Relative mobility of the pelvis and spine during trunk axial rotation in chronic low back pain patients: A case-control study.
Trunk axial rotation is a risk factor for chronic low back pain (CLBP). The characteristics of rotational mobility in the pelvis and spine among CLBP patients are not fully understood. The purpose of this study was to examine three-dimensional kinematic changes, and to compare the differences of rotational mobility and coupled motion, in patients with and without CLBP. Fifteen patients with CLBP and 15 age and sex matched healthy subjects participated in this study. Each subject performed trunk rotation to maximum range of motion (ROM) in a standing position. The kinematics data was collected using a three-dimensional motion analysis system. The outcomes measured were the rotational ROM and the spine/pelvis ratio (SPR) in transvers plane at both maximum and 50% rotation position. The coupled angles in sagittal and frontal planes were also measured. No significant differences in rotational ROM of the thorax, pelvis, and spine were observed between two groups at maximum rotation position. However, there was a significant interaction between groups and rotational ROM of pelvis and spine (F = 4.57, p = 0.04), and the SPR in CLBP patients was significantly greater than that of the healthy subjects (CLBP; 0.50 ± 0.10 Control; 0.41 ± 0.12, p = 0.04). The results at 50% rotation position were similar to that at maximum rotation. This indicates a relative increase in spinal rotation in the CLBP patients during trunk rotation. Moreover, the CLBP patients exhibited a significantly higher anterior tilt of the pelvis and extension of the spine in the sagittal plane coupled with rotation. CLBP patients had relative hyper rotational mobility of the spine as well as excessive spinal extension coupled with trunk rotation. These results suggest that uncoordinated trunk rotation might be a functional failure associated with CLBP.


Sphingobacterium lactis sp. nov. and Sphingobacterium alimentarium sp. nov., isolated from raw milk and a dairy environment.
Four non-fermenting, rod-shaped, Gram-staining-negative bacterial strains, designated WCC 4512(T), WS 4555, WCC 4521(T) and WS 4556, were isolated from raw milk and the dairy environment. Phylogenetic analyses based on 16S rRNA and groEL gene sequences demonstrated the affiliation of the four strains to two distinct clusters within the class Sphingobacteriia, phylum 'Bacteroidetes'. Strains WCC 4512(T) and WS 4555 showed the highest 16S rRNA gene sequence similarity to the type strain of S. daejeonense (97.3 and 97.2%, respectively), whereas strains WCC 4521(T) and WS 4556 were most closely related to S. composti LMG 23401(T) (97.6% 16S rRNA gene sequence similarity). The DNA G+C contents of strains WCC 4512(T) and WCC 4521(T) were 44.2 and 39.3 mol%, respectively. The major cellular fatty acids and the presence of menaquinone MK-7 as the predominant quinone for both strains WCC 4512(T) and WCC 4521(T) supported their affiliation to the genus Sphingobacterium. DNA-DNA hybridization experiments between strain WCC 4512(T) and S. daejeonense LMG 23402(T) and between strain WCC 4521(T) and S. composti LMG 23401(T) revealed DNA relatedness values of 2% (repetition, 3%) and 8% (repetition, 17%), respectively. On the basis of phenotypic and genetic properties, as well as phylogenetic distinctiveness, it is suggested that the four strains represent two novel Sphingobacterium species with strain WCC 4512(T) (=DSM 22361(T)=LMG 25272(T)) as the type strain of Sphingobacterium lactis sp. nov. (WS 4555 is a reference strain of S. lactis) and strain WCC 4521(T) (=DSM 22362(T)=LMG 25273(T)) as the type strain of Sphingobacterium alimentarium sp. nov. (WS 4556 is a reference strain of S. alimentarium).


Orm2 Deficiency Aggravates High-Fat Diet-Induced Obesity through Gut Microbial Dysbiosis and Intestinal Inflammation.
Orosomucoid 2 (Orm2) is a hepatocyte-secreted protein that plays a crucial role in regulating obesity-type metabolic disease and immunity. The imbalance of gut microbiota is one of the causes of obesity, but the mechanism of the relationship between Orm2 and gut microbiota in obesity remains unclear. Orm2-/- (Orm2 knockout) mice on a normal diet developed spontaneous obesity and metabolic disturbances at the 20th week. Through 16S rRNA gene sequencing, the study finds that the gut microbiota of Orm2-/- mice has a different microbial composition compared to wild type (WT) mice. Furthermore, a high-fat diet (HFD) for 16 weeks exacerbates obesity in Orm2-/- mice. Lack of Orm2 promotes dysregulation of gut microbiota under the HFD, especially a reduction of Clostridium spp. Supplementation with Clostridium butyricum alleviates obesity and alters the gut microbial composition in WT mice, but has minimal effects on Orm2-/- mice. In contrast, co-housing of Orm2-/- mice with WT mice rescues Orm2-/- obesity by reducing pathogenic bacteria and mitigating intestinal inflammation. These findings suggest Orm2 deficiency exacerbates HFD-induced gut microbiota disturbance and intestinal inflammation, providing a novel insight into the complex bacterial flora but not a single probiotic administration in the therapeutic strategy of obesity.


Amount of information on case illustrations in self-help psychology books.
40 books on self-help psychology were examined in a 2 x 2 multivariate analysis of covariance design for the number of case illustrations, number of lines of text about case illustrations, and average number of lines per case illustration. The covariate was pages per book and the independent variables were status of the book (bestseller or nonbestseller) and decade of publication (1970-1979 or 1980-1989). It was hypothesized that bestsellers would contain more case illustrations and lines of text describing case illustrations than nonbestsellers. Case illustrations per book in nonbestsellers increased significantly in number over the two decades when compared to bestsellers.


Development of a Model for the Prediction of Treatment Response of Uterine Leiomyomas after Uterine Artery Embolization.
Background: Uterine artery embolization (UAE) is one of the minimally-invasive alternatives to hysterectomy for treatment of uterine leiomyomas. There are various factors affecting the outcomes of UAE, but these have only been sporadically studied. Study Objective: To identify factors associated with the efficacy of UAE for the treatment of uterine leiomyoma, and to develop a model for the prediction of treatment response of uterine leiomyomas to UAE. Study design: A retrospective cohort study (Canadian Task Force Classification II-2) Patients: One hundred ninety-eight patients with symptomatic uterine leiomyomas. Intervention: UAE Measurements and Main Results: Among 198 leiomyoma patients who were treated with UAE, 104 who underwent pelvic magnetic resonance imaging (MRI) with diffusion-weighted imaging were selected for developing prediction model. Variables that were statistically significant from the univariate analysis were: location of leiomyoma, total number of lesions, sum of leiomyomas diameters, T2 signal intensity of largest leiomyoma, and T2 leiomyoma:muscle ratio. After a logistic regression analysis, leiomyoma location and T2 signal intensity of the largest leiomyoma were found to be statistically significant variables. Using intramural myomas defined as controls, submucosal leiomyomas showed a greater response to UAE with an odds ratio of 7.6904. The odds ratio of T2 signal intensity with an increase in signal intensity of 10 was 1.093. Using these two variables, we developed a prediction model. The AUC in the prediction model was 0.833, and the AUC in the validation set was 0.791. Conclusion: We identified that submucosal leiomyomas and those leiomyomas that show high signal intensity on T2-weighted imaging will exhibit a greater response to UAE. Prediction models are clinically helpful in selecting UAE as an appropriate treatment option for managing uterine leiomyoma.


Utilization of EKOS in Patients With Pulmonary Embolism.
Objective: Current guidelines recommend utilization of catheter-directed thrombolysis systems for management of patients with submassive pulmonary embolism (PE) who have relative contraindications to systemic thrombolysis. Evidence from previous trials have demonstrated the short-term efficacy and safety of one of these systems, the EkoSonic Endovascular System (EKOS). The objective of this study was to evaluate the long-term efficacy and safety of EKOS in submassive PE. Methods: This single-center, retrospective study evaluated subjects ≥18 years old with submassive PE and baseline right ventricular to left ventricular (RV/LV) diameter ratio ≥1. The primary outcome evaluated change in RV/LV diameter ratio from baseline to first follow-up. The secondary outcomes evaluated need for further intervention after EKOS, major bleeding within 72 hours and 6 months, all-cause mortality at 6 months, and all-cause 30-day readmission rate. Results: Overall, 41 subjects received EKOS for submassive PE. Of the 26 subjects evaluated for the primary outcome, the RV/LV diameter ratio decreased by an average of 0.56 (P < 0.05). Of the 41 subjects evaluated for the secondary outcomes, 1 subject required pulmonary embolectomy after EKOS intervention, 1 major bleed occurred within 72 hours, 1 major bleed occurred within 6 months, 1 subject died within 6 months, and 3 subjects were readmitted within 30 days. Conclusions: Intervention with EKOS further reduced right heart strain and resulted in few complications compared with previous trials providing evidence that EKOS is effective and safe long-term for management of submassive PE. Use should be considered in patients with relative contraindications to systemic thrombolytic therapy.


