation PV-1, but their antiviral activity was manifested at 25 and 500 times higher concentrations. It, respectively, influenced the decrease of their selectivity index, which was 8400 for PV-1, 400 and 440--for PV-2 and PV-10. These studies suggest possible ways of further modification of the PV-1 molecule to create highly specific inhibitors of Epstein-Barr virus. The paper is presented in Ukrainian.


Hepatitis B Virus Immunopathology, Model Systems, and Current Therapies.
Most people develop acute hepatitis B virus (HBV)-related hepatitis that is controlled by both humoral and cellular immune responses following acute infection. However, a number of individuals in HBV-endemic areas fail to resolve the infection and consequently become chronic carriers. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities. However, immunological control of the virus is often not durable. A robust T-cell response is associated with control of HBV infection and liver damage; however, HBV-specific T cells are deleted, dysfunctional, or become exhausted in chronic hepatitis patients. As a result, efforts to restore virus-specific T-cell immunity in chronic HBV patients using antiviral therapy, immunomodulatory cytokines, or therapeutic vaccination have had little success. Adoptive cell transfer of T cells with specificity for HBV antigen+ cells represents an approach aiming to ultimately eliminate residual hepatocytes carrying HBV covalently closed circular DNA (cccDNA). Here, we discuss recent findings describing HBV immunopathology, model systems, and current therapies.


Pulmonary hypertension due to left heart disease.
Pulmonary hypertension (PH) is frequent in left heart disease (LHD), as a consequence of the underlying condition. Significant advances have occurred over the past 5 years since the 5th World Symposium on Pulmonary Hypertension in 2013, leading to a better understanding of PH-LHD, challenges and gaps in evidence. PH in heart failure with preserved ejection fraction represents the most complex situation, as it may be misdiagnosed with group 1 PH. Based on the latest evidence, we propose a new haemodynamic definition for PH due to LHD and a three-step pragmatic approach to differential diagnosis. This includes the identification of a specific "left heart" phenotype and a non-invasive probability of PH-LHD. Invasive confirmation of PH-LHD is based on the accurate measurement of pulmonary arterial wedge pressure and, in patients with high probability, provocative testing to clarify the diagnosis. Finally, recent clinical trials did not demonstrate a benefit in treating PH due to LHD with pulmonary arterial hypertension-approved therapies.


Long-term follow-up for immunity after monovalent or combined live measles, mumps, and rubella virus vaccines.
Antibody in human subjects persisted without substantial decline for 8 years after mumps vaccine (Jeryl Lynn), for 6 years after measles (Attenuvax), for 5 1/2 years after rubella vaccine (HPV-77 duck), for 5 years after measles-mumps-rubella and mumps-rubella combined vaccines, for 4 years after measles and rubella, and for 2 years after measles-mumps vaccines, the longest periods tested. Protective immunity against mumps illness persisted through the eighth year. The patterns for antibody following vaccination parallel those for natural infection and indicate that immunity will be lasting. Subclinical reinfection evidenced by antibody increase was commonly seen in persons who had been vaccinated, much as follows the natural infection.


Insect GABA receptors: splicing, editing, and targeting by antiparasitics and insecticides.
Ionotropic GABA receptors are abundant in both vertebrate and invertebrate nervous systems, where they mediate rapid, mostly inhibitory synaptic transmission. A GABA-gated chloride channel subunit from Drosophila melanogaster [Resistant to Dieldrin (RDL)] has been cloned, functionally expressed, and found to exhibit many aspects of the pharmacology of native, bicuculline-insensitive insect GABA receptors. RDL is the target of the commercially important insecticide fipronil. A point mutation in the channel-lining region of the RDL molecule is known to underlie most cases of resistance to insecticides acting on GABA receptors. RDL is widely distributed throughout the insect nervous system, but the subunit composition of RDL-containing in native receptors is unknown. It is possible that in some instances, RDL coexpresses with glutamate-gated chloride channel subunits. Other ionotropic receptor subunits (LCCH3 and GRD) form GABA-gated cation channels when heterologously expressed. Interest in RDL as a model ligandgated anion channel has been enhanced by the recent discovery of pre-mRNA A-to-I editing, which, together with alternative splicing, adds to the functional diversity of this GABA receptor subunit.


The antidepressant hypericin inhibits progression of experimental proliferative vitreoretinopathy.
Hypericin, a polycyclic dione used as an antidepressant, has been shown to inhibit the protein kinase C (PKC) pathway. Many of the pathologic responses found in proliferative vitreoretinopathy (PVR) are dependent upon PKC. Therefore, we studied the effect of hypericin on the treatment of experimental PVR. PVR was induced in pigmented rabbits by intravitreal injection of 50,000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the eyes received an intravitreal injection of either balanced salt solution (BSS, 0.1 mL) (group A, control) or hypericin (0.1 mL) in doses of 1 muM (group B), 10 muM (group C), and 100 muM (group D). The eyes were examined ophthalmoscopically on days 1, 3, 7, 14, and 28 after surgery and the stage of PVR was evaluated (0 to V). The effect of hypericin on retinal morphology and function was also determined for the eyes injected with 100 muM hypericin with no fibroblasts by light microscopy and electroretinogram (ERG). In the control eyes, the retina was detached after 5 days, membranes had formed on and beneath it, and the PVR had progressed to higher stages over time. In the eyes injected with hypericin, the PVR also progressed; however, the severity of PVR on each day was lower than that in control eyes on that day. PVR was significantly inhibited in groups C and D as compared with the control eyes after day 5 (P < 0.05). Histological examination of the hypericin-treated control eyes disclosed no morphological change, and ERG analysis revealed no significant functional change. Intravitreal injection of hypericin is a safe and effective means of reducing experimental PVR.


