Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects.
In type 2 diabetes, metformin reduces cardiovascular risk beyond the effect of glycaemic control. Since oxidative stress and the consequent enhanced platelet activation contribute to accelerated atherosclerosis in diabetes, we hypothesized that metformin could reduce oxidative stress in this condition. We randomized 26 newly diagnosed type 2 diabetic subjects to assume either metformin (M, n = 13) or gliclazide (G, n = 13) for 12 weeks. Drugs were titrated as needed to achieve good glycaemic control. Before and after treatment, we determined blood glucose, insulin, HbA(1c), vitamin A and E levels and 8-iso-PGF(2alpha) and 11-dehydro-thromboxane B(2) urinary excretion, an in vivo oxidative stress and a thromboxane-dependent platelet activation marker, respectively. Notwithstanding a comparable improvement in metabolic control, 8-iso-PGF(2alpha) (M from 708 +/- 32 to 589 +/- 45 pg/mg cr, p < 0.001; G from 646 +/- 80 to 665 +/- 79, pg/mg cr, p = ns) and 11-dehydro-thromboxane B(2) (M from 2190 +/- 196 to 1753 +/- 150 pg/mg cr, p < 0.05; G from 2048 +/- 202 to 1923 +/- 223, pg/mg cr, p = ns) urinary excretion decreased after metformin but not after gliclazide treatment. After metformin, vitamin A and E levels significantly increased while they remained unchanged after gliclazide. These data suggest that metformin could improve oxidative stress, preserve antioxidant function and restrain platelet activation in type 2 diabetes.


Neuropathology of the locus ceruleus: a semi-quantitative study.
The locus ceruleus was studied in 86 brains of the elderly, with or without degenerative disease. Parkinson's disease, multiple system atrophy, progressive supranuclear palsy and senile dementia were among the diseases studied. Nerve cell loss, the appearance of neurofibrillary changes and Lewy bodies were examined semi-quantitatively. The number of nerve cells diminished in old age, especially over 90 years. The decrease of nerve cells was greater in cases with Lewy bodies. A marked loss of nerve cell was observed in multiple system atrophies, including Shy-Drager syndrome, olivopontocerebellar atrophy and striatonigral degeneration, and in some cases of Parkinson's disease and senile dementia. The number of nerve cells did not decrease in cases of progressive supranuclear palsy. Lewy bodies and neurofibrillary tangles appeared increasingly in old age. However, the incidence of both changes in the same neuron was rare, and in such cases their structures appeared not to be related.


Revision of total shoulder arthroplasty.
In France, the number of revisions for total shoulder arthroplasty (TSA) has increased by 29% between 2006 and 2010. Published studies have reported a revision rate of approximately 11% for hemi-arthroplasty and total anatomical implants, and 10% for reversed implants. The decision to revise or not revise a TSA requires that a rigorous, clinical, laboratory and imaging initial assessment be done in order to answer five questions. Is it infected? Is it unstable? Is it worn? Is it loosened? How is the rotator cuff? This assessment and an evaluation of the bone stock are required to decide whether or not to revise. If the problem is infection, the best solution is not always complete removal of the implant, which results in very poor shoulder function. In such a situation, a multidisciplinary consultation is essential in the decision-making. If the problem is instability, the cause must be identified and rectified. Instability is often caused by insufficient restoration of the humerus length. If the problem is loosening, the type of revision must take into account the patient's age, the rotator cuff status and the available bone stock. The possibilities to reimplant an anatomical glenoid are scarce, and only for cases with minor bone loss and an intact cuff. If a bone graft without reimplantation of a glenoid component is preferred, it should be a tricortical graft to resist wear and medialisation. In the other cases, a reversed shoulder implant with an autograft is preferable. Whether or not the humeral stem is loose, it must often be removed. However, its removal is very difficult, risky and it often causes complications, with humerus fracture being the most common. The possibility of reconstruction depends on the quality of the remaining bone stock. In all these risky situations, the patient should be duly informed and should take part in the decision-making process.


Long-term outcomes and life satisfaction of adults who had pediatric spinal cord injuries.
To determine long-term outcomes and life satisfaction of adults who sustained pediatric spinal cord injury (SCI). Structured interview of adults who were 25 years or older who had pediatric SCI. Community. A convenience sample of 46 patients from a total of 81 patients who received care in an SCI program: 1 refused participation, 4 died, and 30 were lost to follow-up. A structured questionnaire including physical, psychosocial, and medical information. The Craig Handicap Assessment and Reporting Technique and two measures of life satisfaction were also administered. Participants were 25 to 34 years old, mean 27 years. Thirty-two had tetraplegia and 14 had paraplegia. Thirty-one were men. Mean years of education was 14. Fifty-four percent were employed, 48% lived independently, and 15% were married. Life satisfaction was associated with education, income, satisfaction with employment, and social/recreation opportunities, and was inversely associated with some medical complications. Life satisfaction was not significantly associated with level of injury, age at injury, or duration of injury. Individuals who had pediatric SCI, much like adult-onset SCI, have the greatest opportunity for a satisfying adult life if rehabilitation emphasizes psychosocial factors such as education, employment, and long-term health management.


Chromosome aberrations in spermatogonia and sperm abnormalities in Curacron-treated mice.
Curacron is an organophosphorus pesticide widely used in cotton fields. In order to assay its mutagenic potential in mammalian germ cells chromosomal aberrations in spermatogonial cells and sperm abnormalities were examined in mice after Curacron treatment. For studying chromosomal aberrations mice were treated both acutely (single treatment) and subacutely (for 5 consecutive days) with 3 dose levels of Curacron, 12, 36 and 72 mg/kg. Curacron was found to produce a significant increase in structural chromosomal aberrations after acute and subacute treatments. This increase was dose-dependent. A dose-dependent inhibition in mitotic activity in spermatogonia was also found. For studying sperm abnormalities mice were treated for 5 consecutive days with 20, 40 and 60 mg/kg. Morphological sperm abnormalities increased significantly after treatment with Curacron. The increase was dose-dependent. An inhibition of 40.2% in sperm count and of 74.5% in sperm motility occurred after treatment with 60 mg/kg Curacron. These results show that Curacron has a damaging effect on spermatogonial cells as well as on sperm morphology.


Novel approaches to identify low-penetrance cancer susceptibility genes using mouse models.
Studies of cancer predisposition have largely concentrated on the role of high-penetrance susceptibility genes. Less than 10% of the total human tumor burden, however, is accounted for by mutations in these genes. More genetic variation in cancer risk is likely to be due to commoner but lower penetrance alleles. In man, such modifier genes will be difficult to find since they do not segregate as single Mendelian traits. The mouse offers a powerful system for studying polygenic traits such as cancer and has been widely used for this purpose. Novel approaches that might accelerate the identification of these low-penetrance cancer susceptibility genes by using mouse models will be discussed.


Non-invasive imaging criteria for the diagnosis of hepatocellular carcinoma in non-cirrhotic patients with chronic hepatitis B.
Criteria defined by the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) enable hepatocellular carcinoma (HCC) diagnosis based on imaging in cirrhosis. Non-cirrhotic patients require biopsy given the lower pre-test probability of HCC. The objective of our study was to assess the performance of EASL and LI-RADS criteria for the diagnosis of HCC in non-cirrhotic patients with chronic HBV infection. This was a cross-sectional study performed at a referral center. We included all patients with HBV without cirrhosis with focal liver lesions who underwent contrast-enhanced CT or MRI at our clinic between 2005-2018. Studies were reviewed by 2 radiologists blinded to the diagnosis. We included 280 patients, median age was 56.8 (IQR 48.2-65.45) years and 223 (80%) were male. In 191 (79%) cases the lesion was found as a result of screening. Cirrhosis was excluded based on pathology in 252 (90%) cases. We assessed 338 nodules: 257 (76%) HCC, 40 (12%) non-HCC malignant lesions, and 41 (12%) benign lesions. EASL criteria and LR-5/LR-tumor-in-vein (TIV) categories had a 100% agreement in categorizing lesions as HCC, and 226 nodules (67%) were classified as HCCs. The sensitivity, specificity, positive predictive value, and negative predictive value were 82.1 (76.9-86.6), 81.5 (71.3-89.2), 93.4 (89.3-96.2), and 58.9 (49.2-68.1), respectively. When the pre-test probability of HCC is >70%, estimated as a PAGE-B score above 9, and EASL or LR-5/LR-TIV criteria are met, post-test probability would be >90%. EASL criteria and LR-5/LR-TIV categories show a positive predictive value in patients with HBV without cirrhosis that is comparable to that seen in patients with cirrhosis. These criteria can be used when the pre-test probability of HCC is >70%. Current guidelines recommend performing a biopsy to confirm the diagnosis of presumed hepatocellular carcinoma (HCC) in patients without cirrhosis. We showed that specific imaging criteria had a 100% agreement for categorizing lesions as HCC, with a positive predictive value of 93.4%. These imaging criteria could be used to diagnose HCC in HBV patients without cirrhosis with a pre-test probability of HCC of ≥70%, avoiding the need for a liver biopsy.