Metacognition in Auditory Distraction: How Expectations about Distractibility Influence the Irrelevant Sound Effect.
Task-irrelevant, to-be-ignored sound disrupts serial short-term memory for visually presented items compared to a quiet control condition. We tested whether disruption by changing state irrelevant sound is modulated by expectations about the degree to which distractors would disrupt serial recall performance. The participants' expectations were manipulated by providing the (bogus) information that the irrelevant sound would be either easy or difficult to ignore. In Experiment 1, piano melodies were used as auditory distractors. Participants who expected the degree of disruption to be low made more errors in serial recall than participants who expected the degree of disruption to be high, independent of whether distractors were present or not. Although expectation had no effect on the magnitude of disruption, participants in the easy-to-ignore group reported after the experiment that they were less disrupted by the irrelevant sound than participants in the difficult-to-ignore group. In Experiment 2, spoken texts were used as auditory distractors. Expectations about the degree of disruption did not affect serial recall performance. Moreover, the subjective and objective distraction by irrelevant speech was similar in the easy-to-ignore group and in the difficult-to-ignore group. Thus, while metacognitive beliefs about whether the auditory distractors would be easy or difficult to ignore can have an effect on task engagement and subjective distractibility ratings, they do not seem to have an effect on the actual degree to which the auditory distractors disrupt serial recall performance.


Metals in tern eggs in a New Jersey estuary: A decade of change.
We compared levels of eight heavy metals in common tern eggs collected in 1982 (n=24) from coastal New Jersey with archived specimens collected from the same colonies in 1971 (N=9). Levels of all metals, except cobalt, showed a significant decrease over the 11 year period, with lead and nickel showing the greatest decline. Mercury levels declined over 50% based on geometric means. Cadmium and mercury showed the lowest levels in both years. Pair-wise correlation coefficients on log-transformed data revealed lower correlations in 1971, whereas most metal pairs showed significant correlations in 1982. Mercury levels showed significant positive correlations with cobalt, cadmium, and nickel in 1971, but were not correlated with levels of any other metal in 1982.


Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.
Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol or hemagglutinin. The alternate views of plasma membrane organization suggested by these findings are discussed.


Enhancing Phenotypic Detection of ESBL in AmpC co-producers by using Cefepime and Tazobactam.
Routine phenotypic methods employing clavulanate and third generation cephalosporins to detect ESBL are not promising for isolates that co-produce an inhibitor-resistant beta lactamase like AmpC. Enhancing phenotypic detection of ESBL in AmpC co-producers by using cefepime and tazobactam. A total of 245 isolates of Escherichia coli (123), Klebsiella spp. (87), Proteus spp.(20), Enterobacter spp. (9) and Citrobacter spp.(6) obtained over a period of 2 years from January 2013 to December 2014 from urine samples of hospitalized patients were studied. The isolates were simultaneously screened for ESBL and AmpC production. AmpC production was confirmed by modified three -dimensional test (MTDT). ESBL production was confirmed by original double disc synergy test, phenotypic disc confirmatory test (PDCT) and modified double disc synergy test (MDDST) and the results compared. AmpC production was confirmed in 113 (46.1%) isolates by modified three dimensional test out of 143 screened positive for AmpC. Of the 192 isolates screened positive for ESBL, ESBL production was confirmed in 162 (66.1%). DDST detected ESBLs in only134 (54.7%) while additional 28 (11.4%) ESBL positive isolates were detected by MDDST. PDCT detected total 145(59.2%) ESBL positive isolates, with cefotaxime and cefotaxime + clavulanate detecting 139 (56.7%) and ceftazidime and ceftazidime + clavulanate detecting additional 6 isolates. All the 28 (11.4%) isolates which were additionally detected ESBL producers by MDDST showed positive three dimensional test i.e. AmpC co producers. DDST detected ESBL in none of AmpC positive isolates while PDCT detected ESBL in 11 isolates showing AmpC co-production. In MDDST cefepime was the best cephalosporin in detecting ESBL in presence of AmpC production. It showed synergism with amoxicillin-clavulanate in 11(39.3%) isolates and in 24(85.7%) isolates with piperacillin-tazobactam. Third generation cephalosporins -cefotaxime, ceftazidime and cefpodoxime were not able to detect ESBL in AmpC-co producers. Modification of double disc synergy tests that combine piperacillin-tazobactum with cefepime enhances the possibility of ESBL detection.


Long-term follow-up after complete ablation of Barrett's esophagus with argon plasma coagulation.
To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. In 70 patients with histologically proven non-neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P = 0.0004). The long-term relapse rate of non-neoplastic BE following complete ablation with high-power APC is low (3% per year).


Drug-induced lupus due to anti-tumor necrosis factor alpha agents.
To evaluate the reported cases of drug-induced lupus erythematosus (DILE) due to anti-tumor necrosis factor (TNF) alpha therapy and to compare "classic" DILE with DILE secondary to anti-TNFalpha therapy. We also add 3 case reports related to 3 different anti-TNFalpha drugs to the literature. We searched the Medline database for cases published in English and evaluated 53 cases in 27 papers purported to be TNFalpha-induced DILE. We compared the clinical and laboratory features of cases that fulfilled our criteria for TNFalpha DILE to those of DILE due to non-TNFalpha drugs as found in standard texts. We also report the clinical and laboratory findings of our 3 patients with drug-induced lupus related to anti-TNFalpha drugs, 1 each in patients treated with adalimumab, etanercept, and infliximab. Of the 53 purported cases of DILE due to anti-TNFalpha therapy, we excluded 17 with cutaneous manifestations alone and 3 with overlap syndromes and mixed connective tissue disease. In the 33 cases that met our criteria for systemic DILE, 21 cases were due to infliximab, 10 cases were due to etanercept, and only 2 cases were related to adalimumab. TNFalpha-blocker-induced DILE cases had a higher prevalence of antibodies to double-stranded DNA, rash, and hypocomplementemia than DILE due to other drugs. Fever is common in both types of DILE. Renal disease, which is rare in classic DILE, has been reported in cases of TNFalpha DILE. TNFalpha DILE has significant clinical and laboratory manifestations which distinguish it from DILE due to drugs other than anti-TNF agents and may be difficult to diagnose in patients treated for autoimmune diseases. It is appropriate to consider whether all patients who are begun on anti-TNF therapy should have pretreatment serologic evaluation for systemic lupus erythematosus.


Protein Subdomain Enrichment of NUP155 Variants Identify a Novel Predicted Pathogenic Hotspot.
Functional variants in nuclear envelope genes are implicated as underlying causes of cardiopathology. To examine the potential association of single nucleotide variants of nucleoporin genes with cardiac disease, we employed a prognostic scoring approach to investigate variants of NUP155, a nucleoporin gene clinically linked with atrial fibrillation. Here we implemented bioinformatic profiling and predictive scoring, based on the gnomAD, National Heart Lung and Blood Institute-Exome Sequencing Project (NHLBI-ESP) Exome Variant Server, and dbNSFP databases to identify rare single nucleotide variants (SNVs) of NUP155 potentially associated with cardiopathology. This predictive scoring revealed 24 SNVs of NUP155 as potentially cardiopathogenic variants located primarily in the N-terminal crescent-shaped domain of NUP155. In addition, a predicted NUP155 R672G variant prioritized in our study was mapped to a region within the alpha helical stack of the crescent domain of NUP155. Bioinformatic analysis of inferred protein-protein interactions of NUP155 revealed over representation of top functions related to molecular transport, RNA trafficking, and RNA post-transcriptional modification. Topology analysis revealed prioritized hubs critical for maintaining network integrity and informational flow that included FN1, SIRT7, and CUL7 with nodal enrichment of RNA helicases in the topmost enriched subnetwork. Furthermore, integration of the top 5 subnetworks to capture network topology of an expanded framework revealed that FN1 maintained its hub status, with elevation of EED, CUL3, and EFTUD2. This is the first study to report novel discovery of a NUP155 subdomain hotspot that enriches for allelic variants of NUP155 predicted to be clinically damaging, and supports a role for RNA metabolism in cardiac disease and development.


[Intragastric and subcutaneous administration of yolk antibodies against adipocyte plasma membrane proteins on growth and fat deposition in rats].
To study the effects of different administrations of antibodies against adipocyte plasma membrane proteins on growth and fat deposition in rats. Ninety six female SD rats that weighed approximately 140 g were allotted randomly into four groups which were given negitive control yolk and positive yolk containing antibody (IgY) against adipocyte plasma membrane (APM) proteins by intragastric administration (i.g.) and subcutaneous injection (s.c.) respectively. Rats were given 1 ml of yolk for every three days in i.g. groups. Rats were given 1 ml of yolk for 4 consecutive days, and the procedure was repeated after one month. The trial lasted for 75 days after which rats were slaughtered for carcass analysis and sampling. The body weight gain and food intake of rats were not different between treatment and control groups. In i.g. goups, positive yolk decreased mesemteric fat index, paramertrial fat index and perirenal fat index (P < 0.05), reduced serum triglycerides (P < 0.05) and increased serum free fatty acids (FFA) (P < 0.01), and also decreased serum leptin, insulin and TNF-alpha levels ( P < 0.01 or P < 0.05), but did not affect gastrocnemius muscle index and serum cholesterol. In s.c. groups, positive yolk increased gastrocnemius muscle index (P < 0.05), reduced serum triglycerides and serum leptin (P < 0.01), increased serum TNF-alpha (P < 0.05), but did not affect adipose tissue depots, serum FFA, cholesterol and insulin. Administration of yolk antibody against APM proteins could effectively improve body composition of rats, and the treatment by intragastric administration could give better effect than by subcutaneous injection.


