Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma.
Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathological phenotypes of RCC and incidence of the 3p loss revealed that the loss of heterozygosity in clear cell type tumors (75%, 12 of 16) was significantly (P less than 0.01) more frequent than that in granular cell type tumors (14%, 1 of 7). In addition, three mixed cell type tumors, consisting predominantly of granular cell components, showed no loss of chromosome 3p loci. These findings may support the notion that the loss of heterozygosity on chromosome 3p is a nonrandom event in the tumorigenesis of sporadic RCC, and suggest that this type of chromosomal rearrangement is specific to the clear cell phenotype of RCC.


Insulin-like growth factor (IGF)-binding protein-4 proteolytic degradation in bovine, equine, and porcine preovulatory follicles: regulation by IGFs and heparin-binding domain-containing peptides.
We recently showed that insulin-like growth factor-binding protein-4 (IGFBP-4) proteolytic degradation in ovine preovulatory ovarian follicles is IGF-dependent and regulated by the heparin-binding domain (HBD) from IGFBP-3 and from connective tissue growth factor (CTGF), heparan/heparin-interacting protein (HIP), and vitronectin. The present study investigated regulation of IGFBP-4 proteolytic degradation in porcine, bovine, and equine ovarian preovulatory follicles. Follicular fluid from such preovulatory follicles contains proteolytic activity, degrading exogenous IGFBP-4. An excess of IGF-I enhanced IGFBP-4 degradation. In contrast, IGFBP-2 or -3 or monoclonal antibodies against IGF-I or -II dose-dependently inhibited IGFBP-4 degradation, and IGF-I or -II reversed this inhibition in a dose-dependent manner. Heparin-binding peptides derived from the C-terminal domain of IGFBP-3 or -5 inhibited IGFBP-4 degradation. Other heparin-binding peptides derived from CTGF, HIP, and vitronectin also inhibited IGFBP-4 degradation, except in porcine follicles. Finally, IGFBP-3 that was mutated in its HBD was less effective at inhibiting IGFBP-4 degradation. Thus, in bovine, porcine, and equine preovulatory follicles, IGFBP-4 proteolytic degradation both depends on IGFs and is inhibited by peptides containing HBD. Overall, these results suggest that during terminal development of follicles to the preovulatory stage in domestic animal species, the increase in IGF bioavailability might enhance IGFBP-4 degradation. In contrast, in atretic follicles, the decrease in IGF bioavailability, resulting partly from the increase in IGFBP-2 (sow, heifer, mare) and IGFBP-5 (heifer) expression would participate in the decrease of IGFBP-4 degradation. In bovine atretic follicles, IGFBP-5 would also strengthen the inhibition of IGFBP-4 degradation by direct interaction of its HBD with the protease. The involvement of other HBD-containing proteins in the modulation of intrafollicular proteases degrading IGFBP-4 remains to be investigated.


The effects of obesity in orthopaedic care.
Obesity is a costly, difficult, and increasingly prevalent challenge facing orthopaedic care. It adds complexity to caring for patients throughout all types and stages of treatment in all orthopaedic subspecialties. There are medical complications to mitigate, anesthetic challenges to meet, and surgical complexities to overcome. The financial implications of treating patients who are obese will continue to challenge surgeons, especially as new payment models are encountered. Research continues to provide more evidence of the unfavorable effects of obesity on outcomes after various orthopaedic procedures. An increasing awareness of the effects of obesity on patients undergoing orthopaedic procedures and educating orthopaedic providers on methods of countering the challenges associated with obesity should ultimately benefit both the provider and the patient.


African-American HLA class II allele and haplotype diversity.
Molecular genetic techniques were used to type nine loci in the HLA class II region in 241 unrelated African-Americans from New York City (NYC). Several effects attributable to recent genetic admixture were evident: the number of distinct class II alleles and haplotypes was larger in the African-Americans than in people of African or European origin, the allele frequencies were more consistently even, and linkage disequilibrium was present across the entire class II region. The African-American DRB1 allele frequencies almost always fell between frequencies among samples from northern Europe and the Gambia, two possible founding populations. The exceptions are attributed to the contribution of other genetically dissimilar African groups to the African-American gene pool. DRB1 allele frequencies (specifically DRB1*1501) and some haplotypes of DRB1-DPB1 were different in our NYC and the 11th International Histocompatibility Workshop (IHW) samples of African-Americans. The high level of allele and haplotype diversity found in African-Americans has important implications for the construction of pools of unrelated potential donors for tissue transplantation.