Relaxin/serelaxin for cardiac dysfunction and heart failure in hypertension.
The pregnancy related hormone relaxin is produced throughout the reproductive system. However, relaxin also has important cardiovascular effects as part of the adaptation that the cardiovascular system undergoes in response to the extra demands of pregnancy. These effects are primarily mediated by the relaxin family peptide receptor 1, which is one of four known relaxin receptors. The effects of relaxin on the cardiovascular system during pregnancy, as well as its anti-fibrotic and anti-inflammatory properties, have led to extensive studies into the potential of relaxin therapy as an approach to treat heart failure. Cardiomyocytes, cardiac fibroblasts, and endothelial cells all possess relaxin family peptide receptor 1, allowing for direct effects of therapeutic relaxin on the heart. Many pre-clinical animal studies have demonstrated a beneficial effect of exogenous relaxin on adverse cardiac remodeling including inflammation, fibrosis, cardiomyocyte hypertrophy and apoptosis, as well as effects on cardiac contractile function. Despite this, clinical studies have yielded disappointing results for the synthetic seralaxin, even though seralaxin was well tolerated. This article will provide background on relaxin in the context of normal physiology, as well as the role of relaxin in pregnancy-related adaptations of the cardiovascular system. We will also present evidence from pre-clinical animal studies that demonstrate the potential benefits of relaxin therapy, as well as discussing the results from clinical trials. Finally, we will discuss possible reasons for the failure of these clinical trials as well as steps being taken to potentially improve relaxin therapy for heart failure.


p16INK4A Expression in Condyloma Acuminata Lesions Associated with High-Risk Human Papillomavirus Infection.
The objective of this study was to discover the possible correlation between p16INK4A expression and the LR/HR-HPV infection in condyloma acuminate (CA) lesions. This cross-sectional study was conducted during January-December 2017 on 33 CA patients. The expression of p16INK4A was detected by immunohistochemistry (IHC) staining. The positive interpretation was carried out by scoring which score 0 was negative, score 1 was sporadic, score 2 was focal, and score 3 was diffuses. The HPV genotypes were identified by reverse line blot, and 40 genotypes of HPV detected, including HR-HPV (HPVs 16, 18, 26, 31, 33,35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68a, 68b, 69, 73, and 82) and LR-HPV (HPVs 6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 64, 70, 71, 72, 81, 83, 84, 87, 89, and 90). The expression of p16INK4A was significantly correlated with HR-HPV infection. Patients infected with HR-HPV had 0.644 times higher possibility to express p16INK4A gene compared to those infected with LR-HPV. LR-HPV genotypes detected in CA patients were HPVs 6, 11, 42, 61, 54, 81, 87, 89, and 90 and HR-HPV genotypes were HPVs 18, 26, 45, 51, 52, 67, 68B, 69, and 82. LR-HPV was found in 19/33 of patients and HR-HPV was in 14/33 of patients. The expression of p16INK4A in CA lesions was diffuse in15.2% of patients, was focal in 24.2% of patients , was sporadic in 39.4% of patients were, and was negative in 21.2% of patients . In LR-HPV group, there was no diffuse expression, focal expression was observed in 15.8%, sporadic in 47.4%, and negative in 36.8%, while in HR-HPV group, p16INK4A expression was detected in all lesions , in a way that its expression was diffuse in 35.7%, focal in 35.7%, and sporadic in 28.6%. IHC is a routine method in histopathological diagnosis, therefore the detection of p16INK4A expression by IHC can be used as a biomarker for HR-HPV infection diagnosis.


Methods for meta-analysis of genetic data.
Modern genetic association studies, using genome-wide genotype data, are often underpowered. Meta-analyses of multiple studies performing genome-wide genotyping improve power and have led to the identification of thousands of genotype-trait associations. This unit provides an overview of the key concepts required for genetic meta-analyses, and presents strategic approaches and key decisions that must be made in the process of performing genome-wide association study (GWAS) meta-analyses. The commentary discusses the interpretation of GWAS meta-analysis results, complications, and some of the possible next steps once a GWAS meta-analysis has successfully identified regions associated with a trait.


Exposure, susceptibility, and breast cancer risk: a hypothesis regarding exogenous carcinogens, breast tissue development, and social gradients, including black/white differences, in breast cancer incidence.
At present, known risk factors account for only one-third of breast cancer cases diagnosed in the United States. They explain an even smaller fraction of the ten-fold variation in international breast cancer incidence rates. The low population-attributable risk of these identified risk factors, plus the existence of phenomena that cannot be easily explained by current etiologic hypotheses (such as the higher rate of breast cancer among black as compared to white women under age 40 within the United States), suggests that unidentified risk factors contribute substantially to breast cancer causation. This paper summarizes evidence to propose that two socially-conditioned factors determine a society's breast cancer incidence and its social gradients in risk: 1) the extent of exposure to exogenous carcinogens, and 2) breast tissue susceptibility to these exposures. It is further hypothesized that breast tissue susceptibility is inversely related to breast tissue differentiation, and that socially-mediated reproductive patterns (involving both early-terminated and full-term pregnancies) affect susceptibility both by altering (via hormonally-mediated mechanisms) the number and ratio of undifferentiated and differentiated cells, and by stimulating the growth of initiated and transformed cells. This view is presented in contrast to hypotheses that propose exposure to endogenous hormones as the major determinant of breast cancer risk.


Sodium hyaluronate for the treatment of chronic shoulder pain associated with glenohumeral osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled trial.
Nonoperative treatments for glenohumeral osteoarthritis (GH-OA) are limited. Intra-articular therapy with sodium hyaluronate (HA) has been effective in treating OA of the knee. Therefore, we sought to evaluate the efficacy and safety of HA in treating chronic pain associated with GH-OA. This double-blind, randomized, controlled multicenter trial enrolled 300 patients with GH-OA: 150 received HA and 150 received phosphate-buffered saline (PBS) in 3 weekly injections and were evaluated over 26 weeks. Primary and secondary outcome measurements were visual analog scale (VAS) for pain and the percentage of Outcome Measures in Rheumatoid Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) high responders. In HA and PBS intent-to-treat (ITT) patients, there was a mean improvement from baseline in VAS of 19.88 mm and 16.29 mm at week 26, respectively. Similarly, the percentage of OMERACT-OARSI high responders in the HA group was higher (40.8% vs 34.9%); however, neither difference was statistically significant (P = .1121 and P = .0690, respectively). In a subset of patients without concomitant shoulder pathologies, the differences of VAS and OMERACT-OARSI high-responder rates between groups were 4.0 mm and 8.37%, respectively, which reached statistical significance. Safety analyses showed comparable rates of adverse events between groups, and neither group reported serious treatment-related adverse events. A numeric advantage, but without statistical significance, was found for HA ITT patients with GH-OA. Although data for a subset of HA patients without concomitant pathologies reached statistical significance, additional randomized trials are needed to confirm the clinical implication of this outcome.


The androgen system across the menstrual cycle: Hormonal, (epi-)genetic and psychometric alterations.
The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studies investigated alterations of these parameters throughout the menstrual cycle and there is a lack of studies exploring a link towards epigenetic and genetic regulation. This multisite longitudinal study examines behavioral parameters including affectivity, stress perception and various diary parameters of mental and physical well-being in conjunction with testosterone and LH plasma levels in 87 menstruating women. Additionally, Cysteine-Adenenine-Guanin (CAG) repeat length and methylation of the androgen receptor gene collected at four time points across two cycles comprising the menstrual, pre-ovulatory, mid-luteal and premenstrual phase were assesed. There was a significant increase of LH and testosterone plasma levels during the pre-ovulatory phase as well as a decrease of methylation of the androgen receptor at mid-luteal phase. Subjective ratings of physical condition and sexual interest peaked during the pre-ovulatory phase and the former correlated negatively with the androgen receptor gene methylation level. This longitudinal study shows alterations of the androgen system including epigenetic measurements throughout the menstrual cycle. While a link between peripheral testosterone and sexual activity and between increased physical condition and an upregulation of testosterone receptor protein expression can be assumed, the majority of parameters remained unchanged. These initial findings need validation by subsequent studies.


Influence of the albumin concentration and temperature on the lysis of human erythrocytes by sodium dodecyl sulfate.
The stability of human erythrocytes to sodium dodecyl sulfate (SDS) was assessed spectrophotometrically in the presence of different concentrations of bovine serum albumin (BSA) and at different temperatures (27-45 °C). The absorbance at 540 nm (A₅₄₀) was correlated with the SDS concentration by sigmoidal regression based on the Boltzmann equation. Erythrocyte stability was characterized on the basis of the SDS concentration that induces hemolysis in 50% of the cells (D₅₀). Progressive increases in the albumin concentration led to increases in the D₅₀ value. The protective effect of BSA against SDS-induced hemolysis was attributed to the binding of the surfactant to the hydrophobic binding sites of this protein. The D₅₀ values decreased sigmoidally with an increase in the temperature. This trend, which could not be explained by changes in the spectral properties of hemoglobin, maybe due to heterogeneity in the erythrocyte population.


Reporting demographics in randomized control trials in spine surgery - we must do better.
Demographic factors contribute significantly to spine surgery outcomes. Although race and ethnicity are not proxies for disease states, the intersection between these patient characteristics and socioeconomic status significantly impact patient outcomes. The purpose of this study is to investigate the frequency of demographic reporting and analysis in randomized controlled clinical trials (RCTs) published in the three highest impact spine journals. Systematic review. We analyzed 278 randomized control trials published in The Spine Journal, Spine, and Journal of Neurosurgery: Spine between January 2012 - January 2022. Extracted manuscript characteristics included the frequency of demographic reporting, sample size, and demographic composition of studies. We conducted a systematic review of RCTs published between January 2012 - January 2022 in the three highest impact factor spine journals in 2021: The Spine Journal, Spine, and Journal of Neurosurgery: Spine. We determined if age, gender, BMI, race, and ethnicity were reported and analyzed for each study. The overall frequency of demographic reporting was assessed, and the reporting trends were analyzed for each individual year and journal. Among studies that did report demographics, the populations were analyzed in comparison to the national population per United States (US) census reports. Studies were evaluated for bias using Cochrane risk-of-bias. Our search identified 278 RCTs for inclusion. 166 were published in Spine, 65 in The Spine Journal, and 47 in Journal of Neurosurgery: Spine. Only 9.35% (N=26) and 3.9% (N=11) of studies reported race and ethnicity, respectively. Demographic reporting frequency did not vary based on the publishing journal. Reporting of age and BMI increased over time, but reporting of race and ethnicity did not. Among RCTs that reported race, 88% were conducted in the US, and 85.71% of the patients in these US studies were White. White subjects were overly represented compared to the US population (85.71% vs. 61.63%, p<.001), and non-White or Black patients were most underrepresented (2.89% vs. 25.96%, p<.001). RCTs published in the three highest impact factor spine journals failed to frequently report patient race or ethnicity. Among studies published in the US, study populations are increasingly represented by non-Hispanic White patients. As we strive to care for an increasingly diverse population and reduce disparities to care, spine surgeons must do a better job reporting these variables to increase the external validity and generalizability of RCTs.