Postoperative pain: strategy for improving patient experiences.
Many patients continue to suffer moderate pain following surgery. Much of this may be unnecessary and could be alleviated with careful strategic pain management. It appears that the knowledge and attitudes of both health care professionals and patients are pivotal to patients' pain experiences. This paper reports the introduction and evaluation of a nurse-led intervention to improve pain management after surgery. The study design was experimental (pretest-post-test), comparing patients' pain scores in a control and an intervention hospital over time. The control hospital was included to assess if temporal effects reduced pain scores during the study period. A convenience patient sample was used, and patients' pain scores were measured in two phases (n = 800). Baseline data were compared with subsequent data collected after the introduction of the nurse-led intervention. The intervention included education for nurses in the form of short pain courses, introduction of regular pain assessment and profiling of pain at hospital level. Introduction of the nurse-led intervention reduced patients' pain scores. This reduction, in the order of 0.73 cm (7.3%) on a visual analogue scale (0-10 cm), was statistically significant for day of surgery and 2 days postsurgery (P < 0.05) in the intervention hospital. A reduction was not seen in the control hospital. Improvements in pain management can be made by embracing basic pain management principles.


Secondary metabolites from Verbascum bugulifolium Lam. and their bioactivities.
Five iridoid glycosides catalpol (1), specioside (2), ajugol (3), ajugoside (4), 8-O-acetylharpagide (5), two phenylethanoid glycosides, verbascoside (6) and glucopyranosyl-(1→Gi-6)-martynoside (7), four flavonoids, luteolin (8), luteolin 7-O-β-glucopyranoside (9), luteolin 7-O-rutinoside (10), apigenin 7-O-rutinoside (11), quercetin 3-O-rutinoside (12) and β-sitosterol (13) were isolated from the aerial parts of Verbascum bugulifolium Lam. for the first time. Their structures were elucidated by NMR and MS experiments. The extracts, and the isolates were evaluated for their in vitro antioxidant (DPPH•, ABTS• and CUPRAC), anti-inflammatory (LOX inhibition) and antimicrobial activities. Compounds 6 and 8 showed the highest antioxidant activity in all tests, where luteolin (8) showed the relatively best anti-inflammatory activity compared to other samples with 54.1 ± 5.0% inhibition at 1 µg/mL. All the tested compounds showed weak antimicrobial activity against tested microorganisms. This is the first phytochemical and bioactivity study on V. bugulifolium.[Figure: see text].


Increased autophagy in CD4+ T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance.
Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4+ T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4+ T cells in the autoimmune process. A better knowledge of the mechanisms determining such impaired homeostasis could contribute significantly to both the understanding and the treatment of the disease. Here we investigated whether autophagy, is dysregulated in CD4+ T cells of RA patients, resulting in disturbed T-cell homeostasis. We demonstrate that the rate of autophagy is significantly increased in CD4+ T cells from RA patients, and that increased autophagy is also a feature of in vitro activated CD4+ T cells. The increased apoptosis resistance observed in CD4+ T cells from RA patients was significantly reversed upon autophagy inhibition. These mechanisms may contribute to RA pathogenesis, as autophagy inhibition reduced both arthritis incidence and disease severity in a mouse collagen induced arthritis mouse model. Conversely, in Atg5flox/flox -CD4-Cre+ mice, in which all T cells are autophagy deficient, T cells showed impaired activation and proliferation. These data provide novel insight into the pathogenesis of RA and underscore the relevance of autophagy as a promising therapeutic target.


Automatic deep learning-based pleural effusion classification in lung ultrasound images for respiratory pathology diagnosis.
Lung ultrasound (LUS) imaging as a point-of-care diagnostic tool for lung pathologies has been proven superior to X-ray and comparable to CT, enabling earlier and more accurate diagnosis in real-time at the patient's bedside. The main limitation to widespread use is its dependence on the operator training and experience. COVID-19 lung ultrasound findings predominantly reflect a pneumonitis pattern, with pleural effusion being infrequent. However, pleural effusion is easy to detect and to quantify, therefore it was selected as the subject of this study, which aims to develop an automated system for the interpretation of LUS of pleural effusion. A LUS dataset was collected at the Royal Melbourne Hospital which consisted of 623 videos containing 99,209 2D ultrasound images of 70 patients using a phased array transducer. A standardized protocol was followed that involved scanning six anatomical regions providing complete coverage of the lungs for diagnosis of respiratory pathology. This protocol combined with a deep learning algorithm using a Spatial Transformer Network provides a basis for automatic pathology classification on an image-based level. In this work, the deep learning model was trained using supervised and weakly supervised approaches which used frame- and video-based ground truth labels respectively. The reference was expert clinician image interpretation. Both approaches show comparable accuracy scores on the test set of 92.4% and 91.1%, respectively, not statistically significantly different. However, the video-based labelling approach requires significantly less effort from clinical experts for ground truth labelling.


Targeting the insulin-like growth factor-1 receptor by picropodophyllin for lung cancer chemoprevention.
Insulin-like growth factor-1 receptor (IGF-1R) is a transmembrane heterotetramer that is activated by Insulin-like growth factor 1 and is crucial for tumor transformation and survival of malignant cells. Importantly, IGF-1R overexpression has been reported in many different cancers, implicating this receptor as a potential target for anticancer therapy. Picropodophyllin (PPP) is a potent inhibitor of IGF-1R and has antitumor efficacy in several cancer types. However, the chemopreventive effect of PPP in lung tumorigenesis has not been investigated. In this study, we investigated the chemopreventive activity of PPP in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and PPP was given by nasal inhalation to female A/J mice. Lung tumorigenesis was assessed by tumor multiplicity and tumor load. PPP significantly decreased tumor multiplicity and tumor load. Tumor multiplicity and load were decreased by 52% and 78% respectively by 4 mg/ml aerosolized PPP. Pharmacokinetics analysis showed good bioavailability of PPP in lung and plasma. Treatment with PPP increased staining for cleaved caspase-3 and decreased Ki-67 in lung tumors, suggesting that the lung tumor inhibitory effects of PPP were partially through inhibition of proliferation and induction of apoptosis. In human lung cancer cell lines, PPP inhibited cell proliferation, and also inhibited phosphorylation of IGF-1R downstream targets, AKT and MAPK, ultimately resulting in increased apoptosis. PPP also reduced cell invasion in lung cancer cell lines. In view of our data, PPP merits further investigation as a promising chemopreventive agent for human lung cancer.


Nonpalpable breast lesions: stereotactic automated large-core biopsies.
One hundred two patients with mammographically suspicious, nonpalpable lesions underwent stereotactic breast biopsy with a biopsy gun and an automated 14-gauge cutting needle. After biopsy, a localization wire was placed and surgical biopsy performed. There was agreement of the histologic results from the gun biopsy and the surgical biopsy specimens in 98 cases (96%), including 22 of 23 carcinomas (96%) (kappa = 0.936). The gun biopsy yielded findings that led to the correct diagnosis in two cases involving lesions that were missed at surgical biopsy; two lesions found at surgery were missed at gun biopsy. The results of this study suggest that the use of 14-gauge needles improves agreement between surgical and needle core biopsy findings and that stereotactic biopsy with an automated needle and gun can be an acceptable alternative to surgical biopsy in women with mammographically suspicious breast lesions.


Lsh, an SNF2/helicase family member, is required for proliferation of mature T lymphocytes.
Lsh (Hells) is closely related to SNF2/helicase family members that remodel chromatin and thus regulate gene transcription. In the adult mouse Lsh is expressed primarily in lymphoid tissue, showing the highest level in thymocytes. Lsh gene expression can be induced in thymic pro-T cells by pre-T cell receptor crosslinking and in mature T cells by T cell receptor crosslinking together with costimulation via CD28. The time course of Lsh gene and protein expression correlated closely with the onset of S phase of the cell cycle. To explore the function of Lsh during lymphoid development or activation, we deleted the Lsh gene by homologous recombination in ES cells. Fetal liver cells from Lsh-/- were used as a source of hematopoietic precursors to reconstitute lymphoid development in Rag2-/- mice. Lsh-/- (compared to Lsh+/+ or +/-) chimeras showed a modest reduction in thymocyte numbers due to a partial arrest at the transition from the CD4(-)CD8(-) stage to the CD4(+)CD8(+) stage of T cell development. Mature peripheral lymphocytes were reduced in number to approximately 60% for T cells and 40% for B cells; however, V(D)J recombination of the immune receptor genes was normal. Although polyclonal activation of Lsh-/- T cells induced normal levels of cytokines, cell proliferation was severely suppressed and cells underwent apoptosis. Several genes involved in the regulation of apoptosis were expressed normally with the exception of Bcl-2 that was actually elevated. These findings demonstrate that Lsh is not obligatory for normal lymphoid development but is essential for normal proliferation of peripheral T lymphocytes.