Coffee rings as low-resource diagnostics: detection of the malaria biomarker Plasmodium falciparum histidine-rich protein-II using a surface-coupled ring of Ni(II)NTA gold-plated polystyrene particles.
We report a novel, low-resource malaria diagnostic platform inspired by the coffee ring phenomenon, selective for Plasmodium falciparum histidine-rich protein-II (PfHRP-II), a biomarker indicative of the P. falciparum parasite strain. In this diagnostic design, a recombinant HRP-II (rcHRP-II) biomarker is sandwiched between 1 μm Ni(II)nitrilotriacetic acid (NTA) gold-plated polystyrene microspheres (AuPS) and Ni(II)NTA-functionalized glass. After rcHRP-II malaria biomarkers had reacted with Ni(II)NTA-functionalized particles, a 1 μL volume of the particle-protein conjugate solution is deposited onto a functionalized glass slide. Drop evaporation produces the radial flow characteristic of coffee ring formation, and particle-protein conjugates are transported toward the drop edge, where, in the presence of rcHRP-II, particles bind to the Ni(II)NTA-functionalized glass surface. After evaporation, a wash with deionized water removes nonspecifically bound materials while maintaining the integrity of the surface-coupled ring produced by the presence of the protein biomarker. The dynamic range of this design was found to span 3 orders of magnitude, and rings are visible with the naked eye at protein concentrations as low as 10 pM, 1 order of magnitude below the 100 pM PfHRP-II threshold recommended by the World Health Organization. Key enabling features of this design are the inert and robust gold nanoshell to reduce nonspecific interactions on the particle surface, inclusion of a water wash step after drop evaporation to reduce nonspecific binding to the glass, a large diameter particle to project a large two-dimensional viewable area after ring formation, and a low particle density to favor radial flow toward the drop edge and reduce vertical settling to the glass surface in the center of the drop. This robust, antibody-free assay offers a simple user interface and clinically relevant limits of biomarker detection, two critical features required for low-resource malaria detection.


The current status and future directions of impedance cardiography in ICU.
Impedance cardiography has not achieved popularity in the Intensive Care Unit (ICU) to date probably because of the limitations in technique and interpretation associated with the altered physiology of critically ill patients, and also because of interference from other machinery in the ICU. The current climate of questioning the existing technology for bedside cardiovascular assessment however spurs the need to evaluate impedance cardiography as a noninvasive alternative. Validation in noncritically ill patients is good when compared to other technologies (e.g., thermodilution, Fick, dye dilution (r greater than 0.9)). Reliability is good with a coefficient of variation in an ICU population of 8.9%, (compared to 18.6% for thermodilution). It has also shown promise in detecting the clinically significant changes of central intravascular volume. Impedance cardiography appears to be useful for measurement of stroke volume (SV) and ejection fraction (EF). From these, left ventricular end-diastolic volume (VED) can be calculated, probably a more reliable estimate of left ventricular filling than pulmonary capillary wedge pressure (PW), measured by pulmonary artery (PA) catheter. In addition, VES can be calculated and with the knowledge of left ventricular end-systolic pressure (PES) (from invasive arterial monitoring), an end-systolic pressure-volume (ES-PV) relationship can be derived. This is thought to be a measure of contractility that is independent of preload and afterload. The ultimate test in the ICU for impedance cardiography is whether clinical outcome of critically ill patients is altered by the use of this technology. Such outcome testing is essential before the true value of impedance cardiography in the management of critically ill patients can be determined.


Visual memory predicts Alzheimer's disease more than a decade before diagnosis.
Recent studies have suggested that AD may reflect a chronic process that begins many years before the clinical expression of dementia. The current study examines premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA). Participants are volunteers from the BLSA, a multidisciplinary study of normal aging conducted by the National Institute on Aging. A total of 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD. The relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period. A greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis.


Adipokines and Migraine: A Systematic Review.
Migraine is comorbid with obesity. Recent research suggests an association between migraine and adipocytokines, proteins that are predominantly secreted from adipose tissue and which participate in energy homeostasis and inflammatory processes. In this review, we first briefly discuss the association between migraine and obesity and the importance of adipose tissue as a neuroendocrine organ. We then present a systematic review of the extant literature evaluating circulating levels of adiponectin and leptin in those with migraine. A search of the PubMed database was conducted using the keywords "migraine," "adiponectin," and "leptin." In addition reference lists of relevant articles were reviewed for possible inclusion. English language studies published between 2005 and 2015 evaluating circulating blood concentration of adiponectin or leptin in those with migraine were included. While the existing data are suggestive that adipokines may be associated with migraine, substantial study design differences and conflicting results limit definitive conclusions. Future research utilizing carefully considered designs and methodology is warranted. In particular careful and systematic characterization of pain states at the time of samples, as well as systematic consideration of demographic (e.g., age, sex) and other vital covariates (e.g., obesity status, lipids) are needed to determine if adipokines play a role in migraine pathophysiology and if any adipokine represents a viable, novel migraine biomarker, or drug target.


