Fluorocholine PET/CT predicts skeletal progression, skeletal event and cancer specific survival in patients with biochemical relapse for prostate cancer.
The aim of our study is to evaluate the prognostic impact of 18F-Choline (FCh) positron emission tomography (PET)/computed tomography (CT), CT alone and methylene diphophonate bone scan (MDP-BS) in prostate cancer (PCa) patients with biochemical relapse. We retrospectively selected 58 patients who underwent, between June 2010 and February 2013, both FCh-PET/CT and MDP-BS within a maximum time interval of 5months. All patients had a biochemical PCa recurrence after radical prostatectomy and/or radiation therapy. Two independent observers reviewed FCh-PET/CT and MDP-BS images. The bone window of CT portion from FCh-PET/CT was separately assessed. Time to progression (TTP), skeletal event free survival (SES) and cancer specific survival (CSS) were defined as the length of time between imaging and progression of disease, skeletal related events and cancer specific mortality, respectively. A patient based and a K agreement analysis was used to compare the findings of all three imaging modalities. Kaplan-Meier and log-rank analysis were computed for survival assessment. A multivariate Cox regression analysis was used to identify the independent predictors for TTP. Bone metastases were detected in 22 (38%) patients at FCh-PET/CT, in 27 (47%) at MDP-BS and in 24 (41%) at CT. The agreement between FCh-PET/CT and MDP-BS, CT and MDP-BS, and FCh-PET/CT and CT were moderate/fair (respectively, k: 0.474, 0.267 and 0.424; all p<0.05). After 38months (IQR: 27-54months) of follow-up, 33 (57%) patients had a new recurrence of disease, 12 (21%) had skeletal related events and 19 (33%) died. Three subjects (5%) were lost during the observational period. At survival analyses, a worse TTP, SES and CSS were found in patients with a positive FCh-PET/CT at bone level than those with a negative scan (all p≤0.05). Conversely, any significant difference in TTP, SES and CSS was found for patients with both a positive MDP-BS and CT scan. At univariate analysis, a positive FCh-PET/CT at skeletal level was associated with all events (all p<0.05). However, only a positive FCh-PET/CT at any site was an independent prognostic variable of TTP (HR: 3.08; CI 95%: 1.85-9.05; p=0.04). PET/CT should be preferred to CT and BS in patients with prostate cancer with bone metastasis because it allows a better stratification of TTP, SES and CCS compared to CT and BS.


Differentiation of Salmonella enterica serovars and strains in cultures and food using infrared spectroscopic and microspectroscopic techniques combined with soft independent modeling of class analogy pattern recognition analysis.
Detection of pathogenic microorganisms in food is often a tedious and time-consuming exercise. Developing rapid and cost-effective techniques for identifying pathogens to subspecies is critical for tracking causes of foodborne disease outbreaks. The objective of this study was to develop a method for rapid identification and differentiation of Salmonella serovars and strains within these serovars through isolation on hydrophobic grid membrane filters (HGMFs), examination by infrared (IR) spectroscopy and microspectroscopy, and data analysis by multivariate statistical techniques. Salmonella serovars (Anatum, Enteritidis, Heidelberg, Kentucky, Muenchen, and Typhimurium), most of which were represented by multiple strains, were grown in tryptic soy broth (24 h at 42 degrees C), diluted to 10(2) to 10(3) CFU/ml, and filtered using HGMFs. The membranes were incubated on Miller-Mallinson agar (24 h at 42 degrees C), and typical Salmonella colonies were sonicated in 50% acetonitrile and centrifuged. Resulting pellets were vacuum dried on a ZnSe crystal and analyzed using IR spectroscopy. Alternatively, the membranes containing Salmonella growth were removed from the agar, vacuum dried, and colonies were analyzed directly by IR microspectroscopy. Soft independent modeling of class analogy (SIMCA) models were developed from spectra. The method was validated by analyzing Salmonella-inoculated tomato juice, eggs, milk, and chicken. Salmonella serovars exhibited distinctive and reproducible spectra in the fingerprint region (1,200 to 900 cm(-1)) of the IR spectrum. SIMCA permitted distinguishing Salmonella strains from each other through differences in bacterial lipopolysaccharides and other membrane components. The model correctly predicted Salmonella in foods at serovar (100%) and strain (90%) levels. Isolation of Salmonella on HGMF and selective agar followed by IR spectroscopic analysis resulted in rapid and efficient isolation, identification, and differentiation of Salmonella serovars and strains.


[Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection].
To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection. Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded. All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients. Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.


Providing Oral Healthcare to Older Patients-Do We Have What It Takes?
Over the past decades, there has been an increase in the number of natural teeth that are maintained into older age, and this has represented an increase in the need for more complex dental treatment for this population. A trained workforce is needed in order to provide dental care to the different groups of elderly. Currently, the undergraduate training in gerodontology offered by dental schools seems to be limited, with great variation among dental schools worldwide. Given the heterogeneity of elderly groups, it is unlikely that new graduates from dental schools can be deemed competent to deal with the different groups of elderly. In this article, barriers to oral healthcare's provision to older adults are discussed, including the lack of appropriately trained dental professionals. Training pathways are discussed, including the preparation of undergraduate education to provide a suitable foundation to be developed further in postgraduate education. It is also proposed that older adults are classified according to their dependency level and each level is managed by properly trained dental professionals. In order to upskill general dental practitioners to care for these patients, postgraduate certification programmes could be structured to provide additional training. Furthermore, the development of geriatric oral health educational programmes for non-dental healthcare workers is recommended.


Genomic analysis of an infant with intractable diarrhea and dilated cardiomyopathy.
We describe a case of an infant presenting with intractable diarrhea who subsequently developed dilated cardiomyopathy, for whom a diagnosis was not initially achieved despite extensive clinical testing, including panel-based genetic testing. Research-based whole-genome sequences of the proband and both parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy integrating features of variants, genes, and phenotypes, which was implemented using publicly available tools. Although the intestinal morphological abnormalities characteristic of congenital tufting enteropathy (CTE) were not observed in the initial clinical gastrointestinal tract biopsies of the proband, an intronic variant, EPCAM c.556-14A>G, previously identified as pathogenic for CTE, was found in the homozygous state. A newborn cousin of the proband also presenting with intractable diarrhea was found to carry the same homozygous EPCAM variant, and clinical testing revealed intestinal tufting and loss of EPCAM staining. This variant, however, was considered nonexplanatory for the proband's dilated cardiomyopathy, which could be a sequela of the child's condition and/or related to other genetic variants, which include de novo mutations in the genes NEDD4L and GSK3A and a maternally inherited SCN5A variant. This study illustrates three ways in which genomic sequencing can aid in the diagnosis of clinically challenging patients: differential diagnosis despite atypical clinical presentation, distinguishing the possibilities of a syndromic condition versus multiple conditions, and generating hypotheses for novel contributory genes.


Baricitinib 2 mg for the treatment of atopic dermatitis in North America: Long-term efficacy and patient-reported outcomes.
To address the need for long-term efficacy and patient-reported outcomes (PROs) data for patients with atopic dermatitis (AD) treated with baricitinib 2 mg, a study was conducted to evaluate the efficacy of baricitinib 2 mg in adult patients with moderate-to-severe AD. Data presented here provided efficacy and outcomes data for patients treated for 52 weeks. Patients who participated in the originating study, BREEZE-AD5 (NCT03435081), and met additional eligibility criteria could enroll in the multicenter, open-label, Phase 3, long-term extension study BREEZE-AD6 (NCT03559270). Patients received baricitinib 2 mg for the duration of BREEZE-AD6. In BREEZE-AD6, the proportion of patients who achieved a 75% improvement in the Eczema Area and Severity Index (EASI75) and validated Investigator Global Assessment for AD (vIGA-AD™) of 0 (clear) or 1 (almost clear) were assessed through 52 weeks, in addition to several PROs. At week 52, the proportion of patients treated with baricitinib 2 mg daily achieving EASI75 was 48.6% (70/144), and 31.3% (45/144) of patients achieved a vIGA-AD score of 0 or 1 (clear or almost clear). Improvements in PROs such as SCORing Atopic Dermatitis (SCORAD, itch and sleep) scores, Dermatology Life Quality Index (DLQI) total score, and DLQI ≤5 response were observed, and these responses were sustained through 52 weeks. Long-term efficacy of baricitinib in patients with AD was demonstrated by both clinician and patient-reported outcome measures.


Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture.
Adipose-derived mesenchymal stem cells (ADMSCs) are a promising strategy for orthopaedic applications, particularly in bone repair. Ex vivo expansion of ADMSCs is required to obtain sufficient cell numbers. Xenogenic supplements should be avoided in order to minimise the risk of infections and immunological reactions. Human platelet lysate and human plasma may be an excellent material source for ADMSC expansion. In the present study, use of blood products after their recommended transfusion date to prepare human platelet lysate (HPL) and human plasma (Hplasma) was evaluated for in vitro culture expansion and osteogenesis of ADMSCs. Human ADMSCs were cultured in medium supplemented with HPL, Hplasma and a combination of HPL and Hplasma (HPL+Hplasma). Characteristics of these ADMSCs, including osteogenesis, were evaluated in comparison with those cultured in fetal bovine serum (FBS). HPL and HPL+Hplasma had a significantly greater growth-promoting effect than FBS, while Hplasma exhibited a similar growth-promoting effect to that of FBS. ADMSCs cultured in HPL and/or Hplasma generated more colony-forming unit fibroblasts (CFU-F) than those cultured in FBS. After long-term culture, ADMSCs cultured in HPL and/or Hplasma showed reduced cellular senescence, retained typical cell phenotypes, and retained differentiation capacities into osteogenic and adipogenic lineages. HPL and Hplasma prepared from blood products after their recommended transfusion date can be used as an alternative and effective source for large-scale ex vivo expansion of ADMSCs.Cite this article: J. Phetfong, T. Tawonsawatruk, K. Seenprachawong, A. Srisarin, C. Isarankura-Na-Ayudhya, A. Supokawej. Re-using blood products as an alternative supplement in the optimisation of clinical-grade adipose-derived mesenchymal stem cell culture. Bone Joint Res 2017;6:414-422. DOI: 10.1302/2046-3758.67.BJR-2016-0342.R1.


