Nonrandom karyotype abnormalities in 36 multiple myeloma patients.
G-banded analysis performed on pretreated bone marrow samples of 36 multiple myeloma patients allowed the identification of clonal chromosome abnormalities. Abnormalities consisting of trisomies, monosomies, translocations, deletions, and marker chromosomes apparently followed a nonrandom pattern. The chromosomes involved in the production of abnormal karyotypes were numbers 1,2,3,11,12,14,17, and 18. Even though no specific chromosome pattern has been identified, the involvement of chromosomes 1, 3, and 14 was found to be more frequent. Many of the chromosomes and chromosomal breakpoints involved in these abnormalities correspond to the location of identified oncogenes or tumor suppressor genes. Hence, it is presumed that these chromosome abnormalities may be playing an important role in the genesis of multiple myeloma by altering the structure or function of oncogenes or tumor suppressor genes.


Update on Surgical Principles and Equipment.
The diversity implicit in exotic animal surgery requires a tailored approach to optimize successful outcomes. Outlined is information on patient preparation, instrumentation, hemostatic techniques, and magnification as it pertains to the exotic animal. Application of topical antiseptic solutions and judicious removal of pelage and feathers will decrease bacterial load during patient preparation. The use of specific barrier protection ensures proper aseptic technique and enables optimal patient monitoring. Magnification combined with a focal light source enhances visual acuity, allowing for better use of delicate instrumentation and identification of anatomic structures.


Leukaemia and lymphoma risks derived from solvents.
Results of epidemiologic studies indicating an association between solvent exposure and the development of malignancies affecting haematopoietic and lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this association are discussed. A variety of malignant disorders have been associated with solvent exposure, i.e. acute leukaemia, Hodgkin's disease (odds ratio 2.8-6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are some indications that solvent exposure may be a risk factor for myelofibrosis. The carcinogenic effect of benzene is epidemiologically and experimentally well documented and there are some indications that other solvents may also be hazardous. Possible mechanisms bringing about malignant transformation are discussed. The need for further epidemiologic, cytogenetic and clinical studies on the association between solvent exposure and malignant diseases is emphasised.


Isolation and primary structure of rat secretin.
A major form of rat secretin was purified to homogeneity from small intestine, being detected with a porcine secretin radioimmunoassay throughout 7 chromatographic steps. The sequence of the heptacosapeptide amide H-S-D-G-T-F-T-S-E-L-S-R-L-Q-D-S-A-R-L-Q-R-L-L-Q-G-L-V-NH2 shows that rat secretin has a glutamine residue in position 14 instead of arginine as in pig secretin.


Morphine-induced RACK1-dependent autophagy in immortalized neuronal cell lines.
Autophagy is a critical cellular catabolic process in cell homoeostasis and brain function. Recent studies indicate that receptor for activated C kinase 1 (RACK1) is involved in autophagosome formation in Drosophila and mice, and that it plays an essential role in morphine-associated memory. However, the exact mechanism of the role of RACK1 in morphine-induced autophagy is not fully understood. SH-SY5Y cells were cultured and morphine, rapamycin, 3-methyladenine and RACK1 siRNA were used to evaluate the regulation of RACK1 protein in autophagy. Western blotting and immunofluorescence were used to assess protein expression. Activation of autophagy (i.e. autophagosome accumulation and an increase in the LC3-II/LC3-I ratio) induced by morphine contributes to the maintenance of conditioned place preference (CPP) memory in mice. Moreover, morphine treatment significantly increased Beclin-1 expression and decreased the p-mTOR/mTOR and SQSTM1/p62 levels, whereas knockdown of RACK1 prevented morphine-induced autophagy in vitro. Furthermore, we found that in the mouse hippocampus, knockdown of RACK1 also markedly suppressed morphine-induced autophagy (decreased LC3-II/LC3-I ratio and increased p-mTOR/mTOR ratio). Importantly, morphine-induced autophagy in a RACK1-dependent manner. Conversely, morphine-induced RACK1 upregulation in vitro is partially inhibited by autophagy feedback. Our findings revealed a critical role for RACK1-dependent autophagy in morphine-promoted maintenance of CPP memory in mice and supported the notion that control of RACK1-dependent autophagic pathways may become an important target for novel therapeutics for morphine-associated memory.


Late effects in survivors of high-risk neuroblastoma following stem cell transplant with and without total body irradiation.
Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI. Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit. All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts. Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects.


[Melanoma in invisible naevus spilus].
Diagnosis of naevus lesions may be complex where they contain little or no pigmentation. Naevus spilus (or naevus on naevus) is, generally, readily identified by the difference in pigmentation between overlying and underlying naevi and healthy skin. Malignant transformation of naevus spilus is rare. We report two cases of melanoma in which surgical procedures revealed underlying melanocyte lesions, diagnosed at histology but undetectable on clinical examination. Two patients were operated for melanoma in which surgery, at a site remote from the melanoma, suggested incomplete relapse despite the fact that previous clinical examination had indicated healthy skin. A diagnosis was made of melanoma in invisible naevus spilus. Diagnosis of melanoma in invisible naevus spilus may be suspected where several naevi are found together in a specific area. The main problem is the therapeutic stance to be adopted since complete excision of the underlying naevi is difficult in practice. Wood's light examination may be helpful.


SERS-based Au@Ag NPs Solid-phase substrate combined with chemometrics for rapid discrimination of multiple foodborne pathogens.
In this study, a surface enhanced Raman scattering (SERS) sensor based on Au@Ag NPs solid-phase substrate combined with chemometrics was constructed for the discrimination of three pathogenic bacteria (Staphylococcus aureus, Escherichia coli and Listeria monocytogenes). The Au@Ag NPs were synthesized and self-assembled on filter paper using the dip-coating method. The good absorbency of the filter paper immobilized the bacteria on the substrate, increased the interaction between the bacteria and the substrate, and enhanced the SERS signal of the bacteria. The main peaks of the bacterial spectra were close to each other, but the relative intensities of the vibrational peaks were significantly different, and each strain exhibited unique Raman peaks. The combination of partial least squared discriminant analysis (PLS-DA) method with bacterial SERS allowed the effective identification of the three bacteria. Moreover, the method was applied for the quantitative detection of Staphylococcus aureus with a minimum detection concentration of 104 cfu/mL.


Synaptic responses produced in lobster abdominal postural motor neurons by mechanical stimulation of the swimmeret.
1. Intracellular recordings were obtained from the somata of identified abdominal postural motor neurons in lobster to examine their subthreshold and suprathreshold responses to tactile stimulation of the swimmeret. 2. Pressure stimulation of the swimmeret surface evoked abdominal extension by producing tonic spiking in the extensor excitors and the synergistic flexor inhibitor (f5) and hyperpolarizing responses in the extensor inhibitor and antagonistic flexor excitors. These responses often continued for several seconds following the termination of the stimulus. The receptive fields of these motor responses extended over most of the swimmeret surface. 3. More localized tactile stimulation of the swimmeret surface elicited EPSPs in f5 and the extensor excitors, and IPSPs in the flexor excitors. The amplitude of these synaptic potentials decreased as the stimulus intensity was reduced. 4. Stimulation of feathered hair (both sexes) and smooth hair (female only) sensilla produced responses characteristic of extension whereas bristly spines on the male accessory lobe excited only two flexor excitors without affecting any of the other postural motor neurons. 5. Summed synaptic responses recorded from the motor neurons differed in their amplitudes and latencies according to the type of mechanoreceptor stimulated-cuticular receptors, feathered hairs or smooth hairs. Stimulation of the swimmeret cuticle produced the strongest responses (shortest latency, largest amplitude), while feathered hair stimulation initiated the weakest responses (longest latency, smallest amplitude). 6. The relatively long latencies (greater than 35 ms) and the complex form of the EPSPs and IPSPs indicate the involvement of multisynaptic interneuronal pathways in the reflex arcs.


Brain-derived neurotrophic factor (BDNF) protects cultured rat cerebellar granule neurons against glucose deprivation-induced apoptosis.
In the present study, cell death induced by glucose deprivation in primary cultures of cerebellar granule neurons was examined. Glucose deprivation-induced apoptotic cell death was demonstrated using the terminal transferase-mediated (TdT) deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL) method and DNA fragmentation assays. When the effects of different neurotrophins on the survival of cerebellar granule neurons after glucose deprivation were assessed, BDNF, but not NT-3 or NGF, was found to protect cerebellar granule neurons against glucose deprivation-induced cell death. In addition, BDNF treatment increased c-Fos immunoreactivity in the cerebellar granule neurons. These results are consistent with the hypothesis that neuronal death due to glucose deprivation has a significant apoptotic component and that neurotrophins can protect against hypoglycemic damage.


Effect of small bowel transit time on accuracy of video capsule endoscopy in evaluating suspected small bowel bleeding.
Obscure small bowel bleeding is defined as gastrointestinal bleeding (GIB) that is unidentifiable with esophagogastroduodenoscopy and a colonoscopy with video capsule endoscopy (VCE) being the next gold standard step for evaluation. Small bowel transit time (SBTT) is a metric of a VCE study that is defined as the time the capsule takes to travel through the small intestine. To determine if SBTT within the VCE study, correlates to overall detection of obscure small bowel bleeds. Furthermore, we attempted to identify any existing correlation between SBTT and re-bleeding after a negative VCE study. This is a single center retrospective analysis of VCE studies performed for overt and occult GIB at Einstein Medical Center, Philadelphia, between 2015 and 2019. Inclusion criteria primarily consisted of patients 18 years or older who had a VCE study done as part of the workup for a GIB. Patients with incomplete VCEs, poor preparation, or with less than 6 mo of follow up were excluded. A re-bleeding event was defined either as overt or occult within a 6-mo timeframe. Overt re-bleeding was defined as Visible melena or hematochezia with > 2 gm/dL drop in hemoglobin defined an overt re-bleeding event; whereas an unexplained > 2 gm/dL drop in hemoglobin with no visible bleeding defined an occult re-bleed. Results indicated that there was a significant and positive point biserial correlation between SBTT of 220 min and detection of a bleeding focus with a statistically significant p value of 0.008. However, the area under the curve was negligible when trying to identify a threshold time for SBTT to discriminate between risk of re-bleeding events after a negative VCE. In terms of SBTT and association with accuracy of VCE finding a bleeding focus, 220 min was found to be adequate transit time to accurately find a bleeding focus, when present. It was found that no threshold SBTT could be identified to help predict re-bleeding after a negative VCE.