Structures of 2-Hydroxyisobutyric Acid-CoA Ligase Reveal Determinants of Substrate Specificity and Describe a Multi-Conformational Catalytic Cycle.
2-Hydroxyisobutyric acid (2-HIBA) is a biomarker of adiposity and associated metabolic diseases such as diabetes mellitus. It is also formed in the bacterial degradation pathway of the fuel oxygenate methyl tert-butyl ether (MTBE), requiring thioesterification with CoA prior to isomerization to 3-hydroxybutyryl-CoA by B12-dependent acyl-CoA mutases. Here, we identify the adenylating enzymes superfamily member 2-HIBA-CoA ligase (HCL) in the MTBE-degrading bacterium Aquincola tertiaricarbonis L108 by knockout experiments. To characterize this central enzyme of 2-HIBA metabolism, ligase activity kinetics of purified HCL and its X-ray crystal structures were studied. We analyzed the enzyme in three states, which differ in the orientation of the two enzyme domains. A 154° rotation of the C-terminal domain accompanies the switch from the adenylate- into the thioester-forming state. Furthermore, a third conformation was obtained, which differs by 50° and 130° from the adenylation and thioesterification states, respectively. Phylogenetic and structural analysis reveals that HCL defines a new subgroup within phenylacetate-CoA ligases (PCLs) thus far described to exclusively accept aromatic acyl substrates. In contrast, kinetic characterization clearly demonstrated that HCL catalyzes CoA activation of several aliphatic short-chain carboxylic acids, preferentially 2-HIBA. Compared to the classical PCL representatives PaaK1 and PaaK2 of Burkholderia cenocepacia J2315, the acyl binding pocket of HCL is significantly smaller and more polar, due to unique active-site residues Y164 and S239 forming H-bonds with the OH-group of the acyl substrate moiety. Furthermore, HCL and PaaK topologies illustrate the evolutionary steps leading from a homodimeric to the fused monomeric core fold found in other ligases.


Suppressed ubiquitination of Nrf2 by p47phox contributes to Nrf2 activation.
Although critical in phagocytosis in innate immunity, reactive oxygen species (ROS) collaterally inflict damage to host phagocytes because they indiscriminate targets. Since Nrf2 increases the expression of anti-oxidant enzymes that nullifies ROS, ROS activating Nrf2 is a critical negative regulatory step for countering the deleterious effects of ROS. Here, we postulate whether, along with ROS activating Nrf2, NADPH oxidase components also participate in direct activation of Nrf2, contributing to protection from ROS. Our results show that the p47phox of the NADPH oxidase, but not p65phox or p40phox, physically binds to Nrf2, activating the Nrf2 function. p47phox binding to Nrf2/Keap1 complex suppresses the ubiquitination of Nrf2, while p47phox becomes ubiquitinated by Keap1. p47phox increases the nuclear translocation of Nrf2 and the expression of Nrf2-dependent genes, whereas genetic ablation of p47phox decreases the expression of those genes. In a lipopolysaccharide-induced acute lung inflammation mouse model, selective expression of p47phox in mouse lungs induces the expression of Nrf2-dependent genes and is sufficient to suppress neutrophilic lung inflammation. Therefore, our findings suggest that p47phox is a novel regulator of Nrf2 function.


Glucoregulatory feeding by rats after intraventricular 6-hydroxydopamine or lateral hypothalamic lesions.
Rats given intravenricular injections of 6-hydroxydopamine or bilateral electrolytic lesions of the lateral hypothalamus do not show the normal increase in food intake in response to large decreases in glucose utilization or exposure to severe cold stress. However, they will eat more during chronic glucoprivation that is less intense, or during exposure to more moderate cold stress. Thus, the feeding deficits of these lesioned rats may not reflect an inability to respond to certain qualitatively different stimuli, but rather an inability to respond to quantitatively different intensities of the same stimulus.


Itaconate inhibits CD103 + T RM cells and alleviates hepatobiliary injury in mouse models of primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease characterized by the infiltration of intrahepatic tissue-resident memory CD8 + T cells (T RM ). Itaconate has demonstrated therapeutic potential in modulating inflammation. An unmet need for PSC is the reduction of biliary inflammation, and we hypothesized that itaconate may directly modulate pathogenic T RM . The numbers of intrahepatic CD103 + T RM were evaluated by immunofluorescence in PSC (n = 32), and the serum levels of itaconate in PSC (n = 64), primary biliary cholangitis (PBC) (n = 60), autoimmune hepatitis (AIH) (n = 49), and healthy controls (n = 109) were determined by LC-MS/MS. In addition, the frequencies and immunophenotypes of intrahepatic T RM using explants from PSC (n = 5) and healthy donors (n = 6) were quantitated by flow cytometry. The immunomodulatory properties of 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) on CD103 + T RM were studied in vitro. Finally, the therapeutic potential of itaconate was studied by the administration of 4-OI and deficiency of immune-responsive gene 1 (encodes the aconitate decarboxylase producing itaconate) in murine models of PSC. Intrahepatic CD103 + T RM was significantly expanded in PSC and was positively correlated with disease severity. Serum itaconate levels decreased in PSC. Importantly, 4-OI inhibited the induction and effector functions of CD103 + T RM in vitro. Mechanistically, 4-OI blocked DNA demethylation of RUNX3 in CD8 + T cells. Moreover, 4-OI reduced intrahepatic CD103 + T RM and ameliorated liver injury in murine models of PSC. Itaconate exerted immunomodulatory activity on CD103 + T RM in both in vitro and murine PSC models. Our study suggests that targeting pathogenic CD103 + T RM with itaconate has therapeutic potential in PSC.