Mechanisms of insulin-resistant glucose utilization in rat skeletal muscle.
Defects in glucose uptake are among the primary defects associated with peripheral insulin resistance, but fundamental mechanisms leading to this state are poorly understood. In order to elucidate mechanisms leading toward defects in glucose transport, we have used a partially pancreatectomized infusion (PxI) animal model with infusions of saline, glucose, or insulin to examine individual and combined effects of hyperglycemia and hyperinsulinemia on skeletal muscle glucose utilization. Moderate hyperglycemia induced by pancreatectomy reduced basal hindlimb muscle glucose utilization by 57% without affecting maximal insulin-stimulated glucose utilization; insulin administered in an amount sufficient to correct this hyperglycemia did not alter basal glucose utilization, but maximal insulin-stimulated glucose utilization was sharply diminished (75%); hyperglycemia with hyperinsulinemia similarly reduced basal and maximal insulin-stimulated glucose utilization. In order to establish the role of the glucose transporter protein in these insulin-resistant states, we quantified GLUT 4 content by immunoblotting and GLUT 4 mRNA by solution hybridization/RNAse protection assays. Hyperglycemia (2 weeks) reduced total muscle GLUT 4 protein content (53%) and mRNA (46%), while subsequent hyperinsulinemia (72 h) with either normo- or hyperglycemia partially restored both total GLUT 4 protein and mRNA levels. As insulin-stimulated GLUT 4 content in plasma membranes was not diminished by combined hyperglycemia/hyperinsulinemia, these results indicate functional GLUT 4 translocation in this model and suggest suppression of GLUT 4 transporter activity.


Collective modes of quasi-two-dimensional Yukawa liquids.
Particles in dusty plasmas are often confined to a quasi-two-dimensional arrangement. In such layers--besides the formation of compressional and (in-plane) shear waves--an additional collective excitation may also show up, as small-amplitude oscillations of the particles perpendicular to the plane are also possible. We explore through molecular dynamics simulations the properties (fluctuation spectra, dispersion relation, Einstein frequency) of this out-of-plane transverse mode in the strongly coupled liquid phase of Yukawa systems.


Genetic markers and biomarkers for age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the USA. Although the treatment of AMD has evolved to include laser photocoagulation, photodynamic therapy, surgical macular translocation and antiangiogenesis agents, treatment options for advanced AMD are limited. Furthermore, the dry form of AMD, albeit less devastating than the wet form, has even fewer viable treatment options. This review summarizes the various biomarkers of AMD and analyzes whether or not they may one day be exploited to determine risks of disease onset, measure progression of disease or even assess the effects of treatment of AMD. Potential biomarkers are important to identify since some might be utilized to reflect the disease state of a particular patient and to individualize therapy. Although studies have yielded promising results for nutrient and inflammatory biomarkers, these results have been inconsistent. At present, the best available markers of AMD risk are single nucleotide polymorphisms (SNPs). SNPs in complement factor H (CFH) and PLEKHA1/ARMS2/HtrA1 capture a substantial fraction of AMD risk and permit the identification of individuals at high risk of developing AMD.


Detection of infectious simian immunodeficiency virus in B- and T-cell lymphomas of experimentally infected macaques.
An increasing frequency of malignant lymphomas occurs among patients infected by human immunodeficiency virus. Because of the close similarities to human malignancies, we used a nonhuman primate model to study the pathogenesis of simian immunodeficiency virus (SIV)-associated malignancies. Specifically, we investigated (1) the presence of the SIV genome in tumor cells, (2) the presence of coinfecting viruses, and (3) the presence of a rearrangement of the immunoglobulin and c-myc genes. We observed 5 cases of non-Hodgkin's lymphomas (4 of B- and 1 of T-cell origin) among 14 SIV-infected cynomolgus monkeys. No c-myc translocation was observed in the tumors, whereas B-cell lymphomas were characterized either by a monoclonal (in 2 of 4) or by an oligoclonal (in 2 of 4) VDJ rearrangements of the immunoglobulin heavy chain gene. Molecular, biological, and immunological analyses did show the presence of infectious SIV in the tumor cells of 1 T-cell and 2 oligoclonal B-cell lymphomas. Neither Simian T-lymphotropic nor Epstein-Barr viruses were detectable, whereas Simian herpes virus Macaca fascicularis-1 was detectable at a very low copy number in 3 of 4 B-cell lymphomas; however, only 1 of these also harbored the SIV genome. These results support the possibility that SIV may be directly involved in the process of B or T lymphomagenesis occurring in simian acquired immunodeficiency syndrome.


Sex differences in the pattern of innominate motion during passive hip abduction and external rotation.
The objective of the study was to evaluate sex differences in the pattern of innominate motion about the sacroiliac joint (SIJ) during hip movement. Although the magnitude of intrinsic SIJ motion is influenced by joint congruence and ligament elasticity sex differences in pelvic joint kinematics are under-investigated. Forty healthy and active males and females between the ages of 18 and 35 were recruited. 3D motion of the innominate bones and femur were recorded with a magnetic tracking device as the hips were loaded in standardised increments of 10 degrees in 3 positions - external rotation (ER), abduction (AB), and combined external rotation and abduction (AB+ER). While females had greater overall innominate motion, two distinct sex dominant patterns emerged. Patterns of innominate motion also differed when load was applied to the dominant rather than non-dominant limb. As the main motion within the pelvis is intrinsic, the results of the present study point to a differing viscoelastic response and different movement strategies to passive load between the sexes. In addition, careful attention to limb dominance should be considered when testing SIJ motion.


Teenage pregnancy: "having a baby won't affect me that much".
This qualitative study explored the experience of pregnancy from the perspectives of female adolescents. Interviews were conducted over a 16-week period with eight pregnant students who attended an alternative school program for pregnant teens. The hermeneutic social science method based on the work of Kockelmans (1975) and Steeves and Kahn (1995) guided the analysis. Overall, participants expressed a sense of optimism and confidence in their abilities to manage single parenthood, achieve educational goals, and maintain supportive relationships with the fathers of their babies. The findings support previous research and raise questions that warrant further study, particularly in relation to fighting behaviors.


Atrial fibrillation detection on compressed sensed ECG.
Compressive sensing (CS) approaches to electrocardiogram (ECG) analysis provide efficient methods for real time encoding of cardiac activity. In doing so, it is important to assess the downstream effect of the compression on any signal processing and classification algorithms. CS is particularly suitable for low power wearable devices, thanks to its low-complex digital or hardware implementation that directly acquires a compressed version of the signal through random projections. In this work, we evaluate the impact of CS compression on atrial fibrillation (AF) detection accuracy. We compare schemes with data reconstruction based on wavelet and Gaussian models, followed by a P&T-based identification of beat-to-beat (RR) intervals on the MIT-BIH atrial fibrillation database. A state-of-the-art AF detector is applied to the RR time series and the accuracy of the AF detector is then evaluated under different levels of compression. We also consider a new beat detection procedure which operates directly in the compressed domain, avoiding costly signal reconstruction procedures. We demonstrate that for compression ratios up to 30[Formula: see text] the AF detector applied to RR intervals derived from the compressed signal exhibits results comparable to those achieved when employing a standard QRS detector on the raw uncompressed signals, and exhibits only a 2% accuracy drop at a compression ratio of 60%. We also show that the Gaussian-based reconstruction approach is superior in terms of AF detection accuracy, with a negligible drop in performance at a compression ratio ⩽75%, compared to a wavelet approach, which exhibited a significant drop in accuracy at a compression ratio ⩾65%. The results suggest that CS should be considered as a plausible methodology for both efficient real time ECG compression (at moderate compression rates) and for offline analysis (at high compression rates).


Cold acclimation increases cardiac myofilament function and ventricular pressure generation in trout.
Reducing temperature below the optimum of most vertebrate hearts impairs contractility and reduces organ function. However, a number of fish species, including the rainbow trout, can seasonally acclimate to low temperature. Such ability requires modification of physiological systems to compensate for the thermodynamic effects of temperature on biological processes. The current study tested the hypothesis that rainbow trout compensate for the direct effect of cold temperature by increasing cardiac contractility during cold acclimation. We examined cardiac contractility, following thermal acclimation (4, 11 and 17°C), by measuring the Ca(2+) sensitivity of force generation by chemically skinned cardiac trabeculae as well as ventricular pressure generation using a modified Langendorff preparation. We demonstrate, for the first time, that the Ca(2+) sensitivity of force generation was significantly higher in cardiac trabeculae from 4°C-acclimated trout compared with those acclimated to 11 or 17°C, and that this functional change occurred in parallel with a decrease in the level of cardiac troponin T phosphorylation. In addition, we show that the magnitude and rate of ventricular pressure generation was greater in hearts from trout acclimated to 4°C compared with those from animals acclimated to 11 or 17°C. Taken together, these results suggest that enhanced myofilament function, caused by modification of existing contractile proteins, is at least partially responsible for the observed increase in pressure generation after acclimation to 4°C. In addition, by examining the phenotypic plasticity of a comparative model we have identified a strategy, used in vivo, by which the force-generating capacity of cardiac muscle can be increased.