Membrane-bound macrophage colony-stimulating factor and its receptor play adhesion molecule-like roles in leukemic cells.
Membrane-bound macrophage colony-stimulating factor (m-M-CSF) is the membrane form M-CSF by alternative splicing. J6-1 leukemic cell line spontaneously forms cell clusters, whose growth depends on the auto-juxtacrine mediated by m-M-CSF and its receptor (M-CSFR). In this study, M-CSFR isolated from J6-1 cells and recombinant human M-CSF soluble receptor (rh-M-CSFsR) were used to study their effects on J6-1 cells. Both receptors inhibited cell proliferation. Use of M-CSFR monoclonal antibodies, M-CSFR or rh-M-CSFsR to block either M-CSFR or m-M-CSF on cell surface inhibited the cluster forming process, while both receptors stimulated cells adhering to culture plate. Furthermore, M-CSFR and/or rh-M-CSFsR caused multiple cellular changes including cytoplasmic pH, multinuclear cell ratio, antigen expression and cell diameter. A [Ca(2+)] rise was induced within 90 s by both receptors. Western blot experiments showed that rh-M-CSFsR caused tyrosine phosphorylation on multiple cytoplasmic proteins of 45 kDa and 55-90 kDa, which could be blocked by H7. These observations suggested that m-M-CSF and M-CSFR mediate J6-1 cell intercellular adhesion with bi-directional signal transduction, and Ca(2+), protein tyrosine kinases, PKC and/or other H7 sensitive kinase(s) involve in the counter-directional signal transduction.


Cannabinoid-Based Therapies and Brain Development: Potential Harmful Effect of Early Modulation of the Endocannabinoid System.
The endocannabinoid retrograde signaling pathway is widely expressed in the central nervous system, where it plays major roles in regulating synaptic plasticity (excitatory and inhibitory) through long-term potentiation and long-term depression. The endocannabinoid system (ECS) components-cannabinoid receptors, endocannabinoids and synthesis/degradation enzymes-are expressed and are functional from early developmental stages and throughout adolescent cortical development, regulating progenitor cell fate, neural differentiation, migration and survival. This may potentially confer increased vulnerability to adverse outcomes from early cannabinoid exposure. Cannabidiol (CBD) is one of the most studied exogenous cannabinoids, and CBD-enriched Cannabis extracts have been widely (and successfully) used as adjuvants to treat children with refractory epilepsy, and there is even a Food and Drug Administration (FDA)-approved drug with purified CBD derived from Cannabis. However, there is insufficient information on possible long-term changes in the central nervous system caused by cannabinoid treatments during early childhood. Like the majority of cannabinoids, CBD is able to exert its effects directly and indirectly through the ECS, which can perturb the regulatory processes mediated by this system. In addition, CBD has a large number of non-endocannabinoid targets, which can explain CBD's effects. Here, we review the current knowledge about CBD-based therapies-pure and CBD-enriched Cannabis extracts-in studies with pediatric patients, their side effects, and their mechanisms of action regarding the central nervous system and neurodevelopment aspects. Since Cannabis extracts contain Δ9-tetrahydrocannabinol (Δ9-THC), we consider that pure CBD is possibly safer for young patients. Nevertheless, CBD, as well as other natural and/or synthetic cannabinoids, should be studied in more detail as a therapeutic alternative to CBD-enriched Cannabis extracts for young patients.


A cross-sectional observational study of unmet health needs among homeless and vulnerably housed adults in three Canadian cities.
Homeless persons experience a high burden of health problems; yet, they face significant barriers in accessing health care. Less is known about unmet needs for care among vulnerably housed persons who live in poor-quality or temporary housing and are at high risk of becoming homeless. The objectives of this study were to examine the prevalence of and factors associated with unmet needs for health care in a population-based sample of homeless and vulnerably housed adults in three major cities within a universal health insurance system. Participants were recruited at shelters, meal programs, community health centers, drop-in centers, rooming houses, and single room occupancy hotels in Vancouver, Toronto, and Ottawa, Canada, throughout 2009. Baseline interviews elicited demographic characteristics, health status, and barriers to health care. Logistic regression was used to identify factors associated with self-reported unmet needs for health care in the past 12 months. Of the 1,181 participants included in the analysis, 445 (37%) reported unmet needs. In adjusted analyses, factors associated with a greater odds of reporting unmet needs were having employment in the past 12 months (AOR = 1.40, 95% CI = 1.03-1.91) and having ≥3 chronic health conditions (AOR = 2.17, 95% CI = 1.24-3.79). Having higher health-related quality of life (AOR = 0.21, 95% CI = 0.09-0.53), improved mental (AOR = 0.97, 95% CI = 0.96-0.98) or physical health (AOR = 0.98, 95% CI = 0.96-0.99), and having a primary care provider (AOR = 0.63, 95% CI = 0.46-0.85) decreased the odds of reporting unmet needs. Homeless and vulnerably housed adults have a similar likelihood of experiencing unmet health care needs. Strategies to improve access to primary care and reduce barriers to accessing care in these populations are needed.