To Go or Stay: The Development, Benefit, and Detriment of Tissue-Resident Memory CD8 T Cells during Central Nervous System Viral Infections.
CD8 T cells coordinate immune defenses against viral infections of the central nervous system (CNS). Virus-specific CD8 T cells infiltrate the CNS and differentiate into brain-resident memory CD8 T cells (CD8 bTRM). CD8 bTRM are characterized by a lack of recirculation and expression of phenotypes and transcriptomes distinct from other CD8 T cell memory subsets. CD8 bTRM have been shown to provide durable, autonomous protection against viral reinfection and the resurgence of latent viral infections. CD8 T cells have also been implicated in the development of neural damage following viral infection, which demonstrates that the infiltration of CD8 T cells into the brain can also be pathogenic. In this review, we will explore the residency and maintenance requirements for CD8 bTRM and discuss their roles in controlling viral infections of the brain.


Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome.
Several models have been proposed to explain the neurodevelopmental syndrome induced by exposure of human embryos to alcohol, which is known as fetal alcohol spectrum disorder (FASD). One of the proposed models suggests a competition for the enzymes required for the biosynthesis of retinoic acid. The outcome of such competition is development under conditions of reduced retinoic acid signaling. Retinoic acid is one of the biologically active metabolites of vitamin A (retinol), and regulates numerous embryonic and differentiation processes. The developmental malformations characteristic of FASD resemble those observed in vitamin A deficiency syndrome as well as from inhibition of retinoic acid biosynthesis or signaling in experimental models. There is extensive biochemical and enzymatic overlap between ethanol clearance and retinoic acid biosynthesis. Several lines of evidence suggest that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for the aldehyde dehydrogenase activity available. In adults, this competition also extends to the alcohol dehydrogenase activity. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase, further supporting the competition model. All of the evidence supports the reduction of retinoic acid signaling as the etiological trigger in the induction of FASD.


Replacement of a tooth with a fiber-reinforced direct bonded restoration.
Today's methods and materials for tooth replacement are multiple and varied. Modern materials now allow for highly conservative abutment preparations that can retain bonded single tooth replacement fixed prostheses. A case report is presented in which fiber reinforced with composite resin was used for placement of a three-unit fixed long-term provisional restoration, providing fracture resistance while achieving an esthetically pleasing, durable restoration.


Life satisfaction among individuals with opioid use disorder receiving extended-release naltrexone: A 12-week randomized controlled trial and a 36-week follow-up.
Life satisfaction (LS) in opioid-dependent individuals is lower than in the general population. This study aimed to explore changes in LS during short- and long-term treatment with extended-release naltrexone (XR-NTX). This open-label 12-week clinical trial randomized 159 participants to either monthly XR-NTX or daily buprenorphine-naloxone (BP-NLX). In a subsequent 36-week follow-up study on XR-NTX, participants either continued or switched to XR-NTX. The study collected data on the Temporary Satisfaction with Life (TSWL) and illicit opioid use every fourth week. The research team assessed changes in TSWL by a linear mixed model and growth mixture model. The study assessed relationship between opioid use and TSWL by a linear mixed model. Change in LS differed significantly between the groups in both study periods. TSWL scores were significantly higher in the XR-NTX group at week 4 (p = 0.013) and week 8 (p = 0.002). In the follow-up period, the groups were significantly different only at week 16 (p = 0.031) and week 48 (p = 0.025), with the higher TSWL scores in the XR-NTX continued group. Increase in opioid use by one day was associated with a 0.12 point lower mean TSWL score. Both study periods identified groups with low and high LS levels. In the trial period, the TSWL scores exhibited a significant increase from baseline to week 12 in both groups, p < 0.001 and p = 0.011 in the low and high LS group, respectively. In the follow-up period, the TSWL scores exhibited a significant increase from week 16 to week 48 (p = 0.003) in the high LS group, while the low LS group showed persistently lower values throughout that period. XR-NTX treatment given once monthly is associated with higher LS, as measured by TSWL, compared to daily use of BP-NLX. The majority of the participants had relatively low TSWL scores and did not report any change in TSWL during longer-term treatment. The study found a significant association between more frequent illicit opioid use and a low or decreased LS during follow-up.


Prevalence and correlates of foot pain in a population-based study: the North West Adelaide health study.
Few population-based studies have examined the prevalence of foot pain in the general community. The aims of this study were therefore to determine the prevalence, correlates and impact of foot pain in a population-based sample of people aged 18 years and over living in the northwest region of Adelaide, South Australia. The North West Adelaide Health Study is a representative longitudinal cohort study of n = 4,060 people randomly selected and recruited by telephone interview. The second stage of data collection on this cohort was undertaken between mid 2004 and early 2006. In this phase, information regarding the prevalence of musculoskeletal conditions was included. Overall, n = 3,206 participants returned to the clinic during the second visit, and as part of the assessment were asked to report whether they had pain, aching or stiffness on most days in either of their feet. Data were also collected on body mass index (BMI); major medical conditions; other joint symptoms and health-related quality of life (the Medical Outcomes Study Short Form 36 [SF-36]). Overall, 17.4% (95% confidence interval 16.2 - 18.8) of participants indicated that they had foot pain, aching or stiffness in either of their feet. Females, those aged 50 years and over, classified as obese and who reported knee, hip and back pain were all significantly more likely to report foot pain. Respondents with foot pain scored lower on all domains of the SF-36 after adjustment for age, sex and BMI. Foot pain affects nearly one in five of people in the community, is associated with increased age, female sex, obesity and pain in other body regions, and has a significant detrimental impact on health-related quality of life.


Prevalence of Venous Thromboembolism Following Acute Spinal Cord Injury in an Urban Inner City Hospital.
Venous thromboembolism (VTE) is known to occur at high rates in patients who suffer spinal cord injury (SCI). Large population studies in the United States have shown a prevalence of approximately 4-5%, with some studies suggesting higher prevalence. While the specific mechanism behind increased VTE incidence in the SCI population is unknown, it is likely tied to immobility and functional decline. Previous studies have also linked social determinants of health to higher VTE prevalence in certain populations. The purpose of this study is to determine the prevalence of VTE after acute SCI in the inner urban city population and to identify factors that place patients at increased VTE risk. Patients who suffered SCI between 2014 and 2019 were identified from one inner city urban hospital. A retrospective chart review was completed to record the development of VTE after SCI. Medical comorbidities, type of thromboprophylaxis used, patient demographics, injury characteristics, and postinjury sequelae were compared between individuals who did and did not develop VTE. A total of 148 patients were included. These patients were from a low socioeconomic demographic when compared with the larger US population. Average household income based on zip code data for included patients was $56 647, $30 315 below the national average. The prevalence of VTE in this patient population was 19.59%. Weight, deep vein thrombosis history, chemoprophylaxis use, mobility impairment postinjury, neurologic level of SCI, malignancy history, and history of smokeless tobacco were associated with VTE (all P < .05). Low molecular weight heparin (LMWH) use was associated with fewer occurrences of VTE (P < .001). Patients from our urban inner city hospital have a higher VTE prevalence after SCI than shown in previous US-based studies. These patients may be at increased risk due to increased numbers of medical comorbidities, social factors, or undiagnosed medical conditions. Thromboprophylaxis with LMWH appears to lower the risk of VTE after SCI. 3. Patients with the previously mentioned risk factors are at increased risk for VTE development during their acute recovery process. These patients should have a much lower screening threshold for VTE evaluation and likely would benefit from more routine screening to prevent complications related to VTE development or progression. Furthermore, these patients should, when medically appropriate, be treated with low molecular weight heparin for VTE prophylaxis as previously recommended by the Consortium for Spinal Cord Medicine.


A centralized dose calculation system for radiation therapy.
Centralization of treatment planning in a radiation therapy department is a realistic strategy to achieve an integrated and quality-controlled planning system, especially for institutions with numerous affiliations. The rapid evolution of computer hardware and software technology makes this a distinct possibility. However, the procedure of three-dimensional treatment planning involves a number of steps, such as: (1) input of patient computed tomography (CT) images and contour information; (2) interactions with local devices such as a film digitizer; and (3) output of beam information to be integrated with the record and verify the system. A full-fledged realization of the web-based centralized three-dimensional treatment planning system will require an extensive commercial development effort. We have developed and incorporated a web-based Timer/Monitor Unit (MU) program as a first step towards the full implementation of a centralized treatment planning system. The software application was developed in JAVA language. It uses the internet server and client technology. With one server that can handle multiple threads, it is a simple process to access the application anywhere on the network with an internet browser. Both the essential data needed for the calculation and the results are stored on the server, which centralizes the maintenance of the software and the storage of patient information.