Is zygosity or chorionicity the main determinant of fetal outcome in twin pregnancies?
The purpose of this study was to examine whether fetal outcome in twin pregnancies is dependent on zygosity or chorionicity. This was a prospective observational study comprised of women with twin pregnancies who attended the fetal medicine unit at St Michael's Hospital, Bristol, Ireland, during the years 1998 to 2000 and who were delivered in hospitals in south west England. After delivery, zygosity was determined with umbilical cord blood with the use of microsatellite markers that were amplified by polymerase chain reaction. Placentae were examined histologically for chorionic type. The perinatal outcomes of 3 groups of monozygotic monochorionic, monozygotic dichorionic, and dizygotic pregnancies were compared with the use of the Mann-Whitney U test and the Fisher's exact test. All 92 dizygotic and 15 monozygotic dichorionic pregnancies resulted in live births. In 7 of the 39 cases in the monozygotic monochorionic group, either both twins were not live born or delivery occurred <24 weeks of gestation. The gestational age at delivery and birth weight were significantly lower, and there were a greater number of cases with birth weight discordancy of >25% in the monochorionic pregnancies compared with the other 2 groups (P < .05). There were no significant differences in any of the study parameters between the monozygotic dichorionic and dizygotic groups. Fetal outcome in twin pregnancies is related to chorionicity rather than zygosity.


A Review of the Usefulness of Catheter-Directed Thrombolysis for Pulmonary Embolism.
Venous thromboembolic disease (VTE) is a health problem; around 10 million cases occur yearly with substantial morbidity and mortality. Those who survive may be left with long-term sequelae. Those sequelae might include chronic thromboembolic pulmonary hypertension, persistent right ventricular dysfunction, exercise intolerance, and reduced quality of life. Current PE management consists of anticoagulation alone, systemic thrombolysis, catheter-directed thrombolysis, and surgical embolectomy. The severity of patients with pulmonary embolism (PE) depends on the clinic and not exclusively on the extent of radiological or anatomical involvement. In this review, we present the main clinical and functional characteristics of patients in whom thrombotic fragmentation plus catheter-guided thrombolysis is used to manage acute PE of intermediate-high risk and torpid evolution within the first hours of admission.


Assessment of the early effects of 5,6-dimethylxanthenone-4-acetic acid using macromolecular contrast media-enhanced magnetic resonance imaging: ectopic versus orthotopic tumors.
To investigate the early effects of a vascular disrupting agent (VDA) in ectopic and orthotopic tumors by using macromolecular contrast media (MMCM)-enhanced magnetic resonance imaging (MMCM-MRI). The MMCM-MRI of ectopic and orthotopic MCA205 murine fibrosarcomas was performed using the intravascular contrast agent albumin-(gadopentetate dimeglumine)(35). Change in longitudinal relaxation rate (DeltaR1) was measured 24 hours after treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA; 30 mg/kg) and used to compute tumor vascular volume and permeability. Correlative histologic and immunohistochemical evaluation was carried out, along with measurement of tumor necrosis factor alpha and vascular endothelial growth factor levels in whole tumor extracts using the enzyme-linked immunosorbent assay. Orthotopic tumors showed higher vascular volume (p < 0.05) than ectopic tumors before treatment. Twenty-four hours after DMXAA treatment, a significant (p < 0.0001), but differential, decrease in DeltaR1 (70% in ectopic and 50% in orthotopic tumors) was observed compared with baseline estimates. Consistent with this observation, greater levels of tumor necrosis factor alpha, an important mediator of the antivascular activity of DMXAA, were measured in ectopic tumors 3 hours posttreatment compared with orthotopic tumors (p < 0.05). Immunohistochemical (CD31) and histologic (hematoxylin and eosin) sections of ectopic and orthotopic tumors showed highly tumor-selective vascular damage after treatment with the presence of viable surrounding normal tissue. The MMCM-MRI provided early quantitative estimates of change in tumor perfusion after VDA treatment that showed good correlation with cytokine induction. Differences in the response of ectopic and orthotopic tumors highlight the influence of the host microenvironment in modulating the activity of VDAs.


[Pancreas. Part I: congenital changes, acute and chronic pancreatitis].
The pancreas develops from ventral and the dorsal buds, which undergo fusion. Failure to fuse results in pancreas divisum, which is defined by separate pancreatic ductal systems draining into the duodenum. Risk of developing pancreatitis is increased in pancreas divisum because of insufficient drainage. MR cholangiopancreatography (MRCP) is the technique of choice for detecting pancreas divisum non-invasively. Annular pancreas is the result of incomplete rotation of the pancreatic bud around the duodenum with the persistence of parenchyma or a fibrous band encircling (and sometimes stenosing) the duodenum. Acute pancreatitis is usually caused by bile duct stones or alcohol abuse. The Atlanta classification differentiates between mild acute and severe acute pancreatitis associated with organ failure and/or local complications such as necrosis, abscess or pseudocyst. Contrast-enhanced multi-detector row CT is the method of choice to assess the extent of disease. Balthazar et al.'s CT severity index assesses the risk of mortality and morbidity. In acute pancreatitis, the role of MRCP is mainly limited to finding bile duct stones in patients with suspected biliary pancreatitis. Chronic pancreatitis results in relentless and irreversible loss of exocrine (and sometimes endocrine) function of the pancreas. MDCT even shows subtle calcifications. MRCP is the method of choice for non-invasive assessment of the duct. Inflammatory pseudotumor in chronic pancreatitis and groove pancreatitis are difficult to differentiate from pancreatic cancer. In these cases, multiple imaging methods such as MDCT, MRI and endosonography including biopsy may be used to make a diagnosis.


Pathological effects of lyngbyatoxin A upon mice.
Histopathological changes induced in mice by lyngbyatoxin A were studied in connection with the occurrence of the toxin in marine turtles implicated in human intoxication. Lyngbyatoxin A showed an i.p. lethal dose 250 microg/kg in immature mice (3-week old) and most severely damaged capillaries of villi in the small intestine. Immature mice were more sensitive than matured ones and died of bleeding from the small intestines. With sublethal doses were observed erosion in the stomach, small intestine, cecum, and large intestine, as well as inflammation in the lung. Time course changes observed after p.o. administration of sublethal doses indicated severe mucus secretion and injuries to occur within 60 min in the intestine and within 24h in the stomach. Increased inflammatory cells followed these injuries. The injuries in the lung, stomach, and small intestine took a few weeks for recovery. The cause of death and the effective dose levels resembled those of aplysiatoxin poisoning.


Investigating models of protein function and allostery with a widespread mutational analysis of a light-activated protein.
To investigate the relationship between a protein's sequence and its biophysical properties, we studied the effects of more than 100 mutations in Avena sativa light-oxygen-voltage domain 2, a model protein of the Per-Arnt-Sim family. The A. sativa light-oxygen-voltage domain 2 undergoes a photocycle with a conformational change involving the unfolding of the terminal helices. Whereas selection studies typically search for winners in a large population and fail to characterize many sites, we characterized the biophysical consequences of mutations throughout the protein using NMR, circular dichroism, and ultraviolet/visible spectroscopy. Despite our intention to introduce highly disruptive substitutions, most had modest or no effect on function, and many could even be considered to be more photoactive. Substitutions at evolutionarily conserved sites can have minimal effect, whereas those at nonconserved positions can have large effects, contrary to the view that the effects of mutations, especially at conserved positions, are predictable. Using predictive models, we found that the effects of mutations on biophysical function and allostery reflect a complex mixture of multiple characteristics including location, character, electrostatics, and chemistry.


Adsorption of heavy metal tolerance strains to Pb2+ and Cd2+ in wastewater.
The functional strains with high tolerance to heavy metal Pb2+ and Cd2+ were screened from soil obtained in a heavy metal waste accumulation area. The immobilized biological adsorbent was made by embedding method and used for treatment of wastewater containing heavy metals. The effects of initial concentration of heavy metals, adsorption time, pH value of wastewater, and dosage of adsorbent on adsorption performance were investigated. The study showed (1) the strains tested were Brevibacterium and their maximum tolerable concentrations for Pb2+ and Cd2+ were 2200 and 700 mg/L, respectively; (2) the maximum adsorption rate for Pb2+ and Cd2+ was 87.77% and 57.50% respectively when the dosage of adsorbent was 10 g/L and the pH value of wastewater was 6; (3) Pb2+ and Cd2+ could be adsorbed in the equilibrium solution for 40 min and the maximum adsorption capacity reached 114.36 mg/g and 82.12 mg/g, respectively; and (4) when the initial pH value of the wastewater was 5-7, the adsorption rate decreased with the increase of the concentration, and the initial concentration of Pb2+ had a greater effect on the adsorption rate than Cd2+. Langmuir and Freundlich equation showed that the adsorption of Pb2+ and Cd2+ was mainly on the surface of monolayer. And the pseudo-second-order kinetic equation indicates that Cd2+ has a relatively greater adsorption rate than Pb2+ does.


Object-level complete coverage path planning for excavators in earthwork construction.
Autonomous excavators are gradually gaining attention because they can reduce the waste of human resources and improve the efficiency. This study proposed a complete coverage path planning algorithm for autonomous excavators based on the Rotating Calipers Path Planning (RCPP) algorithm, which called the Excavator-Rotating Calipers Path Planning (E-RCPP) algorithm. This study uses boustrophedon cellular decomposition (BCD) to decompose the construction area to obtain the convex and non-convex sub-areas without obstacles, and describes a non-decomposition principle to determine whether to decompose non-convex areas that are difficult to plan. To obtain the optimal path, an adaptive spacing adjustment model which is used to adjust the spacing between parallel paths is designed. To improve the coverage rate at the corner, this study proposed a novel boundary corner turning method. The algorithm's cost function considers the path length, the number of turns, the coverage rate and the overlap rate. The Digital Orthophoto Map (DOM) of the construction area is created by Unmanned Aerial Vehicle (UAV) and cropped into three polygonal areas, the 2D top-views of the them are used for simulation experiments to verify the performance of E-RCPP algorithm, the results show that the E-RCPP algorithm has better performance when applied to the complete coverage path planning for excavator compared with the traditional RCPP algorithm.