Activation of mammalian target of rapamycin in transformed B lymphocytes is nutrient dependent but independent of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, insulin growth factor-I, and serum.
The study examines the preponderance and mechanism of mammalian target of rapamycin (mTOR) activation in three distinct types of transformed B lymphocytes that differ in expression of the EBV genome. All three types [EBV-immortalized cells that express a broad spectrum of the virus-encoded genes (type III latency; EBV+/III), EBV-positive cells that express only a subset of the EBV-encoded genes (EBV+/I), and EBV-negative, germinal center-derived cells (EBV-)] universally displayed activation of the mTOR signaling pathway. However, only the EBV+/III transformed B cells displayed also activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that is considered to be the key activator of mTOR and of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway that coactivates one of the immediate targets of mTOR, p70 S6K1. Activation of the PI3K/Akt and MEK/ERK, but not of the mTOR pathway, was inhibited by serum withdrawal and restored by insulin growth factor-I. In contrast, activation of mTOR, but not PI3K/Akt and MEK/ERK, was sensitive to nutrient depletion. Both direct Akt (Akt inhibitors I-III) and a PI3K inhibitor (wortmannin at 1 nmol/L) suppressed Akt phosphorylation without significantly affecting mTOR activation. Furthermore, rapamycin, a potent and specific mTOR inhibitor, suppressed profoundly proliferation of cells from all three types of transformed B cells. U0126, a MEK inhibitor, had a moderate antiproliferative effect only on the EBV+/III cells. These results indicate that mTOR kinase activation is mediated in the transformed B cells by the mechanism(s) independent of the PI3K/Akt signaling pathway. They also suggest that inhibition of mTOR signaling might be effective in therapy of the large spectrum of B-cell lymphomas.


Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct.
Reaction of isonitriles with 3-(arylamino)isobenzofuran-1(3H)-ones in the presence of a catalytic amount of an octahydro (R)-binol-derived chiral phosphoric acid afforded 3-oxo-2-arylisoindoline-1-carboxamides in high yields with good to high enantioselectivities. An enantioselective Ugi four-center three-component reaction of 2-formylbenzoic acids, anilines, and isonitriles was subsequently developed for the synthesis of the same heterocycle. Mechanistic studies indicate that the enantioselectivity results from the dynamic kinetic resolution of the primary Ugi adduct, rather than from the C-C bond-forming process. The resulting heterocycle products are of significant medicinal importance.


Successful salvage with high-dose sequential chemotherapy coupled with in vivo purging and autologous stem cell transplantation in 2 patients with primary refractory mantle cell lymphoma presenting in the leukemic phase.
We report the results of an aggressive salvage regimen in 2 patients with advanced-stage leukemic-phase mantle cell lymphoma who were refractory to previous conventional therapies. We combined multiple phases of a cytoreductive regimen including rituximab and sequential high-dose treatment with autologous stem cell transplantation (ASCT). The regimen consisted of a debulking phase with fludarabine, idarubicin, high-dose cytarabine, and high-dose methotrexate; a mobilization and in vivo purging phase with rituximab, cyclophosphamide, and granulocyte colony-stimulating factor; high-dose sequential chemotherapy with etoposide, mitoxantrone, and melphalan followed by ASCT; and, finally, posttransplantation consolidation with rituximab for treatment of minimal residual disease. With this regimen, these 2 refractory patients with multiple poor prognostic factors are in complete remission at 41 and 42 months following transplantation. Although the fact that these 2 patients are still in remission beyond 3 years after ASCT is encouraging, we need a longer follow-up to comment on their long-term survival.