Scoliosis and kyphosis in adolescents: diagnosis and management.
Scoliosis and kyphosis are spinal deformities that are commonly detected in the adolescent years. Scoliosis has many etiologies but is usually idiopathic. The natural history concerns pulmonary restriction, back pain, and self-image. Young children with large curves are at the greatest risk for progression. Treatment includes observation, bracing, or surgery. Kyphosis is a pathologic increase in sagittal curves of the spine. Scheuermann kyphosis is a distinct category of deformity that is diagnosed on the basis of the radiographic criteria of 3 adjacent vertebral levels with 5 degrees of wedging. The deformity is the main concern for teenage patients and their families, whereas pain is the main complaint in adults.


An attention-based multi-modal MRI fusion model for major depressive disorder diagnosis.
Objective.Major depressive disorder (MDD) is one of the biggest threats to human mental health. MDD is characterized by aberrant changes in both structure and function of the brain. Although recent studies have developed some deep learning models based on multi-modal magnetic resonance imaging (MRI) for MDD diagnosis, the latent associations between deep features derived from different modalities were largely unexplored by previous studies, which we hypothesized may have potential benefits in improving the diagnostic accuracy of MDD.Approach.In this study, we proposed a novel deep learning model that fused both structural MRI (sMRI) and resting-state MRI (rs-fMRI) data to enhance the diagnosis of MDD by capturing the interactions between deep features extracted from different modalities. Specifically, we first employed a brain function encoder (BFE) and a brain structure encoder (BSE) to extract the deep features from fMRI and sMRI, respectively. Then, we designed a function and structure co-attention fusion (FSCF) module that captured inter-modal interactions and adaptively fused multi-modal deep features for MDD diagnosis.Main results.This model was evaluated on a large cohort and achieved a high classification accuracy of 75.2% for MDD diagnosis. Moreover, the attention distribution of the FSCF module assigned higher attention weights to structural features than functional features for diagnosing MDD.Significance.The high classification accuracy highlights the effectiveness and potential clinical of the proposed model.


Does Local Zoledronate Applied to Pasteurized Bone Autografts Improve the Likelihood of Union of Graft-Host Junctions after Limb-sparing Surgery?
Pasteurized bone autograft is a recycling biological reconstruction method for limb-sparing surgery when an allograft or other reconstruction technique is unavailable. Since the application of a local bisphosphonate to morselized allografts can reduce graft resorption and enhance bone formation without systemic complications, adding the local bisphosphonate to pasteurized bone autografts should reduce the graft resorption and improve the graft incorporation to host bone. However, no study that we know of has described the outcomes of local bisphosphonate application to massive allografts or pasteurized bone autografts. Thus, this study compared the outcomes of pasteurized bone autografts with and without local zoledronate. (1) What is the survival of pasteurized bone autografts and what complications lead to graft removal? (2) Does treatment of pasteurized bone autografts with zoledronate alter the survival of pasteurized bone autografts compared with grafts without treatment? (3) Does the local application of zoledronate reduce the proportion of patients with fractures because of metaphyseal graft resorption? (4) Does local application of zoledronate improve union at the graft-host bone junction compared with untreated grafts? Between July 2011 and December 2019, we performed 538 musculoskeletal bone tumor resections. Of these, 101 patients underwent reconstruction with pasteurized bone autografts. Other reconstructions included tumor prostheses (150 patients), allografts (70 patients), reconstruction using a bone cement-plate construct (62 patients), and resection only (155 patients). We generally used pasteurized bone autograft when tumors showed an osteoblastic pattern, had less than one-third cortical destruction, and less than half of metaphyseal bone destruction. Six percent (6 of 101) were lost to follow-up, 6% (6 of 101) had incomplete clinical data, and 16% (16 of 101) had a follow-up period less than 2 years without an event, leaving 73 patients for evaluation. The median (interquartile range) age of the patients was 18 years (15 to 26). Ninety-seven percent (71 of 73) had a diagnosis of bone sarcoma. The median follow-up time was 46 months (33 to 75). From 2011 to 2014, 21 pasteurized bone autografts were prepared without local zoledronate, and from 2014 to 2019, 52 pasteurized bone autografts were prepared with local zoledronate because we thought it might improve union and reduce resorption of the graft. From our tumor registry database, we obtained age, sex, use of chemotherapy, graft length and location, pasteurized bone graft type, fixation methods, the use of local zoledronate, osteotomy gap, complications, proportion of grafts that united by 2 years, and local recurrences. Curves for graft survival were determined using the Kaplan-Meier method with the endpoint of autograft removal and metaphyseal fracture from graft resorption. The probabilities of graft removal were estimated by cumulative incidences using the competing risk analysis, where death was considered as the competing event. Intergroup differences in survival and multivariable analyses were performed using the log-rank test and a Cox regression analysis. A logistic regression model was used to evaluate the association between graft-host osseous union by 2 years and other baseline factors. Union was defined when a callus was seen to bridge the osteotomy line for at least three cortices in both the AP and mediolateral planes. The 5-year survival rate of all 73 pasteurized grafts was 85% (95% confidence interval 74% to 92%). With the numbers available, we found no difference in the 5-year survival rates between grafts with and without local zoledronate (90% [95% CI 78% to 96%] versus 74% [95% CI 48% to 89%]; p = 0.30). Eleven percent (8 of 73) of patients had metaphyseal fractures because of graft resorption, primarily associated with osteoarticular grafts (5-year fracture-free survival 56% [95% CI 20 to 80]) rather than pasteurized graft-prosthesis composites (94% [95% CI 78% to 98%]) and intercalary grafts (91% [95% CI 50 to 99]; p = 0.001); there was no association with the use of local zoledronate (13%; 7 of 52) compared with those without local zoledronate (5%; 1 of 21) (odds ratio 3.1 [95% CI 0.4 to 27]; p = 0.43). Of the 84 graft-host bone junctions, 85% (71) of the grafts unified within 2 years, 7% (6) unified after 2 years, and 8% (7) of grafts showed nonunion. Union within 2 years was associated with fixation using plate compared with those with stem and with both stem and plate (odds ratio 6.6 [95% CI 1.4 to 31]; p = 0.02) and grafts treated with local zoledronate compared with those without treatment (OR 5.9 [95% CI 1.3 to 28]; p = 0.02). The application of local zoledronate to pasteurized bone autografts for limb-sparing surgery improved the likelihood of graft union compared with untreated grafts, especially when the osteotomy junctions were fixed using plate osteosynthesis, but it did not appear to alter the proportion of patients who experience metaphyseal fracture of the grafts because of graft resorption. Although this is a small study, it suggests that the treatment of pasteurized bone autografts and perhaps bone allografts should be studied further to determine whether bisphosphonates or other adjuncts can improve the union time and return to function in patients undergoing bone tumor resections using these reconstruction types. Level III, therapeutic study.


Thermally induced intracellular alteration of ribosomal ribonucleic acid.
Heating at 55 C causes the intracellular degradation of ribosomes of Staphylococcus aureus MF-31. The 30S subunit of heated cells appears to be selectively attacked. Analysis of ribonucleic acid (RNA) showed that 16S RNA was destroyed and that the secondary structure of 23S RNA was altered.


Periodontal disease and anemias associated with Crohn's disease. A case report.
Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.


Global Landscape of m6A Methylation of Differently Expressed Genes in Muscle Tissue of Liaoyu White Cattle and Simmental Cattle.
Liaoyu white cattle (LYWC) is a local breed in Liaoning Province, China. It has the advantages of grow quickly, high slaughter ratew, high meat quality and strong anti-stress ability. N6 methyladenosine (m6A) is a methylation modification of N6 position of RNA adenine, which is an important modification mechanism affecting physiological phenomena. In this study, we used the longissimus dorsi muscle of LYWC and SIMC for m6A-seq and RNA-seq high-throughput sequencing, and identified the key genes involved in muscle growth and m6A modification development by bioinformatics analysis. There were 31532 m6A peaks in the whole genome of LYWC and 47217 m6A peaks in the whole genome of SIMC. Compared with Simmental cattle group, LYWC group had 17,351 differentially expressed genes: 10,697 genes were up-regulated, 6,654 genes were down regulated, 620 differentially expressed genes were significant, while 16,731 differentially expressed genes were not significant. Among the 620 significantly differentially expressed genes, 295 genes were up-regulated and 325 genes were down regulated. In order to explore the relationship between m6A and mRNA expression in the muscles of LYWC and SIMC, the combined analysis of MeRIP-seq and RNA-seq revealed that 316 genes were m6A modified with mRNA expression. To identify differentially methylated genes related to muscle growth, four related genes were selected for quantitative verification in LYWC and SIMC. GO enrichment and KEGG analysis showed that the differentially expressed genes modified by m6A are mainly involved in skeletal muscle contraction, steroid biosynthesis process, redox process, PPAR pathway and fatty acid metabolism, and galactose metabolism. These results provide a theoretical basis for further research on the role of m6A in muscle growth and development.


[Pseudomonas stutzeri osteitis: A case study].
We report a case of osteitis in a 46-year-old patient, caused by Pseudomonas stutzeri following an open fracture of the left femur. The patient was treated with 1g ceftazidime every 8 hours for two weeks combined with 160 mg/day of amikacin for 10 days. A second-line ofloxacin oral treatment at 400 mg/day was then given during 4 weeks. Surgical treatment consisted in debridement of the fracture region. Sterilization of the fracture region led to an osteosynthesis by blade plate and bone graft. The result was favorable.