Comparison of outcomes after plasma therapy or eculizumab in pediatric patients with atypical hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare and life-threatening disease. For decades, plasma therapy was used to manage patients with aHUS. Since eculizumab, a recombinant humanized anti-C5 monoclonal antibody, was approved for treatment of aHUS, it has been used to treat patients with aHUS. Here, we examined the effectiveness of eculizumab and plasma therapy, respectively in the treatment of pediatric patients with aHUS. Data were collected from questionnaires sent to 75 institutions known to be treating thrombotic microangiopathy (TMA). A total of 24 patients were evaluable, in which no recurrence of TMA was reported at last observation. There were four therapy groups: two patients receiving supportive therapy, one receiving plasma therapy alone, 17 switching from plasma therapy to eculizumab (therapy switched), and four receiving eculizumab alone. Among 17 patients of therapy-switched group, only one patient achieved complete remission at the end of plasma therapy, 15 patients achieved complete remission after eculizumab initiation, and two patients reached end-stage renal disease. Adverse events were reported in nine cases; among these, meningococcal infection, anaphylaxis, and eculizumab-related infusion reaction were reported among those treated with eculizumab. This study provided substantial evidence from a Japanese population that the conversion from plasma therapy to eculizumab therapy should be considered in patients with aHUS who show an incomplete response to plasma therapy. In addition, although no new safety events were detected, careful attention should be paid to meningococcal infection, eculizumab-related infusion reactions and allergic reactions with administration of eculizumab.


Purification of cholesterol 7 alpha-hydroxylase from human and rat liver and production of inhibiting polyclonal antibodies.
Cholesterol 7 alpha-hydroxylase, the cytochrome P-450-dependent and rate-controlling enzyme of bile acid synthesis, was purified from rat and human liver microsomes. The purified fractions were assayed in a reconstituted system containing [4-14C]cholesterol, and cholesterol 7 alpha-hydroxylase activities in these fractions increased 500-600-fold relative to whole microsomes. Polyacrylamide gel electrophoresis of rat microsomes followed by immunoblotting with polyclonal rabbit antisera raised against purified cholesterol 7 alpha-hydroxylases revealed two peaks at molecular masses of 47,000 and 49,000 daltons for both rat and human fractions. Increasing amounts of rabbit anti-rat and anti-human antibodies progressively inhibited rat microsomal cholesterol 7 alpha-hydroxylase activity up to 80%. In contrast, monospecific antibodies raised against other purified cytochrome P-450 enzymes (P-450f, P-450g, and P-450j) did not inhibit rat or human cholesterol 7 alpha-hydroxylase activity. Immunoblots of rat microsomes with the rabbit anti-rat cholesterol 7 alpha-hydroxylase antibody demonstrated that the antibody reacted quantitatively with the rat microsomal enzyme. Microsomes from cholesterol-fed rats showed increased cholesterol 7 alpha-hydroxylase mass, whereas treatment with pravastatin, an inhibitor of hydroxy-methylglutaryl-coenzyme A reductase, reduced enzyme mass. Microsomes from starved rats contained slightly less cholesterol 7 alpha-hydroxylase protein than chow-fed control rats. These results indicate a similarity in molecular mass, structure, and antigenicity between rat and human cholesterol 7 alpha-hydroxylases; demonstrate the production of inhibiting anti-cholesterol 7 alpha-hydroxylase antibodies that can be used to measure the change in cholesterol 7 alpha-hydroxylase enzyme mass under various conditions; and emphasize the unique structure of cholesterol 7 alpha-hydroxylase with respect to other cytochrome P-450-dependent hydroxylases.


Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for modulating the brain activity in mild to moderate major depressive disorder: An fMRI study.
Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is an innovative, non-invasive therapy for major depressive disorder (MDD). However, its effectiveness and underlying neural mechanisms remain not fully understood. This study aimed to investigate the treatment response and neurological effects of TECAS compared to escitalopram, a commonly used depression medication, using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-one patients with mild-to-moderate MDD (34 in the TECAS group and 17 in the Escitalopram group) and 51 healthy controls (HCs) participated in the study. We employed the low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) methods to explore brain abnormalities in MDD patients and HCs. Additionally, seed-based functional connectivity (FC) analysis was conducted to examine altered brain networks before and after treatment.Compared to the HCs group, the MDD group exhibited lower ReHo and ALFF values in the right medial superior frontal gyrus (mSFG_R), indicating altered neural activity in this region. Furthermore, mSFG-based FC analysis revealed abnormal FC values in the right inferior occipital gyrus (IOG_R) and middle temporal gyrus (MTG) between after and before treatment in MDD patients. Interestingly, TECAS treatment was found to normalize these abnormal FC brain regions, suggesting its potential role in restoring neural connectivity in MDD patients. Notably, both TECAS and escitalopram demonstrated equivalent antidepressant efficacy, with both treatments showing modulatory effects on connectivity within the default mode network (DMN). The observed normalization of abnormal FC regions, including mSFG_R, IOG_R, and MTG, all belong to the DMN. In conclusion, this study sheds light on the neurological effects and treatment response of TECAS in MDD, highlighting its potential as a non-invasive therapeutic option for depressed patients.


Emergency department care for patients with mental health problems, a longitudinal registry study and a before and after intervention study.
To describe the numbers and length of stay (LOS) of patients with mental health (MH) problems at a Dutch emergency department (ED) and the effect of a psychiatric intervention team (PIT) on patient flow. A longitudinal design was used to assess number of MH presentations and LOS during a 3-year period (2014-2016). In 2017, we introduced a PIT during ED peak hours, to reduce LOS for patients with MH problems. We evaluate the effects of the PIT on patients' LOS with an 18-month before and after intervention study (2017-2018). Total number of ED presentations increased with 4%. Total number of MH presentations increased with 23% from 2014 to 2016. LOS increased by 28 min (95 min vs. 123 min) for all presentations, while not changing for MH presentations (2014: 195 min, interquartile range (IQR) 120-293 and 2016: 190 min, IQR 116-296). In the before and after intervention study, number of MH presentations increased with 36% while LOS decreased with 46 min (p < 0.001). The number of MH presentations increased over the three years while LOS remained similar. In the before and after intervention study, number of presentations increased even more while LOS decreased significantly. Specialist psychiatric input reduces ED LOS.


Clinical features and patterns of psychopharmacological prescription in bipolar patients with vs without anxiety disorders at onset.
Up to just over half of bipolar disorder (BD) patients report at least one-lifetime anxiety disorder (AD). In some, anxiety represents the earliest psychiatric manifestation, prior to any mood episode. We sought to investigate prevalence of AD subtypes as first psychiatric manifestations and AD's relations with duration of untreated illness (DUI) and treatment among BD outpatients. We recruited patients referred to the Centre for the Treatment of Depressive Disorders in Milan, diagnosed with BD-I, BD-II, BD not otherwise specified (BD-NOS) and cyclothymia according to Diagnostic and Statistical Manual fourth edition-text revision criteria. Several clinical characteristics were assessed through retrospective chart review and/or direct patient interviews. Based on presence/absence of an AD at psychiatric onset, eligible subjects were stratified into two groups (A+ and A-) and clinical features were compared between these groups and between BD subtypes. We analysed 260 BD patients (77 BD-I, 122 BD-II, 45 BD-NOS and 16 cyclothymia). An AD was the first psychiatric manifestation in 69 patients (26.5%). BD-II and BD-NOS more frequently had an AD at psychiatric onset, with panic disorder being the most common AD. Among A+ vs A-, age at BD onset was younger, duration of untreated BD illness (DUI) was longer, and a mood stabilizer/antipsychotic was less often prescribed at psychiatric onset. Considering BD in its longitudinal course, over one in four BD patients presenting with an AD at psychiatric onset belatedly access adequate treatment, with subsequent prolonged DUI and prospective worse outcome compared to patients with a mood episode at psychiatric onset.


Expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma.
To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs). Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study. Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories. Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.


[Changes in intraorganic hemomicrocirculation in renal tuberculosis in the light of experimental morphofunctional studies].
As a result of long-term (from 1969) and extended (800 rabbits) experimental studies using an original complex of specific methods including intravital microscopy with video recording, new evidence on regulation of intrarenal circulation and its impairment in nephrotuberculosis was obtained. The role of the Trueta shunts in this was shown to be insignificant. Of importance was periglomerular shunting. It was concluded that extended microcirculatory disorders in the region of the intact renal parenchima defining development of renal insufficiency were possibly of tuberculosis allergic origin. Measures for their prevention and treatment are proposed.


Parameters of glycemic control and their relationship with zinc concentrations in blood and with superoxide dismutase enzyme activity in type 2 diabetes patients.
This study assessed the relationship between the parameters of glycemic control, and zinc concentrations in blood and superoxide dismutase enzyme activity in type 2 diabetes patients. Seventy-three individuals, aged between 25 and 59 years, were divided into the experimental group (type 2 diabetes patients, n = 36) and control group (n = 37). Plasma and erythrocyte zinc concentrations, superoxide dismutase activity, and parameters of glycemic control were analyzed. Mean plasma zinc concentration was 74.1 ± 10.7 µg/dL and 68.8 ± 9.6 µg/dL, erythrocyte zinc concentration was 48.1 ± 9.5 µg/gHb and 41.2 ± 8.0 µg/gHb, and superoxide dismutase activity was 2248.9 ± 300.0 U/gHb and 2059.6 ± 285.4 U/gHb, in the experimental group and the control group, respectively (p < 0.05). Type 2 diabetes patients showed a positive response to oxidative stress due to adequate zinc concentration in blood and increased activity of superoxide dismutase, and the enzyme was influenced by serum insulin.