Gait and dementia.
Cognitive decline and neurodegenerative disease have been implicated in gait dysfunction via disturbance of top-down control mechanisms. Gait velocity decreases, variability increases, and ability to multitask while walking is impaired as cognition declines. Changes in gait can be used to predict incident mild cognitive impairment states as well as dementia. Slow gait velocity together with a cognitive complaint, the Motoric Cognitive Risk syndrome, can serve as a clinical biomarker for high risk of neurologic decline. While patients with Alzheimer's disease typically have quantitative gait impairment, those with other forms of dementia often manifest more overt, qualitative changes to walking. A variety of interventions may be useful to improve gait, including physical and cognitive rehabilitation, treatment of specific underlying causes of gait problems, and treatment of the dementia itself. Understanding the relationship between gait and dementia can elucidate pathology and improve patient care.


The effects of age and task context on Stroop task performance.
In this study, we investigated the impact of age and task context on Stroop task performance, using error scores, response latencies, and process dissociation estimates (e.g., Lindsay & Jacoby, 1994). Across three experiments, the findings showed that although older adults were able to evaluate Stroop task demands and modify their representations of task context in response to this knowledge, they were less able to maintain and update these representations on a trial-by-trial basis in tasks with high stimulus uncertainty or ambiguity. Moreover, although there was no age-related decline in the ability to modulate print color information, older adults were consistently less able to control the activation of conflicting word information. Together, these findings suggest that whereas age differences in the Stroop task may be magnified under conditions that promote transient failures to maintain task context, the primary source of these differences seems to be a more enduring decline in the efficiency of processes that are responsible for suppressing the activation of irrelevant lexical information.


Switched LPV Glucose Control in Type 1 Diabetes.
The purpose of this paper is to regulate the blood glucose level in Type 1 Diabetes Mellitus patients with a practical and flexible procedure that can switch among a finite number of distinct controllers, depending on the user's choice. A switched linear parameter-varying controller with multiple switching regions, related to hypo-, hyper-, and euglycemia situations, is designed. The key feature is to arrange the controller into a framework that provides stability and performance guaranty. The closed-loop performance is tested on the complete in silico adult cohort of the UVA/Padova metabolic simulator, which has been accepted by the U.S. Food and Drug Administration in lieu of animal trials. The outcome produces comparable or improved results with respect to previous works. The strategy is practical because it is based on a model tuned only with a priori patient information in order to cover the interpatient uncertainty. Results confirm that this control structure yields tangible improvements in minimizing risks of hyper- and hypoglycemia in scenarios with unannounced meals. This flexible procedure opens the possibility of taking into account, at the design stage, unannounced meals and/or patients' physical exercise.


Takayasu arteritis presenting as epileptic seizures: a case report and brief review of the literature.
Neurological manifestations may complicate Takayasu arteritis (TA) but seizures are rare. A 40-year-old man with TA presented with recurrent episodes of epileptic seizures. Episodes consisted of a brief period of unresponsiveness followed by sudden falling, tonic stiffening and limb jerking. A postictal period with drowsiness, urine incontinence and a temporal loss of memory was also present. A carotid and intracranial duplex ultrasound revealed a reverse flow within the left vertebral artery indicating the presence of subclavian stealing syndrome while extracranial MRA suggested some stenosis at the origin of the left common carotid artery. The EEG was consistent with epilepsy. Neurological manifestations are secondary to ischemia caused by decreased blood flow in the involved carotid and vertebral arteries. Antiepileptic treatment proved effective and may be considered as a reasonable first approach. The stenotic lesions can be managed successfully with angioplasty but these procedures are associated with a high failure rate and may not be needed.


Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex.
Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC. TSC1 variants in individuals with mosaic TSC are much less common (9%) than in germline TSC overall (26%) (p < 0.0001). The mosaic variant allele frequency (VAF) is significantly higher in TSC1 than in TSC2, in both blood and saliva (median VAF: TSC1, 4.91%; TSC2, 1.93%; p = 0.036) and facial angiofibromas (median VAF: TSC1, 7.7%; TSC2 3.7%; p = 0.004), while the number of TSC clinical features in individuals with TSC1 and TSC2 mosaicism was similar. The distribution of mosaic variants across TSC1 and TSC2 is similar to that for pathogenic germline variants in general TSC. The systemic mosaic variant was not present in blood in 14 of 76 (18%) individuals with TSC, highlighting the value of analysis of multiple samples from each individual. A detailed comparison revealed that nearly all TSC clinical features are less common in individuals with mosaic versus germline TSC. A large number of previously unreported TSC1 and TSC2 variants, including intronic and large rearrangements (n = 11), were also identified.


PCA3 in the detection and management of early prostate cancer.
Although widely used, the value of prostate-specific antigen (PSA) in the detection of prostate cancer is controversial. The percentage of free PSA increases the specificity of PSA, but results are not enough. Prostate cancer gene 3 (PCA3) has been proposed as an option that may complement these markers in the detection and management of early prostate cancer. Our aim has been to review the value of PCA3 as tumor marker. The available results suggest that PCA3 is particularly useful to select in which patients the biopsy should be repeated when the first biopsy was negative. However, some points should be specified with further studies, including the most appropriate PCA3 cutoff level and the significance of a high PCA3 score in patients with negative biopsy. False-negative results are also a conflictive point in the use of PCA3, because prostate cancer, including aggressive tumors, may be present in patients with a low PCA3 score. Probably, a proper interpretation of this test requires its management together with other tests, through multivariate models for the detection of prostate cancer. On the other hand, several studies showed the relation between PCA3 score and Gleason score, and also the utility of PCA3 to select patients for active surveillance. To summarize, the available studies show the utility of PCA3 in the detection and management of early prostate cancer, although some aspects referred to its use need to be retested after further studies to confirm the actual value and the limitations of this test.


Decreased Preoperative Estimated Glomerular Filtration Rate Was Related With Poor Prognosis of NSCLC Patients.
The coexistence of chronic kidney disease (CKD) and cancer is common due to the increased incidence of cancer in patients with CKD. Glomerular filtration rate is the optimal way to measure kidney function. To date, little is known about the role preoperative renal function plays in the prognosis of NSCLC patients. The study enrolled 140 patients who had been newly diagnosed NSCLC and received potential radical surgery for treatment from 2009 January to 2012 December. The detailed characteristics were collected including gender, age, smoking and drinking habits, KPS score, hemoglobin levels, tumor size, pathology type, differentiation, pTNM stage and serum creatinine before surgery. Univariate and multivariate analyses of overall survival (OS) and disease-free survival (DFS) were performed using Kaplan-Meier method and Cox model. The univariate analysis identified that the pTNM stage (p < 0.001), eGFR level (p = 0.006), and adjuvant treatment (p = 0.007) were prognostic factors for OS, while drinking habit (p = 0.032), pTNM stage (p = 0.002) and eGFR level (p = 0.006) were the prognostic factors for DFS. Further multivariate analysis found that pTNM stage (HR = 2.091, 95% CI 1.424-3.071; p < 0.001) and eGFR level (HR = 1.890, 95% CI 1.424-3.071; p = 0.004) were independent factors associated with OS. The pTNM stage (HR = 1.735, CI 1.215-2.479; p = 0.002) and eGFR (HR = 1.793, CI 1.193-2.696; p = 0.005) were independent factors associated with DFS. Further subgroup analyses found that in female patients/ no smoking patients/ patients younger than 60 years, better eGFR level was significantly associated with better OS and DFS. Decreased preoperative eGFR was associated with poor clinical outcome of NSCLC patients.


Structure of the extrachromosomal ribosomal RNA chromatin of Physarum polycephalum.
Isolated nucleoli from exponentially growing microplasmodia of Physarum polycephalum were digested with micrococcal nuclease or DNAase I, or were photoreacted with trimethyl psoralen. In the coding region for the precursor of the ribosomal RNA, micrococcal nuclease and DNAase I digestions show predominantly a smear, and treatment with psoralen leads to a fairly continuous crosslinking of the DNA. All three assays are compatible with the absence of a typical nucleosomal array in most of the gene copies. In contrast, in the central non-transcribed spacer, except in the immediate 5'-flanking region, micrococcal nuclease and DNAase I digestions yield fragments that are multiples of a basic repeat, compatible with a nucleosomal packing of this region. The crosslinking pattern with psoralen confirms this conclusion. In addition, there are three sites over 400 base-pairs long that are inaccessible for psoralen crosslinking. Two of these sites have been mapped to the putative origins of replication. In the terminal non-transcribed spacer, except in the immediate 3'-flanking region, digestions with micrococcal nuclease and DNAase I give a smeared repeat. The crosslinking pattern after treatment with psoralen suggests that this region is packed in nucleosomes, except for about 900 base-pairs constituting the telomere regions of the linear extrachromosomal palindromic rDNA. Micrococcal nuclease digestion of the immediate 5'-flanking region shows a complete absence of any nucleosomal repeat, but digestion with DNAase I leads to a faint ten base-pair repeat. In contrast, in the 3'-flanking regions both nuclease assays indicate a chromatin structure similar to the coding region. Both flanking regions are unusual with respect to psoralen crosslinking, in that crosslinking is reduced both in chromatin and deproteinized DNA. On the basis of the known sequence-dependent psoralen crosslinking and the established sequences in these regions, crosslinking should be expected to occur. However, it does not and we therefore propose the presence of an unusual DNA conformation in these regions.


Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. III. Inhibition of growth and necrosis of tumors implanted subcutaneously.
Administration of highly purified interferon to DBA/2 mice inhibited the growth of interferon-sensitive or interferon-resistant Friend erythroleukemia cells implanted subcutaneously. Injection of interferon at the site of tumor inoculation was more effective than injection of interferon intraperitoneally. Histologic examination of tumors in interferon-treated mice showed extensive areas of tumor-cell necrosis in the absence of an obvious host-cell infiltrate. Interferon inhibited the growth of established subcutaneous tumors and induced complete tumor regression in some mice. Interferon treatment also resulted in an inhibition of tumor metastases in the liver and spleen.


Short tandem repeat polymorphic markers for the rat genome from marker-selected libraries.
In an effort to generate a genome-wide set of high-quality polymorphic markers for the rat, we used the marker-selection method, which has already been proven useful for the development of markers, especially for the human genome. Small-insert (300-900 bp) rat genomic libraries were constructed with an estimated complexity of three genome equivalents and enriched for short tandem repeat sequences (STRs). The enriched libraries were found to contain 45% (CA)n and 27% (GATA)n, representing at least a 50-fold enrichment over unselected small insert genomic libraries. A subset of 2160 STR-containing clones, primarily of the (GATA)n class of repeats, were sequenced. PCR primers flanking the repeats were synthesized from some of the sequences from the (CA)n and (GATA)n classes of STRs and tested for polymorphism in a panel of eight inbred rat strains. This strategy yielded 147 polymorphic markers, which mapped with high odds to all chromosomes by linkage in three F2 populations. The integration of these STR markers with other rat genetic markers and mapping reagents will facilitate the mapping of disease genes in the rat and the identification of loci associated with complex mammalian phenotypes.


[Optimized hemodilution with hydroxyethyl starch. A blood saving method in malocclusion operations].
OPTIMIZED HEMODILUTION: To avoid blood transfusions, the method of optimized hemodilution (OHD) was developed. OHD consists of preoperative hypervolemic hemodilution with 500 ml hydroxyethyl starch (HES) and consecutive volume replacement with HES in the case of intraoperative intravasal fluid loss. This study verifies the efficacy of OHD. Mono- and bimaxillary operations (n = 213) performed between January 1995 and May 1999 were evaluated retrospectively with respect to reduction of blood transfusions due to application of OHD. The average blood loss in the OHD group (n = 127) was 593 ml, and no blood transfusion was required. In contrast, the control group (n = 86) showed an average blood loss of 738 ml, and 15% of these patients (n = 13) required transfusion of a total of 18 blood units. Based on our results, provision of autologous blood is only necessary for patients who do not receive OHD. The costs of fluid replacement and transfusion are increased by a factor of 5.7 when OHD is not used. OHD should be preferably used in cases of elective surgery on patients with good cardiopulmonary health. It is an easy to handle infusion regimen, which does not require additional monitoring, has no risk of infection, and results in a significant cost reduction.


"You" speaks to me: Effects of generic-you in creating resonance between people and ideas.
Creating resonance between people and ideas is a central goal of communication. Historically, attempts to understand the factors that promote resonance have focused on altering the content of a message. Here we identify an additional route to evoking resonance that is embedded in the structure of language: the generic use of the word "you" (e.g., "You can't understand someone until you've walked a mile in their shoes"). Using crowd-sourced data from the Amazon Kindle application, we demonstrate that passages that people highlighted-collectively, over a quarter of a million times-were substantially more likely to contain generic-you compared to yoked passages that they did not highlight. We also demonstrate in four experiments (n = 1,900) that ideas expressed with generic-you increased resonance. These findings illustrate how a subtle shift in language establishes a powerful sense of connection between people and ideas.


Lateral Center-edge Angle of 18° (Bone-Edge): Threshold for Hip Arthroscopy Treatment in Patients with Borderline Developmental Dysplasia of the Hip?
Hip arthroscopy for the treatment of symptomatic borderline developmental dysplasia of the hip (BDDH) has been controversial. The purpose of this study was to retrospectively analyze minimum 2-year outcomes of BDDH after arthroscopic surgery and explore the criteria and thresholds of the lateral center-edge angle (LCEA) in arthroscopic surgery for BDDH. Data were retrospectively collected from patients aged 18-50 who underwent arthroscopic surgery for BDDH and had an LCEA 18-25° between September 2016 and June 2020. The consistency of interobserver and intraobserver measurements of bone-edge LCEA was analyzed. Patients were divided into two groups based on LCEA (18-20°and 20-25°) and the results of arthroscopy compared between groups. Patient-reported outcome (PRO) scores, consisting of the modified Harris hip score (mHHS), the visual analogue scale (VAS) and the international hip outcome tool-12 (IHOT-12), the minimal clinically important difference (MCID) and patient acceptable symptom status (PASS) were calculated. In 52 patients with ≥2-year follow-up, female patients accounted for 71.2% and the mean age was 30.8 ± 8.4 years (range: 18 to 49 years). There was a high level of agreement when measuring the bone-edge LCEA definition of BDDH (Kappa = 0.921). Interobserver repeatability (ICC = 0.909, 95%CI: 0.847-0.947) and intraobserver repeatability (ICC = 0.944, 95%CI: 0.905-0.968) were excellent for bone-edge LCEA measurements. In addition to LCEA and Tönnis angle, there were no significant differences in α angle, neck stem angle, femoral anteversion angle, medial joint space, Tönnis grade of osteoarthritis, acetabular retroversion (8 sign), Cam deformity and anterior inferior iliac spine (AIIS) morphology between the two groups (p > 0.05). Intraoperative findings and procedures showed no statistical difference between groups (p > 0.05). The mean follow-up time was 44.4 ± 11.0 months (range: 25 to 64 months). Postoperative VAS, mHHS and IHOT-12 scores in the LCEA 18-20° group and the LCEA 20-25° group were significantly improved compared with those before surgery, and there was no statistically significant difference in the percentage of MCID and PASS (mHHS and iHOT-12) between the groups (p > 0.05). Patients in the LCEA 18-20° group and the LCEA 20-25° group achieved favorable outcomes after arthroscopic surgery. LCEA 18° (bone-edge) should be the threshold for hip arthroscopic surgery in BDDH patients without obvious hip instability.


Synergy Mechanisms of Rhizoma Paridis Saponins on Non-small Cell Lung Cancer: Segmented Solid Phase Extraction, Bioactivity Screening, and Network Pharmacology.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Rhizoma paridis saponins (RPS), the main bioactive ingredients of Paris polyphylla Smith var. yunnanensis (PPY), have been proved to have remarkable effects on NSCLC cell lines. However, the multi-component synergistic effects and mechanisms of RPS on NSCLC have not been elucidated. To decipher the multi-RPS synergistic effects and mechanisms against NSCLC based on network pharmacology combined with segmented solid-phase extraction (SPE) and bioactivity screening method. Firstly, segmented SPE and cytotoxicity assays were performed to screen the RPS-enrichment fraction of PPY, and the steroidal saponins in it were identified by LC-MS/MS. Then, a network pharmacology analysis was performed to predict the potential therapeutic targets of RPS on NSCLC. Finally, viable cell counting tests and RT-qPCR were utilized to verify the synergistic effects and mechanisms of RPS. 48 potentially active compounds were identified from the 30% MeOH/EtOAc fraction of PPY (30% M/E PPY). The results of the network pharmacology analysis indicated that RPS exerted joint effects by regulating six key targets in the PI3K-AKT signaling pathway. In vitro experiments showed that due to the synergistic effects, 30% M/E PPY at 13.90 μg/mL could exert a stronger inhibitory activity on A549 cells by reducing the overexpression of six hub genes compared with the parallel control groups. This research elaborates on the multi-RPS synergy mechanisms against NSCLC and provides a way to develop new combination medicines for NSCLC.


Characteristics of cervical intervertebral disc signal intensity: an analysis of T2-weighted magnetic resonance imaging in 5843 asymptomatic Chinese subjects.
The study aimed to observe cervical intervertebral discs (IVDs) in asymptomatic subjects and to explore the factors associated with cervical intervertebral disc degeneration (IVDD). Cervical spine MRI of 5843 subjects was retrospectively analyzed. On the sagittal T2-weighted MR images, the mean signal intensities of the nucleus pulposus were obtained. Standard signal intensity (SSI) of intervertebral discs was defined as the ratio of mean disc signal intensity to mean CSF signal intensity. In subjects under 70 years old, the SSI of IVD was lowest at the C5/6 level. In those over 70, the SSI of IVD was similar among the disc levels from C2/3 to C7/T1. The disc SSI decreased significantly with age in both genders. In subjects under 70 years old, the SSI of the discs at each level was higher in females than in males. In those over 70 years old, no difference was found in disc SSI between two genders at most disc levels. Logistic regression analysis showed that kyphotic and straight cervical spine, obesity and older age were associated with higher risk of having lower disc SSI. To our knowledge, this is the largest cross-sectional study using MRI-based quantitative assessment to characterize cervical IVDD in asymptomatic subjects. Cervical IVDD was shown to progress with age and significantly correlated with gender, BMI and cervical alignment. Early intervention of related factors may help delay cervical IVDD and prevent future neck and shoulder pain.