Toward Efficient Palmprint Feature Extraction by Learning a Single-Layer Convolution Network.
In this article, we propose a collaborative palmprint-specific binary feature learning method and a compact network consisting of a single convolution layer for efficient palmprint feature extraction. Unlike most existing palmprint feature learning methods, such as deep-learning, which usually ignore the inherent characteristics of palmprints and learn features from raw pixels of a massive number of labeled samples, palmprint-specific information, such as the direction and edge of patterns, is characterized by forming two kinds of ordinal measure vectors (OMVs). Then, collaborative binary feature codes are jointly learned by projecting double OMVs into complementary feature spaces in an unsupervised manner. Furthermore, the elements of feature projection functions are integrated into OMV extraction filters to obtain a collection of cascaded convolution templates that form a single-layer convolution network (SLCN) to efficiently obtain the binary feature codes of a new palmprint image within a single-stage convolution operation. Particularly, our proposed method can easily be extended to a general version that can efficiently perform feature extraction with more than two types of OMVs. Experimental results on five benchmark databases show that our proposed method achieves very promising feature extraction efficiency for palmprint recognition.


ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres.
Diffuse spread through brain parenchyma and the presence of hypoxic foci rimmed by neoplastic cells are two cardinal features of glioblastoma, and low oxygen is thought to drive movement of malignant gliomas in the core of the lesions. Transcription factors associated with epithelial-to-mesenchymal transition (EMT) have been linked to this invasion, and we found that hypoxia increased in vitro invasion up to fourfold in glioblastoma neurosphere lines and induced the expression of ZEB1. Immunohistochemical assessment of 295 surgical specimens consisting of various types of pediatric and adult brain cancers showed that ZEB1 expression was significantly higher in infiltrative lesions than less invasive tumors such as pilocytic astrocytoma and ependymoma. ZEB1 protein was also present in human fetal periventricular stem and progenitor cells and ZEB1 inhibition impaired migration of in vitro propagated human neural stem cells. The induction of ZEB1 protein in hypoxic glioblastoma neurospheres could be partially blocked by the HIF1alpha inhibitor digoxin. Targeting ZEB1 blocked hypoxia-augmented invasion of glioblastoma cells in addition to slowing them in normoxia. These data support the role for ZEB1 in invasive and high-grade brain tumors and suggest its key role in promoting invasion in the hypoxic tumor core as well as in the periphery.


A cold-atom Fermi-Hubbard antiferromagnet.
Exotic phenomena in systems with strongly correlated electrons emerge from the interplay between spin and motional degrees of freedom. For example, doping an antiferromagnet is expected to give rise to pseudogap states and high-temperature superconductors. Quantum simulation using ultracold fermions in optical lattices could help to answer open questions about the doped Hubbard Hamiltonian, and has recently been advanced by quantum gas microscopy. Here we report the realization of an antiferromagnet in a repulsively interacting Fermi gas on a two-dimensional square lattice of about 80 sites at a temperature of 0.25 times the tunnelling energy. The antiferromagnetic long-range order manifests through the divergence of the correlation length, which reaches the size of the system, the development of a peak in the spin structure factor and a staggered magnetization that is close to the ground-state value. We hole-dope the system away from half-filling, towards a regime in which complex many-body states are expected, and find that strong magnetic correlations persist at the antiferromagnetic ordering vector up to dopings of about 15 per cent. In this regime, numerical simulations are challenging and so experiments provide a valuable benchmark. Our results demonstrate that microscopy of cold atoms in optical lattices can help us to understand the low-temperature Fermi-Hubbard model.


The EORTC QLU-C10D: The Canadian Valuation Study and Algorithm to Derive Cancer-Specific Utilities From the EORTC QLQ-C30.
Objective. The EORTC QLQ-C30 is widely used for assessing quality of life in cancer. However, QLQ-C30 responses cannot be incorporated in cost-utility analysis because they are not based on general population's preferences, or utilities. To overcome this limitation, the QLU-C10D, a cancer-specific utility algorithm, was derived from the QLQ-C30. The aim of this study was to obtain Canadian population utility weights for the QLU-C10D. Methods. Respondents from a Canadian research panel expressed their preferences for 16 choice sets in an online discrete choice experiment. Each choice set consisted of two health states described by the 10 QLU-C10D domains plus an attribute representing duration of survival. Using a conditional logit model, responses were converted into utility decrements by evaluating the marginal rate of substitution between each QLU-C10D domain level with respect to duration. Results. A total of 3,363 individuals were recruited. A total of 2,345 completed at least one choice set and 2,271 completed all choice sets. The largest utility decrements were associated with the worse levels of Physical Functioning (-0.24), Pain (-0.18), Role Functioning (-0.15), Emotional Functioning (-0.12), and Nausea (-0.12). The remaining domains and levels had decrements of -0.05 to -0.09. The utility of the worst possible health state was -0.15. Conclusion. Respondents from the general population were most concerned with generic health domains, but Nausea and Bowel Problems also had an impact on the individual's utility. It is unclear as to whether cancer-specific domains will affect cost-utility analysis when evaluating cancer treatments; this will be tested in the next phase of the study.


Prevention of hypertension.
This review summarizes papers and reports published during the past year that contribute important knowledge or perspectives about prevention of elevated arterial blood pressure. Emphasis is on controlled intervention trials, particularly the large, multicenter Trials of Hypertension Prevention-Phase I, but all relevant randomized trials known to the author are included. Observational epidemiologic studies that are cross-sectional, eg, the INTERSALT study and the US Pitt County Study, or longitudinal, eg, the large Health Professionals Followup Study and the National Health and Nutrition Examination Survey (I) Epidemiologic Followup Study, are also discussed. The recent evidence, when viewed in the context of the previously accumulated literature, supports the recommendations of two recent expert reports to the effect that 1) much knowledge is available to help avoid the rise of blood pressure with age that is the hallmark of the epidemic of hypertension in industrialized societies, and 2) efforts should be particularly directed toward control of obesity, increased physical activity, reduced salt intake, and moderation of alcohol use.


Cytoreductive nephrectomy and its role in the present-day period of targeted therapy.
The beneficial effect of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma in the immunotherapy era was based on two prospective randomized trials. Unfortunately, such evidence does not yet exist in the present-day period of targeted therapy. Despite this, cytoreductive nephrectomy remains integral in the multimodal management of patients with metastatic renal cell carcinoma. Multiple retrospective studies as well as data from prospective studies examining targeted therapy support the continued use of cytoreductive nephrectomy in the properly selected patient. Ongoing studies will hopefully fine-tune the role and timing of cytoreductive nephrectomy in the context of targeted therapy.


Neutrophil migration through test end tissues of bovine mammary quarters experimentally challenged with Staphylococcus aureus.
Diapedesis and infiltration of neutrophils into internal epithelial tissues of the distal teat end and migration into milk were studied in bovine mammary quarters infected with Staphylococcus aureus. Neutrophil extravasation, penetration of the epithelium, and mode of passage into milk were evaluated by light and transmission electron microscopy. Collection of observations from 10 infected quarters of six cows provided morphologic evidence for the following sequence of events as neutrophils passed from blood into milk. In capillaries of the subepithelial stroma, neutrophils adhered to luminal walls, penetrated endothelia and basal lamina, then migrated across the periendothelial cell layer into extravascular connective tissues adjacent to epithelial linings. The leukocytes then penetrated epithelial basal laminae and migrated between basal epithelial cells to gain access to the luminal cell layer. Possible modes of migration across luminal cells into milk included 1) projection through individual, degenerate luminal cells, 2) penetration between intact epithelia, and 3) passage into milk as luminal cells desquamated in areas of epithelial metaplasia. The first method appeared to be the predominant mechanism of migration. These data suggest that elevated numbers of neutrophils in distal teat end epithelium and in cisternal milk may be instrumental in the initial events that prevent establishment of infection in the bovine mammary gland.


Incorporation of Salivary Gland Ultrasonography Into the American College of Rheumatology/European League Against Rheumatism Criteria for Primary Sjögren's Syndrome.
To assess whether the addition of salivary gland ultrasonography (SGUS) or replacement of current criteria items by SGUS influences the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for primary Sjögren's syndrome. Included were consecutive patients with complete data on all ACR/EULAR items (n = 243) who underwent SGUS in our primary Sjögren's syndrome expertise center. Clinical diagnosis by the treating physician was used as the gold standard. Separate analyses were performed for patients who underwent labial or parotid gland biopsies. The average score for hypoechogenic areas in 1 parotid and 1 submandibular gland was determined (range 0-3). Next, performance of the ACR/EULAR criteria was evaluated after addition of SGUS or replacement of current items by SGUS. Receiver operating characteristic analysis showed an optimal cutoff value of ≥1.5 for SGUS. The optimal weight for SGUS positivity was 1. Cutoff for ACR/EULAR fulfilment remained ≥4. In patients who underwent a labial gland biopsy (n = 124), the original criteria showed an area under the curve (AUC) of 0.965, sensitivity of 95.9%, and specificity of 92.2%. After the addition of SGUS, the AUC was 0.966, with a sensitivity of 97.3% and specificity of 90.2%. In patients who underwent a parotid gland biopsy (n = 198), similar results were found. Sensitivity of the criteria decreased substantially when SGUS replaced salivary gland biopsy or anti-SSA antibodies, while performance remained equal when SGUS replaced the ocular staining score, Schirmer's test, or unstimulated whole saliva flow. Validity of the ACR/EULAR criteria remains high after incorporation of SGUS. With SGUS, clinicians are offered a larger array of tests to evaluate fulfillment of the ACR/EULAR criteria.