Pterin and folate reduction by the Leishmania tarentolae H locus short-chain dehydrogenase/reductase PTR1.
Overproduction of the short-chain dehydrogenase/reductase PTR1 confers resistance to the dihydrofolate reductase inhibitor methotrexate in the protozoan parasite Leishmania. Genetic analysis has previously implicated PTR1 in pterin and folate metabolism. PTR1 was purified from a fusion protein expressed in Escherichia coli. Purified PTR1 exhibits NADPH-dependent biopterin, dihydrobiopterin, folate, and dihydrofolate reductase activities. The highest activity was found with the most oxidized pterins. The active protein was found to be a tetramer as demonstrated by gel-filtration chromatography. Kinetic constants (K(m)), as determined by double-reciprocal plots, were calculated for NADPH and for several of PTR1's substrates. The PTR1 of Leishmania tarentolae had a K(m) of 16.9 microM for the cofactor NADPH and K(m) values ranging from 3.5 to 85 microM for the various substrates. The dissociation constant (KD), as determined by fluorescence titration, for NADPH was estimated to be 130 microM. The biochemical characterization of this important and novel enzyme involved in folate and pterin metabolism of Leishmania should be useful for structure-function analysis and for developing specific inhibitors against this putative important chemotherapeutic target.


Heterogeneity in COVID-19 Patients at Multiple Levels of Granularity: From Biclusters to Clinical Interventions.
Several studies have shown that COVID-19 patients with prior comorbidities have a higher risk for adverse outcomes, resulting in a disproportionate impact on older adults and minorities that fit that profile. However, although there is considerable heterogeneity in the comorbidity profiles of these populations, not much is known about how prior comorbidities co-occur to form COVID-19 patient subgroups, and their implications for targeted care. Here we used bipartite networks to quantitatively and visually analyze heterogeneity in the comorbidity profiles of COVID-19 inpatients, based on electronic health records from 12 hospitals and 60 clinics in the greater Minneapolis region. This approach enabled the analysis and interpretation of heterogeneity at three levels of granularity (cohort, subgroup, and patient), each of which enabled clinicians to rapidly translate the results into the design of clinical interventions. We discuss future extensions of the multigranular heterogeneity framework, and conclude by exploring how the framework could be used to analyze other biomedical phenomena including symptom clusters and molecular phenotypes, with the goal of accelerating translation to targeted clinical care.


Classification criteria and distinction between migraine and tension-type headache in children.
The International Headache Society (IHS) classification system (1988) was developed primarily for headache disorders in adults and its validity for paediatric age is currently under discussion; in 1995 Seshia et al. proposed a revision of the criteria for migraine without aura to make diagnostic criteria more applicable to children. The purposes of the current study were to: (1) compare the IHS classification with the Seshia proposal, (2) compare the children affected by migraine without aura (MO) with the children affected by tension headache (TH) as defined by Seshia, for characteristics which are not included in the classification. The patients are a series of 320 children (mean age 9.9, SD 2.6 years; 144 males, 176 females) with recurrent or chronic headaches referred to a headache clinic in Milan, Italy. Using the Seshia criteria instead of the IHS criteria a higher number of children were included in the MO category: bilateral pain and family history of migraine were the most important factors which allowed a shift of children into this category. However, with the Seshia classification there was no reduction in the number of unclassifiable children. The reason why some children could not be classified was a short duration of attacks; the majority of unclassifiable children were 6 years old or less. No relevant difference was found between children with MO and children with TH for the following variables: occurrence of attacks in the afternoon or evening after school, reduction of attacks during school holidays, full-time schooling, after-school activities on school days, disordered daily life. On the contrary children with MO when compared with those with TH showed a higher number of precipitating factors and for the following factors a significant difference was found: exposure to TV or a computer, sleep deficiency, and strong emotions. Furthermore, children with MO showed a greater severity of attacks.


Antispasmodic and spasmogenic effects of Scolymus hispanicus and taraxasteryl acetate on isolated ileum preparations.
Taraxasteryl acetate (1) was identified as the major triterpenoid of the ethanolic extract of the root bark of Scolymus hispanicus L. Antispasmodic and spasmogenic effects of the ethanolic extract, its fractions, taraxasteryl acetate, and a fluid extract of this plant were tested on isolated rat ileum preparations. The strong biphasic responses observed suggested a possible lithuretic activity of the compounds and the fractions tested.


Area Deprivation Index Predicts Mortality for Critically Ill Surgical Patients With Sepsis.
Background: The impact of socioeconomic status on outcomes after sepsis has been challenging to define, and no polysocial metric has been shown to predict mortality in sepsis. The primary objective of this study was to evaluate the association between the Area Deprivation Index (ADI) and mortality in patients admitted to the surgical intensive care unit (SICU) with sepsis. Patients and Methods: All patients admitted to the SICU with sepsis (Sequential Organ Failure Assessment [SOFA] score ≥2) were retrospectively reviewed. The ADI scores were obtained and classified as "high ADI" (≥85th percentile, n = 400, representative of high socioeconomic deprivation) and "control ADI" (ADI <85th percentile, n = 976). Baseline demographic and clinical characteristics were compared between groups. The primary outcome was 90-day mortality. Results: High ADI patients were younger (mean age 58.5 vs. 60.8; p = 0.01) and more likely to be non-white (23.7% vs. 10.0%; p < 0.0005) and to present with chronic obstructive pulmonary disease (26.5% vs. 19.0%; p = 0.002). High ADI patients had increased in-hospital (27.3% vs. 21.6%; p = 0.025) and 90-day mortality (35.0% vs. 28.9%; p = 0.03). High ADI patients also had increased rates of renal failure (20.3% vs. 15.3%; p = 0.02). Both cohorts had similar intensive care unit (ICU) lengths of stay and median hospital stay, Charlson comorbidity index, and rate of discharge to home. High ADI is an independent risk factor for 90-day mortality after admission for surgical sepsis (odds ratio [OR], 1.39 ± 0.24; p = 0.014). Conclusions: High ADI is an independent predictor of 90-day mortality in patients with surgical sepsis. Targeted community interventions are needed to reduce sepsis mortality for these at-risk patients.