Design, implementation and initial assessment of the Northern Territory Point-of-Care Testing Program.
The objective of the study was to improve pathology services in selected remote health centres from the Northern Territory (NT) through the implementation of a quality managed point-of-care pathology testing (POCT) service. Study of the efficacy of the POCT service after 1 year and qualitative survey of POCT device operators. The study was set in thirty-three remote health centres in the NT administered by the NT Department of Health. Remote health centre staff at participating remote health centres participated in the study. The introduction of the i-STAT device to perform on-site POCT. The main outcome measures used in the study were the number of remote staff trained, volume of testing performed and satisfaction of POCT device operators. One hundred and sixty-four health professional staff were trained to perform i-STAT POCT during the first year of the program. A total of 2290 POCT tests were performed on the i-STAT. The volume of testing consistently increased across the year. Tests for international normalised ratio were the most frequently performed (averaging 70 tests per month). Stakeholder satisfaction with the i-STAT device was high, with a statistically significant improvement in satisfaction levels with pathology service provision being reported after the introduction of POCT. Greater than 80% of respondents stated POCT was more convenient than the laboratory service and assisted in the stabilisation of acutely ill patients. The NT POCT Program has been operationally effective and well received by staff working as i-STAT POCT operators in remote health centres. Retention of remote health centre staff is the most significant challenge to ensuring the program's long-term viability.


Visual short-term memory for sequential arrays.
The capacity of visual short-term memory (VSTM) for a single visual display has been investigated in past research, but VSTM for multiple sequential arrays has been explored only recently. In this study, we investigate the capacity of VSTM across two sequential arrays separated by a variable stimulus onset asynchrony (SOA). VSTM for spatial locations (Experiment 1), colors (Experiments 2-4), orientations (Experiments 3 and 4), and conjunction of color and orientation (Experiment 4) were tested, with the SOA across the two sequential arrays varying from 100 to 1,500 msec. We find that VSTM for the trailing array is much better than VSTM for the leading array, but when averaged across the two arrays VSTM has a constant capacity independent of the SOA. We suggest that multiple displays compete for retention in VSTM and that separating information into two temporally discrete groups does not enhance the overall capacity of VSTM.


Anxiety and depression symptoms and migraine: a symptom-based approach research.
Anxiety and mood disorders have been shown to be the most relevant psychiatric comorbidities associated with migraine, influencing its clinical course, treatment response, and clinical outcomes. Limited information is available on how specific anxiety and depression symptoms are related to migraine. Symptoms-based approach, a current trend in mental health research, may improve our understanding in migraine comorbidity. The purpose of this study was to analyze how anxiety and depression aspects are related to migraine through a symptom-based approach. We studied 782 patients from the general population who completed a self-administered questionnaire assessing demographics, headache features, anxiety and depression symptoms. A binary logistic regression analyses were conducted to test the association between all four ratings in GAD-7 (anxiety) and PHQ-9 (depression) scales subitems as covariates, and migraine vs no headache as the outcome. The leading Odd Ratios (OR) observed in individuals with migraine relative to those without migraine were anxiety related, "Not being able to stop or control worrying" on a daily basis [OR (CI 95%)] 49.2 (13.6-178.2), "trouble relaxing" 25.7 (7.1-92.6), "Feeling nervous, anxious or on edge" on a daily basis 25.4 (6.9-93.8), and "worrying too much about different things" 24.4 (7.7-77.6). Although the hallmark symptoms of depression are emotional (hopelessness and sadness), the highest scores found were physical: apetite, fatigue, and poor sleep. Irritability had a significant increase in migraine risk [OR 3.8 (1.9-7.8) if experienced some days, 7.5 (2.7-20.7) more than half the days, and 22.0 (5.7-84.9) when experienced nearly every day]. Anxiety was more robustly associated with increase in migraine risk than depression. Lack of ability to properly control worrying and to relax are the most prominent issues in migraine psychiatric comorbidity. Physical symptoms in depression are more linked to migraine than emotional symptoms. A symptom-based approach helps clarifying migraine comorbidity and should be replicated in other studies.


Syntheses of ferulic acid derivatives and their suppressive effects on cyclooxygenase-2 promoter activity.
Novel ferulic acid derivatives in which feruloyl groups were attached to the hydroxyl groups of myo-inositol 1,3,5-orthoformate derivatives were synthesized. These feruloyl-myo-inositols suppressed the cyclooxygenase-2 (COX-2) promoter activity in a concentration-dependent manner. Among the examined compounds, compound 9 showed the highest activity. A treatment with 100 microM of compound 9 for 24 h resulted in a 50% decrease of COX-2 promoter activity without marked cytotoxicity. Both the molecular structure in which two ferulic acid moieties are facing each other and the molecular hydrophobicity may be essential for the suppression of COX-2 promoter activity.


Treatment of patients with acute myocardial infarction with intravenous magnesium.
Acute myocardial infarction (AMI) accounts for a large number of deaths annually. The major cause of early deaths is ventricular fibrillation. During the past few years, intravenous magnesium has been instituted as a therapy for AMI. This report reviews the latter literature and discusses the potential mechanisms whereby intravenous Mg is beneficial in AMI. Intravenous Mg is a safe and inexpensive drug whose use reduces the incidence of arrhythmias, infarct size and early mortality following AMI.


Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells.
Reversible phosphorylation is the cell's most prevalent form of posttranslational modification, yet its role in the regulation of mitochondrial functions is poorly understood. We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria. PTPMT1 is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. Knockdown of PTPMT1 expression in the pancreatic insulinoma cell line INS-1 832/13 alters the mitochondrial phosphoprotein profile and markedly enhances both ATP production and insulin secretion. These data define PTPMT1 as a potential drug target for the treatment of type II diabetes and strengthen the notion that mitochondria are an underappreciated site of signaling by reversible phosphorylation.


Regional air pollution caused by dioxins from numerous emission sources: lessons from a domestic experience in Japan.
In this study, a large-scale field study was performed in order to distinguish between the contribution of the municipal solid waste incinerator and small clustered industrial waste incinerators in Fuchu city. The dioxin concentrations when only the municipal solid waste incinerator was being operated were found to range from 0.047 to 0.090 pg TEQ/m(3). The dioxin concentrations when only the clustered small industrial waste incinerators were being operated ranged from 0.085 to 0.25 pg TEQ/m(3). The concentrations in ambient air were more strongly affected by the clustered industrial waste incinerators than the municipal solid waste incinerator. Furthermore, the predicted concentrations by an atmospheric dispersion simulation model were consistent with the measured concentrations. From these results, the dioxin concentrations in ambient air were attributed primarily to the clustered small industrial waste incinerators.


Charcot-Marie-Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges.
This study analyzes and describes atypical presentations of Charcot-Marie-Tooth disease type 4C (CMT4C). We present clinical and physiologic features of 5 patients with CMT4C caused by biallelic private mutations of SH3TC2. All patients manifested scoliosis, and nerve conduction study indicated results in the demyelinating range. All patients exhibited signs of motor impairment within the first years of life. We describe 2 or more different genetic diseases in the same patient, atypical presentations of CMT, and 3 new mutations in CMT4C patients. A new era of unbiased genetic testing has led to this small case series of individuals with CMT4C and highlights the recognition of different genetic diseases in CMT4C patients for accurate diagnosis, genetic risk identification, and therapeutic intervention. The phenotype of CMT4C, in addition, appears to be enriched by a number of features unusual for the broad CMT category. Muscle Nerve 57: 749-755, 2018.


Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.
The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.


Anorexia nervosa: a cause of pericardial effusion?
Echocardiographic studies revealed the presence of pericardial effusion in 4 patients with anorexia nervosa, whose weights had fallen by 38 to 53% of their body weight at the onset of disease. Each patient had a normal or small cardiac image on chest roentgenogram. The presence of increased pericardial fluid may partially explain the decreased voltage on the electrocardiogram, and the distant heart sounds heard in some of these patients. The cause of the pericardial effusion is not clear. It may possibly occur in other diseases that produce marked weight loss and cachexia.


Steady-state model for plasma free and platelet serotonin in man.
A steady-state physiological flow model has been developed for predicting plasma free serotonin (5-HT), and platelet 5-HT, concentrations in man. The basic assumptions of the model are that 5-HT is produced in the wall of the intestine, enters the portal circulation at a constant rate, and is cleared by the lung, liver, kidney, and capillary bed. When a priori best estimates of the 5-HT production rate and organ extraction efficiencies were substituted into formulae describing the model, a predicted value for plasma free 5-HT of 304 pg/ml was obtained, in good agreement with a previously observed mean (+/- SE) of 387 +/- 84 pg/ml. The effects of varying production rate and extraction efficiency parameters on predicted levels of plasma free 5-HT are examined. The practical implications of the model and its possible utility in elucidating the causes of altered plasma free or platelet 5-HT seen in certain conditions are discussed.


Co-administration of statins with cytochrome P450 3A4 inhibitors in a UK primary care population.
The co-administration of cytochrome P450 3A4 (CYP3A4) inhibitors with simvastatin or atorvastatin (CYP3A4-metabolised statins) is associated with increased statin exposure and can increase the risk of adverse drug reactions. The aim of this study was to measure the concomitant exposure of patients to CYP3A4-metabolised statins and CYP3A4 inhibitors in the UK primary care population. The co-administration of statins and CYP3A4 inhibitors during 2008 was examined in the General Practice Research Database, a large nationally representative UK primary care database. All known inhibitors were included with labelled inhibitors identified using the Medicines and Healthcare products Regulatory Agency Drug Safety Update and UK summary of product characteristics for statins. Exposure was examined in patients overall, patients 65 years and older and those prescribed higher doses of statins. There were 364,574 patients included in the analyses. Ninety-three percent of the patients were prescribed CYP3A4-metabolised statins, most whom received simvastatin (72%) and atorvastatin (24%). Approximately one third (30%) of the patients prescribed a CYP3A4-metabolised statin had also been prescribed a concomitant CYP3A4 inhibitor during the study period, including 11% prescribed a concomitant labelled inhibitor, with an annualised median days of concomitant use of 173 days, predominantly involving macrolide antibiotics and calcium channel blockers co-prescriptions. Rates were higher in the subgroup aged 65 and over and in those on high dose statins. The co-prescription of CYP3A4-metabolised statins and CYP3A4 inhibitors is common in UK primary care. This co-prescription suggests the limited appreciation of potential interactions and Medicines and Healthcare products Regulatory Agency safety advice, with the potential to increase likelihood for side effects amongst patients. Strategies to reduce drug interactions with potential adverse effects should be targeted at prescribers and pharmacists.