Gallium-68-labeled fibroblast activation protein inhibitor-46 PET in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma: A phase 2, multicenter, single arm, open label non-randomized study protocol.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease prone to widespread metastatic dissemination and characterized by a desmoplastic stroma that contributes to poor outcomes. Fibroblast activation protein (FAP)-expressing Cancer-Associated Fibroblasts (CAFs) are crucial components of the tumor stroma, influencing carcinogenesis, fibrosis, tumor growth, metastases, and treatment resistance. Non-invasive tools to profile CAF identity and function are essential for overcoming CAF-mediated therapy resistance, developing innovative targeted therapies, and improved patient outcomes. We present the design of a multicenter phase 2 study (clinicaltrials.gov identifier NCT05262855) of [68Ga]FAPI-46 PET to image FAP-expressing CAFs in resectable or borderline resectable PDAC. We will enroll up to 60 adult treatment-naïve patients with confirmed PDAC. These patients will be eligible for curative surgical resection, either without prior treatment (Cohort 1) or after neoadjuvant therapy (NAT) (Cohort 2). A baseline PET scan will be conducted from the vertex to mid-thighs approximately 15 minutes after administering 5 mCi (±2) of [68Ga]FAPI-46 intravenously. Cohort 2 patients will undergo an additional PET after completing NAT but before surgery. Histopathology and FAP immunohistochemistry (IHC) of initial diagnostic biopsy and resected tumor samples will serve as the truth standards. Primary objective is to assess the sensitivity, specificity, and accuracy of [68Ga]FAPI-46 PET for detecting FAP-expressing CAFs. Secondary objectives will assess predictive values and safety profile validation. Exploratory objectives are comparison of diagnostic performance of [68Ga]FAPI-46 PET to standard-of-care imaging, and comparison of pre- versus post-NAT [68Ga]FAPI-46 PET in Cohort 2. To facilitate the clinical translation of [68Ga]FAPI-46 in PDAC, the current study seeks to implement a coherent strategy to mitigate risks and increase the probability of meeting FDA requirements and stakeholder expectations. The findings from this study could potentially serve as a foundation for a New Drug Application to the FDA. @ClinicalTrials.gov identifier NCT05262855.


Integrative Metabolomic and Transcriptomic Landscape during Akebia trifoliata Fruit Ripening and Cracking.
Akebia trifoliata fruit is prone to crack after ripening, but little is known about the mechanism underlying the cracking process. This study integrated transcriptomic and metabolomic data, revealing significant changes in 398 metabolites and 8414 genes during ripening and cracking, mainly impacting cell-wall metabolism. Multi-omics joint analysis indicated that genes related to polygalacturonase, pectate lyase, α-amylase, and glycogen phosphorylase were up-regulated after cracking, degrading cell wall and starch. Concurrently, diminished photosynthetic metabolism and heightened phenylpropanoid metabolism suggested alterations in cuticle structure, potentially impacting cell-wall robustness. Numerous auxin and abscisic acid signaling-related genes were expressed, and we assume that they contributed to the promoting peel growth. These alterations collectively might compromise peel strength and elevate expanding pressure, potentially leading to A. trifoliata cracking. Transcription factors, predominantly ethylene response factors and helix-loop-helix family members, appeared to regulate these metabolic shifts. These findings provide valuable insights into A. trifoliata cracking mechanisms; however, direct experimental validation of these assumptions is necessary to strengthen these conclusions and expedite their commercial utilization.


[Cardiac adverse effects of domperidone in adult patients: a systematic review].
Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.


Post-infarction ventricular septal defect: risk factors and early outcomes.
Rupture of the ventricular septum complicates acute myocardial infarction in 0.2% of cases in the thrombolytic era. Ventricular septal defect (VSD) has a mortality of 90-95% in medically managed and 19-60% in surgically treated patients. A retrospective analysis was performed of 41 patients, 26 females (63.4%) and 15 males (36.6%), average age 67.5 ± 15 years, with post-infarction VSD who were treated in the VUL SK intensive cardiology unit between 1991 and 2007. Thirty-seven patients had hypertension (90.2%); anterior wall acute myocardial infarction (AMI) was found in 27 patients (68%). VSD was more frequent in women than in men (p=0.043). In 36 patients (87%) treatment was started 24 hours or later after the development of AMI symptoms. In 34 patients (83%) the rupture occurred during the first episode of AMI and in the majority of these (19 patients, 46.3%), preoperative coronary angiography demonstrated disease of only one coronary artery. During the first 10 days after the onset of AMI, 5 patients (12.2%) were treated surgically but did not survive the operation; 33 patients (80.5%) underwent operation 3-4 weeks after the onset of AMI and all survived. Female sex, advanced age, arterial hypertension, anterior wall AMI, absence of previous AMI, and late arrival at hospital are associated with a higher risk of mortality from acute VSD. The most important factor that determines operative mortality and intra-hospital survival is the time from the onset of AMI to operation.


Effect of partial hydrolyzates of casein and soybean protein on serum lipoproteins and fecal neutral steroids.
Effect of partial hydrolyzate of casein and soybean protein on serum lipoproteins and fecal neutral steroids in cholesterol-fed rats was studied. In rats fed partial hydrolyzate of casein, the levels of plasma and liver cholesterol, liver triglyceride and the ratio of serum beta/alpha lipoprotein had a tendency to decrease compared with those in rats fed intact protein. On the other hand, no difference was observed between soybean protein and partial hydrolyzate of soybean protein diet groups. The excretion of neutral steroids to feces and the amount of fecal coprostanol were increased in rats fed soybean protein and partial hydrolyzate of soybean protein.