Tubulointerstitial macrophage accumulation is regulated by sequentially expressed osteopontin and macrophage colony-stimulating factor: implication for the role of atorvastatin.
Infiltration and local proliferation are known factors that contribute to tubulointerstitial macrophage accumulation. This study explored the time course of these two contributors' roles as tubulointerstitial inflammation and fibrosis progressing, and evaluated the mechanisms of the protective effect of atorvastatin. Unilateral ureteral obstructive (UUO) rats were treated with atorvastatin (10 mg/Kg) or vehicle. Expression of osteopontin (OPN) and macrophage colony-stimulating factor (M-CSF) was evaluated by RT-PCR and immunohistochemistry. Immunohistochemistry staining of ED1 was used to assess macrophage accumulation in interstitium. Histological evaluation was performed to semiquantify tubulointerstitial fibrosis. The results showed that on day 3 after UUO operation, OPN expression significantly increased and positively correlated with the number of the interstitial ED1(+) cells, while on day 10, M-CSF expression upregulated and correlated with interstitial ED1(+) cells. In atorvastatin treatment group, the increments of these two factors were attenuated significantly at the two time points, respectively. ED1(+) cell accumulation and fibrosis also ameliorated in the treatment group. For all the samples of UUO and treatment group on day 10, ED1(+) cells also correlated with interstitial fibrosis scores. The results suggest that OPN may induce the early macrophage/monocyte infiltration and M-CSF may play an important role in regulating macrophage accumulation in later stage of UUO nephropathy. Statin treatment decreases interstitial inflammation and fibrosis, and this renoprotective effect may be mediated by downregulating the expression of OPN and M-CSF.


Mutations in the TSC1 gene account for a minority of patients with tuberous sclerosis.
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterised by tumour-like malformations (hamartomas) of the brain, skin, and other organs, often associated with seizures and learning disability. There is genetic heterogeneity with loci for TSC on chromosomes 9q34 (TSC1) and 16p13.3 (TSC2). The recently cloned TSC1 gene has 23 exons spanning some 40 kb of genomic DNA with an 8.6 kb transcript. We now report the results of mutation screening by SSCP and heteroduplex analysis of genomic DNA for all 21 coding exons of TSC1 in 83 unrelated cases of tuberous sclerosis. TSC1 gene mutations were found in 16 of the 83 cases (19%). These comprised base substitutions, small insertions, or small deletions giving rise to six nonsense mutations, eight frameshifts, and two splice site mutations, all of which would be expected to result in a truncated or absent protein. In the 10 cases predicted to have TSC1 mutations by linkage analysis or loss of heterozygosity studies, the mutation was identified in eight (80%). In the remaining 73 unassigned cases, only eight mutations were found (11%). From these data we estimate that TSC1 mutations accounted for 24% of the cases in this sample (and an estimated 22% of all TSC cases). This contrasts with data from linkage studies suggesting that TSC1 and TSC2 mutations account for approximately equal numbers of families.


The chondrocyte: biology and clinical application.
Chondrocyte is a unique cell type in articular cartilage tissue and is essential for cartilage formation and functionality. It arises from mesenchymal stem cells (MSCs) and is regulated by a series of cytokine and transcription factor interactions, including the transforming growth factor-beta super family, fibroblast growth factors, and insulin-like growth factor-1. To understand the biomechanisms of the chondrocyte differentiation process, various cellular model systems have been employed, such as primary chondrocyte culture, clonal normal cell lines (HCS-2/8, Ch-1, ATDC5, CFK-2, and RCJ3.1C5.18), and transformed clonal cell lines (T/C-28a2, T/C-28a4, C-28/I2, tsT/AC62, and HPV-16 E6/E7). Additionally, cell culture methods, including conventional monolayer culture, three-dimensional scaffold culture, bioreactor culture, pellet culture, and organ culture, have been established to create stable environments for the expansion, phenotypic maintenance, and subsequent biological study of chondrocytes for clinical application. Knowledge gained through these study systems has allowed for the use of chondrocytes in orthopedics for the treatment of cartilage injury and epiphyseal growth plate defects using tissue-engineering approaches. Furthermore, the potential of chondrocyte implantation for facial reconstruction, the treatment of long segmental tracheal defects, and urinary incontinence and vesicoureteral reflux are being investigated. This review summarizes the present study of chondrocyte biology and the potential uses of this cell in orthopedics and other disciplines.


Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery.
Functionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2-3.8μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.


Obesity and perceived severity of obstructive sleep apnea-related conditions.
This study examined risk factors and perceived severity of obstructive sleep apnea-related conditions among college students based on weight categories. Data collected from 1399 college students were analyzed using multinomial and binary logistic regressions. Overweight and obese participants were more likely to snore and report familial risk for cardiovascular disease compared with their normal weight counterparts. Relative to normal weight participants, obese participants perceived snoring (odds ratio [OR] = 1.10), irritability (OR = 1.16), and high blood pressure (OR = 1.21) as more severe; they perceived erectile dysfunction (OR = 0.89) and cardiovascular disease (OR = 0.71) as less severe. Efforts are needed to identify obstructive sleep apnea risk and create systems for weight loss interventions, screening, and diagnosis.