[Iatrogenic agitation in elderly patient: prevalence, aetiologies and management].
Iatrogenic agitation is frequently drug-induced in the elderly. The management of the iatrogenic agitation is based on: a detailed analysis of the patient's medications, stopping non-essential drugs, prescribing drugs to the lowest and effective dose possible. This management of the iatrogenic agitation is also based on: adjustment of drugs according to renal function and limitation of polypharmacy. Special attention is necessary when prescribing treatments for patients with cognitive impairment.


5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat.
The effect of 5-hydroxytryptamine on the spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. The most frequent response to 5-hydroxytryptamine (84% of 57 neurons tested) was an increase (twofold of basal at 10 microM) of the discharge frequency. The EC50 for the 5-hydroxytryptamine-induced effect was 1.8 +/- 0.5 microM (mean +/- SEM). The response was dose-dependently blocked by the serotoninergic antagonist mianserin and was not prevented by removal of calcium ions from the perfusing buffer. These results indicate that the serotoninergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action on most neurons of the nucleus.


Recovery of polyclonal immunoglobulins during treatment in patients ineligible for autologous stem-cell transplantation is a prognostic marker of longer progression-free survival and overall survival.
Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem-cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31-40]. Immunoparesis was present in 81.2% of patients at diagnosis and was associated with a trend to a worse overall response rate (ORR: 84.8% vs. 74.9%; OR 1.88 (95% CI: 0.97-3.63), shorter progression-free survival (PFS) [22.0 vs. 18.2 months; hazard ratio (HR) 0.775; 95%CI: 0.590-1.018; p = 0.066], and overall survival (OS) (45.9 vs. 34.2 months; HR 0.746; 95% CI: 0.551-1.010; p = 0.057). Twenty-four per cent of patients who had immunoparesis at diagnosis recovered polyclonal immunoglobulins in the follow-up period. Interestingly, these patients had a better ORR (96.3% vs. 68.2%; OR 12.29 (95% CI: 3.77-40.06), PFS (HR 0.703; 95CI%: 0.526-0.941; p = 0.018) and OS (HR 0.678; 95 CI%: 0.503-0.913; p = 0.011) than patients who did not recover it. In summary, restoring a healthy immune system along with first-line treatment in patients with MM, not receiving ASCT, is associated with better outcomes.


Metabolic and toxic behaviours of phthalimide derivatives in albino rat II. Placental passage of chloromethyl phthalimide, oxymethyl phthalimide and phthalimide--their fetal metabolism.
Chloromethyl phthalimide, oxymethyl phthalimide, and phthalimide are absorbed by the albino rat at a comparatively high rate. Only phthalimide, the metabolic product, will be recordable from fetuses, following oral administration of chloromethyl phthalimide and oxymethyl phthalimide topregnant rats. Those findings, in conjunction with metabolic studies applied to fetuses isolated by caesarian section, appear to suggest the occurrence of an intensive metabolism in fetal tissue. Certain differences established between results of thin-layer chromatography, on the one hand, and 15N studies, on the other, are likely to support the assumption that phthalimide is further metabolised by splitting the imide ring yielding phthalamic acid.


Rapid and efficient isolation platform for plasma extracellular vesicles: EV-FISHER.
Extracellular vesicles (EVs) have found diverse applications in clinical theranostics. However, the current techniques to isolate plasma EVs suffer from burdensome procedures and limited yield. Herein, we report a rapid and efficient EV isolation platform, namely, EV-FISHER, constructed from the metal-organic framework featuring cleavable lipid probes (PO4 3- -spacer-DNA-cholesterol, PSDC). The EV-FISHER baits EVs from plasma by cholesterol and separates them with an ordinary centrifuge. The captured EVs could be released and collected upon subsequent cleavage of PSDC by deoxyribonuclease I. We conclude that EV-FISHER dramatically outperforms the ultracentrifugation (UC) in terms of time (∼40 min vs. 240 min), isolation efficiency (74.2% vs. 18.1%), and isolation requirement (12,800 g vs. 135,000 g). In addition to the stable performance in plasma, EV-FISHER also exhibited excellent compatibility with downstream single-EV flow cytometry, enabling the identification of glypican-1 (GPC-1) EVs for early diagnosis, clinical stages differentiation, and therapeutic efficacy evaluation in breast cancer cohorts. This work portrays an efficient strategy to isolate EVs from complicated biological fluids with promising potential to facilitate EVs-based theranostics.


Incidence of complications in the post-anesthesia care unit and associated healthcare utilization in patients undergoing non-cardiac surgery requiring neuromuscular blockade 2005-2013: A single center study.
The use of neuromuscular blockade agents (NMBA), had been associated with significant residual post-operative paralysis and morbidity. There is a lack of clinical evidence on incidence of postoperative complications within the post-anesthesia care unit (PACU) in patients exposed to intraoperative NMBA's. This study aims to estimate the incidence of post-operative complications associated with use of NMBAs and assessing its association with healthcare resource utilization. Retrospective cohort. Post-anesthesia care unit in tertiary care center. Adults having non-cardiac surgery and receiving NMBAs between April-2005 and December-2013 MEASUREMENTS: We assessed: 1) incidences of major and minor PACU complications, 2) incidence of any postoperative complication in patients receiving a NMBA reversal (neostigmine) vs. without. 3) We secondarily assessed the relationship between PACU complications and use of healthcare resources. The incidence of any major complications was 2.1% and that of any minor complication was 35.2%. ICU admission rate was 1.3% in patients without any complications, versus 5.2% in patients with any minor and 30.6% in patients with any major complication. ICU length of stay was prolonged in patients with any major (52.1±203h), compared to patients with any minor (6.2±64h) and with no complications (1.7±28h). Patients who received a NMBA and neostigmine, compared to without neostigmine, had a lower incidence of any major complication (1.7% vs. 6.05%), rate of re-intubation (0.8% vs. 4.6%) and unplanned ICU admission (0.8% vs. 3.2%). This study documents that incidence of major PACU complications after non-cardiac surgery was 2.1%, with the most frequent complications being re-intubation and ICU admission. Patients receiving NMBA reversal were at a lower risk of re-intubation and unplanned ICU admission, justifying routine use of reversals. Complete NMBA reversals are crucial in reducing preventable patient harm and healthcare utilization.


Real World Outcomes in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma Receiving Palliative Intent Therapies.
Outcomes in patients with relapsed/refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who are ineligible for and/or fail high-dose chemotherapy and autologous stem cell transplantation in the second line are poor. There is no preferred palliative-intent treatment for patients in this setting. A retrospective cohort study was performed using the nationwide de-identified electronic health record-derived Flatiron Health database. Event-free survival (EFS) and overall survival (OS) was evaluated for patients with R/R DLBCL who were ineligible for and/or failed autologous stem cell transplantation in the second line and received bendamustine, gemcitabine, or lenalidomide. Three hundred eighty-three patients were included. Therapy received was bendamustine in 158 patients, gemcitabine in 142 patients, and lenalidomide in 83 patients. The median EFS and OS for all patients was 4.1 months and 8.7 months, respectively. Compared with patients receiving bendamustine or gemcitabine, those receiving lenalidomide demonstrated significantly longer median EFS (6.8 vs. 3.8 months; P = .006) and median OS (15.4 vs. 7.7 months; P = .045). Survival outcomes were also improved for lenalidomide-treated patients specifically in the second- as well as third- or fourth-line settings. Use of lenalidomide resulted in prolonged EFS and OS as compared with bendamustine or gemcitabine in this cohort of patients with R/R DLBCL receiving palliative therapy. This first large-scale analysis of real-world outcomes for this patient population may guide current clinical management as well as serve as a benchmark for survival outcomes in the standard-of-care setting, which may aid in the design of future clinical trials.


Diverging trends in gastroenteritis hospitalizations during 2 decades in western Australian Aboriginal and non-Aboriginal children.
Gastroenteritis is a major cause of pediatric morbidity. We describe temporal, spatial and seasonal trends in age-specific gastroenteritis hospitalizations among Aboriginal and non-Aboriginal Australian children during 2 decades, providing a baseline to evaluate the impact of a rotavirus vaccine program begun in 2007. We conducted a population-based, data linkage study of Aboriginal and non-Aboriginal births in Western Australia, 1983 to 2006, and analyzed gastroenteritis-coded hospitalizations before age 15 years in the cohort of 596,465 births. Hospitalization rates in Aboriginal and non-Aboriginal children and between geographical regions were compared between 1983 to 1994 and 1995 to 2006. Gastroenteritis rates were highest in children 6-11 months of age (Aboriginal: 259.3/1000/annum; non-Aboriginal: 22.7/1000/annum). Rates declined in Aboriginal children between 1983 to 1994 and 1995 to 2006, particularly in those 12-17 months of age (309/1000 to 179/1000). Rates in non-Aboriginal children<5 years increased 10-40%. The disparity for gastroenteritis rates between Aboriginal and non-Aboriginal children<5 years declined from being 15.4 times higher to 7.6 times higher in those aged 12-17 months and from 8.4 to 4.4 in those aged 2-4 years. Rates were highest in rural and remote regions, and diverging temporal trends were seen in different geographical regions. Seasonality varied between Aboriginal and non-Aboriginal children and climatic zones. This is the largest study of gastroenteritis hospitalization trends in children. We found diverging trends of gastroenteritis hospitalization rates in Aboriginal and non-Aboriginal children. Although rates have declined in Aboriginal children, disparity between Aboriginal and non-Aboriginal children continues. Our findings highlight the need to consider age, ethnicity, seasonality and climate when evaluating rotavirus vaccine programs.