Preparation of a Lactobacillus plantarum starter culture for cucumber fermentations that can meet kosher guidelines.
A method is described for growth of a Lactobacillus plantarum starter culture in jars of commercially available pasteurized fresh-pack kosher dill cucumbers so that jars can be used to inoculate commercial scale cucumber fermentation tanks. A procedure is also described to transfer lactic acid bacteria from frozen storage in MRS broth into cucumber juice and commercial jars of kosher dill cucumbers so that a selected strain of lactic acid bacteria can be kosher certified for commercial fermentations in processing plants that operate under kosher certification. The strain of L. plantarum used in these experiments grew to maximum cell numbers in 4 d at 20 to 25 °C and then maintained viable cell numbers for 2 wk at >10(8) CFU/mL so the culture was suitable for inoculation of fermentation tanks. Refrigeration of jars of culture after they grow to maximum numbers minimizes die-off of cells sufficiently so that a pure culture can be maintained by aseptically transferring brine containing viable bacteria to a new pH-adjusted jar only once every 4 mo. This report describes a method to prepare a lactic acid bacteria starter culture suitable for kosher vegetable fermentations.


Smoking in Pregnancy Among Indigenous Women in High-Income Countries: A Narrative Review.
Pregnant women in socioeconomically disadvantaged circumstances, such as Indigenous women, have a high prevalence of smoking. Tobacco smoking is the most significant reversible risk factor for the health of Indigenous pregnant women and their babies. As researchers working in this specialized area, we conducted a narrative review of the literature on smoking among Indigenous pregnant women in the United States, Canada, New Zealand, and Australia. We summarize prevalence and factors influencing tobacco use, interventions, and evidence gaps for tobacco control and smoking cessation. Recommendations are made for future interventions, policy changes, and much-needed research. Common themes emerging across the four countries reveal opportunities for cross-cultural collaborative studies and trials. These include the social-normative use of tobacco as barriers to quitting in pregnancy and the need for evaluations of interventions at the family and community level. Socioeconomic disparities underscore the importance of enhancing the implementation and reach of strategies to prevent and reduce prenatal tobacco smoking among Indigenous women. Elders and community health care providers as role models for nontobacco use could be explored. Qualitative work is needed to understand the barriers and opportunities, such as cultural strengths supporting quitting tobacco to develop more effective approaches. Although a high-priority group, there remains a dearth of research on Indigenous women's smoking in pregnancy. Studies have assessed knowledge and attitudes to smoking in pregnancy, and small feasibility studies and a few empirical trials have been conducted. Recommendations for promising culturally appropriate cessation interventions have been made. Larger trials are warranted. Strategies to support quitting among pregnant Indigenous women need to be multifactorial and take account of the social determinants of smoking including historical antecedents, community norms, cultural strengths, and recognition of individual and community needs. Cross-country research collaborations have the potential to leverage funding, share expertise, and strengthen approaches to tackle an important and poorly attended health disparity that has a profound impact on the entire life course for Indigenous peoples.


Epidemiology of diabetes and diabetes-related complications.
In 2005, it was estimated that more than 20 million people in the United States had diabetes. Approximately 30% of these people had undiagnosed cases. Increased risk for diabetes is primarily associated with age, ethnicity, family history of diabetes, smoking, obesity, and physical inactivity. Diabetes-related complications--including cardiovascular disease, kidney disease, neuropathy, blindness, and lower-extremity amputation--are a significant cause of increased morbidity and mortality among people with diabetes, and result in a heavy economic burden on the US health care system. With advances in treatment for diabetes and its associated complications, people with diabetes are living longer with their condition. This longer life span will contribute to further increases in the morbidity associated with diabetes, primarily in elderly people and in minority racial or ethnic groups. In 2050, the number of people in the United States with diagnosed diabetes is estimated to grow to 48.3 million. from randomized controlled trials provide evidence that intensive lifestyle interventions can prevent or delay the onset of diabetes in high-risk individuals. In addition, adequate and sustained control of blood sugar levels, blood pressure, and blood lipid levels can prevent or delay the onset of diabetes-related complications in people with diabetes. Effective interventions, at both the individual and population levels, are desperately needed to slow the diabetes epidemic and reduce diabetes-related complications in the United States. This report describes the current diabetes epidemic and the health and economic impact of diabetes complications on individuals and on the health care system. The report also provides suggestions by which the epidemic can be curbed.


Suicidal intent among young suicides in rural China.
To understand psychometric characteristics of Beck Suicide Intent Scale (SIS) and different characteristics of suicides between high and low intent in Chinese culture. Data of 386 suicides and 416 living controls aged 15-34 years were used to analyze psychometric characteristics of SIS with 6 items. SIS with 6 items had high reliability and validity. Different characteristics were found between suicides with high intent and low intent. Hopelessness, depression, impulsivity, and approach coping skill were common factors of suicide with high and low intent. Education years, marriage, social support, and mental disorders were specific factors of suicide with low intent. High intent suicides had different characteristics from low intent suicides. SIS with 6 items is suitable for use in young rural China.


Illness severity scoring in status epilepticus-When STESS meets APACHE II, SAPS II, and SOFA.
To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.


The importance of Internet usage for urologic patients.
To evaluate Internet usage frequency, rate of searched diseases and impact of Internet derived data on future patient physician relationship in patients applying to an Urology Department. A well prepared questionnaire has been given to 1000 referring cases, out of which 589 accepted to participate on a volunteer basis to a face to face interview. Patients were divided into subgroups with respect to age, gender and as well as their educational and economical status. Regarding Internet, questions inquired the use of Internet, the point of view about it, opinions about healthcare system and most commonly urological diseases searched in Internet. Of 589 patients participating, 38.2% reported access to the Internet; in relation to subgroup analysis of data, there was a statistically significant relationship between the use of Internet and age (p < 0.001), gender (p = 0.048), educational status (p < 0.001) and economical status of (p = 0.002) the cases evaluated. Disease specific information was most frequently sought: 18.2% searched for urolithiasis, 14.2% for non-cancer related kidney diseases, and 14.2% for urologic cancers. Younger patients with higher educational status tended to use Internet and the majority of these cases share all these information with their physicians during their visit. These findings indicate that all physicians should consider this fact seriously and make their future plans in the light of internet based activities which provides numerous advantages.


Health, wealth, and air pollution: advancing theory and methods.
The effects of both ambient air pollution and socioeconomic position (SEP) on health are well documented. A limited number of recent studies suggest that SEP may itself play a role in the epidemiology of disease and death associated with exposure to air pollution. Together with evidence that poor and working-class communities are often more exposed to air pollution, these studies have stimulated discussion among scientists, policy makers, and the public about the differential distribution of the health impacts from air pollution. Science and public policy would benefit from additional research that integrates the theory and practice from both air pollution and social epidemiologies to gain a better understanding of this issue. In this article we aim to promote such research by introducing readers to methodologic and conceptual approaches in the fields of air pollution and social epidemiology; by proposing theories and hypotheses about how air pollution and socioeconomic factors may interact to influence health, drawing on studies conducted worldwide; by discussing methodologic issues in the design and analysis of studies to determine whether health effects of exposure to ambient air pollution are modified by SEP; and by proposing specific steps that will advance knowledge in this field, fill information gaps, and apply research results to improve public health in collaboration with affected communities.


Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells.
Nicotine contributes to the onset and progression of several pulmonary diseases. Among the various pathophysiological mechanisms triggered by nicotine, oxidative stress and cell death are reported in several cell types. We found that chronic exposure to nicotine (48h) induced NOX1-dependent oxidative stress and apoptosis in primary pulmonary cells. In murine (MLE-12) and human (BEAS-2B) lung epithelial cell lines, nicotine acted as a sensitizer to cell death and synergistically enhanced apoptosis when cells were concomitantly exposed to hyperoxia. The precise signaling pathway was investigated in MLE-12 cells in which NOX1 was abrogated by a specific inhibitor or stably silenced by shRNA. In the early phase of exposure (1h), nicotine mediated intracellular Ca(2+) fluxes and activation of protein kinase C, which in its turn activated NOX1, leading to cellular and mitochondrial oxidative stress. The latter triggered the intrinsic apoptotic machinery by modulating the expression of Bcl-2 and Bax. Overexpression of Bcl-2 completely prevented nicotine's detrimental effects, suggesting Bcl-2as a downstream key regulator in nicotine/NOX1-induced cell damage. These results suggest that NOX1 is a major contributor to the generation of intracellular oxidative stress induced by nicotine and might be an important molecule to target in nicotine-related lung pathologies.


From student to therapist: exploring the first year of practice.
The transition from classroom to clinical practice challenges many health professional students. This study used a phenomenological approach to explore the lived experience of rehabilitation students during their final placement and first year of practice. Students (n = 6) in occupational therapy and physical therapy wrote reflective journals every 2 weeks during their final fieldwork placement and first year of practice. The researchers independently analyzed the journals for common themes. An independent peer completed a blind analysis of two journals. Data were also compared with published first-person accounts of novice practitioners. The lived experience of the first year of practice included four consecutive stages: Transition, Euphoria and Angst, Reality of Practice, and Adaptation. Themes from the journals included great expectations, competence, politics, shock, education, and strategies. Recognizing the stages in the process of transition from student to therapist may assist in educational curriculum development and clinical support and supervision for new graduates. Educators need to continue to make education practice relevant while maintaining a theoretical perspective.