A neural network - based algorithm for predicting stone - free status after ESWL therapy.
The prototype artificial neural network (ANN) model was developed using data from patients with renal stone, in order to predict stone-free status and to help in planning treatment with Extracorporeal Shock Wave Lithotripsy (ESWL) for kidney stones. Data were collected from the 203 patients including gender, single or multiple nature of the stone, location of the stone, infundibulopelvic angle primary or secondary nature of the stone, status of hydronephrosis, stone size after ESWL, age, size, skin to stone distance, stone density and creatinine, for eleven variables. Regression analysis and the ANN method were applied to predict treatment success using the same series of data. Subsequently, patients were divided into three groups by neural network software, in order to implement the ANN: training group (n=139), validation group (n=32), and the test group (n=32). ANN analysis demonstrated that the prediction accuracy of the stone-free rate was 99.25% in the training group, 85.48% in the validation group, and 88.70% in the test group. Successful results were obtained to predict the stone-free rate, with the help of the ANN model designed by using a series of data collected from real patients in whom ESWL was implemented to help in planning treatment for kidney stones.


Preoperative photocoagulation reduces corneal endothelial cell damage after vitrectomy in patients with proliferative diabetic retinopathy.
Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes and is a leading cause of visual decline and irreversible blindness. So we designed this study to investigate retrospectively the effect of preoperative photocoagulation on corneal endothelial cells after vitrectomy in patients with PDR.The study included 52 eyes of 46 patients with PDR complicated with vitreous hemorrhage, who underwent vitrectomy. Patients were apportioned to a photocoagulation group (26 eyes/23 patients) or nonphotocoagulation group (26/23 patients), according to their history of preoperative photocoagulation. A specular microscope was used to assess the corneal endothelial cell density and percentage of hexagonal cells (PHC) before surgery, and at 1 week, 1 month, and 3 months after surgery.The cell density was lower 3 months after surgery in the photocoagulation group, but at 1 month in the nonphotocoagulation group, all cases were significantly different from the preoperative value (P < .05 or P < .01). One week after surgery, the mean cell densities between the photocoagulation and nonphotocoagulation groups were not statistically different (P > .05). However, the mean cell densities at 1 and 3 months after surgery in the photocoagulation group were significantly higher than those in the nonphotocoagulation group (P < .05). The PHC values in the photocoagulation group at 1 week and in the nonphotocoagulation group at 1 week, 1 month, and 3 months were much lower than their respective preoperative values (P < .05 or P < .01). More importantly, at 1 and 3 months, the PHC had recovered to preoperative values in the photocoagulation group, but not in the nonphotocoagulation group. As for cell density and PHC, they were both significantly higher 1 and 3 months after surgery in the photocoagulation group than in the nonphotocoagulation group (P < .05).Photocoagulation before vitrectomy reduces subsequent corneal endothelial cell damage in PDR patients.


[Evaluation of the interrelations among auditory potential parameters by means of the technic of correlation-regression analysis].
The characteristics (amplitude, latency) of two types of evoked potentials, action potential of the 8th nerve recorded at the cochlea round window and sonomotor evoked potential recorded from the postauricular region and the back of the guinea pigs were studied in response to sound stimulation. The degree and type of interrelation between the parameters of the auditory evoked potentials were established employing the method of correlation-regression analysis. A close linear dependence was established for amplitude values ( r = 0.93) of the action potential and the sonomotor potential irrespective of the recording site of the latter. The similar dependence (r = 0.91) was established when analysing the latency of the action potential and the evoked sonomotor potential, if the latter was in the postauricular region. The performed mathematical simulation permitted justifying the correction of disturbed functions of the auditory system.


Spontaneous rupture of renal pelvis as a rare complication of ureteral lithiasis.
Spontaneous rupture of renal pelvis with urine extravasation is a rare condition and usually associated with obstructing ureteric calculus. It poses diagnostic and therapeutic dilemmas, while a stepwise approach for the confirmation of diagnosis, treatment and follow up is needed. We present a case of a 75-year old male patient who had a renal pelvis rupture with perirenal extravasation of urine due to a 4 mm stone located at the right ureterovesical junction. Diagnosis was confirmed by computed tomography, while the patient was treated successfully with the placement of a percutaneous nephrostomy. A week later a CT- nephrostomography showed the healing of renal pelvis with no extravasation and no evidence of the obstructing stone.


"We are exhausted, worn out, and broken": Understanding the impact of service satisfaction on caregiver well-being.
Few studies exist that have examined the impact of service-related factors and system-level disruptions (i.e., the pandemic) on families of autistic children in Canada using large sample sizes. To address this gap, the goal of this research was to examine the impact of satisfaction with autism services on caregiver stress, controlling for important demographic variables, such as family income, marital status, and child level of support needs. The impact of navigating and accessing services on parent well-being was also explored. A total of 1810 primary caregivers of autistic children or youth living in Ontario, Canada completed a survey with both closed- and open-ended questions in the summer of 2021. A hierarchical multiple regression was conducted to examine the impact of satisfaction with autism services on caregiver stress. Open-ended responses on the survey from a subset of the sample (n = 637) were coded using thematic analysis to understand the impact of navigating and accessing services on parent well-being. Satisfaction with services significantly predicted caregiver stress after controlling for marital support, family income, and child level of support needs. Qualitative analysis revealed impacts of navigating and accessing services in three areas: (1) Physical, (2) Emotional/Psychological, and (3) Financial Well-being. Understanding parent perceptions of satisfaction with services can shed light on strategies for improving services that support parent well-being.