Glutathione kinetically outcompetes reactions between dimedone and a cyclic sulfenamide or physiological sulfenic acids.
Dimedone and its derivates are used as selective probes for the nucleophilic detection of sulfenic acids in biological samples. Qualitative analyses suggested that dimedone also reacts with cyclic sulfenamides. Furthermore, under physiological conditions, dimedone must compete with the highly concentrated nucleophile glutathione. We therefore quantified the reaction kinetics for a cyclic sulfenamide model peptide and the sulfenic acids of glutathione and a model peroxiredoxin in the presence or absence of dimedone and glutathione. We show that the cyclic sulfenamide is stabilized at lower pH and that it reacts with dimedone. While reactions between dimedone and sulfenic acids or the cyclic sulfenamide have similar rate constants, glutathione kinetically outcompetes dimedone as a nucleophile by several orders of magnitude. Our comparative in vitro and intracellular analyses challenge the selectivity of dimedone. Consequently, the dimedone labeling of cysteinyl residues inside living cells points towards unidentified reaction pathways or unknown, kinetically competitive redox species.


Inhibition of canine lung angiotensin converting enzyme by substance P.
We have studied inhibition of purified canine angiotensin converting enzyme by substance P and its nonapeptide derivative using Hip-His-Leu as the substrate. Kinetic studies indicated that both substance P and its nonapeptide derivative inhibited the hydrolysis of Hip-His-Leu at different concentrations. The mode of inhibition was competitive with a Ki of 1.15 microM for substance P. These results indicate that substance P is a potent inhibitor of angiotensin converting enzyme in vitro.


Individual differences among undergraduate women in methods of coping with stressful events: the impact of cumulative childhood stressors and abuse.
The purpose of the current study was to determine if a history of greater exposure to different types of adverse and/or abusive experiences in childhood would influence coping strategies used by undergraduate women to deal with new stressful events in young adulthood. A sample of 828 women undergraduates from a New England state university participated in this questionnaire study. Disengagement and engagement coping strategies used in response to recent stressors were compared in groups who had none, one, two, or three or more types of adverse and/or abusive childhood experiences (sexual abuse, physical abuse, witnessing domestic violence, having an alcoholic parent, and parental rejection). There was an increased reliance on disengagement methods of coping (wishful thinking, problem avoidance, social withdrawal, and self-criticism) as a function of more extensive child abuse histories. Engagement methods of coping (problem solving, cognitive restructuring, social support, and express-emotions), however, did not show a corresponding decrease as a function of increased exposure to different types of childhood stressors and/or abuse. This study demonstrates that undergraduate women with cumulative adverse and/or abusive childhood histories are particularly at-risk of relying on maladaptive disengagement coping strategies to deal with various new stressors later in life.


Symptom dimensions are associated with progressive brain volume changes in schizophrenia.
There is considerable variation in progressive brain volume changes in schizophrenia. Whether this is related to the clinical heterogeneity that characterizes the illness remains to be determined. This study examines the relationship between change in brain volume over time and individual variation in psychopathology, as measured by five continuous symptom dimensions (i.e. negative, positive, disorganization, mania and depression). Global brain volume measurements from 105 schizophrenia patients and 100 healthy comparison subjects, obtained at inclusion and 5-year follow-up, were used in this study. Symptom dimension scores were calculated by factor analysis of clinical symptoms. Using linear regression analyses and independent-samples t-tests, the relationship between symptom dimensions and progressive brain volume changes, corrected for age, gender and intracranial volume, was examined. Antipsychotic medication, outcome and IQ were investigated as potential confounders. In patients, the disorganization dimension was associated with change in total brain (β=-0.295, p=0.003) and cerebellar (β=-0.349, p<0.001) volume. Furthermore, higher levels of disorganization were associated with lower IQ, irrespective of psychiatric status (i.e. patient or control). In healthy comparison subjects, disorganization score was not associated with progressive brain volume changes. Heterogeneity in progressive brain volume changes in schizophrenia is particularly associated with variation in disorganization. Schizophrenia patients with high levels of disorganization exhibit more progressive decrease of global brain volumes and have lower total IQ. We propose that these patients form a phenotypically and biologically homogenous subgroup that may be useful for etiological (e.g., genetic) studies.


Sexual dimorphic porcine pituitary response to growth hormone-releasing hormone.
The aim of this study was to compare growth hormone (GH) response of barrows and gilts to porcine growth hormone-releasing hormone (pGRH) at the pituitary level. Anterior pituitary cells from barrows and gilts responded to pGRH in a dose-dependent manner. The median effective pGRH concentration (EC50) which stimulated GH release from cells of barrows was greater (P less than .05) than that for cells obtained from intact female siblings. Maximal pGRH mediated GH secretion from barrows was not different (P greater than 0.05) than that from gilt stimulated cells. These data demonstrate that somatotrophs of growing peripubertal gilts are more responsive to pGRH stimulation than are cells from their castrated male siblings. This difference could be caused by castration of the neonatal male.


Advanced laparoscopic bariatric surgery Is safe in general surgery training.
Bariatric surgery makes up an increasing percentage of general surgery training. The safety of resident involvement in these complex cases has been questioned. We evaluated patient outcomes in resident performed laparoscopic bariatric procedures. Retrospective review of patients undergoing a laparoscopic bariatric procedure over seven years at a tertiary care single center. Procedures were primarily performed by a general surgery resident and proctored by an attending surgeon. Primary outcomes included operative volume, operative time and leak rate with perioperative outcomes evaluated as secondary outcomes. A total of 1649 bariatric procedures were evaluated. Operations included laparoscopic bypass (690) and laparoscopic sleeve gastrectomy (959). Average operating time was 136 min. Eighteen leaks (0.67%) were identified. Graduating residents performed an average of 89 laparoscopic bariatric cases during their training. There were no significant differences between resident levels with concern to operative time or leak rate (p 0.97 and p = 0.54). General surgery residents can safely perform laparoscopic bariatric surgery. When proctored by a staff surgeon, a resident's level of training does not significantly impact leak rate.


Peripheral blood microRNA and VEGFA mRNA changes following electroconvulsive therapy: implications for psychotic depression.
MicroRNAs are short, non-coding molecules that regulate gene expression. Here, we investigate the role of microRNAs in depression and electroconvulsive therapy (ECT). We performed three studies: a deep sequencing discovery-phase study of miRNA changes in whole blood following ECT (n = 16), followed by a validation study in a separate cohort of patients pre-/post-ECT (n = 37) and matched healthy controls (n = 34). Changes in an experimentally validated gene target (VEGFA) were then analysed in patients pre-/post-ECT (n = 97) and in matched healthy controls (n = 53). In the discovery-phase study, we found no statistically significant differences in miRNA expression from baseline to end of treatment in the group as a whole, but post hoc analysis indicated a difference in patients with psychotic depression (n = 3). In a follow-up validation study, patients with psychotic depression (n = 7) had elevated baseline levels of miR-126-3p (t = 3.015, P = 0.006) and miR-106a-5p (t = 2.598, P = 0.025) compared to healthy controls. Following ECT, these differences disappeared. Baseline VEGFA levels were significantly higher in depressed patients compared to healthy controls (F(1,144) = 27.688, P = <0.001). Following ECT, there was a significant change in VEGFA levels in the psychotic group only (t = 2.915, P = 0.010). Molecular differences (miRNA and VEGFA) may exist between psychotic and non-psychotic depression treated with ECT.


Pull-through intraurethral bladder flap.
A new surgical technique for post-prostatectomy incontinence is described. A simple surgical procedure was developed using a tube from a bladder flap and was applied successfully to 4 patients. Of the 4 patients 3 with total incontinence as a result of different surgical procedures on the prostate were cured and 1 was improved.


Immunomodulatory effects of silymarin in patients with β-thalassemia major.
Silymarin, a flavonolignan complex isolated from milk thistle, is a cytoprotective, antioxidant, and hepatoprotective agent. The present study was designed to investigate the immunomodulatory effects of orally administered silymarin in patients with β-thalassemia major. The immunomodulatory effects of silymarin were investigated in a 12-week clinical trial in two groups of patients. In combined therapy group (n=25), patients continued desferrioxamine at the dose of 40mg/kg/day and Legalon® tablets (420mg daily) were added to desferrioxamine. In silymarin group (n=5), patients who were unable or unwilling to use desferrioxamine received only silymarin. Immunological tests were assessed at the beginning and the end of the trial. No differences were detected between treatment groups regarding the percentage of lymphocyte subsets, concentration of serum immunoglobulins, complement levels, or T cell proliferation in vitro. Serum tumor necrosis factor (TNF-α) levels were significantly decreased in both groups, whereas the serum levels of neopterin significantly decreased in both groups after silymarin therapy. The analysis of cell culture supernatants of activated T cells showed increased production of interferon gamma (IFNγ) and interleukin (IL)-4 after silymarin treatment in both groups. Silymarin stimulates cell-mediated immune response in β-thalassemia major, possibly through a direct action on cytokine-producing mononuclear cells. Because of its immunostimulatory, antioxidant, and iron-chelating activities, silymarin could be a good candidate in the therapy of chronic iron overload in combination with routine iron chelators in clinical use like desferrioxamine.


Low dose spironolactone-mediated androgen-adiponectin modulation alleviates endocrine-metabolic disturbances in letrozole-induced PCOS.
Polycystic ovarian syndrome (PCOS), is a multifactorial endocrine disorder in women of reproductive age. It usually associates with metabolic disorders (MDs), which aggravates the risk of infertility, cardiometabolic events and associated comorbidities in women with PCOS. Adiponectin, a circulating protein produced by adipocytes, which has been suggested to inversely correlate with MDs. Spironolactone, a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. Herein, we investigated the effects of low dose spironolactone (LDS) and the role of adiponectin in endocrine-metabolic disturbances in experimentally-induced PCOS rats. Eighteen female Wistar rats (160-180 g) were randomly allotted into 3 groups and treated with vehicle (p.o.), letrozole (LET; 1 mg/kg) and LET + LDS (0.25 mg/kg), once daily for 21 days, respectively. The results showed that LET-treated animals had features of PCOS, characterized by elevated plasma testosterone and prolactin, increased body weight gain and ovarian weight as well as disrupted ovarian cytoarchitecture and degenerated follicles. Additionally, elevated fasting blood glucose, 1 h-postload glucose and plasma insulin, impaired glucose tolerance, insulin resistance, reduced insulin sensitivity, increased plasma and ovarian lipid profile, plasma lipid peroxidation, TNF-α, IL-6 and decreased plasma glutathione peroxidase and glutathione content were observed. These alterations were associated with decreased circulating adiponectin and were reversed when treated with LDS. The present results suggest that LDS ameliorates endocrine-metabolic disturbances and inflammation-related comorbidities associated with LET-induced PCOS by modulating circulating androgen-adiponectin status.