A comparative study of the clinical effects of pentobarbital and diazepam given orally as preoperative medication.
The clinical effects of pentobarbital, 100 mg, and diazepam, 10 mg, given orally as preoperative medications before dental surgery were tested in a double-blind study in 50 adult patients. The concnetrations of pentobarbital and diazepam (plus its three active metabolites) in plasma, measured by gas chromatography, were correlated with their clinical effects as assessed both subjectively and objectively (sedation, apprehension, excitement, dizziness, pre- and post-operative emetic effect, increase or decrease in systolic blood pressure, pulse rate, and ease of venipuncture). No significant difference in the effects of these two agents was observed, nor was there any obvious relationship between the concentration in plasma and clinical effect.


The Senses of Agency and Ownership in Patients With Borderline Personality Disorder.
Patients with borderline personality disorder (BPD) not only experience a strong instability in their affect and interpersonal relations but also disturbances in their self-experience, including dissociation and body-alienation symptoms. It is not yet understood whether an altered sense of ownership (SoO) or sense of agency (SoA) may contribute to these disturbances. One recent hypothesis is that patients with BPD have a reduced sense of self and are therefore more likely to misattribute external objects or actions to their own self than healthy individuals. The present study followed up this hypothesis by investigating whether BPD patients have a more flexible body representation than healthy participants. More specifically, the active rubber hand illusion (aRHI) was applied to 21 patients with BPD and the same number of healthy participants. Using established subjective, electrodermal, and behavioral measures, the participants' SoO and SoA were assessed during the aRHI. The findings show self-reported evidence for higher SoO under anatomical hand congruency as compared to anatomical incongruency, but no evidence for group differences between BPD patients and healthy participants. This finding is inconsistent with previous findings of an enhanced SoO-related body plasticity in BPD patients. Regarding SoA, the findings show self-report evidence of higher SoA in BPD patients versus healthy participants, although this group difference was not evident in the implicit SoA measure (intentional binding). In summary, the present study only reveals partial evidence for a higher body plasticity in BPD patients. Instead, the observed variability in results appears better explainable by some generally elevated perceptual suggestibility of BPD individuals.


Investigating the connections between health lean management and clinical risk management.
The purpose of this paper is to investigate connections and overlaps between health lean management (HLM) and clinical risk management (CRM) understanding whether and how these two approaches can be combined together to pursue efficiency and patient safety improvements simultaneously. A systematic literature review has been carried out. Searching in academic databases, papers that focus not only on HLM, but also on clinical errors and risk reduction, were included. The general characteristics of the selected papers were analysed and a content analysis was conducted. In most of the papers, pursing objectives of HLM and CRM and adopting tools and practices of both approaches, results of quality and, particularly, of safety improvements were obtained. A two-way arrow between HLM and CRM emerged but so far, none of the studies has been focused on the relationship between HLM and CRM. Results highlight an emerging research stream, with many useful theoretical and practical implications and opportunities for further research.


BAD1, an essential virulence factor of Blastomyces dermatitidis, suppresses host TNF-alpha production through TGF-beta-dependent and -independent mechanisms.
We investigated how BAD1, an adhesin and virulence factor of Blastomyces dermatitidis, suppresses phagocyte proinflammatory responses. Wild-type yeast cocultured with murine neutrophils or macrophages prompted release of a soluble factor into conditioned supernatant that abolished TNF-alpha production in response to the fungus; isogenic, attenuated BAD1 knockout yeast did not have this effect. Phagocytes released 4- to 5-fold more TGF-beta in vitro in response to wild-type yeast vs BAD1 knockout yeast. Treatment of inhibitory, conditioned supernatant with anti-TGF-beta mAb neutralized detectable TGF-beta and restored phagocyte TNF-alpha production. Similarly, addition of anti-TGF-beta mAb into cultures of phagocytes and wild-type yeast reversed BAD1 inhibition of TNF-alpha production. Conversely, TGF-beta treatment of phagocytes cultured with knockout yeast suppressed TNF-alpha production. Hence, TGF-beta mediates BAD1 suppression of TNF-alpha by wild-type B. dermatitidis cultured in vitro with phagocytes. In contrast to these findings, neutralization of elevated TGF-beta levels during experimental pulmonary blastomycosis did not restore BAD1-suppressed TNF-alpha levels in the lung or ameliorate disease. Soluble BAD1 was found to accumulate in the alveoli of infected mice at levels that suppressed TNF-alpha production by phagocytes. However, in contrast to yeast cell surface BAD1, which induced TGF-beta, soluble BAD1 failed to do so and TNF-alpha suppression mediated by soluble BAD1 was unaffected by neutralization of TGF-beta. Thus, BAD1 of B. dermatitidis induces suppression of TNF-alpha and progressive infection by both TGF-beta-dependent and -independent mechanisms.


[Results of a clinical and experimental study of the safety and efficacy of Cytoflavin in combination with reperfusion therapy for ischemic stroke].
To study the efficacy and safety of Cytoflavin in combination with thrombolytic therapy. At the first preclinical stage, the effect of Cytoflavin, solution for intravenous administration, on the fibrinolytic activity of alteplase (Actilyse) was studied in vitro. At the second, clinical stage, the safety and efficacy of Cytoflavin treatment, initiated within in the first 24 hours from the stroke onset and continued for 10 days, was evaluated in patients with acute stroke who received reperfusion therapy. At the clinical stage of the study, 200 patients were examined: 100 subjects of the main group who received reperfusion therapy in combination with Cytoflavin; 100 control subjects who received reperfusion therapy in combination with other drugs from the neuroprotective group as part of routine clinical practice. The preclinical study has demonstrated that alteplase in the studied concentrations debulks the mass of a thrombus by 2131%. There were no statistically significant differences in the reduction of thrombus weight with addition of Cytoflavin at various concentrations combined with alteplase to the incubation medium. The addition of Cytoflavin to the incubation medium with alteplase had no effect on the concentration of D-dimer in the rat's plasma. In the clinical study, there were no statistically significant differences in the frequencies of intracranial hemorrhages of various types between the study groups. In the multivariable analysis, significant predictors of intracranial hemorrhage were baseline NIHSS score, systolic blood pressure, history of diabetes and anticoagulant use, baseline CT ASPECTS score, but not the treatment group. The use of Cytoflavin in combination with thrombolytic therapy is safe. Up-to-date treatment of stroke which includes timely reperfusion and neurometabolic support of recovery leads to the rapid manifest regression of the neurological deficit and to the improvement in functioning and activity of patients with cerebral infarction.


Examination of a deformable motion model for respiratory movements and 4D dose calculations using different driving surrogates.
The aim of this study was to evaluate a surrogate-driven motion model based on four-dimensional computed tomography that is able to predict CT volumes corresponding to arbitrary respiratory phases. Furthermore, the comparison of three different driving surrogates is examined and the feasibility of using the model for 4D dose re-calculation will be discussed. The study is based on repeated 4DCTs of twenty patients treated for bronchial carcinoma and metastasis. The motion model was estimated from the planning 4DCT through deformable image registration. To predict a certain phase of a follow-up 4DCT, the model considers inter-fractional variations (baseline correction) and intra-fractional respiratory parameters (amplitude and phase) derived from surrogates. The estimated volumes resulting from the model were compared to ground-truth clinical 4DCTs using absolute HU differences in the lung region and landmarks localized using the Scale Invariant Feature Transform. Finally, the γ-index was used to evaluate the dosimetric effects of the intensity differences measured between the estimated and the ground-truth CT volumes. The results show absolute HU differences between estimated and ground-truth images with median value (± standard deviation) of (61.3 ± 16.7) HU. Median 3D distances, measured on about 400 matching landmarks in each volume, were (2.9 ± 3.0) mm. 3D errors up to 28.2 mm were found for CT images with artifacts or reduced quality. Pass rates for all surrogate approaches were above 98.9% with a γ-criterion of 2%/2 mm. The results depend mainly on the image quality of the initial 4DCT and the deformable image registration. All investigated surrogates can be used to estimate follow-up 4DCT phases, however, uncertainties decrease for volumetric approaches. Application of the model for 4D dose calculations is feasible.


CVD Synthesis of MoS2 Using a Direct MoO2 Precursor: A Study on the Effects of Growth Temperature on Precursor Diffusion and Morphology Evolutions.
In this study, the influence of growth temperature variation on the synthesis of MoS2 using a direct MoO2 precursor was investigated. The research showed that the growth temperature had a strong impact on the resulting morphologies. Below 650 °C, no nucleation or growth of MoS2 occurred. The optimal growth temperature for producing continuous MoS2 films without intermediate-state formation was approximately 760 °C. However, when the growth temperatures exceeded 800 °C, a transition from pure MoS2 to predominantly intermediate states was observed. This was attributed to enhanced diffusion of the precursor at higher temperatures, which reduced the local S:Mo ratio. The diffusion equation was analyzed, showing how the diffusion coefficient, diffusion length, and concentration gradients varied with temperature, consistent with the experimental observations. This study also investigated the impact of increasing the MoO2 precursor amount, resulting in the formation of multilayer MoS2 domains at the outermost growth zones. These findings provide valuable insights into the growth criteria for the effective synthesis of clean and large-area MoS2, thereby facilitating its application in semiconductors and related industries.