Stepwise evolution of the centriole-assembly pathway.
The centriole and basal body (CBB) structure nucleates cilia and flagella, and is an essential component of the centrosome, underlying eukaryotic microtubule-based motility, cell division and polarity. In recent years, components of the CBB-assembly machinery have been identified, but little is known about their regulation and evolution. Given the diversity of cellular contexts encountered in eukaryotes, but the remarkable conservation of CBB morphology, we asked whether general mechanistic principles could explain CBB assembly. We analysed the distribution of each component of the human CBB-assembly machinery across eukaryotes as a strategy to generate testable hypotheses. We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs. Unexpectedly, other players (SAK/PLK4, SPD2/CEP192 and CP110) emerged in a taxon-specific manner. We report that gene duplication plays an important role in the evolution of CBB components and show that, in the case of BLD10/CEP135, this is a source of tissue specificity in CBB and flagella biogenesis. Moreover, we observe extreme protein divergence amongst CBB components and show experimentally that there is loss of cross-species complementation among SAK/PLK4 family members, suggesting species-specific adaptations in CBB assembly. We propose that the UNIMOD theory explains the conservation of CBB architecture and that taxon- and tissue-specific molecular innovations, gained through emergence, duplication and divergence, play important roles in coordinating CBB biogenesis and function in different cellular contexts.


[Development and current status of silicone oil surgery].
On the basis of a series of 500 patients the authors describe the development of silicone oil surgery, the surgical technique, and present-day indications for it, as well as the results that can be achieved with this procedure. The postoperative problems (cataract, glaucoma, and keratopathy) are analyzed and guidelines presented for reducing the complication rate.


Waveguide coupling of SAW resonators with different properties.
In contrast to conventional transversely coupled resonator filters, waveguide coupling of two one-port resonators with different resonance frequencies is described. The different resonance frequencies are implemented by different central finger gaps or gratings differing by a scaling factor. Consequently, the equivalent fingers and reflecting strips of different resonators are shifted with respect to each other, and the waveguide modes are, therefore, no longer independent of each other. This effect is called mutual coupling of waveguide modes and requires a new type of modeling. The main characteristics of the new modeling method are described. The advantage of the design principle consists of a wider bandwidth without changing the waveguide parameters and different input and output impedance.


Effect of synthetic combinations and tobacco root extract and the mixture of them on broomrape seed germination.
Various types of broomrape (Orobanche cermua), such as parasitic weeds, live on the roots of many important crops. Different methods may be advised to eradicate this parasite. But the seed size is so tiny with high stability in the soil and having strong connection with the host, it is very difficult to eradicate this parasite and there is no useful and economic method has not been suggested in this regard yet. The seeds of all types of broomrape germinate in the soil only when they are exposed to the secretions of the host's roots, therefore, providing special combinations that cause the parasite's seeds germinate in the absence of the host, can be an effective way in controlling this parasite. The effect of the tobacco root's extract and the synthetic combinations as well as their mixtures with different concentrations on the germination of the seeds of Orobanche cermua Loefi were tested to introduce an effective combination that can be used in controlling this parasite. This experiment includes 28 treatments in three replications. The tobacco root's extract was derived from the tobacco roots planted in pots containing Perlit in different stages and were prepared in different concentrations. Synthetic combinations (including combinations 1, 2 and 3) were also prepared with concentration of 1, 2 and 3 parts per million (ppm), then these combinations were tested as treatments on Broomrape's seeds. At the end of experiment, it was concluded that all the combinations used in different concentrations in this experiment significantly differ from the control treatment in their effects in causing the Broomrape's seeds germinate. Among all the combinations examined, the following were the most effective ones in the process of the germination of the Broomrape's seeds: 1. combination 2 with the concentration of one part per million, 2. combination 2 with the concentration of two parts per million, and 3 tobacco root's extract in the third stage.


Polyamines inhibit phospholipase C-catalysed polyphosphoinositide hydrolysis. Studies with permeabilized GH3 cells.
[3H]Inositol-labelled GH3 rat anterior pituitary tumour cells were permeabilized with digitonin and were incubated at 37 degrees C in the presence of ATP and Mg2+. [3H]Polyphosphoinositide breakdown and [3H]inositol phosphate production were stimulated by hydrolysis-resistant GTP analogues and by Ca2+. Of the nucleotides tested, guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) was the most effective stimulus. Activation by GTP gamma S appeared to be mediated by a guanine nucleotide-binding (G) protein as GTP gamma S-stimulated [3H]inositol phosphate production was inhibited by other nucleotides with a potency order of GTP = GDP = guanosine 5'-[beta-thio]diphosphate greater than ITP greater than GMP greater than UTP = CTP = adenosine 5'-[gamma-thio]triphosphate. The stimulatory effects of 10 microM-GTP gamma S on [3H]inositol phosphate levels were reversed by spermine and spermidine with IC50 values of approx. 0.25 and 2 mM respectively. Putrescine was inhibitory only at higher concentrations. Similarly, GTP gamma S-induced decreases in [3H]polyphosphoinositide levels were reversed by 2.5 mM-spermine. The inhibitory effects of spermine were not overcome by supramaximal concentrations of GTP gamma S. In contrast, [3H]inositol phosphate production stimulated by addition of 0.3-0.6 mM-Ca2+ to incubation media was only partially inhibited by spermine (5 mM), and spermine was not inhibitory when added Ca2+ was increased to 1 mM. These data show that polyamines, particularly spermine, inhibit phospholipase C-catalysed polyphosphoinositide hydrolysis with a marked selectivity towards the stimulatory effects of GTP gamma S.


Total synthesis of Trichosanthes trypsin inhibitor and its analogue.
Trichosanthes trypsin inhibitor (TTI) is a peptide consisting of 27 amino acid residues with three pairs of disulfide bonds. This paper reports the total synthesis and disulfide bond refolding of this inhibitor and its analogue. After purification, the amino acid sequence and stoichiometrical inhibitory activity against trypsin of the synthetic inhibitor were compatible with those of the natural inhibitor. The analogue of this inhibitor in which residue Met in position 6 was replaced by Ala was also synthesized. The antitrypsin activity of this synthetic analogue was also approximate to that of the natural inhibitor.


How new concepts become universal scientific approaches: insights from citation network analysis of agent-based complex systems science.
Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems or societies, is-like many scientific endeavours-limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, I advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). I analysed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modelling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. Accessible broad-spectrum software similarly contributed to this change. From the modelling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviours of agents and system-level dynamics are inseparably bound.


Risk and protective influences in the lives of siblings of youths with spina bifida.
The impact of childhood chronic health conditions like spina bifida (SB) is a shared family experience. However, the lived experience of siblings is not well known. One hundred and fifty-five brothers and sisters of a child with SB responded to an open-ended question included in an anonymous self-administered mail questionnaire designed to enhance awareness of how adolescent siblings experience this chronic condition. Content analysis performed by interdisciplinary authors identified four domains--Rewards and Consequences of Spina Bifida, Journey Toward Acceptance of Spina Bifida, Emotional Climate of Siblings, and Qualities of the Social Environment--that depict emotional complexity in response to the diverse risk and protective influences present in the lives of siblings. By bolstering the siblings' strengths and resources found in their adaptive coping mechanisms, spirituality, cohesive family ties, and supportive peer friendships, social workers and other health care professionals may help them to successfully navigate the intense and confusing emotions that may naturally spring from the challenges and opportunities associated with SB.


Axonal CB1 Receptors Mediate Inhibitory Bouton Formation via cAMP Increase and PKA.
Experience-dependent formation and removal of inhibitory synapses are essential throughout life. For instance, GABAergic synapses are removed to facilitate learning, and strong excitatory activity is accompanied by the formation of inhibitory synapses to maintain coordination between excitation and inhibition. We recently discovered that active dendrites trigger the growth of inhibitory synapses via CB1 receptor-mediated endocannabinoid signaling, but the underlying mechanism remained unclear. Using two-photon microscopy to monitor the formation of individual inhibitory boutons in hippocampal organotypic slices from mice (both sexes), we found that CB1 receptor activation mediated the formation of inhibitory boutons and promoted their subsequent stabilization. Inhibitory bouton formation did not require neuronal activity and was independent of Gi/o-protein signaling, but was directly induced by elevating cAMP levels using forskolin and by activating Gs-proteins using DREADDs. Blocking PKA activity prevented CB1 receptor-mediated inhibitory bouton formation. Our findings reveal that axonal CB1 receptors signal via unconventional downstream pathways and that inhibitory bouton formation is triggered by an increase in axonal cAMP levels. Our results demonstrate an unexpected role for axonal CB1 receptors in axon-specific, and context-dependent, inhibitory synapse formation.SIGNIFICANCE STATEMENT Coordination between excitation and inhibition is required for proper brain function throughout life. It was previously shown that new inhibitory synapses can be formed in response to strong excitation to maintain this coordination, and this was mediated by endocannabinoid signaling via CB1 receptors. As activation of CB1 receptors generally results in the suppression of synaptic transmission, it remained unclear how CB1 receptors can mediate the formation of inhibitory synapses. Here we show that CB1 receptors on inhibitory axons signal via unconventional intracellular pathways and that inhibitory bouton formation is triggered by an increase in axonal cAMP levels and requires PKA activity. Our findings point to a central role for axonal cAMP signaling in activity-dependent inhibitory synapse formation.