Cell-density-dependence for growth in agarose of two human lymphoma lines and its decrease after Epstein-Barr virus conversion.
We have compared the growth in agarose medium of two EBV-negative Burkitt lymphoma lines, BJAB and Ramos, and that of their EBV-converted derivatives. Optimal conditions for growth in agarose medium are described. The original EBV-negative lines can grow in agarose to a high efficiency, provided a critical level of cell concentration is attained. Below this level, there is no growth at all. EBV-converted sublines form colonies at a much lower cell concentration, and their maximal plating efficiency is higher. These differences may be related to a super-transformation state induced in these cells by EBV.


Macrophage migration inhibitory factor promotes expression of GLUT4 glucose transporter through MEF2 and Zac1 in cardiomyocytes.
Evidence shows that both macrophage migration inhibitory factor (MIF) and GLUT4 glucose transporter are involved in diabetic cardiomyopathy (DCM), but it remains largely unknown whether and how MIF regulates GLUT4 expression in cardiomyocytes. The present study aims to investigate the mechanism underlying the modulation of GLUT4 by MIF in cardiomyocytes. Activations of AKT and AMPK signaling, and expressions of MIF, GLUT4 and the candidate GLUT4 regulation associated transcription factors in the diabetic mouse myocardium were determined. The screened transcription factors mediating MIF-promoted GLUT4 expression were verified by RNA interference (RNAi) and electrophoretic mobility shift assay (EMSA), respectively. MIF was increased, but GLUT4 was decreased in the diabetic mouse myocardium. MIF could enhance glucose uptake and up-regulate GLUT4 expression in NMVCs. Expressions of transcription factor MEF2A, -2C, -2D and Zac1 were significantly up-regulated in MIF-treated neonatal mouse ventricular cardiomyocytes (NMVCs), and markedly reduced in the diabetic myocardium. Knockdown of MEF2A, -2C, -2D and Zac1 could significantly inhibit glucose uptake and GLUT4 expression in cardiomyocytes. Moreover, EMSA results revealed that transcriptional activities of MEF2 and Zac1 were significantly increased in MIF-treated NMVCs. AMPK signaling was activated in MIF-stimulated NMVCs, and AMPK activator AICAR could enhance MEF2A, -2C, -2D, Zac1 and GLUT4 expression. Additionally, MIF effects were inhibited by an AMPK inhibitor compound C and siRNA targeting MIF receptor CD74, suggesting the involvement of CD74-dependent AMPK activation. Transcription factor MEF2 and Zac1 mediate MIF-induced GLUT4 expression through CD74-dependent AMPK activation in cardiomyocytes.


Poly(imidazole/DMAEA)phosphazene/DNA self-assembled nanoparticles for gene delivery: synthesis and in vitro transfection.
A new cationic derivate of polyphosphazene with imidazole and 2-dimethylaminoethylamino (DMAEA) as side groups, poly(imidazole/DMAEA)phosphazene (PIDP), was synthesized and investigated for gene delivery. The half-lives of PIDP degradation under neutral (pH 7.4) and acidic conditions (pH 5.0) were 22 and 3 days at 37 degrees C, respectively. The cytotoxicity of PIDP assayed by MTT was much lower than that of poly(2-dimethylaminoethylamino)phosphazene (PDAP) and PEI 25K. PIDP could condense DNA into nanoparticles with a size around 100 nm and zeta potential (+25 mV) at the ratio of 10:1 (PIDP/DNA, w/w). The transfection efficiency of PIDP/DNA complex nanoparticles (PICNs) against 293T, COS-7 and Hela cells was much higher than that of PDAP/DNA complexes nanoparticles (PDCNs) and PEI/DNA complexes nanoparticles (PECNs) at 10:1 (polymer/DNA, w/w). Therefore, PIDP could be a safe, efficient and promising cationic polymer for gene therapy.


Comparison of commonly-used microwave radiative transfer models for snow remote sensing.
This paper reviews four commonly-used microwave radiative transfer models that take different electromagnetic approaches to simulate snow brightness temperature (TB): the Dense Media Radiative Transfer - Multi-Layer model (DMRT-ML), the Dense Media Radiative Transfer - Quasi-Crystalline Approximation Mie scattering of Sticky spheres (DMRT-QMS), the Helsinki University of Technology n-Layers model (HUT-nlayers) and the Microwave Emission Model of Layered Snowpacks (MEMLS). Using the same extensively measured physical snowpack properties, we compared the simulated TB at 11, 19 and 37 GHz from these four models. The analysis focuses on the impact of using different types of measured snow microstructure metrics in the simulations. In addition to density, snow microstructure is defined for each snow layer by grain optical diameter (Do) and stickiness for DMRT-ML and DMRT-QMS, mean grain geometrical maximum extent (Dmax) for HUT n-layers and the exponential correlation length for MEMLS. These metrics were derived from either in-situ measurements of snow specific surface area (SSA) or macrophotos of grain sizes (Dmax), assuming non-sticky spheres for the DMRT models. Simulated TB sensitivity analysis using the same inputs shows relatively consistent TB behavior as a function of Do and density variations for the vertical polarization (maximum deviation of 18 K and 27 K, respectively), while some divergences appear in simulated variations for the polarization ratio (PR). Comparisons with ground-based radiometric measurements show that the simulations based on snow SSA measurements have to be scaled with a model-specific factor of Do in order to minimize the root mean square error (RMSE) between measured and simulated TB. Results using in-situ grain size measurements (SSA or Dmax, depending on the model) give a mean TB RMSE (19 and 37 GHz) of the order of 16-26 K, which is similar for all models when the snow microstructure metrics are scaled. However, the MEMLS model converges to better results when driven by the correlation length estimated from in-situ SSA measurements rather than Dmax measurements. On a practical level, this paper shows that the SSA parameter, a snow property that is easy to retrieve in-situ, appears to be the most relevant parameter for characterizing snow microstructure, despite the need for a scaling factor.


Health risks posed by environmental benzophenone-type ultraviolet filters (BP-UVFs): An investigation into the binding of BP-UVFs to trypsin and their adverse effects.
Benzophenone-type ultraviolet filters (BP-UVFs) are ubiquitous in the environment, and people frequently ingest them via food chain and drinking water. However, there is no clear information about whether BP-UVFs are detrimental to human health. Herein, experiments using multi-spectroscopy revealed typical BP-UVFs, i.e., benzophenone (BP), 2-hydroxybenzophenone (2-OHBP), 4-hydroxybenzophenone (4-OHBP), 2,2'-dihydroxybenzophenone (2,2'-OHBP), 2,4-dihydroxybenzophenone (2,4-OHBP), 4,4'-dihydroxybenzophenone (4,4'-OHBP), 2,4,4'-trihydroxybenzophenone (2,4,4'-OHBP), 2,2',4,4'-tetraphydroxybenzophenone (2,2',4,4'-OHBP), 2-hydroxy-4-methoxybenzophenone (2-OH-4-MeOBP) and 2,2'-dihydroxy-4-methoxybenzophenone (2,2'-OH-4-MeOBP), could bind to the active site of trypsin with different binding constants (2.69 × 104-1.07 × 106 L/mol), cause structural abnormalities and inhibit the enzymatic activity in varying degrees, indicating that the BP-UVFs ingestion poses a risk to human health. In contrast to previous research, this study systematically analysed the binding mechanism using an innovative combination of molecular docking and advanced quantum chemistry calculations, including molecular dynamics simulations, energy calculations, etc. The results revealed that most amino acids that make up trypsin have a greater positive electrostatic surface potential (ESP). Therefore, the greater the area and distribution of negative ESP in a particular BP-UVFs, the more easily it will bind to trypsin. This provides new insight into the binding of pollutants to proteins. This study suggests a need for better monitoring and control of environmental BP-UVFs.


Tinea nigra: report of twelve cases in Venezuela.
Tinea nigra is a superficial mycotic infection produced by Hortaea werneckii, formerly known as Phaeoannelomyces werneckii, formerly known as Exophiala werneckii, and Stenella araguata, the latter autochthonous in Venezuela, it was first described and named as Cladosporium castellanii in 1973. The present report describes 12 cases in the period of 1972-2002, diagnosed at the Medical Mycology Section at the Tropical Institute of the Universidad Central de Venezuela, in Caracas. This mycosis is more prevalent among young people, with fair skin, from 3 to 28 years of age, who visited beaches and in whom the lesions are more evident. Out of these 12 patients, 8 (66.66%) had Phaeoannelomyces werneckii as the causal agent and 2 (16.67%) Stenella araguata was isolated. Two patients had more than one macule, and curiously in these cases, each lesion was caused by a different species of the aforementioned fungus.


Laparoscopic cholecystectomy in situs inversus-our experience of 6 cases.
Laparoscopic cholecystectomy is the standard procedure for symptomatic gall stone disease. Situs inversus is a condition where the visceral anatomy is reversed. Laparoscopic cholecystectomy in a patient of situs inversus is a technically difficult procedure. Six patients of situs inversus underwent laparoscopic cholecystectomy from January 2003 to December 2009. In the first patient of situs inversus, we operated by placing the ports in mirror image fashion as that of standard laparoscopic cholecystectomy. However in next five patients we modified the technique by interchanging the epigastric and left mid clavicular line ports to overcome the problem of handedness. The procedure was successfully completed in all six patients. No intraoperative or postoperative complications occurred. The mean operating time was 65 mins (45-85 mins). Laparoscopic cholecystectomy is safe in patients of situs inversus. However, extreme care and skill is required to identify the reversed anatomy and to overcome the problem of handedness. Interchanging the epigastric and left mid clavicular line ports makes the procedure easier.