Association Between Clinicopathological Features and Programmed Death Ligand 1 Expression in Non-small Cell Lung Cancer.
Programmed cell death ligand 1 (PD-L1) expression is a predictive marker for immunotherapy effects in advanced non-small cell lung cancer (NSCLC), but its association with patient characteristics or specimens is controversial. We aimed to retrospectively analyze the association of PD-L1 expression with clinicopathological features of NSCLC patients. The PD-L1 expression and clinicopathological features of NSCLC patients were assessed from January 2017 to June 2017 in the Tokyo Metropolitan Cancer and Infectious Diseases Centre, Komagome Hospital were reviewed (n=108). For PD-L1 expressions of 0% and >1%, multivariate analysis showed that lymph node sample results were associated with positive PD-L1 expression. Archival samples and high serum carcinoembryonic antigen (CEA) levels were associated with negative PD-L1 expression. Sample preservation time and CEA levels correlated with PD-L1 expression. Nodal metastasis, sample preservation time and CEA levels were associated with PD-L1 expression in NSCLC.


Barriers to Gait Training among Stroke Survivors: An Integrative Review.
Gait recovery is vital for stroke survivors' ability to perform their activities associated with daily living. Consequently, a gait impairment is a significant target for stroke survivors' physical rehabilitation. This review aims to identify barriers to gait training among stroke survivors. An integrative review was conducted following Whittemore and Knafl's methodology. The research was carried out on the electronic databases Scopus, PubMed, and B-on, applying a time span of 2006 to 2022. A total of 4189 articles were initially identified. After selecting and analyzing the articles, twelve studies were included in the sample. This review allowed for the identification of several barriers to gait training among stroke survivors, which can be grouped into three categories: individual, environmental, and rehabilitation workforce-related barriers. These findings highlight that participation in gait training is not solely dependent on the stroke survivor. Instead, the uptake of rehabilitation programs may also depend on environmental and rehabilitation workforce-related factors.


Specific sensitization to Dermatophagoides pteronyssinus and cutaneous reactivity to histamine in Brazilian children.
The immediate hypersensitivity cutaneous test is a recognized method for etiologic diagnosis of allergic diseases. It is easily conducted, painless and can be quickly interpreted, making it deal for use with children. However, its low positivity in infants limits its use this population. The purpose of our study was to evaluate the skin reactivity to atopic and non-atopic children of different ages to increasing concentrations of histamine and to an extract of Dermatophagoides pteronyssinus (Dpt). Atopic children (A, n = 217) and non-atopic children (C, n = 198), under 15 years of age were grouped by age and administered skin prick tests. Increasing concentrations of histamine (1, 9, 81 and 243 mg/ml) and Dpt (10,000 AU/ml) were applied to the forearm. Skin reactions were recorded after 15 minutes and expressed as the mean of the largest wheal and its midpoint perpendicular diameter. Cutaneous reactions were observed in the early phases of life with a progressive increase observed in both groups. Significant differences were noted between the two groups starting at 48 months of life. As the concentration of histamine was increased, we observed a higher level of cutaneous reactivity in younger children. Comparative analysis of cutaneous reactivity to the histamine solution (1 mg/ml) and the Dpt extract showed parallelism between them and wheals with diameters larger than 3 mm after 12 months of age. We concluded that the skin prick test with Dpt is reliable in atopic children after 1 year of age. Reactivity to higher concentrations of histamine was observed after 3 months of age for all children. However, considering all age groups, the skin reactivity in atopic children to histamine (1 mg/ml) was more precocious when compared to controls.


In-Depth Genomic and Transcriptomic Analysis of Five K+ Transporter Gene Families in Soybean Confirm Their Differential Expression for Nodulation.
Plants have evolved a sophisticated network of K+ transport systems to regulate growth and development. Limited K+ resources are now forcing us to investigate how plant demand can be satisfied. To answer this complex question, we must understand the genomic and transcriptomic portfolio of K+ transporters in plants. Here, we have identified 70 putative K+ transporter genes from soybean, including 29 HAK/KT/KUP genes, 16 genes encoding voltage-gated K+ channels, 9 TPK/KCO genes, 4 HKT genes, and 12 KEA genes. To clarify the molecular evolution of each family in soybean, we analyzed their phylogeny, mode of duplication, exon structures and splice sites, and paralogs. Additionally, ortholog clustering and syntenic analysis across five other dicots further explored the evolution of these gene families and indicated that the soybean data is suitable as a model for all other legumes. Available microarray data sets from Genevestigator about nodulation was evaluated and further confirmed with the RNA sequencing data available by a web server. For each family, expression models were designed based on Transcripts Per Kilobase Million (TPM) values; the outcomes indicated differential expression linked to nodulation and confirmed the genes' putative roles. In-depth studies such as ours provides the basis for understanding K+ inventories in all other plants.


Oxidative intercalation for monometallic Ni(2+) -Ni(3+) layered double hydroxide and enhanced capacitance in exfoliated nanosheets.
Monometallic Ni(2+) -Ni(3+) layered double hydroxide (LDH) is prepared using a simple oxidative intercalation process and may be further exfoliated into positively charged Ni(OH)2 unilamellar sheets. The superior capacitive behavior of the unilamellar sheets stranded in carbon nanotubes (CNTs) networks is achieved because of the complete interfacial charge storage arising from the confined Faradaic reactions at the interfacial region. 3D nanosheet/CNT composites are prepared using an in situ electrostatic assembly of positive charged sheets with CNTs bearing negative charges. The restacking of active nanosheets during electrochemical cycling is effectively prohibited. Consequently, the outstanding specific capacitance and remarkable rate capability of the nanosheet/CNT hybrid electrodes are demonstrated, making them promising candidates for high performance supercapacitors, combining high-energy storage densities with high levels of power delivery.


[Endocrine crises in patients with kidney diseases].
Among surgical patients renal diseases association with diabetes mellitus was found in 117, with thyroid affection in 82 patients. Twenty-six patients were treated for primary hyperparathyroidism, 46 were operated on for adrenal tumors: pheochromocytoma (23 cases), Conn's syndrome (3 cases). Hyperglycemic coma in patients with acute purulent renal diseases was primarily due to overlooked diabetes mellitus. Thyrotoxic crises emerged after urgent ureterolithotomy in a female patient suffering from toxic goiter, hypothyroid coma occurred in a male subject with undetected hypothyroidism following pyelolithotomy. Clinical variability of the symptoms, no attempts oriented on their detection led to diagnosis of pheochromocytoma, Conn's syndrome, primary hyperparathyroidism in emergency situations or at autopsy. Timely diagnosis and pathogenetic therapy of endocrine crises produced favourable outcomes.


RAS-MAPK pathway disorders: important causes of congenital heart disease, feeding difficulties, developmental delay and short stature.
The disorders described as the neuro-cardio-facio-cutaneous conditions (NCFCs) may all present with symptoms that are common in paediatric practice. They result from germline mutations in genes encoding kinases and other proteins interacting in the RAS-MAPK pathway. This review summarises these disorders, discussing their presenting features and clinical course, identifying overarching similarities and, conversely, features that can help to discriminate one condition from another. The genetic basis and importance of precise clinical diagnosis and molecular diagnostic confirmation when possible is discussed, given each condition's different prognosis, and the need to remain vigilant for specific complications.


8-spot smFRET analysis using two 8-pixel SPAD arrays.
Single-molecule Förster resonance energy transfer (smFRET) techniques are now widely used to address outstanding problems in biology and biophysics. In order to study freely diffusing molecules, current approaches consist in exciting a low concentration (<100 pM) sample with a single confocal spot using one or more lasers and detecting the induced single-molecule fluorescence in one or more spectrally- and/or polarization-distinct channels using single-pixel Single-Photon Avalanche Diodes (SPADs). A large enough number of single-molecule bursts must be accumulated in order to compute FRET efficiencies with sufficient statistics. As a result, the minimum timescale of observable phenomena is set by the minimum acquisition time needed for accurate measurements, typically a few minutes or more, limiting this approach mostly to equilibrium studies. Increasing smFRET analysis throughput would allow studying dynamics with shorter timescales. We recently demonstrated a new multi-spot excitation approach, employing a novel multi-pixel SPAD array, using a simplified dual-view setup in which a single 8-pixel SPAD array was used to collect FRET data from 4 independent spots. In this work we extend our results to 8 spots and use two 8-SPAD arrays to collect donor and acceptor photons and demonstrate the capabilities of this system by studying a series of doubly labeled dsDNA samples with different donor-acceptor distances ranging from low to high FRET efficiencies. Our results show that it is possible to enhance the throughput of smFRET measurements in solution by almost one order of magnitude, opening the way for studies of single-molecule dynamics with fast timescale once larger SPAD arrays become available.


Predicament of Chinese legislation on genetically modified food (GMF) labeling management and solutions - from the perspective of the new food safety law.
This paper considers the background of Article 69 of the newly revised Food Safety Law in China in combination with the current situation of Chinese legislation on GMF labeling management, compared with a foreign genetically modified food labeling management system, revealing deficiencies in the Chinese legislation with respect to GMF labeling management, and noting that institutions should properly consider the GMF labeling management system in China. China adheres to the principle of mandatory labeling based on both product and processes in relation to GMFs and implements a system of process-centered mandatory labeling under a negotiation-construction form. However, China has not finally defined the supervision mode of mandatory labeling of GMFs through laws, and this remains a challenge for GMF labeling management when two mandatory labeling modes coexist. Since April 2015 and October 1, 2015 when the Food Safety Law was revised and formally implemented respectively, the applicable judicial interpretations and enforcement regulations have not made applicable revisions and only principle-based terms have been included in the Food Safety Law, it is still theoretically and practically difficult for mandatory labeling of GMFs in juridical practices and conflicts between the principle of GMF labeling and the purpose that safeguards consumers' right to know remain. The GMF labeling system should be legislatively and practically improved to an extent that protects consumers' right to know. © 2017 Society of Chemical Industry.