High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype.
Regenerating islet-derived protein 3 alpha (REG3A) is a biomarker of lower gastrointestinal graft-versus-host disease (GVHD); however, the biological role of REG3A in the pathophysiology of GVHD is not understood. Here, we examined the association between a single nucleotide polymorphism in the REG3A gene, rs7588571, which is located upstream and within 2 kb of the REG3A gene, and transplant outcomes including the incidence of GVHD. The study population consisted of 126 adult Japanese patients who had undergone bone marrow transplantation from a HLA-matched sibling. There was no association between rs7588571 polymorphism and the incidence of acute GVHD. However, a significantly higher incidence of extensive chronic GVHD was observed in patients with the rs7588571 non-GG genotype than in those with the GG genotype (Odds ratio 2.6; 95% confidence interval, 1.1-6.0; P = 0.029). Semi-quantitative reverse transcription PCR demonstrated that the rs7588571 non-GG genotype exhibited a significantly lower REG3A mRNA expression level than the GG genotype (P = 0.032), and Western blot analysis demonstrated that the rs7588571 non-GG genotype exhibited a trend toward lower REG3A protein expression level than the GG genotype (P = 0.053). Since REG proteins have several activities that function to control intestinal microbiota, and since intestinal dysbiosis is in part responsible for the development of GVHD, our findings lead to the novel concept that REG3A could have some protective effect in the pathogenesis of GVHD through the regulation of gut microbiota.


Growth of high-density titanium silicide nanowires in a single direction on a silicon surface.
Understanding the growth mechanisms of nanowires is essential for their successful implementation in advanced devices applications. In situ ultrahigh-vacuum transmission electron microscopy has been applied to elucidate the interaction mechanisms of titanium disilicide nanowires (TiSi2 NWs) on Si(111) substrate. Two phenomena were observed: merging of the two NWs in the same direction, and collapse of one NW on a competing NW in a different direction when they meet at the ends. On the other hand, as one NW encounters the midsection of the other NW in a different direction, it recedes in favor of bulging of the other NW at the midsection. Since crystallographically the nanowires are favored to grow on Si(110) only in the [1 -1 0] direction, this crucial information has been fruitfully exploited to focus on the growth of a high density of long and high-aspect-ratio Ti silicide NWs parallel to the surface on Si(110) in a single direction. The achievement in growth of high-density NWs in a single direction represents a significant advance in realizing the vast potential for applications of silicide NWs in nanoelectronics devices.


The effects of ideological value framing and symbolic racism on pro-environmental behavior.
Environmental degradation continues to be one of the greatest threats to human well-being, posing a disproportionate burden on communities of color. Environmental action, however, fails to reflect this urgency, leaving social-behavioral research at the frontier of environmental conservation, as well as environmental justice. Broad societal consensus for environmental action is particularly sparse among conservatives. The lack of even small personal sacrifices in favor of the environment could be attributed to the relatively low salience of environmental threats to white Americans and the partisan nature of environmentalism in America. We evaluate if (1) environmental action is causally related to the ideological value framing of an environmental issue; and (2) if the perceived race of impacted communities influences environmental action as a function of racial resentment. With this large-scale, original survey experiment examining the case of air-pollution, we find weak support for the first, but we do not find evidence for the second. We advance our understanding of environmental justice advocacy and environmental inaction in the United States. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 10 June 2021. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.14769558 .


Computerised 3-D anatomical modelling using plastinates: an example utilising the human heart.
Computerised modelling methods have become highly useful for generating electronic representations of anatomical structures. These methods rely on crosssectional tissue slices in databases such as the Visible Human Male and Female, the Visible Korean Human, and the Visible Chinese Human. However, these databases are time consuming to generate and require labour-intensive manual digitisation while the number of specimens is very limited. Plastinated anatomical material could provide a possible alternative to data collection, requiring less time to prepare and enabling the use of virtually any anatomical or pathological structure routinely obtained in a gross anatomy laboratory. The purpose of this study was to establish an approach utilising plastinated anatomical material, specifically human hearts, for the purpose computerised 3-D modelling. Human hearts were collected following gross anatomical dissection and subjected to routine plastination procedures including dehydration (-25(o)C), defatting, forced impregnation, and curing at room temperature. A graphics pipeline was established comprising data collection with a hand-held scanner, 3-D modelling, model polishing, file conversion, and final rendering. Representative models were viewed and qualitatively assessed for accuracy and detail. The results showed that the heart model provided detailed surface information necessary for gross anatomical instructional purposes. Rendering tools facilitated optional model manipulation for further structural clarification if selected by the user. The use of plastinated material for generating 3-D computerised models has distinct advantages compared to cross-sectional tissue images.


Calculation of volatile anaesthetics consumption from agent concentration and fresh gas flow.
The assessment of volatile agents' consumption can be performed by weighing vapourisers before and after use. This method is technically demanding and unavailable for retrospective analysis of anaesthesia records. Therefore, a method based on calculations from fresh gas flow and agent concentration is presented here. The presented calculation method herein enables a precise estimation of volatile agent consumption when average fresh gas flows and volatile agent concentrations are known. A pre-condition for these calculations is the knowledge of the vapour amount deriving from 1 ml fluid volatile agent. The necessary formulas for these calculations and an example for a sevoflurane anaesthesia are presented. The amount of volatile agent vapour deriving from 1 ml of fluid agent are for halothane 229 ml, isoflurane 195 ml, sevoflurane 184 m, and desflurane 210 ml. The constant for sevoflurane is used in a fictitious clinical case to exemplify the calculation of its consumption in daily routine resulting in a total expenditure of 23.6 ml liquid agent. By application of the presented specific volatile agent constants and equations, it becomes easy to calculate volatile agent consumption if the fresh gas flows and the resulting inhaled concentration of the volatile agent are known. By this method, it is possible to extract data about volatile agent consumption both ways: (1) retrospectively from sufficiently detailed and accurate anaesthesia recordings, as well as (2) by application of this method in a prospective setting. Therefore, this method is a valuable contribution to perform pharmacoeconomical surveys.


Clinical chronopharmacology.
Circadian (approximately or equal to 24 h), circannual (approximately or equal to 1 year) and other biological rhythms of endogenous origin, detectable at all levels of organization, constitute a temporal structure in all animal species, including man. Circadian, circannual and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical as well as chemical agents including medications and foods are rather common phenomena. Modern chronopharmacology investigates drug effects: a) as a function of biological timing and b) upon parameters characterising the endogenous bioperiodicities. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts: the chronokinetics of a drug (rhythmic changes in its pharmacokinetics): the chronesthesy (rhythmic changes in susceptibility of target biosystem to this drug), and the chronergy (the drug-integrated overall effects). One of the aims of chronopharmacology is solving problems of drug optimization. Knowledge of those administration times coinciding with best effectiveness or tolerance is required to optimize both timing(s) and dosage(s) of a medication. Illustrative examples of both experimental and clinical investigative chronopharmacology are corticosteroids and anticancerous agents.


Artificial molecular machines driven by light.
The bottom-up construction and operation of machines and motors of molecular size is a topic of great interest in nanoscience, and a fascinating challenge of nanotechnology. The problem of the energy supply to make molecular machines work is of the greatest importance. Research in the last ten years has demonstrated that light energy can be used to power artificial nanomachines by exploiting photochemical processes in appropriately designed systems. More recently, it has become clear that under many aspects light is the best choice to power molecular machines; for example, systems that show autonomous operation and do not generate waste products can be obtained. This review is intended to discuss the design principles at the basis of light-driven artificial nanomachines, and provide an up-to-date overview on the prototype systems that have been developed.


Lipid modifications of a Ras peptide exhibit altered packing and mobility versus host membrane as detected by 2H solid-state NMR.
The human N-ras protein binds to cellular membranes by insertion of two covalently bound posttranslational lipid modifications, which is crucial for its function in signal transduction and cell proliferation. Mutations in ras may lead to unregulated cell growth and eventually cancer, making it an important therapeutic target. Here we have investigated the molecular details of the membrane binding mechanism. A heptapeptide derived from the C-terminus of the human N-ras protein was synthesized including two hexadecyl modifications. Solid-state 2H NMR was used to determine the packing and molecular dynamics of the ras lipid chains as well as the phospholipid matrix. Separately labeling the chains of the peptide and the phospholipids with 2H enabled us to obtain atomically resolved parameters relevant to their structural dynamics. While the presence of ras only marginally affected the packing of DMPC membranes, dramatically lower order parameters (S(CD)) were observed for the ras acyl chains indicating modified packing properties. Essentially identical projected lengths of the 16:0 ras chains and the 14:0 DMPC chains were found, implying that the polypeptide backbone is located at the lipid-water interface. Dynamical properties of both the ras and phospholipid chains were determined from spin-lattice 2H relaxation (R1Z) measurements. Plots of R1Z rates versus the corresponding squared segmental order parameters revealed striking differences. We propose the ras peptide is confined to microdomains containing DMPC chains which are in exchange with the bulk bilayer on the 2H NMR time scale (approximately 10(-5) s). Compared to the host DMPC matrix, the ras lipid modifications are extremely flexible and undergo relatively large amplitude motions. It is hypothesized that this flexibility is a requirement for the optimal anchoring of lipid-modified proteins to cellular membranes.