Hematologic Malignancies.
Radiation therapy plays a critical role in the management of a wide range of hematologic malignancies. The optimal radiation dose and target volume, and safe and effective ways of integrating radiation with systemic agents, vary depending on the histologic subtypes, stage at presentation, patient performance status, response to systemic therapy if given, treatment intent, and patient preferences. Limiting doses to surrounding organs without sacrificing disease control is of paramount importance. Reducing radiation doses and treatment volume in selected cases, and the use of advanced radiotherapy technology, can improve the therapeutic ratio of patients receiving radiation therapy for hematologic malignancies.


[Prediction of peritoneal fluid pancreatic amylase to histopathological change and prognosis of acute experimental necrotic pancreatitis of monkey].
To observe the significance of peritoneal fluid pancreatic amylase in predicting the degree of histopathological change and prognosis of acute necrotic pancreatitis (ANP) of monkey. Injection of the mixture of bile and trypsin into the pancreatic duct set up ANP monkey model. The severity of ANP depended on the injection rate and volume, in correlation to the peritoneal fluid pancreatic amylase (PF Amylase) in the early stage of ANP. With the rate (3-13 ml/min) and volume (0.1-1.0 ml/kg) of injection increase, the PF Amylase in the early stage of the ANP significantly went up. Meanwhile, the survival time was negatively correlated to the PF Amylase in the early stage (0.5 hour) of ANP (t = -9.06 InX + 129.85, r = -0.88, P < 0.01). The PF Amylase in the early stage of ANP can effectively predict the severity of ANP and prognosis.


Post-column derivatization for fluorescence and chemiluminescence detection in capillary electrophoresis.
Instrumental developments and applications of post-column derivatization for fluorescence and chemiluminescence detection in capillary electrophoresis (CE) are reviewed. Various systems to merge the reagent solution with the separation medium have been developed, including coaxial capillary reactors, gap reactors and free solution or end-column systems. For all reactor types the geometry of the system, as well as the method to propel the reaction mixture (by pressure or by voltage) appeared to be critical to preserve the separation efficiency. Plate numbers of over 100,000 could be realised with different reactors. The strict requirements on the rate of post-column derivatization reactions to be applied in CE limit the number of different reagents that have been used. For fluorescence detection, with laser or lamps as the excitation source, so far mainly o-phthalaldehyde and its naphthalene analogue have been used as reagent. Derivatization systems that are based on complexation reactions also showed good promise for application in CE. Detection limits could be obtained that were comparable to those obtained after pre-column derivatization. Various reagents for chemiluminescence detection (e.g. the luminol and peroxyoxalate systems) have been studied. The often complicated chemistry involved made application of these reagents in CE even more difficult. Results obtained so far, in terms of sensitivity, have not been up to expectation, with detection limits usually in the order of micromol l(-1).


ROS-responsive microneedles loaded with integrin avβ6-blocking antibodies for the treatment of pulmonary fibrosis.
Pulmonary fibrosis (PF) is a fibrotic interstitial pneumonia with poor prognosis and limited treatment methods. Inhibition of integrin αVβ6 expression could prevent pulmonary fibrosis, however, a phase II clinical trial of αVβ6-blocking antibody treating PF stopped prematurely due to low bioavailability and toxic side effects of systematic administration. Here, we describe a micro-invasive percutaneous transthoracic and hydrogen peroxide-responsive microneedle composed of degradable gel for smart delivery of integrin αvβ6-blocking antibody which has the advantages of rapid response, excellent biocompatibility, protection of bioactivity, high tissue permeation and specific targeting to lesions. This microneedle could partially release integrin αvβ6-blocking antibodies when exposed to hydrogen peroxide generated during PF, thus reducing activation of the pro-fibrotic factor TGF-β1 from its latent precursor and showing excellent therapeutic efficacy for PF.


Long-term toxicity of chemotherapy for testicular cancer--the cost of cure.
Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group although serum free thyroxine and free T3 were while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. The levels of FSH and LH were both independently correlated with age of the patient while FSH was higher in patients having more chemotherapy and had a tendency to fall towards normal with time since treatment. Over half the patients had normal sperm concentrations although 74% had a raised proportion of abnormal sperm. Indices of sperm function were worse in patients having more chemotherapy but sperm number increased towards normal with time since treatment, particularly after the second year. The long-term side-effects of chemotherapy for testicular cancer are thus generally mild but are largely irreversible and their severity is related to the total amount of chemotherapy received. As their longer term significance is not clear we would recommend that, in the treatment of testicular cancer, doses of chemotherapy are reduced to the minimum required for cure. Assessment of long-term side-effects of chemotherapy for testicular cancer should be a mandatory part of any study of such treatment and should be considered in any comparison of different therapies.


Numerically simulated pH-induced reactivation of catalytic activity of horseradish peroxidase.
A model mechanism that accounts for the experimentally observed pH-dependent enhancement of enzymatic activity of horseradish peroxidase through the catalase-like pathway is proposed. Predictions of the model are tested against a number of experimental results to confirm that kinetic constants used in the numerical simulation are correctly chosen and that the model can be used to emulate the reaction between horseradish peroxidase and hydrogen peroxide in a wide range of conditions.


Experience with percutaneous transhepatic cholangiography using the Japanese needle.
Percutaneous transhepatic cholangiography using a very thin needle has been performed in 885 patients with a variety of underlying hepatic, biliary, and pancreatic disorders. The procedure was successful in 99% of the patients with dilated intrahepatic bile ducts and in 85% of those with non-dilated ducts. Complications which required surgical intervention occurred only in two cases (0.2%). In patients with obstructive jaundice, external bile drainage was performed immediately after visualization of the bile duct. Percutaneous transhepatic cholangiography is an extremely useful and safe method for investigating disorders of the biliary tract, for localizing the cause of obstructive jaundice, and for reducing the degree of jaundice and improving the general status of patients with obstructive jaundice.


Heterologous Expression, Purification and Characterization of a Peroxidase Isolated from Lepidium draba.
Peroxidase is one of the most widely used enzymes in biotechnology and medicine. In the current study, cDNA encoding peroxidase from Lepidium draba (LDP) was cloned and expressed in Escherichia coli BL21 (DE3) cells in the form of inclusion bodies (IBs). To achieve purified active enzyme, IBs were solubilized before being purified and refolded. The deduced amino acid sequence (308) of the LDP gene (924 bp) revealed 88.96% identity to horseradish peroxidase C1A (HRP C1A). The results of basic local alignment search tool (BLAST) and phylogenetic analysis of the protein sequence showed that this enzyme belongs to the neutral group of class III plant peroxidases. According to sequence analysis and structural modeling, critical amino acids in heme and calcium binding domain as well as cysteine residues were conserved as HRP C1A except for calcium binding domain where valine228 was replaced with isoleucine. The far-UV circular dichroism (CD) results were confirmed by homology modeling data showing the enzyme consists mainly of α-helices as other plant peroxidases. Overall, according to the results of catalytic activity and refolding yield, LDP can be introduced as a novel peroxidase for medical and biotechnology applications.


Vitamin C and gallstone formation: a preliminary report.
Gallstone formation in hypovitaminotic C guinea-pig fed a high cholesterol diet was associated with qualitative changes in the gallbladder bile, namely, a high cholesterol concentration, a lowered bile acid content and diminished phospholipid-to-cholesterol and bile acid-to-cholesterol ratio.


Validation of skinfold equations and alternative methods for the determination of fat-free mass in young athletes.
To cross-validate skinfold (SKF) equations, impedance devices, and air-displacement plethysmography (ADP) for the determination of fat-free mass (FFM). Male and female youth athletes were evaluated (n = 91[mean ± SD] age: 18.19 ± 2.37 year; height: 172.1 ± 9.8 cm; body mass: 68.9 ± 14.5 kg; BMI: 23.15 ± 3.2 kg m-2; body fat: 19.59 ± 6.9%) using underwater weighing (UWW), ADP, and SKF assessments. A 3-compartment (3C) model (i.e., UWW and total body water) served as the criterion, and alternate body density (Db) estimates from ADP and multiple SKF equations were obtained. Validity metrics were examined to establish each method's performance. Bioelectrical impedance analysis (BIA), bioimpedance spectroscopy (BIS), and the SKF equations of Devrim-Lanpir, Durnin and Womersley, Jackson and Pollock (7-site), Katch, Loftin, Lohman, Slaughter, and Thorland differed from criterion. For females, Pearson's correlations between the 3C model and alternate methods ranged from 0.51 to 0.92, the Lin's concordance correlation coefficient (CCC) ranged from 0.41 to 0.89, with standard error of the estimate (SEE) ranges of 1.9-4.6 kg. For SKF, the Evans 7-site and J&P 3 Site equations performed best with CCC and SEE values of 0.82, 2.01 kg and 0.78, 2.21 kg, respectively. For males, Pearson's correlations between the 3C model and alternate methods ranged from 0.50 to 0.95, CCC ranges of 0.46-0.94, and SEE ranges of 3.3-7.6 kg. For SKF, the Evans 3-site equation performed best with a mean difference of 1.8 (3.56) kg and a CCC of 0.93. The Evans 7-site and 3-site SKF equations performed best for female and male athletes, respectively. The field 3C model can provide an alternative measure of FFM when necessary.


Amplifying fluorescent polymer sensors for the explosives taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB).
Structural and electronic effects on the efficiency of DMNB detection with fluorescent conjugated polymers are described.