Oxidative stress increases internal calcium stores and reduces a key mitochondrial enzyme.
Fibroblasts from patients with genetic and non-genetic forms of Alzheimer's disease (AD) show many abnormalities including increased bombesin-releasable calcium stores (BRCS), diminished activities of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC), and an altered ability to handle oxidative stress. The link between genetic mutations (and the unknown primary event in non-genetic forms) and these other cellular abnormalities is unknown. To determine whether oxidative stress could be a convergence point that produces the other AD-related changes, these experiments tested in fibroblasts the effects of H(2)O(2), in the presence or absence of select antioxidants, on BRCS and KGDHC. H(2)O(2) concentrations that elevated carboxy-dichlorofluorescein (c-H(2)DCF)-detectable ROS increased BRCS and decreased KGDHC activity. These changes are in the same direction as those in fibroblasts from AD patients. Acute treatments with the antioxidants Trolox, or DMSO decreased c-H(2)DCF-detectable ROS by about 90%, but exaggerated the H(2)O(2)-induced increases in BRCS by about 4-fold and did not alter the reduction in KGDHC. Chronic pretreatments with Trolox more than doubled the BRCS, tripled KGDHC activities, and reduced the effects of H(2)O(2). Pretreatment with DMSO or N-acetyl cysteine diminished the BRCS and either had no effect, or exaggerated the H(2)O(2)-induced changes in these variables. The results demonstrate that BRCS and KGDHC are more sensitive to H(2)O(2) derived species than c-H(2)DCF, and that oxidized derivatives of the antioxidants exaggerate the actions of H(2)O(2). The findings support the hypothesis that select abnormalities in oxidative processes are a critical part of a cascade that leads to the cellular abnormalities in cells from AD patients.


The endoplasmic reticulum in the cortex of developing guard cells: coordinate studies with chlorotetracycline and osmium ferricyanide.
The distribution of endoplasmic reticulum (ER) was investigated in young guard cells of Vicia faba and Allium cepa in order to gain more information on the control of guard cell development. Young, living guard cells of V. faba fluoresce when exposed to 25-100 microM chlorotetracycline (CTC). Intense fluorescence is restricted to the cytoplasm between the nucleus and adjacent regions of the ventral and paradermal walls. Much of the fluorescence is fibrillar in appearance and seems to arise from endomembranes, but not from particulate organelles such as mitochondria and plastids. A similar fluorescence pattern is produced by the membrane probes oxytetracycline and N-phenyl-1-napthylamine. Procaine and dibucaine render the fluorescence highly prone to photobleaching. Fluorescence appears near the ventral wall during early stages of cell development but declines when the guard cells mature. Epidermal tissue of V. faba and A. cepa was examined in the electron microscope with the aid of osmium ferricyanide staining. ER appears to be concentrated in regions of the guard cell that exhibit intense CTC fluorescence, while no other organelles (e.g., mitochondria) are similarly distributed. Much of the ER consists of a tubular network in close proximity to the plasmalemma. Our results indicate that the ER becomes asymmetrically distributed in young guard cells adjacent to those regions of the cell wall that undergo extensive thickening during cell differentiation. Furthermore, these membranes appear to sequester divalent cations such as Ca2+.


The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea.
This study was performed to determine whether serum pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in Korea. Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and gastrin levels were measured in 1006 patients with gastroduodenal diseases including cancer. Follow-up tests were performed 1 year after Helicobacter pylori eradication. sPGI and sPGII levels increased and PG I/II ratios decreased in line with the severity of activity, chronic inflammation, and the presence of H. pylori (p < .01). In contrast, sPGI levels and PG I/II ratios decreased in proportion with the severity of atrophic gastritis (AG)/intestinal metaplasia (p < .01). Gastrin levels were found to be correlated with chronic inflammation negatively in the antrum but positively in the corpus. H. pylori eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios to the levels of H. pylori-negative patients, and was found to be correlated with reductions in activity and chronic inflammation of gastritis. The sensitivity and specificity of a PG I/II ratio of < or = 3.0 for the detection of dysplasia or cancer were 55.8-62.3% and 61%, respectively. In addition, sPGI and sPGII levels of intestinal-type cancer were significantly lower than those of the diffuse type, respectively (p = .008 and p = .05, respectively). Gastric cancer risk was highest in the H. pylori-positive, low PGI/II ratio (< or = 3.0) group with an odds ratio of 5.52 (confidence interval: 2.83-10.77). PG I/II ratio (< or = 3.0) was found to be a reliable marker for the detection of dysplasia or gastric cancer, especially of the intestinal type. This detection power of PG I/II ratio (< or = 3.0) significantly increased in the presence of H. pylori, and thus, provides a means of selecting those at high risk of developing gastric cancer in Korea.


Role of Peripheral Chemoreceptors on Enhanced Central Chemoreflex Drive in Nonischemic Heart Failure.
Heart failure (HF) is a prevalent disease in elderly population. Potentiation of the ventilatory chemoreflex drive plays a pivotal role in disease progression, at least in part, through their contribution to the generation/maintenance of breathing disorders. Peripheral and central chemoreflexes are mainly regulated by carotid body (CB) and the retrotrapezoid nuclei (RTN), respectively. Recent evidence showed an enhanced central chemoreflex drive in rats with nonischemic HF along with breathing disorders. Importantly, increase activity from RTN chemoreceptors contribute to the potentiation of central chemoreflex response to hypercapnia. The precise mechanism driving RTN potentiation in HF is still elusive. Since interdependency of RTN and CB chemoreceptors has been described, we hypothesized that CB afferent activity is required to increase RTN chemosensitivity in the setting of HF. Accordingly, we studied central/peripheral chemoreflex drive and breathing disorders in HF rats with and without functional CBs (CB denervation). We found that CB afferent activity was required to increase central chemoreflex drive in HF. Indeed, CB denervation restored normal central chemoreflex drive and reduced the incidence of apneas by twofold. Our results support the notion that CB afferent activity plays an important role in central chemoreflex potentiation in rats with HF.


Failure of severe maternal stress or ACTH during pregnancy to affect emotionality of male rat offspring: implications of litter effects for prenatal studies.
Daily maternal neck restraint, whole body restraint, hyperthermia, and ACTH treatment during the last 3rd of gestation had no reliable effect on open-field and cage-emergence behavior in male Sprague-Dawley offspring. Many of these treatments, however, produced considerable maternal pathology and evidence for maternal adrenocorticoid release. Significant litter effects were found for almost every morphological and behavioral measure. Failure to control for the litter variable may account for many previously reported effects of prenatal stress on emotionality in rats. Female rats showed greater activity and less defecation than males on postpubertal open-field and cage emergence tests.


What does it mean to say that cultured meat is unnatural?
Cultured meat offers a potential alternative to factory farming and its associated problems. Despite this, public opinion about cultured meat is mixed. One concern cited by many potential consumers is that cultured meat is "unnatural". Although there has been much interest in this perspective, there has been virtually no research exploring the psychological factors that motivate this view. The current study (N = 904) examines the beliefs, worldviews, and attitudes associated with the conclusion that cultured meat is unnatural. We found little evidence that naturalness perceptions flowed from a process of analytic reasoning; rather, ratings of unnaturalness appear to be grounded in affective mechanisms such as disgust and fear. This suggests that acceptance strategies that target analytic processing (e.g. information) may have limited success, which has indeed been the case with the strategies tested to date. Our findings are informative for research programs and cultured meat marketing strategies going forward.


Wasp sting anaphylaxis with cerebral infarction.
A cerebral infarction occurred in a 37-year-old man following wasp stings. Computerized axial tomography documented the neurologic lesion.


Early development and degeneration of vestibular hair cells in bronx waltzer mutant mice.
In bronx waltzer mouse mutants, inner hair cells die at an early stage in their development, from around 17.5 days of gestation onwards. In contrast, outer hair cells appear to develop normally. Vestibular hair cells also degenerate, but the earliest signs of vestibular abnormalities have not yet been described. We looked at prenatal and early postnatal stages of vestibular development by scanning electron microscopy in the mutants, and established that vestibular hair cells (types I and II) never reach beyond the middle stages of differentiation (at least up to P2) and instead show signs of degeneration. Thus, it appears that the bronx waltzer gene product is required for the continued survival and differentiation of inner and vestibular hair cells past a set point in their development.


Quantification of serial changes in plaque burden using multi-detector computed tomography in experimental atherosclerosis.
Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested. We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI). Rabbits (n=12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I(Milano), n=8) or placebo (n=4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI. MDCT detected a significant decrease in plaque burden caused by recombinant apoA-I(Milano) (464 [423-535] to 405 [363-435]mm(3), p=0.03) that was confirmed by MRI (324 [286-412] to 298 [282-399]mm(3), p=0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r=0.750, p<0.001) and change in plaque burden (r=0.657, p=0.020). MDCT overestimated plaque burden compared to MRI. On MDCT, the mean interobserver variability for plaque burden was 2.5+/-0.4%. In an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.


Efficacy of nitroglycerin in stress-induced regional myocardial dysfunction is dependent on the chosen model: investigations in anesthetized and conscious dogs.
The antianginal efficacy of nitroglycerin (1 microgram/kg per min) was investigated in two different experimental models, one using chloralose-anesthetized open-chest dogs, the other using conscious, chronically instrumented dogs. Heart rate, arterial pressure, left ventricular dp/dtmax, and left ventricular end-diastolic pressure were registered. Left ventricular regional contractile function in the area supplied by the left circumflex coronary artery (LCX) and the left anterior descending artery (LAD) were assessed using sonomicrometry. In both models, the coronary flow reserve was limited by a hydraulic occluder around the LCX. Cardiac stimulation was achieved by a bolus injection of isoproterenol (ISO 0.5 microgram/kg) in the anesthetized animals and by graded treadmill exercise in the conscious animals. In both cases, transient contractile dysfunction occurred in the area supplied by the stenosed vessel. This contractile dysfunction was completely abolished by nitroglycerin in the conscious animals, while nitroglycerin failed to show any antianginal effect in the anesthetized dogs. Although hemodynamic differences in open and closed chest should be considered, remarkable differences in mechanisms of blood-pressure regulation according to the mode of stimulation were observed: in contrast to the situation during treadmill exercise, the ISO-induced decrease in arterial blood pressure does not correspond to the clinical picture of an anginal attack. These results show that it is most important to mimic the complex pathophysiological reactions of angina pectoris in man as closely as possible in the experimental model.