Automatic detection of small bowel tumors in capsule endoscopy based on color curvelet covariance statistical texture descriptors.
Traditional endoscopic methods do not allow the visualization of the entire Gastrointestinal (GI) tract. Wireless Capsule Endoscopy (CE) is a diagnostic procedure that overcomes this limitation of the traditional endoscopic methods. The CE video frames possess rich information about the condition of the stomach and intestine mucosa, encoded as color and texture patterns. It is known for a long time that human perception of texture is based in a multi-scale analysis of patterns, which can be modeled by multi-resolution approaches. Furthermore, modeling the covariance of textural descriptors has been successfully used in classification of colonoscopy videos. Therefore, in the present paper it is proposed a frame classification scheme based on statistical textural descriptors taken from the Discrete Curvelet Transform (DCT) domain, a recent multi-resolution mathematical tool. The DCT is based on an anisotropic notion of scale and high directional sensitivity in multiple directions, being therefore suited to characterization of complex patterns as texture. The covariance of texture descriptors taken at a given detail level, in different angles, is used as classification feature, in a scheme designated as Color Curvelet Covariance. The classification step is performed by a multilayer perceptron neural network. The proposed method has been applied in real data taken from several capsule endoscopic exams and reaches 97.2% of sensitivity and 97.4% specificity. These promising results support the feasibility of the proposed method.


[Sotahexal pharmacodynamics in patients with ischemic heart disease].
Therapeutic and prophylactic antiarrhythmic efficacy of sotalol hydrochloride (Sotahexal, "Hexal", Germany) and its effects in intracardiac hemodynamics and ECG parameters were evaluated in 95 patients with ischemic heart disease (IHD). The highest response to the drug was observed in ventricular extrasystoles, arterial flutter and fibrillation. Acute episodes of arrhythmia are managed by bolus administration of Sotahexal [correction of Hexal]. In this case greater risk of side effects exists. It is desirable to decide on the drug dose, mode of administration on the individual basis with due consideration of the risks and dangers which could be avoided in case of adequate instrumental control.


Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort-Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation.
Background: Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy. Objective: To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays. Patients/Methods: Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays. Results: In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype. Conclusion: ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.


The MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care: a psychometric analysis.
Psychometric evaluation of a cross-sectional survey. To determine the validity of measures obtained from the MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care (MRPS) to differentiate between patient satisfaction with internal and external factors. Self-report measures that sample a variety of items provide clinicians with an array of information that may assist in assessing patient satisfaction. An important measurement characteristic of these instruments is the ability to discriminate between different factors that may influence patient reports of satisfaction with care, ie, discriminant validity. In previous work, exploratory factor analysis suggested that the MRPS questionnaire has a 2-factor structure: "internal," relating to the patient-therapist interaction, and "external," describing nontherapist issues such as admissions and clinic environment. One thousand four hundred forty-nine adult patients completed the MRPS questionnaire upon finishing their course of outpatient physical therapy treatment. Discriminant validity of the 2-factor model was assessed using confirmatory factor analysis. The measures from the 2 factors were then evaluated for reliability by calculating the standard error of measurement (SEM), and for concurrent validity by correlating the mean score of the factors and individual items to global measures of satisfaction. Confirmatory factor analysis supported a good to excellent model fit for the internal factor (7 items) and external factor (3 items). The SEM for the 2 factors was 0.19 and 0.24, indicating a low degree of measurement error. Both factors had high significant correlation with global measures of satisfaction (internal, r = 0.83 and 0.80; external, r = 0.71 and 0.71). All individual items within the 2 factors had significant correlations with global measures ranging from r = 0.33 to 0.80. Our findings provide evidence of discriminant and concurrent validity of the 2-factor solution for the MRPS questionnaire for the sample that was tested. This 2-factor solution yields measures that are relatively free of error and may discriminate between internal and external factors influencing patient satisfaction. Patients who complete their course of physical therapy report that the professional interaction between the therapist and patient, especially the meaningful exchange of relevant information, is critical for patient satisfaction with care. The generalizability of our data to patients who do not complete their physical therapy care or who are receiving care in other health care environments is unknown.


The spectrum of bacterial infections in febrile neutropenic patients: effect on empiric antibiotic therapy.
The aim of this retrospective analysis was to look at the spectrum of bacterial isolates and their resistance patterns to the commonly used antibiotics in the setting of febrile neutropenia. A total of 127 bacteria were isolated from patients with acute leukemias, lymphoproliferative disorders, aplastic anaemia and various solid tumours. Fifty-four percent organisms were gram negative; while the rest were gram positive. E. coli, pseudomonas aeruginosa, staphylococcus aureus, enterococcus and streptococci were the commonly isolated organisms. Forty-eight percent organisms were isolated from blood, 16% from urine, 13% from wounds and superficial abscesses and 11% from respiratory tract. E. coli exhibited a great degree of resistance to the commonly used antibiotics, such as pipericillin (70%), ofloxacin (50%) and aztreonam (50%). Pseudomonas and klebsiella also showed varying degree of resistance against the antibiotics. Staphylococcus aureus and staphylococcus epidermidis were almost universally resistant to penicillin and showed a variable degree of resistance to other antibiotics too. Compared to the previous reports, the pattern of bacterial isolates and their resistance to antibiotics has changed over the past years. Aminoglycosides and third generation cephalosporins seem to be the choice of antibiotics for the upfront management of febrile neutropenic patients.


Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors.
The Notch signaling pathway is required in both nonneoplastic neural stem cells and embryonal brain tumors, such as medulloblastoma, which are derived from such cells. We investigated the effects of Notch pathway inhibition on medulloblastoma growth using pharmacologic inhibitors of gamma-secretase. Notch blockade suppressed expression of the pathway target Hes1 and caused cell cycle exit, apoptosis, and differentiation in medulloblastoma cell lines. Interestingly, viable populations of better-differentiated cells continued to grow when Notch activation was inhibited but were unable to efficiently form soft-agar colonies or tumor xenografts, suggesting that a cell fraction required for tumor propagation had been depleted. It has recently been hypothesized that a small population of stem-like cells within brain tumors is required for the long-term propagation of neoplastic growth and that CD133 expression and Hoechst dye exclusion (side population) can be used to prospectively identify such tumor-forming cells. We found that Notch blockade reduced the CD133-positive cell fraction almost 5-fold and totally abolished the side population, suggesting that the loss of tumor-forming capacity could be due to the depletion of stem-like cells. Notch signaling levels were higher in the stem-like cell fraction, providing a potential mechanism for their increased sensitivity to inhibition of this pathway. We also observed that apoptotic rates following Notch blockade were almost 10-fold higher in primitive nestin-positive cells as compared with nestin-negative ones. Stem-like cells in brain tumors thus seem to be selectively vulnerable to agents inhibiting the Notch pathway.


Waveguide effects and implications for cardiac magnetic resonance elastography: A finite element study.
Magnetic resonance elastography (MRE) is increasingly being applied to thin or small structures in which wave propagation is dominated by waveguide effects, which can substantially bias stiffness results with common processing approaches. The purpose of this work was to investigate the importance of such biases and artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries with one or more dimensions that are small relative to the shear wavelength; and (ii) a realistic cardiac geometry. Finite element models were created using simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry, and simulated displacements acquired by MRE from harmonic excitations from 60 to 220 Hz across a range of frequencies. The displacement wave fields were inverted with direct inversion of the Helmholtz equation with and without the application of bandpass filtering and/or the curl operator to the displacement field. In all geometries considered, and at all frequencies considered, strong biases and artifacts were present in inversion results when the curl operator was not applied. Bandpass filtering without the curl was not sufficient to yield accurate recovery. In the 3D geometries, strong biases and artifacts were present in 2D inversions even when the curl was applied, while only 3D inversions with application of the curl yielded accurate recovery of the complex shear modulus. These results establish that taking the curl of the wave field and performing a full 3D inversion are both necessary steps for accurate estimation of the shear modulus both in simple thin-walled or small structures and in a realistic cardiac geometry when using simple inversions that neglect the hydrostatic pressure term. In practice, sufficient wave amplitude, signal-to-noise ratio, and resolution will be required to achieve accurate results.


Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance.
The management of infections due to Klebsiella pneumoniae has been complicated by the emergence of antimicrobial resistance, especially to carbapenems. Resistance to carbapenems in K. pneumoniae involves multiple mechanisms, including the production of carbapenemases (e.g., KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins and the upregulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of β-lactamases (e.g., AmpC). K. pneumoniae sequence type 258 (ST258) emerged during the early to mid-2000s as an important human pathogen and has spread extensively throughout the world. ST258 comprises two distinct lineages, namely, clades I and II, and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatibility group F plasmids with blaKPC have contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producing K. pneumoniae remains unknown. Some newer agents show promise for treating infections due to KPC producers; however, effective options for the treatment of NDM producers remain elusive.