[Dynamics of the formation of 2 types of instrumental behavior in the rabbit].
The work is aimed at studying the dynamics of formation of a complex form of instrumental behaviour in rabbits, satisfying two different requirements of the organism. By pressing one and the same lever, the animals were able to fetch the feeding through with food and to periodically avoid pain stimulation preceded by an acoustic signal. The pairings: acoustic signal - pain stimulus were presented at periods of about 3 min against the background of the cyclic instrumental food-procuring behaviour and produced its temporary cessation. The changes of different parameters of the animals' behaviour in the process of their training are analysed in the aspect of the theory of functional systems.


Herbivory and eutrophication mediate grassland plant nutrient responses across a global climatic gradient.
Plant stoichiometry, the relative concentration of elements, is a key regulator of ecosystem functioning and is also being altered by human activities. In this paper we sought to understand the global drivers of plant stoichiometry and compare the relative contribution of climatic vs. anthropogenic effects. We addressed this goal by measuring plant elemental (C, N, P and K) responses to eutrophication and vertebrate herbivore exclusion at eighteen sites on six continents. Across sites, climate and atmospheric N deposition emerged as strong predictors of plot-level tissue nutrients, mediated by biomass and plant chemistry. Within sites, fertilization increased total plant nutrient pools, but results were contingent on soil fertility and the proportion of grass biomass relative to other functional types. Total plant nutrient pools diverged strongly in response to herbivore exclusion when fertilized; responses were largest in ungrazed plots at low rainfall, whereas herbivore grazing dampened the plant community nutrient responses to fertilization. Our study highlights (1) the importance of climate in determining plant nutrient concentrations mediated through effects on plant biomass, (2) that eutrophication affects grassland nutrient pools via both soil and atmospheric pathways and (3) that interactions among soils, herbivores and eutrophication drive plant nutrient responses at small scales, especially at water-limited sites.


Activation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis.
Hyperinflammation is the hallmark of Kaposi's sarcoma (KS), the most common cancer in AIDS patients caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. However, the role and mechanism of induction of inflammation in KS remain unclear. In a screening for inhibitors of KSHV-induced oncogenesis, over half of the identified candidates were anti-inflammatory agents including dexamethasone functions by activating glucocorticoid receptor (GR) signaling. Here, we examined the mechanism mediating KSHV-induced inflammation. We found that numerous inflammatory pathways were activated in KSHV-transformed cells. Particularly, interleukin-1 alpha (IL-1α) and IL-1 receptor antagonist (IL-1Ra) from the IL-1 family were the most induced and suppressed cytokines, respectively. We found that KSHV miRNAs mediated IL-1α induction while both miRNAs and vFLIP mediated IL-1Ra suppression. Furthermore, GR signaling was inhibited in KSHV-transformed cells, which was mediated by vFLIP and vCyclin. Dexamethasone treatment activated GR signaling, and inhibited cell proliferation and colony formation in soft agar of KSHV-transformed cells but had a minimal effect on matched primary cells. Consequently, dexamethasone suppressed the initiation and growth of KSHV-induced tumors in mice. Mechanistically, dexamethasone suppressed IL-1α but induced IL-1Ra expression. Treatment with recombinant IL-1α protein rescued the inhibitory effect of dexamethasone while overexpression of IL-1Ra caused a weak growth inhibition of KSHV-transformed cells. Furthermore, dexamethasone induced IκBα expression resulting in inhibition of NF-κB pathway and IL-1α expression. These results reveal an important role of IL-1 pathway in KSHV-induced inflammation and oncogenesis, which can be inhibited by dexamethasone-activated GR signaling, and identify IL-1-mediated inflammation as a potential therapeutic target for KSHV-induced malignancies.


In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells.
Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC ≥ 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.


Delivery of CdiA nuclease toxins into target cells during contact-dependent growth inhibition.
Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiA(UPEC536) were used to visualize transfer of CdiA from CDI(UPEC536+) inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiA(UPEC536) protein is deposited onto the surface of target bacteria. CdiA(UPEC536) transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiA(UPEC536) is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiA(UPEC536) prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI(+) inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes.


The epigenetic drug Trichostatin A ameliorates experimental autoimmune encephalomyelitis via T cell tolerance induction and impaired influx of T cells into the spinal cord.
Multiple sclerosis is a T cell mediated chronic demyelinating disease of the central nervous system. Although currently available therapies reduce relapses, they do not facilitate tolerization of myelin antigen-specific T lymphocytes to ensure prolonged protection against multiple sclerosis. Here, we show that treatment of NOD mice with the histone deacetylase inhibitor, Trichostatin A affords robust protection against myelin peptide induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Protection was accompanied by histone hyperacetylation, and reduced inflammation and axonal damage in the spinal cord. Drug treatment diminished the generation of CD4+ memory T cells and induced tolerance in CD4+ T cells recognizing the immunizing myelin peptide. During the early immunization period, CD4+ T cells producing GM-CSF+IFN-γ, GM-CSF+IL-17A, as well as those expressing both IL-17A+IFN-γ (double-producers) were detected in the secondary lymphoid organs followed by the appearance of cells producing IFN-γ and GM-CSF. On the other hand, IFN-γ producing Th1 cells appear first in the spinal cord followed by cells producing IL-17A and GM-CSF. Treatment with Trichostatin A substantially reduced the frequencies of all T cells secreting various lymphokines both in the periphery and in the spinal cord. These data indicate that epigenetic modifications induced by histone hyperacetylation facilitates T cell tolerance induction in the periphery leading to reduced migration of T cells to the spinal cord and mitigation of neuronal damage and improved clinical outcome. These results suggest that epigenetic modulation of the genome may similarly offer benefits to multiple sclerosis patients via abrogating the function of encephalitogenic T lymphocytes without exerting severe side effects associated with currently used disease-modifying therapies.