Chemotherapy for the Management of Cerebral Metastases.
Chemotherapy has played a minor role as adjuvant therapy in treatment of cerebral metastases from solid cancers. The blood-brain barrier and cerebral metastases' considerable machinery of self-preservation have been significant obstacles to delivery and efficacy of chemotherapy. However, several methods intended to surmount these challenges have arisen alongside advent of technology and with the development of targeted molecular therapies. Focused ultrasound and molecular Trojan horses represent two such novel means of increasing permeability of the blood-brain barrier to effector agents. Published data on efficacy of these targeted therapies remain mostly restricted to retrospective studies and phase II prospective clinical trials.


Frequency Measurement of Pure Rotational Transitions of H217O and H218O from 0.5 to 5 THz.
Frequencies of pure rotational transitions of isotopic species of water, H217O, and H218O were measured in the 1-5 THz region with a high-precision far-infrared spectrometer using a tunable radiation source. Measured frequencies of more than 100 spectral lines for each species provide an excellent frequency standard for the far-infrared region. Molecular parameters based on a Watson-type Hamiltonian have been obtained to reproduce the observed frequencies. Copyright 1999 Academic Press.


Overcoming challenges in rare disease registry integration using the semantic web - a clinical research perspective.
The growing number of disease-specific patient registries for rare diseases has highlighted the need for registry interoperability and data linkage, leading to large-scale rare disease data integration projects using Semantic Web based solutions. These technologies may be difficult to grasp for rare disease experts, leading to limited involvement by domain expertise in the data integration process. Here, we propose a data integration framework starting from the perspective of the clinical researcher, allowing for purposeful rare disease registry integration driven by clinical research questions.


Radiomics and machine learning analysis based on magnetic resonance imaging in the assessment of liver mucinous colorectal metastases.
The purpose of this study is to evaluate the Radiomics and Machine Learning Analysis based on MRI in the assessment of Liver Mucinous Colorectal Metastases.Query METHODS: The cohort of patients included a training set (121 cases) and an external validation set (30 cases) with colorectal liver metastases with pathological proof and MRI study enrolled in this approved study retrospectively. About 851 radiomics features were extracted as median values by means of the PyRadiomics tool on volume on interest segmented manually by two expert radiologists. Univariate analysis, linear regression modelling and pattern recognition methods were used as statistical and classification procedures. The best results at univariate analysis were reached by the wavelet_LLH_glcm_JointEntropy extracted by T2W SPACE sequence with accuracy of 92%. Linear regression model increased the performance obtained respect to the univariate analysis. The best results were obtained by a linear regression model of 15 significant features extracted by the T2W SPACE sequence with accuracy of 94%, a sensitivity of 92% and a specificity of 95%. The best classifier among the tested pattern recognition approaches was k-nearest neighbours (KNN); however, KNN achieved lower precision than the best linear regression model. Radiomics metrics allow the mucinous subtype lesion characterization, in order to obtain a more personalized approach. We demonstrated that the best performance was obtained by T2-W extracted textural metrics.


The Burden of Disease in Alopecia Areata: Canadian Online Survey of Patients and Caregivers.
Alopecia areata (AA) is associated with negative impacts on the quality of life (QoL). Data on this impact are lacking for Canadian patients and their caregivers. This study aims to investigate the burden of AA on Canadian patients and their caregivers. We created 4 online surveys for patients 5-11 years old, 12-17 years old, and ≥18 years old and for caregivers of children (<18 years old) with AA. These were disseminated through the Canadian Alopecia Areata Foundation (CANAAF) website and to dermatologists across Canada. In total, 115 adult patients (n=100, 87%, female), 14 pediatric patients (n=13, 92.9%, female), and 15 caregivers completed the surveys online. The majority (n=123, 95%) of patients felt uncomfortable or self-conscious about their appearance. Camouflaging hair loss with hats, scarves, and hairpieces was a common practice for 11 (78.6%) pediatric and 84 (73%) adult patients. Avoidance of social situations was reported by 8 (57.1%) pediatric and 75 (65.2%) adult patients. Constant worry about losing the achieved hair growth was a concern for 8 (57.1%) pediatric and 75 (65.2%) adult patients. On a scale of 1-5, the mean score of caregivers' own feelings of sadness or depression about their child's AA was 4.0 (SD 0.9) and of their feelings of guilt or helplessness was 4.2 (SD 1.2). The impact on the QoL was moderate for both children and adults. Based on the Adjustment Disorder New Module-20 (ADNM-20), 71 (61.7%) of 115 patients were at high risk of an adjustment disorder. Abnormal anxiety scores were recorded in 40 (34.8%) patients compared to abnormal depression scores in 20 (17.4%) patients. This study confirmed a significant burden of AA on Canadian patients' and caregivers' QoL.


Closing Achievement Gaps Through Preschool-To-Third-Grade Programs.
Achievement gaps by family income, race, and ethnicity have persisted for decades. Yet only in recent years has this major social problem become a national priority in the U.S. and many other countries as concern rises over growing economic inequalities. In this paper, we document gaps in school readiness and achievement in the U.S. and how they adversely affect the life course development of children and families from underrepresented groups. We emphasize the promising role of preschool-to-3rd grade (P-3) programs to reduce a variety of achievement gaps through comprehensive strategies that enrich educational and family experiences during most of the first decade of life. Implementation of the core elements of effective learning experiences, collaborative leadership, aligned curriculum, parent involvement and engagement, professional development, and continuity and stability in the Child-Parent Center Program have shown relatively strong and sustained effects on school achievement, especially for Black children growing up in urban poverty. This evidence from the Chicago Longitudinal Study and other projects suggests that broader scale up of truly comprehensive approaches that begin early, continue through most of the first decade, and are multilevel in scope can make a bigger difference than many existing strategies in reducing achievement gaps and their persistence.


Genetic variants in the ITGB6 gene is associated with the risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy.
The αvβ6 integrin is a cell surface adhesion molecule that plays critical roles in the injury and inflammation processes. We hypothesized that polymorphisms in αvβ6 integrin genes (ITGAV and ITGB6) might be associated with the risk of radiation pneumonitis (RP) in lung cancer patients treated with thoracic radiation. We genotyped three potentially functional αvβ6 integrin single-nucleotide polymorphisms (rs1839123 and rs4129787 in ITGAV, and rs4665162 in ITGB6) and found that the genotypes of rs4665162 single-nucleotide polymorphisms were predictors of RP development (for grade ≥2 RP, HR = 1.505, 95 % CI 1.069-2.119, P = 0.019; for grade ≥3 RP, HR = 3.006, 95 % CI 1.431-6.313, P = 0.004). Our results showed that AG/GG genotypes of ITGB6 rs4665162 gene were associated with a higher risk of RP in patients with lung cancer receiving radiotherapy and thus may serve as a reliable predictor of RP. Further studies will be needed to confirm these findings.


Additive manufacturing of Zn-Mg alloy porous scaffolds with enhanced osseointegration: In vitro and in vivo studies.
Biodegradable metals (BM) and additive manufacturing (AM) are regarded revolutionary biomaterials and biofabrication technologies for bone repairing metal implants, the combination of both, namely AM of BM, is thus expected to solve the dual technical difficulties including "conventional medical metals are biologically inert and exist in the human body permanently" and "conventional manufacturing processes are inadequate to fabricate personalized implants of complicated structure". This work additively manufactured biodegradable Zn-Mg alloy porous scaffolds by laser powder bed fusion (L-PBF). By using the pre-alloyed Zn-xMg (x = 1, 2 and 5 wt.%) powder and the optimized processing conditions, high fusion quality with the relative density greater than 99.5% was confirmed for the L-PBF parts. The influence of Mg content on microstructure, mechanical properties, in vitro corrosion, cytocompatibility, in vivo degradation, biocompatibility and osteogenic effect was investigated. Fine α-Zn grains and precipitation phases including Mg2Zn11 and MgZn2 were observed in the Zn-xMg L-PBF parts. The hardness increased, and the strength increases firstly and then decreased with increasing the Mg content. The compressive strength and elastic modulus of Zn-1Mg porous scaffolds reached the highest as 40.9 ± 0.4 MPa and 1.17 ± 0.11 GPa, respectively, equivalent to those of cancellous bone. The corrosion rate and cell viability slightly rose with increasing the Mg content. Histological analysis after 6-week and 12-week implantation in rabbit femurs showed enhanced bone formation around the Zn-1Mg porous scaffolds compared with pure Zn counterparts. In summary, Zn-1Mg porous scaffolds produced by L-PBF presented promising results to fulfill customized requirements of biodegradable bone implants. STATEMENT OF SIGNIFICANCE: Additive manufacturing of biodegradable metal porous scaffolds is expected to solve the dual challenges from customized structures and bioactive function required for bone implants. It was the first to present a systematic in vitro and in vivo investigation into the compositions, microstructure, mechanical properties, biodegradation, biocompatibility and osteogenic effect of additively manufactured Zn-Mg alloy porous scaffolds. Reliable formation quality and performance evaluation was achieved by using the pre-alloyed Zn-xMg (x = 1, 2 and 5 wt.%) powder and the optimized laser powder bed fusion process. Although the Zn-1Mg scaffolds exhibited promising mechanical strength, biocompatibility, and osteogenic effect, their degradation rate needs to be further accelerated compared with the term of bone reconstruction.


Proanthocyanidin biosynthesis--still more questions than answers?
Proanthocyanidins, also known as condensed tannins, are oligomers or polymers of flavan-3-ol units. In spite of important breakthroughs in our understanding of the biosynthesis of the major building blocks of proanthocyanidins, (+)-catechin and (-)-epicatechin, important questions still remain to be answered as to the exact nature of the molecular species that undergo polymerization, and the mechanisms of assembly. We review the structures of proanthocyanidins reported over the past 12 years in the context of biosynthesis, and summarize the outstanding questions concerning synthesis of proanthocyanidins from the chemical, biochemical and molecular genetic perspectives.