[Clinical phenotype and genetic analysis of a Chinese patient featuring X-linked Claes-Jensen type syndromic mental retardation].
To explore the genetic basis of a Chinese patient featuring global developmental delay. Peripheral venous blood samples from the proband and his parents and sister were taken for the extraction of DNA. Target capture and next generation sequencing was carried out to detect genetic variants associated with the disease. Suspected variant was validated by Sanger sequencing. Genetic testing discovered that the proband has carried hemizygous c.150G>T and c.150+1G>T variants of the KDM5C gene which are inherited from his mother. His younger sister also carried the variants. The c.150+1G>A variant was unreported previously, which has altered a splice site and was predicted to be pathogenic by bioinformatics analysis. The hemizygous c.150+1G>T variant of the KDM5C gene, known to underlie X-linked Claes-Jensen type syndromic mental retardation, probably accounts for the disorder in the patient. Identification of this variant has enriched the variant spectrum of the KDM5C gene.


Assessment of pain (distribution and onset), Symptoms, SCL-90-R Inventory responses, and the association with infectious events in patients with chronic orofacial pain.
A visual analog pain scale and scalar responses to 13 pain/symptom indicator Symptom Checklist-90-Revised (SCL-90-R) questions were used to assess symptom prevalence and pain severity in 43 chronic orofacial muscle pain patients and 40 control subjects. The orofacial muscle pain group reported pain in an axial skeletal distribution; neurocognitive, gastrogenitourinary, and musculoskeletal symptoms; infectious events at or preceding onset; similar symptoms in sexual partners; and low prevalence of trauma. Sudden onset was reported by 30.2% of pain patients. Strong associations were found between chronic orofacial muscle pain and (1) onset-related infectious-like events (67.4%); (2) a higher prevalence of history of respiratory and gastrogenitourinary infectious events; and (3) high prevalences of similar pain symptoms in long-term sexual partners. The SCL-90-R somatization scores (> 62) had a higher prevalence in the chronic pain group. No prevalence differences or associations with pain/symptom indicators were found for depression or anxiety dimension scores. These data suggest that patients with recurrent systemic infectious events have a higher prevalence of reporting of chronic orofacial muscle pain compared with control subjects, and these infectious events are associated with the onset of chronic orofacial muscle pain in 67% of patients.


Effects of epidermal growth factor on preimplantation mouse embryos.
When epidermal growth factor (EGF) was added to the medium for culture of preimplantation embryos, morphological development as determined by microscopic observation was unaffected, but 333 nM-EGF stimulated total uptake of [3H]leucine by late morulae/blastocysts which had been cultured for 24 h from morulae. Incorporation of [3H]leucine into protein by these embryos was increased by 0.33, 3.3 and 33 nM-EGF, following a quadratic relationship producing less stimulation at 333 nM, which may indicate down regulation of receptors. The estimated EC50 was approximately 0.25 nM. Manipulation of the culture period indicated that the embryos responded to EGF at the morula/blastocyst transition period and immunosurgery was used to show that the increased protein synthesis was restricted to the trophectoderm cells. No mitogenic effect was observed. The effective concentration of EGF is close to that of serum and to values which stimulate other tissues. It is suggested that EGF receptors appear at compaction and that EGF may have a role in differentiation of the trophectoderm cells.


Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration.
Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell-mediated therapies.


[Pravastatin-induced dermatomyositis].
The toxic myopathy caused by statins (HMG-CoA reductase inhibitors) is well established. Recent reports add to these effects systemic immune diseases including systemic lupus erythematosus, vasculitis, polymyositis or dermatomyositis. We report a case of dermatomyositis in a 69-year-old patient treated with pravastatin [Elisor]. She presented with typical features of dermatomyositis 2 years after she started a treatment with pravastatin. The treatment was discontinued and she slowly improved, with a transient dermocorticosteroid treatment. Eight other patients with dermatomyositis and chronic treatment with HMG-CoA reductase inhibitors are reported in the literature. All of them presented with classical features of dermatomyositis. The discontinuation of the treatment was followed by spontaneous clinical and biological improvement in 3/9 patients. The other patients received high doses of corticosteroids and improved, except one patient who died of respiratory failure (pulmonary fibrosis) despite the adjunction of oral cyclophosphamide [Endoxan]. In these patients, dermatomyositis can be considered as a severe adverse reaction to HMG-CoA reductase inhibitors although a distinct casual link cannot be definitely established. The increasing prescription of statins has led to the parallel increment of reported side-effects, where autoimmune diseases are now described. Among them, our case of dermatomyositis in a patient receiving pravastatin adds to the eight reported cases in the literature and highlights the potential role of statins as triggers of immune systemic diseases.


Genetic mapping of a mutation that causes ribonucleases III deficiency in Escherichia coli.
the mutation that causes ribonuclease III (RNase III) deficiency in strain AB301-105 of Kindler et al. (1973) has been mapped by use of F' merodiploids, Hfr matings, and P1 transduction. This mutation, rnc-105, lies close to nadB, near 49 min on the genetic map of Escherichia coli. The rnc-105 mutation has been transferred from its original genetic background by transduction and conjugation, and these new strains have the same defects in ribonucleic acid processing reported previously for AB301-105. Strains that carry rnc-105 grow more slowly than parental rnc+ strains, but the difference in growth rate seems to depend on the genetic background of each strain. Bacteriophage T7 grows about equally well in RNase III+ and III- female strains of E. coli, even though the specific cuts that RNase III makes in T7 ribonucleic acid are not made in the RNase III- strains. A low-phosphate defined medium in which most E. coli strains seem to grow well was developed. This medium is equally useful for labeling ribonucleic acids with 32PO4 and as a selective medium for genetic manipulations. It was used to determine the growth requirements of strain AB301-105, which are biotin and succinate in addition to the methionine and histidine requirements of the parental strain. The biotin mutation lies near the position expected from known mutations of E. coli, but the succinate mutation apparently does not. The possibility that the succinate requirement could be due to the RNase III deficiency is discussed. A uraP mutation was isolated for use in transferring rnc-105 between strains by conjugation. It lies near 47 min, somewhat removed from the commonly accepted position for uraP.


Cryptococcus depauperatus, a close relative of the human-pathogen C. neoformans, associated with coffee leaf rust (Hemileia vastatrix) in Cameroon.
The genus Cryptococcus is well known for its two species -Cryptococcus neoformans and C. gatii- that are etiological agents of cryptococcosis, an important fungal disease of mammals, including humans, and which is particularly common in immunocompromised patients. Nevertheless, Cryptococcus is a large and widely distributed genus of basidiomycetes occupying a broad range of niches, including mycoparasitism. One such mycoparasitic species is Cryptococcus depauperatus, which was firstly mistakenly described as a pathogen of scale insects under the name Aspergillus depauperatus. The "Aspergillus" conidiophores were later shown to be basidia of a Cryptococcus and the new combination C. depauperatus was proposed. Additionally, instead of an entomopathogen, the fungus was found to be a mycoparasite growing on the entomopathogen Akanthomyces (Lecanicillium) lecanii. Recently, during surveys for mycoparasites of coffee leaf rust (Hemileia vastatrix) in the context of a biocontrol project, white colonies covering rust pustules were observed in Cameroon. Upon close examination, instead of a member of the "white colony forming complex" of Ascomycetes, commonly collected growing on H. vastatrix, such colonies were found to represent a basidiomycete fungus with basidia-bearing chains of basidiospores, typical of the genus Cryptococcus. Morphological and molecular evidence was generated supporting the identification of the fungus on rust pustules as C. depauperatus. This is the first record of C. depauperatus from Africa and of its association with coffee leaf rust.


Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections.
The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR-P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are also discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial resistant infections. This document is current as of December 31, 2022 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.


Low frequency dynamics of disordered XY spin chains and pinned density waves: from localized spin waves to soliton tunneling.
A long-standing problem of the low-energy dynamics of a disordered XY spin chain is reexamined. The case of a rigid chain is studied, where the quantum effects can be treated quasiclassically. It is shown that, as the frequency decreases, the relevant excitations change from localized spin waves to two-level systems to soliton-antisoliton pairs. The linear-response correlation functions are calculated. The results apply to other periodic glassy systems such as pinned density waves, planar vortex lattices, stripes, and disordered Luttinger liquids.


A novel model of atherosclerosis in rabbits using injury to arterial walls induced by ferric chloride as evaluated by optical coherence tomography as well as intravascular ultrasound and histology.
This study aim was to develop a new model of atherosclerosis by FeCl(3)-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (n = 15) by combination of a cholesterol-rich diet and FeCl(3)-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (n = 3), 8 weeks (n = 6), and 12 weeks (n = 6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl(3). The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time.


[Migration and transformation of nitrogen in urban stream located in plain river-net area based on water resources regulation].
To study hydrological features and physical and chemical characteristics of urban stream located in the plain river network area in the process of water resources regulation, and to discuss the forming and composition of nitrogen in urban stream based on water resources regulation. Effects of water regulation on the ammonium release from sediments in urban stream were studied under the condition of experimental simulation. The results showed that diurnal variation of water depth under the action of water resources regulation was significant. The value of DO in the overlying water along the water resources regulation path tended to decrease, while the concentration of permanganate index tended to increase. The concentration of nitrate in overlying water along the water resources regulation path gradually decreased, while the concentration of ammonium significantly increased. DO and permanganate index were the main factors influencing the concentrations of nitrate and ammonium in overlying water. Ammonium released from the sediments was an important source of ammonium in overlying water. Water resources regulation had a significant influence (P < 0. 05) on the concentration of ammonium in overlying water, but had no significant influence on the amount of cumulative ammonium released from sediments (P > 0. 05).