The function of the broad-complex during Drosophila melanogaster oogenesis.
The Broad-Complex (BR-C) is an early ecdysone response gene that functions during metamorphosis and encodes a family of zinc-finger transcription factors. It is expressed in a dynamic pattern during oogenesis. Its late expression in the lateral-dorsal-anterior follicle cells is related to the morphogenesis of the chorionic appendages. All four zinc-finger isoforms are expressed in oogenesis, which is consistent with the abnormal appendage phenotypes resulting from their ectopic expression. We investigated the mechanism by which the BR-C affects chorion deposition by using BrdU to follow the effects of BR-C misexpression on DNA replication and in situ hybridization to ovarian mRNA to evaluate chorion gene expression. Ectopic BR-C expression leads to prolonged endoreplication and to additional amplification of genes, besides the chorion genes, at other sites in the genome. The pattern of chorion gene expression is not affected along the anterior-posterior axis, but the follicle cells at the anterior of the oocyte fail to migrate correctly in an anterior direction when BR-C is misexpressed. We conclude that the target genes of the BR-C in oogenesis include a protein essential for endoreplication and chorion gene amplification. This may provide a link between steroid hormones and the control of DNA replication during oogenesis.


Awareness, practice and views about integrating AYUSH in allopathic curriculum of allopathic doctors and interns in a tertiary care teaching hospital in New Delhi, India.
To assess the knowledge, attitude, perception and practice of Ayurveda, yoga, Unani, Siddha, homeopathy and naturopathy (AYUSH) among allopathic doctors and interns and determine their opinion regarding integration of AYUSH education within the allopathic curriculum. This prospective, cross sectional study was conducted in a tertiary care teaching Hospital, New Delhi, India, from March 2016 to March 2017. A survey of 500 allopathic doctors and 150 interns was performed using a structured questionnaire. A majority of doctors (95.2%) were aware of the term AYUSH and had knowledge of yoga (70.6%), homeopathy (55.6%), Ayurveda (50.3%), Siddha (47.8%), naturopathy (32.9%) and Unani (28.9%). Most of the participants (63.0%) felt that therapies under AYUSH are effective. A majority (84.0%) of the doctors were of the view that more research is required in the field of AYUSH. While homeopathy (44.0%) was the most common system used by doctors for themselves, yoga was the therapy most commonly (60.0%) recommended to patients. Nearly half of the doctors (46.7%) recommended AYUSH to their patients, mainly for chronic illness (74.0%). A majority (77.5%) of the respondents agreed that students of allopathic medicine should be familiarized with AYUSH. The modes of incorporation of AYUSH into the medical curriculum most commonly suggested by respondents were optional courses (54.5%) and introductory lectures (42.3%). Doctors and interns of allopathic medicine are aware of AYUSH systems. They use it for themselves and recommend it to patients. They believe that familiarization of Bachelor of Medicine and Bachelor of Surgery students with AYUSH therapies and their integration with allopathic medicine may help in improving patient care.


Billing I-AIM: a novel framework for ultrasound billing.
Point-of-care ultrasound (POCUS) has an ever-growing footprint in medicine. With this growth POCUS billing and reimbursement has become an area gaining quite a bit of attention as a means of funding and sustaining quality and education programs. Standardization across providers is needed to improve the financial viability of POCUS. We created an institutional collaborative which developed a framework to identify critical POCUS billing and reimbursement checkpoints. The framework, Billing I-AIM, provides a feasible structure to enhance provider-based reimbursement and perform quality improvement efforts across variable POCUS environments. POCUS billing using the Billing I-AIM technique allows administrative oversight, quality assurance, and educational functions as well. A discussion of the framework and respective application is provided.


Clinical implications of atrioventricular and intraventricular conduction abnormalities II. Acute myocardial infarction.
The diagnostic criteria and the clinical implications of atrioventricular and intraventricular conduction defects have been reviewed. Information derived from His bundle electrocardiographic studies has been incorporated in the discussion and the importance of the site of block has been stressed. Defects in the trifascicular intraventricular conduction system and their relation to prognosis and to development of complete heart block are outlined. Data on the prognosis of conduction abnormalities during acute myocardial infarction are reviewed in depth and current indications for temporary and permanent pacemaker implantation are presented.