Use of spectroscopic indicators for the monitoring of bromate generation in ozonated wastewater containing variable concentrations of bromide.
Time-resolved monitoring of bromate and other by-products formed into effluents treated with ozone or advanced oxidation processes in wastewater treatment plants (WWTPs) is time-consuming and expensive. This study examined whether concentrations of bromate formed in wastewater after ozonation in the presence of widely varying bromide levels (from ca. 0.7-21.2 mg/L) can be quantified based on measurements of changes in optical properties (differential UV absorbance (ΔUVA), spectral slopes, total or regional fluorescence) of the ozonated samples. Batch ozonation was carried out using a secondary effluent produced at a major wastewater treatment plant located in the Metropolitan Seattle Area. The tests involved raw and bromide-spiked samples treated with ozone doses from 0.1 to 1 mg O3/mg DOC. Measurements of the absorbance at 254 nm (UVA254), fluorescence and bromate concentrations were performed on the treated samples. In the ozonated wastewater the concentration of bromate increased approximately linearly, from <10 ppb to ca. 200 ppb, without showing the lag phase characteristic for lower ozone doses (<0.4 mg O3/mg DOC) that was observed in previous studies carried out with concentrations of bromide in the range of 0.05-0.5 mg/L. The highest bromide concentrations used in this study (>10 mg/L) tended to inhibit the generation of bromate. Relative reduction of UVA254 and total fluorescence (TF) were found to be good predictors of bromate generation. Specifically, exponential curves could adequately fit the non-linear relationships found to exist between the concentrations of bromate and the relative reductions of the UV254 and TF, for any initial bromide concentrations used in this study. Little formation of bromate was found to occur for reduction ranges for UVA254 and TF of 30-40% and 70-80% respectively. Conversely, rapid increases in bromate generation were observed when the decrease of UVA254 or TF exceeded these threshold values.


Structural changes of cytochrome c(552) from Thermus thermophilus adsorbed on anionic and hydrophobic surfaces probed by FTIR and 2D-FTIR spectroscopy.
The structural changes of cytochrome c(552) bound to anionic and hydrophobic clay surfaces have been investigated by Fourier transform infrared spectroscopy. Binding to the anionic surface of montmorillonite is controlled by electrostatic interactions since addition of electrolyte (0.5 mol L(-1) KCl) causes desorption of more than 2/3 of the protein molecules. Electrostatic binding occurs through the back side of the protein (i.e., remote from the heme site) and is associated only with subtle changes of the secondary structure. In contrast, adsorption to the hydrophobic surface of talc leads to a decrease in alpha-helical structure by ca. 5% and an increase in beta-sheet structure by ca. 6%. These structural changes are attributed to a hydrophobic region on the front surface of cytochrome c(552) close to the partially exposed heme edge. This part on the protein surface is identified as the interaction domain for talc and most likely also serves for binding to the natural reaction partner, a ba(3)-oxidase. Fourier transform infrared spectra of cytochrome c(552) and the clay-cytochrome c(552) complexes have been measured as a function of time following dissolution and suspension in deuterated buffer, respectively. A two-dimensional correlation analysis was applied to these spectra to investigate the dynamics of the structural changes in the protein. For both complexes, adsorption and subsequent unfolding processes in the binding domains are faster than the time resolution of the spectroscopic experiments. Thus, the processes that could be monitored are refolding of peptide segments and side chain rearrangements following the adsorption-induced perturbation of the protein structure and the solvation of the adsorbed protein. In each case, side chain alterations of solvent-exposed tyrosine, aspartate, and glutamate residues were observed. For the cytochrome c(552)-talc complex, these changes are followed by a slow refolding of the peptide chain in the binding domain and, subsequently, a further H/D exchange of amide group protons.


Transient erythroblastopenia of childhood. A review of 26 cases and reassessment of indications for bone marrow aspiration.
Clinical and hematological presentations of 26 consecutive patients with transient erythroblastopenia of childhood diagnosed during July 1979 to September 1986 were compared with 26 patients with acute leukemia who presented with anemia and a normal platelet count. It was easy to distinguish acute leukemia from transient erythroblastopenia of childhood on a clinical and laboratory basis. In most cases, bone marrow examination was not necessary.


Interrelation between two anticomplement cobra venom factors isolated from crude Naja naja cobra venom.
Two moieties occurring in crude Naja naja cobra venom were found to possess anticomplement activity. Both materials possessed similar molecular weights and specific activities but dissimilar elution profiles upon ion-exchange chromatography. The anticomplement activities of these materials were maintained upon digestion with neuraminidase, and their elution profiles from cation-exchange chromatography became identical after this treatment. It was concluded that the differences between the two anticomplement materials were due to their different sialic acid contents.


Aryl hydrocarbon receptors improve migraine-like pain behaviors in rats through the regulation of regulatory T cell/T-helper 17 cell-related homeostasis.
To investigate the effect of the aryl hydrocarbon receptor (AHR)/regulatory T cell (Treg)/T-helper 17 (Th17) cell pathway on the pathogenesis of migraine. Migraine is a disabling neurovascular disease that imposes an enormous burden on both individuals and society. The pathophysiological mechanisms of migraine remain controversial. Recent studies have suggested that immune dysfunction may be involved in the pathogenesis of migraine. The AHR, a receptor expressed on most immune cells, has been implicated in the occurrence of many autoimmune diseases; however, whether it is involved in the pathogenesis of migraine is unclear. A chronic migraine rat model was established through repeated intraperitoneal injection of nitroglycerin (NTG). The mechanical and thermal pain thresholds were assessed using von Frey filaments and radiant heat. Next, the protein expression levels of AHR in the trigeminal nucleus caudalis (TNC) region of chronic migraine (CM)-like rats were quantified and the changes in Treg/Th17-related transcription factors and inflammatory factors in the TNC were explored. To determine the role of AHR in CM, we examined the effects of the AHR agonist 2-(1'-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), and AHR antagonist CH-223191 on pain behavior, c-Fos, calcitonin gene-related peptide (CGRP), AHR, and Treg/Th17-related factor expression in CM-like rats. Repeated administration of NTG significantly enhanced nociceptive hypersensitivity and increased expression of c-Fos and CGRP in rats, while AHR was significantly decreased in the TNC. In addition, the expression of the transcription factor forkhead box protein P3 and the signal transducer and activator of transcription 5 decreased significantly. In contrast, the expression of the transcription factor retinoic acid receptor-related orphan receptor γ t and signal transducer and activator of transcription 3 were significantly increased. Moreover, the mRNA level of transforming growth factor beta-1 was decreased, while that of interleukin (IL)-10 and IL-22 was increased in the TNC. The AHR agonist ITE alleviated migraine-like pain behaviors in rats, activated the AHR signaling pathway, and improved the imbalance of Treg/Th17-related transcription factors and inflammatory factors. Conversely, the AHR antagonist CH-223191 did not alleviate migraine-like pain behaviors in rats; and even exacerbated them. The AHR participates in the development of CM by regulating Treg/Th17-related homeostasis. Therefore, treatments targeting the AHR/Treg/Th17 signaling pathway could be new effective interventions for CM treatment.


The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets.
Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.


Stimulation of aromatase activity in immature porcine Leydig cells by fibroblast growth factor (FGF).
The effects of fibroblast growth factor (FGF) on testicular aromatase activity has been studied using primary cultures of porcine Leydig cells. After culture for 3 days in the absence or presence of FGF, the ability of the cells to produce estrogen was examined in a 4h-test period in which either (a) hCG (10(-9) M) or (b) androstenedione (3 x 10(-6) M) was added to the medium. FGF produced a 3- to 20-fold increase in estrogen formation from endogenous or exogenous substrate during the test period, in spite of a marked decrease (approximately equal to 60%) in [125I]-hCG binding and no significant change in testosterone concentration. Stimulation of estrogen secretion by FGF was dose-(ED50 approximately equal to 2 ng/ml) and time-dependent, the first and maximal effects were observed after 12h and 48h, respectively. Preliminary tests with several other factors (insulin, EGF, TGF-beta, FSH and hCG) showed that hCG alone directly stimulated aromatase activity. From these findings a role is suggested for FGF as a paracrine/autocrine agent in the control of estrogen secretion by Leydig cells.


The DiversiLab system versus pulsed-field gel electrophoresis: characterisation of extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae.
Fast and reliable epidemiological typing methods for identifying outbreaks and epidemic strains of extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae are urgently needed. The DiversiLab system (DL) has been proposed for these purposes. We compared DL to pulsed-field gel electrophoresis (PFGE) on a national collection of ESBL-producing Escherichia coli (n=258; of which 226 isolates were typeable with PFGE) and Klebsiella pneumoniae (n=48) isolated in 2007. For E. coli the Wallace coefficients showed that the probability of two isolates of the same DL type having the same PFGE type was only 19.8% and the probability of two isolates of the same PFGE type having the same DL type was 90.4%. For K. pneumoniae the Wallace coefficients showed that the probability of two isolates of the same DL type having the same PFGE type was 100% and the probability of two isolates of the same PFGE type having the same DL type was 79%, indicating that for this K. pneumoniae strain collection DL was slightly more discriminatory. Only four of 48 isolates had discordant results with the two methods. In E. coli 42% of the isolates were sequence type 131 and these isolates were related at >95% similarity with DL and at ≥60% similarity with PFGE. In summary, for E. coli DL performed well in identifying isolates related by PFGE, but overestimated the genetic relatedness in the studied collection. This indicates that DL could be a primary screening method for excluding unrelated isolates. Isolates shown to be related must be confirmed with a more discriminatory method. For K. pneumoniae, DL discriminated well but overestimated the diversity of the isolates compared to PFGE, assuming a risk of missing possible genetic relatedness.