Silicotuberculosis with oesophagobronchial fistulas and broncholithiasis: a case report.
A 76-year-old woman was admitted to the hospital four times from November 2007 to June 2009. In this complex case, the patient had silicosis complicated by broncholithiasis, oesophagobronchial fistulas, and relapsed tuberculosis. She had worked as a stone crusher for 3 years and was exposed to a large amount of quartz dust. Barium oesophagography, gastroesophageal endoscopy, and biopsy suggested oesophageal-related chronic inflammation and ulceration, which may have caused the repeated oesophagobronchial fistulas. Bronchoscopy revealed a free broncholithiasis in the left mainstem bronchus. The patient was admitted a fourth time because of silicotuberculosis relapse. After 9 months of antituberculosis treatment, the patient recovered and was still clinically well at the time of this writing.


Patients given a hotline to matron.
Patients and visitors at Arrowe Park and Clatterbridge hospitals on Merseyside have been benefiting from a direct 'hotline' to a matron.


Elevated lumbar puncture opening pressure in aseptic meningitis.
Elevated lumbar puncture opening pressure (ELPOP) is a reported but understudied phenomenon in aseptic meningitis. This study aimed to characterize the features of ELPOP in aseptic meningitis patients. An observational, retrospective, single-center study was conducted. We included all adult patients diagnosed with aseptic meningitis or meningoencephalitis from October 2015 to May 2017, for whom lumbar puncture opening pressure (LP OP) was measured. OP > 25 cm H2O was documented as ELPOP. Patients' demographic characteristics, clinical data, laboratory and cerebrospinal fluid (CSF) results, as well as optic disc appearance were analyzed. Among 116 patients (61 males) included, 16 patients (14 %) had ELPOP (11 males). The average age of those patients was 32.4 years (SD = 9.8), and the mean OP was 31.7 cm H2O (SD = 6.02) as opposed to the mean normal LPOP (NLPOP) of16.13 cm H2O (SD = 4.15). Body mass index (BMI) was significantly higher in the ELPOP group (p = 0.0081). Funduscopic examination was documented in 15/16 patients in the ELPOP group and revealed swollen optic discs in 6 (40 %) patients. Fundus examination was performed in 62 patients in the NLPOP group, of whom 2 (3.2 %) had a swollen disc. There was no difference in CSF content between groups. This study fills the void of information lacking on the frequency of ELPOP in aseptic meningitis. Its association with increased BMI may be related to the pathogenesis. LP OP should be measured in all patients with aseptic meningitis. Additional research is needed to determine the threshold of tolerated intracranial pressure (ICP).


Biphasic dose-dependent modulation of cardiac parasympathetic activity by moxonidine, an imidazoline I1-receptor agonist.
Peripheral beta-adrenergic blockade and activation of central alpha2-adrenergic receptors have parasympathomimetic effects. The impact of activation of central imidazoline I1-receptors on vagal activity is not yet clear, but there is some evidence that imidazoline I1-receptors agonists may inhibit the parasympathetic system. Parasympatholytic effects may represent a risk for patient with reduced parasympathetic activity. To clarify the effect of imidazoline I1-receptors stimulation on vagal activity, increasing doses of moxonidine were applied subcutaneously to rats with implanted telemetric transmitters. Heart rate and blood pressure variability and baroreflex sensitivity were analyzed. Both, low (0.04, 0.12, and 0.36 mg/kg) and high (1.08 and 3.24 mg/kg), doses of moxonidine reduced the low-frequency power of systolic pressure variability, an index of sympathetic vascular modulation. Despite this reduction, low moxonidine doses neither reduced heart rate nor increased baroreflex gain. A decline of very low frequency power of heart rate variability, a sign of parasympatholysis, was observed with low doses of moxonidine, which can explain the absence of change in heart rate. High doses of moxonidine profoundly augmented very low and high-frequency power of heart rate variability and baroreflex sensitivity. These data suggest that the stimulation of imidazoline I1-receptors is not only sympatholytic but also seems to have as well a weak parasympatholytic effect. However, high doses of moxonidine are strongly parasympathomimetic through the activation of central alpha2-adrenoceptors. Recruitment of alpha2-adrenoceptors also results in manifestation of several side effects.


Predicting effective drug concentrations for individual patients. Determinants of pharmacodynamic variability.
Variability in the relationship between pharmacological effect intensity and drug concentration (pharmacodynamics) is pronounced, usually exceeding pharmacokinetic variability. Whereas interindividual differences are large, intra-individual differences are much smaller, unless the individual experiences certain pathophysiological changes such as deterioration of renal function or progression of a chronic disease (for example, Parkinson's disease). Failure to appreciate the magnitude of interindividual variability in the pharmacodynamics of a drug can compromise fixed dose clinical trial outcomes, making the drug appear less effective or more toxic. In the face of pharmacodynamic variability it becomes important to identify useful predictors (covariates) of pharmacodynamic individuality to facilitate individually optimised pharmacotherapy. This requires clinical trial designs that incorporate extensive patient profiling, well beyond the usual short list of demographics (such as age, gender, race, bodyweight and smoking habits). In searching for predictors, it is helpful to appreciate the factors that may account for interindividual differences in the relationship between pharmacological effect intensity and drug concentration in plasma or other appropriate fluid. They include receptor density and affinity, the formation and elimination kinetics of endogenous ligands (such as the enkephalins), postreceptor transduction processes, homeostatic responses and the kinetic characteristics of transporters involved in drug transfer between fluids of distribution and the biophase. Correction of drug concentrations in plasma for protein binding, consideration of active and interactive metabolites, stereospecific assays and attention to drug distribution disequilibria are essential for successful identification of factors affecting pharmacodynamic variability. Pharmaceutical delivery systems (the 'hardware') must be combined with guidance for individualising drug dosage (the 'software' or user's manual) to provide for optimal and cost-effective pharmacotherapy.


[Influence of stellate ganglion block on bilateral cervicobrachial arterial and venous blood flow].
This study was designed to investigate the influence of stellate ganglion block (SGB) on cervicobrachial arterial and venous blood flow in 12 mongrel dogs. Following general anesthesia, the animals were mechanically ventilated to maintain a constant PaCO2 (35-40 mmHg). After thoracotomy, each dog was given SGB with 0.5% mepivacaine 1.0 ml. In six dogs we measured bilateral common carotid arterial blood flows (CCAF) and external jugular venous blood flows (EJVF), and in other six dogs we measured bilateral brachial arterial blood flows (BAF) and brachial venous blood flows (BVF) before and after SGB by using an ultrasonic transit time flowmeter. CCAF and EJVF in the blocked side and contra-lateral EJVF increased significantly but contra-lateral CCAF decreased significantly after SGB. BAF and BVF in the blocked side increased significantly and contra-lateral BAF and BVF decreased significantly after SGB. The results suggest that increased arterial blood flow in the blocked side after SGB is due to vasodilatation by sympathetic block and that contra-lateral arterial blood flow decreases by the ensuing lending-borrowing phenomenon. Increased venous blood flow in the blocked side after SGB is probably due to vasodilatation by sympathetic block and passive increase of blood flow from increased arterial blood flow. Contra-lateral increased EJVF may also be due to passive increase from arterial blood flow of the blocked side.


Intraoperative prediction of non-sentinel lymph node metastases in breast cancer using cytokeratin 19 mRNA copy number: A retrospective analysis.
One-step nucleic acid amplification (OSNA) is a molecular procedure used intraoperatively for the detection of sentinel lymph node (SLN) metastases. The aim of the present study was to define a cut-off of cytokeratin (CK)19 mRNA copy number predictive of positive completion axillary lymph node dissection (ALND). The OSNA procedure was employed for SLN analysis in 812 patients with T1-T2 N0 breast cancer. A total of 197 patients with SLN metastases were retrospectively analyzed. A total of 40 patients (20%) had non-SLN metastases. Receiver operating characteristics curve analysis established a cut-off of 5,000 CK19 mRNA copy number with 75% sensitivity and 72% specificity. The positive and negative predictive values were 40.5 and 92%, respectively. Multivariate analysis showed that this cut-off and tumor localization in the outer or lower-outer quadrant of the breast were significantly associated with non-SNL involvement (P<0.001 and P=0.025, respectively). The findings of the present study support the conventional cut-off of 5,000 copies for intraoperative decision to perform ALND, whereas ALND can safely be avoided in patients with tumor located outside the outer or lower-outer quadrant of the breast if the CK19 mRNA copy number is <5,000.


High levels of endemicity of 3-chlorobenzoate-degrading soil bacteria.
Soils samples were obtained from pristine ecosystems in six regions on five continents. Two of the regions were boreal forests, and the other four were Mediterranean ecosystems. Twenty-four soil samples from each of four or five sites in each of the regions were enriched by using 3-chlorobenzoate (3CBA), and 3CBA mineralizers were isolated from most samples. These isolates were analyzed for the ability to mineralize 3CBA, and genotypes were determined with repetitive extragenic palindromic PCR genomic fingerprints and restriction digests of the 16S rRNA genes (amplified ribosomal DNA restriction analysis [ARDRA]). We found that our collection of 150 stable 3CBA-mineralizing isolates included 48 genotypes and 44 ARDRA types, which formed seven distinct clusters. The majority (91%) of the genotypes were unique to the sites from which they were isolated, and each genotype was found only in the region from which it was isolated. A total of 43 of the 44 ARDRA types were found in only one region. A few genotypes were repeatedly found in one region but not in any other continental region, suggesting that they are regionally endemic. A correlation between bacterial genotype and vegetative community was found for the South African samples. These results suggest that the ability to mineralize 3CBA is distributed among very diverse genotypes and that the genotypes are not globally dispersed.