Local differences in human immunodeficiency virus prevalence: a comparison of social venue patrons, antenatal patients, and sexually transmitted infection patients in eastern kinshasa.
This study compares the sexual behavior and HIV prevalence of men and women at social venues where people meet new sexual partners in Eastern Kinshasa with that of sexually transmitted infection (STI) treatment and antenatal clinic (ANC) patients in the same area. ANC patients, STI clinic patients, and social venue patrons were interviewed, asked to provide a blood sample on-site, and provided with information about obtaining test results. Every patron at identified social venues in the study area was invited to participate. One thousand one hundred sixteen pregnant women; 66 male and 229 female STI clinic patients; and 952 male and 247 female patrons of social venues were interviewed and tested for HIV. HIV prevalence differed by group: ANC patients (4%); female venue patrons (12%); female STI patients (16%); male venue patrons (2%); and male STI patients (23%). HIV prevalence among sex workers at social venues (29%) was higher than HIV prevalence among other female patrons with new or multiple partnerships in the past four weeks (19%) and higher than HIV prevalence among female patrons denying sex work (6%). However, the absolute number of infected women was higher among women reporting recent new or multiple partnerships than among the smaller group of sex workers (23 vs. 18). Two-thirds of the infected female STI patients (24/36) reported no more than one and no new sexual partner in the past year. Improving prevention programs in Kinshasa is essential. Prevention efforts should not neglect women at social venues who do not self-identify as sex workers but who have high rates of new sexual partnership formation.


Bilateral pulmonary sequestrations: Distinct types sharing a common celiac artery origin, presented with pneumonia and associated findings in a pediatric case.
A 14-year-old boy presented with shortness of breath, cough, and mild chest pain, with a history of intermittent milder symptoms. Physical examination and initial tests showed mild iron deficiency anemia, elevated C-reactive protein, and normal vital signs. Chest radiograph revealed abnormalities in the left lower zone, leading to contrast-enhanced chest CT. The CT scan revealed bilateral intrapulmonary sequestrations, both deriving blood supply from a common trunk originating from the celiac artery. The patient's symptoms initially attributed to a pulmonary infection improved with antibiotic therapy. Pulmonary sequestration is a congenital anomaly characterized by aberrant lung tissue lacking connections to bronchial tree or pulmonary arteries. It can lead to recurrent pulmonary infections and postinfectious sequelae. This case presented a unique bilateral sequestration, both originating from the celiac artery. Radiologists should be aware of sequestration types and associated anomalies, even in atypical locations. Blood supply can originate from various arteries, not just the aorta.


Spatiotemporal dynamics of effector CD8+ T cell responses within the liver.
CD8(+) T cells play a critical role in controlling hepatotropic viral infections, such as those caused by hepatitis B and hepatitis C viruses. The capacity of these cells to protect against such pathogens is mediated by antigen-experienced effector cells and relies on their ability to home to the liver, recognize pathogen-derived antigens, and deploy effector functions. Here, we review how dynamic imaging of hepatic effector CD8(+) T cell migration and function in mouse models of hepatitis B virus pathogenesis has recently revealed a unique and novel mode of adaptive immune surveillance. Circulating effector CD8(+) T cells initially arrest within liver sinusoids by docking onto adherent platelets and then actively crawl along the liver vasculature, probing hepatocytes for the presence of antigens by extending protrusions through the fenestrated sinusoidal endothelial cells. Hepatocellular antigen recognition and effector functions occur while CD8(+) T cells are still confined to the intravascular space and are inhibited by the pathologic processes that characterize liver fibrosis. A detailed understanding of the spatiotemporal dynamics of effector CD8(+) T cells within the liver is important for the rational design of targeted immunotherapeutic approaches for chronic liver infections.


Adaptive optimal control of under-actuated robotic systems using a self-regulating nonlinear weight-adjustment scheme: Formulation and experimental verification.
This paper formulates an innovative model-free self-organizing weight adaptation that strengthens the robustness of a Linear Quadratic Regulator (LQR) for inverted pendulum-like mechatronic systems against perturbations and parametric uncertainties. The proposed control procedure is devised by using an online adaptation law to dynamically adjust the state weighting factors of LQR's quadratic performance index via pre-calibrated state-error-dependent hyperbolic secant functions (HSFs). The updated state-weighting factors re-compute the optimal control problem to modify the state-compensator gains online. The novelty of the proposed article lies in adaptively adjusting the variation rates of the said HSFs via an auxiliary model-free online self-regulation law that uses dissipative and anti-dissipative terms to flexibly re-calibrate the nonlinear function's waveforms as the state errors vary. This augmentation increases the controller's design flexibility and enhances the system's disturbance rejection capacity while economizing control energy expenditure under every operating condition. The proposed self-organizing LQR is analyzed via customized hardware-in-loop (HIL) experiments conducted on the Quanser's single-link rotational inverted pendulum. As compared to the fixed-gain LQR, the proposed SR-EM-STC delivers an improvement of 52.2%, 16.4%, 55.2%, and 42.7% in the pendulum's position regulation behavior, control energy expenditure, transient recovery duration, and peak overshoot, respectively. The experimental outcomes validate the superior robustness of the proposed scheme against exogenous disturbances.


Herpes simplex virus: 'to disclose or not to disclose.' An exploration of the multi-disciplinary team's role in advising patients about disclosure when diagnosed with genital herpes simplex virus.
The first UK prosecution for genital herpes simplex virus (HSV) transmission in 2011 attracted strong criticism from medical experts. To address the dearth of research on the topic, this study aimed to explore the nature of advice given to patients by the multidisciplinary team (MDT) in the West of Scotland on HSV disclosure to partners. Ten semi-structured interviews with members of the MDT were conducted and the interviews were analysed using Burnard's Thematic Content Analysis. Four themes emerged which explored practitioners' knowledge of HSV and their feelings regarding the emotional aspects of the diagnosis on clients including the challenges of discussing disclosure. Within this framework, participants' attitudes to the legal prosecution were also surveyed. This study revealed that participants had good knowledge about HSV. Furthermore, participants believed disclosure to be the patient's choice and had not altered their practice to advise disclosure to all partners in accordance with local protocol. However, there was a general consensus that disclosure was not required due to the prevalence of HSV and prevalence was used to dissipate emotional reactions to HSV diagnosis.