Intensive aerobic cycling training with lower limb weights in Chinese patients with chronic stroke: discordance between improved cardiovascular fitness and walking ability.
To evaluate the effect of aerobic cycling training with lower limb weights on cardiovascular fitness (peak VO(2)) and walking ability in chronic stroke survivors, and to investigate the relationship between changes in these parameters. 133 Chinese patients with chronic hemiparetic stroke (mean age 58 years) were randomized to either 8-week (5×/week) aerobic cycling training with lower limb weights group (n = 68) or a low-intensity overground walking group (n = 65). Peak VO(2), 6-minute walk distance (6MWD), knee muscle strength, balance and spasticity were measured before and after intervention. Cycling training increased peak VO(2) (24% vs. 3%, p < 0.001), 6MWD (2.7% vs. 0.5%, p < 0.001), paretic (11% vs. 1.6%, p < 0.001) and nonparetic knee strength (16% vs. 1.0%, p < 0.001). In the cycling group, percent changes in peak VO(2) were positively associated with those in paretic (r = 0.491, p < 0.001) and nonparetic knee strength (r = 0.432, p < 0.001). Increased 6MWD correlated significantly with improved balance, spasticity and paretic knee strength by the stepwise regression analysis (r(2) = 0.342, p = 0.004), but not fitness gains. The enhanced cardiovascular fitness after aerobic cycling training in Chinese patients with chronic stroke is not associated with the increased walking ability. Unparallel improvements in these parameters related different determinants may have implications for intervention strategy.


Characterization of infiltrating T cells and Th1/Th2-type cytokines in the synovium of patients with osteoarthritis.
It has been suggested that osteoarthritis (OA) is induced by mechanical stress followed by cartilage destruction, and it is generally accepted that there is little involvement of an immune response in OA compared with that in rheumatoid arthritis (RA). We have previously found clonally expanded transcripts of Vbeta chain of the T cell receptor (TCR) in the synovium of patients with OA. To test the hypothesis that an immune response is involved in OA, we determined: (a) whether CD3+, CD4+, and CD8+ T-cells were infiltrating the synovial membrane of patients with OA; (b) the Th1/Th2-type cytokines produced at the protein level in the synovium of patients with OA. Immunohistochemical analysis was performed to identify T-cells that infiltrated the synovium of patients with OA using specific antibodies against CD3+, CD4+, and CD8+ T-cell differential antigens, interferon-gamma (IFN-gamma as a marker for Th1 cells, and interleukin-4 (IL-4) as a marker for Th2 cells. CD4+ T-cells were strongly detected in the sublining layer of the synovium of patients with OA compared with the number detected in the same synovial layer of normal subjects. The number of IFN-gamma+ cells was significantly higher than that of IL-4+ cells in the synovium of patients with OA (P< 0.05). These observations suggest that Th1 cells predominate in the synovium of patients with OA, which clearly indicates that immune regulation occurs and may play critical roles in inflammation and cartilage destruction in patients with OA.


[Efficacy comparison between endoscopic resection and tradition surgery in the treatment of early gastric cancer].
Endoscopic resection (ER) has been a preferred treatment for early gastric cancer (EGC) based on the guidelines. In recent years the technique is developing rapidly. Surgical operation, a traditional treatment, still has its advantages such as complete tumor removal and low recurrence rate. In this review, a long-term outcome comparison of these two methods in EGC is discussed.


Acute intestinal failure in surgical patients: an audit of incidence, management and outcomes in an irish hospital, and compliance with ASGBI guidelines.
Acute intestinal failure (AIF) is defined as an inability to tolerate 80% of nutritional requirements delivered enterally for a minimum of 48 h. In surgical patients it commonly relates to abdominal sepsis, intestinal obstruction, or ileus. The prevalence of AIF in surgical units in Ireland has not previously been studied. We retrospectively audited the general surgical and ICU departments in St James's Hospital over a 3-month period to identify patients with AIF and followed their management and outcomes focusing on the need for artificial nutrition and surgical intervention. Fifty-four surgical patients (11.4% of surgical emergency admissions) were diagnosed with AIF over the 3-month period. Of these, 30 (55.6%) required nutritional support; 26 (48.2%) had surgical ± radiological intervention and 6 (11.1%) had radiological intervention alone. Abdominal sepsis was present in 17 (31.5%) patients, a group that required significantly longer parenteral (14.6 vs. 6.7 days, p 0.029) and enteral (13.9 vs. 2.2 days, p 0.005) nutrition than AIF patients without abdominal sepsis. AIF also took longer to resolve in (5.8 vs. 4.2 days, p 0.024) in sepsis versus nonsepsis patients. The majority of patients (n = 43, 80%) were referred to clinical nutrition teams early after having symptoms for 3.77 days (range 1-21) and 72% had complete nutritional assessment clearly documented. AIF is common, and can often be treated conservatively. Early linkage with nutrition services is recommended. Early diagnosis of abdominal sepsis is important as this cohort of patients can be particularly difficult to manage.


Weighing in primary-care nurse-patient interactions.
This article analyzes the interactions through which primary-care nurses and patients accomplish patient weighing. The analysis is based on videotaped nurse-adult patient interactions in clinics in the area of Southern California. Detailed examination of co-participants' naturally situated weighing conduct shows that parties recurrently deliver utterances that go beyond that required to accomplish weight measurement-precisely "where" they "are" within the weighing process shaping how they produce and understand these utterances. Using weighing as a locus of epistemic negotiation and potential affiliation, co-participants interactionally achieve the distribution of weight/weighing knowledge and the character of their social relationship. Confronting their numerical weight results in a social/medical setting, patients can use expansive weighing utterances to claim or demonstrate that they possess pre-existing knowledge regarding weight, asserting independent expertise vis-à-vis nurses and claiming result co-recipiency and co-ownership. Speakers can also use expansive utterances to proffer an interactional opportunity for affiliation, inviting recipients to collaborate in producing a more personalized encounter. Through the acceptance or declination of these invitations, the parties work out "who" they "are" to and for one another.


High-precision microscopic phase imaging without phase unwrapping for cancer cell identification.
Experiments for cell identification are presented using a high-precision cell phase measurement system that does not require any phase unwrapping. This system is based on a Mach-Zehnder interferometer using a phase-locking technique, and it measures the change in optical path length while the sample is scanned across the optical axis. The spatial resolution is estimated to be less than 1.1 μm. The sensitivity of optical path length difference is estimated to be less than 2 nm. Using experiments, we investigate the potential of this approach for cancer cell identification. In our preliminary experiments, cancer cells were distinguished from normal cells through comparison of optical path length differences.


Value of nodal drainage patterns and tumor location from lymphoscintigraphic mapping in detecting axillary sentinel lymph node status in breast cancer: experience at Kaohsiung Medical University Hospital.
Sentinel lymph node (SLN) biopsy is an alternative to axillary node dissection for staging breast cancer treatment. In this article, we investigated nodal drainage patterns and tumor location using lymphoscintigraphy to predict the axillary sentinel lymph node status. We enrolled 88 patients with clinically suspicious or biopsy-proven breast cancer from March 2001 to October 2002. The average age of subjects was 48 +/- 4 years and the clinical stage was T(1-2)N0Mx. Tc-99m sulfur colloid was used in a hybrid combination of subdermal and perilesional injections around the selected comers of the tumor or biopsy site. Sentinel lymphoscintigraphy was performed 16-20 hours before surgery. Sentinel nodes were marked on the skin. An intraoperative gamma probe was used to confirm the sentinel lymph node location before biopsy. Most primary tumors were in the outer upper quadrant (52.3%), followed by the inner upper quadrant (17.0%), outer inferior quadrant (12.5%), central areolar area (11.4%), and inner inferior quadrant (6.8%). The nodal drainage patterns on 2-hour lymphoscintigraphy were as follows: axillary alone (76.1%), internal mammary nodes alone (1.1%), both axillary and internal mammary nodes (11.4%), and no drainage (11.4%). Internal mammary lymphatic drainage is related to tumor location in the inner quadrants of the breast. About 11.4% of all patients had poorly identified SLNs on lymphoscintigraphy within a 2-hour period, but there was improvement in the overall detection rate up to 95% by intraoperative gamma probe the next day. Preoperative lymphoscintigraphic mapping has value in providing individual lymphatic drainage patterns and tumor location that are important in the interpretation of the results of SLN biopsy during surgery.


Continuous Lumbar Sympathetic Blockade Enhances the Effect of Lumbar Sympatholysis on Refractory Diabetic Neuropathy: A Randomized Controlled Trial.
There are a number of options for the symptomatic treatment of peripheral neuropathy, but the overall treatment outcomes remain unsatisfactory. A total of 60 patients with refractory diabetic neuropathy were randomly assigned to two groups. Patients in Group A were treated with computed tomography (CT)-guided sympathetic neurolysis with alcohol, and patients in Group B were treated with a combined therapy of CT-guided catheterization to achieve continuous lumbar block for 4 weeks followed by neurolysis with alcohol administered via the catheter. The outcomes of these two treatment strategies were then analyzed in terms of pain relief, blood flow in the lower limb microcirculation, plasma levels of inflammatory mediators, and complications. The visual analog scale (VAS) pain scores of all patients after treatment decreased significantly at the different evaluation time points compared with pre-treatment values, with the intergroup analysis revealing that the VAS scores were lower in Group B patients than in Group A patients at all post-treatment time points. Skin temperature, capillary filling time, and blood oxygen saturation level were significantly improved in all patients at the 1- and 7-day post-treatment assessment compared to pre-treatment values, but patients in Group B showed a greater improvement. The plasma levels of inflammatory mediators were lower in all patients at the 7-day post-treatment assessment compared to pre-treatment values, with those of patients in Group B being statistically significantly lower than those of patients in Group A. Combined treatment with continuous lumbar sympathetic block followed by neurolysis with alcohol provided more benefit in all assessed outcomes than sympathetic alcohol neurolysis alone. The results show that the procedures were associated with satisfactory safety outcomes and sustained analgesic effects, thereby providing clinical evidence supporting the use of this novel treatment for patients with painful diabetic neuropathy.


Neurological manifestations of Hansen's disease and their management.
Hansen's disease is almost eliminated from developed countries but in developing countries of Africa, Asia and Latin America leprosy is still considered to be a public health problem. Mycobacterium leprae have the affinity for peripheral nerves and neuropathy is a cardinal manifestation of the disease. The nerve damage affects sensory, motor, and autonomic fibers resulting in the physical impairments and limitation of physical activities and social participation. Leprosy is a curable disease and treatment provided in the early stages will avert the disabilities. Approach to the neuritic leprosy depends on its clinical characteristics, nerve biopsy, and histological appearance of dermatological and neurological lesions. In this article we review the literature and discuss the pathology, clinical features, diagnosis and management of neurological manifestations of leprosy.