Effect of conjugated linoleic acid overproducing Lactobacillus with berry pomace phenolic extracts on Campylobacter jejuni pathogenesis.
Campylobacter jejuni (CJ) is one of the predominant causative agents of acute gastroenteritis in the US and other developed countries through the handling of raw chicken or the consumption of undercooked poultry and poultry products. Probiotics and their metabolites such as conjugated linoleic acids (CLAs) play a crucial role in improving host health and act as antimicrobials against enteric pathogens. Furthermore, prebiotics or prebiotic-like components such as bioactive phenolics from berry pomace can stimulate the growth of beneficial microbes including Lactobacillus casei (LC) and its metabolites, and competitively inhibit the growth of enteric bacterial pathogens. In this study, we aimed at enhancing the efficiency of antimicrobial/beneficial activities of LC and the extent of production of bioactive compounds by combining berry pomace phenolic extract (BPPE) and overproducing CLA in L. casei (LC-CLA). Under mixed culture conditions, LC-CLA in the presence of BPPE reduced the growth of CJ by more than 3 log CFU ml-1 within 48 h. The cell-free culture supernatant (CFCS) of LC-CLA in the presence of BPPE also reduced significantly the growth of CJ >3.2 log CFU ml-1 at 24 h. The interactions of CJ with cultured chicken fibroblast cells (DF-1), chicken macrophage (HD-11), and human epithelial cells (HeLa) were altered significantly. Treatments with BPPE and/or CFCS also altered the injured cell number, auto-aggregation capacity and cell surface hydrophobicity of CJ, significantly. Furthermore, combined treatments with BPPE and CFCSs of LC-CLA altered the expression of multiple virulence genes such as ciaB, cdtB, cadF, flaA, and flaB of CJ from 0.45 fold to 6.85 fold. Overall, BPPE enhanced the effect of LC-CLA in the reduction of CJ growth, survival ability, host cell-CJ interactions, and virulence gene expression. This finding indicates that a combination of BPPE and LC-CLA may be able to prevent the colonization of CJ in poultry, reduce the cross-contamination of poultry products and control poultry-borne campylobacteriosis in humans.


Immunologic predictors of HIV-related survival among Texas prison inmates.
Research indicates that being incarcerated adversely affects overall health status. Because HIV-infection is a growing problem among the U.S. prison population, understanding how incarceration affects HIV-related survival holds particular clinical and public health relevance. Moreover, while the prognostic roles of CD4 and CD8 lymphocyte count have been well documented in noninstitutionalized populations, little is known about how these factors operate to predict survival among prison populations. The present study examined immunologic determinants of HIV-related survival in a cohort of 752 Texas Department of Criminal Justice (TDCJ) inmates who were treated for HIV/AIDS between 1993 and 1996 at a large south-western medical center. Survival analysis using proportional hazards modeling showed that: (1) the prognostic role of CD4 count among inmates was similar to previous findings among non-incarcerated populations; (2) the prognostic role of CD8 count was slightly weaker than that previously reported for non-incarcerated populations; and (3) inmates who exhibited high levels of both CD4 and CD8 count had a survival advantage over those who had a high score on only one of the two factors.


Characterization of gamma-aminobutyric acid binding sites on crude synaptic membranes.
[3H]GABA binding to crude synaptic membranes of rat brain was studied in an attempt to identify GABA binding to its synaptic receptor in the presence of Na+. Membrane vesicles prepared from crude synaptic membrane fractions were useful as a tool to differentiate synaptic GABA receptors from GABA uptake sites. The crude synaptic membranes treated with Triton X-100 [membranes (TX)] involved two classes of GABA binding sites (KD = 38.7 and 78.0 nM) in the absence of Na+, but the high-affinity sites disappeared in the presence of Na+ and a single class of GABA binding sites (KD = 75.0 nM) was detected. The failure to detect an active uptake of [3H]GABA into the vesicles prepared from membranes (TX) suggests that the [3H]GABA binding in the presence of Na+ was related to synaptic GABA receptors. It is probable that Na+ could mask the presence of the high-affinity class of GABA receptor.


Characterization of a new mouse line triggering transient oligodendrocyte progenitor depletion.
Oligodendrocyte progenitor cells (OPC) are the main proliferative cells in the healthy adult brain. They produce new myelinating oligodendrocytes to ensure physiological myelin remodeling and regeneration after various pathological insults. Growing evidence suggests that OPC have other functions. Here, we aimed to develop an experimental model that allows the specific ablation of OPC at the adult stage to unravel possible new functions. We generated a transgenic mouse expressing a floxed human diphtheria toxin receptor under the control of the PDGFRa promoter, crossed with an Olig2Cre mouse to limit the recombination to the oligodendrocyte lineage in the central nervous system. We determined a diphtheria toxin dose to substantially decrease OPC density in the cortex and the corpus callosum without triggering side toxicity after a few daily injections. OPC density was normalized 7 days post-treatment, showing high repopulation capacity from few surviving OPC. We took advantage of this strong but transient depletion to show that OPC loss was associated with behavioral impairment, which was restored by OPC recovery, as well as disruption of the excitation/inhibition balance in the sensorimotor cortex, reinforcing the hypothesis of a neuromodulatory role of OPC in the adult brain.