Efficacy and safety of hyaluronate membrane in the rabbit cecum-abdominal wall adhesion model.
Tissue adhesion is a well-known postsurgical phenomenon, causing pain, functional obstruction, and difficult reoperative surgery. To overcome these problems, various synthetic and natural polymer membranes have been developed as postoperative tissue adhesion barriers. However, limitation in their use has hindered its actual application. We prepared a hyaluronate membrane (HM) to evaluate its efficacy and safety as an adhesion barrier compared to a commercialized product (Interceed, Ethicon). To evaluate the antiadhesion effect, a cecum-abdominal wall abrasion model was adopted in a rabbit. The denuded cecum was covered by Interceed or HM or neither and apposed to the abdominal wall (each, n = 10). Four weeks after surgery, the level of adhesion was graded. Acute and chronic toxicity of the three groups were also evaluated. Blood samples drawn to evaluate acute toxicity at postoperative day 3 and 7 showed no significant difference among the three groups. The grade and area of adhesion were significantly lower in the HM compared to those of the control and Interceed at four weeks after surgery. Histologic evaluations, which was carried out to estimate tissue reactions at the site of application, as well as to assess chronic toxicity for the major organs, were not significantly different in the three groups. This study showed that the antiadhesion efficacy of HM was superior to commercialized antiadhesion membrane, Interceed. Low inflammatory response and nontoxicity were also demonstrated. From these results, we suggest that the HM is a good candidate as a tissue adhesion barrier.


Natural evolution of infantile regurgitation versus the efficacy of thickened formula.
Regurgitation is frequent in infants. We evaluated changes in regurgitation among patient groups fed standard formula, standard formula subsequently thickened with cereal, or formula manufactured with bean gum as a thickening agent. A prospective, blinded, randomised 1-month intervention trial evaluating the efficacy of parental reassurance of the regurgitating child in combination with 3 formula interventions--standard infant formula (group A); 5 g of rice cereal added to 100 mL standard formula (group B); and formula manufactured with bean gum as a thickening agent (group C)--was performed in 60 infants presenting with more than 4 episodes of regurgitation and/or vomiting per day during the week before inclusion. Formula intake, infant comfort, stool aspects, and weight gain were evaluated. All of the infants and data recorded by parents in a diary were evaluated weekly by a blinded health care professional. At baseline, groups A, B, and C were similar for all of the parameters. After the 1-month intervention, regurgitation/vomiting decreased significantly in all 3 groups (P < 0.0005). Although the decrease was largest in group C (-4.2 +/- 2.1 episodes/day), the incidence did not differ significantly with groups A or B. At no evaluation interval was there a difference in volume of formula intake, infant comfort, stool frequency, or aspect. After 1 month, weight gain was significantly greater in group C compared with group A (19.9% vs 16.4%; P < 0.001). Thickening of formula decreases regurgitation, but not significantly. Parental reassurance remains the cornerstone of the treatment of infant regurgitation.


Evaluation of Postharvest Washing on Removal of Silver Nanoparticles (AgNPs) from Spinach Leaves.
There is increasing use of silver nanoparticles (AgNPs) as pesticides for fruits and vegetables due to the particles' unique antimicrobial and insecticidal properties. However, residual AgNPs in harvested produce may transfer through the food chain and pose a potential risk to public health. The objective of this study is to determine whether postharvest washing can effectively remove AgNPs that had accumulated on fresh produce. Ten microliters of commercially available 40 nm citrate coated AgNPs (0.4 mg/L) was dropped to a (1 × 1 cm(2)) spot on spinach leaves, followed by washing with deionized water (DI water), Tsunami 100 (80 mg/L), or Clorox bleach (200 mg/L). Then, the AgNP removal efficiency of the three treatments was evaluated by surface-enhanced Raman spectroscopy (SERS), scanning electron microscopy (SEM)-energy dispersive spectrometry (EDS), and inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS results showed that deionized water removed statistically insignificant amounts of total Ag (5%), whereas Tsunami 100 and Clorox bleach yielded 21 and 10% decreases in total Ag, respectively (P < 0.05). The increased removal efficiency resulted from AgNP dissolution and Ag(+) release upon contact with the oxidizing agents in Tsunami 100 (peroxyacetic acid, hydrogen peroxide) and Clorox bleach (sodium hypochlorite). According to the SERS results, the deionized water and Tsunami 100 treatments removed nonsignificant amounts of AgNPs. Clorox bleach decreased Ag NPs by >90% (P < 0.05); however, SEM-EDS images revealed the formation of large silver chloride (AgCl) crystals (162 ± 51 nm) on the leaf, which explained the low total Ag removal from ICP-MS. This study indicates current factory washing methods for fresh produce may not be effective in reducing AgNPs (by water and Tsunami 100) and total Ag (by all three means). This highlights the necessity to develop an efficient washing method for NP removal from food surfaces in the future.


Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.
Acute graft-versus-host disease still represents the major factor that limits successful allogeneic bone marrow transplantation. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease. This study was performed to investigate whether the serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were associated with the manifestation of acute graft-versus-host disease. Serum cytokine levels were measured by sandwich ELISA in 18 patients who underwent allogeneic bone marrow transplantation. Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were increased in patients in whom acute graft-versus-host disease developed. However, only serum soluble IL-2 receptor levels were significantly related to disease severity. Serum levels of IL-12 and IL-18, both of which are mainly produced by activated macrophages, were increased in different phases of acute graft-versus-host disease, especially grade I. Serum levels of soluble IL-2 receptor and IFN-gamma were significantly elevated in patients with fever. Serum levels of soluble IL-2 receptor were more closely related to the severity of acute graft-versus-host disease than those of IL-12, IL-18, and IFN-gamma.


Pleomorphism among murine tissue-associated gp70s.
The gp70s isolated from normal mouse tissues by radioimmune precipitation and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) were shown to be highly pleomorphic. Their apparent molecular weights calculated from SDS-PAGE ranged from 75000 for thymus gp70 to 65000 for epididymal secretion gp70. Differences in the Mr of tissue-associated gp70s were confirmed by double-label co-electrophoresis studies. In addition, a high degree of primary structural pleomorphism among tissue-associated gp70s was demonstrated using two-dimensional tryptic peptide fingerprint analysis. These studies showed that most of the conserved peptides of tissue-associated gp70s were also common to xenotropic murine leukaemia virus (MuLV) gp70s. Thus, tissue-associated gp70s are probably encoded by endogenous xenotropic MuLV env genes or gene fragments. Tissue-associated gp70s also showed a very high level of primary structural pleomorphism. These phenomena were observed for gp70s derived from the tissues of several strains of mice. Tissue-associated gp70 pleomorphism may arise as a consequence of at least two simultaneously operating mechanisms. First, the expression of pleomorphic forms of gp70s on murine tissues may be regulated by mechanisms that also determine the differentiated state of the tissues. Second, endogenous xenotropic env genes may be modified by recombinational or mutational events among these genes, or among cellular genes that regulate the expression of endogenous proviral genes.


CD30 Positive Lymphomatoid Angiocentric Drug Reactions: Characterization of a Series of 20 Cases.
Lymphomatoid drug reactions are atypical T cell cutaneous lymphocytic infiltrates induced by pharmacological therapy. Due to phenotypic abnormalities, clonality, and their close clinical and morphologic resemblance to T cell lymphomas, these eruptions have been categorized as drug-associated reversible granulomatous T cell dyscrasias. A total of 20 cases were encountered in which a diagnosis of CD30 lymphomatoid drug reaction was rendered. There were 11 women and 9 men ranging from 31 to 86 years of age presenting with a sudden onset often generalized cutaneous papular eruption. Two patients had vasculitic lesions. In all cases, a positive drug history was elicited and in most the initiation of the drug was temporally associated with the cutaneous eruption. Among the implicated drugs were statins (6 cases), immunomodulators (4 cases), ACE inhibitors (3 cases), antibiotics (3 cases), chemotherapy agents (3 cases), and antidepressants (1 case). Biopsies demonstrated a similar morphology, namely a superficial angiocentric lymphocytic infiltrate containing many immunoblasts. Tissue eosinophilia, interface dermatitis, and supervening eczematous changes in the overlying epidermis were observed in most cases. In all cases, the angiocentric infiltrate was highlighted by CD3, CD30, and CD4. Cytotoxic protein granule expression or monoclonality was not observed. In all cases, there was improvement or complete regression of the eruption upon drug modulation. The CD30 positive lymphomatoid angiocentric drug reaction poses a diagnostic challenge because of its close resemblance to type A lymphomatoid papulosis and potential confusion with a peripheral T cell lymphoma with large cell transformation.


Memory precision of object-location binding is unimpaired in APOE ε4-carriers with spatial navigation deficits.
Research suggests that tests of memory fidelity, feature binding and spatial navigation are promising for early detection of subtle behavioural changes related to Alzheimer's disease. In the absence of longitudinal data, one way of testing the early detection potential of cognitive tasks is through the comparison of individuals at different genetic risk for Alzheimer's dementia. Most studies have done so using samples aged 70 years or older. Here, we tested whether memory fidelity of long-term object-location binding may be a sensitive marker even among cognitively healthy individuals in their mid-60s by comparing participants at low and higher risk based on presence of the ε4-allele of the apolipoprotein gene (n = 26 ε3ε3, n = 20 ε3ε4 carriers). We used a continuous report paradigm in a visual memory task that required participants to recreate the spatial position of objects in a scene. We employed mixture modelling to estimate the two distinct memory processes that underpin the trial-by-trial variation in localization errors: retrieval success which indexes the proportion of trials where participants recalled any information about an object's position and the precision with which participants retrieved this information. Prior work has shown that these memory paradigms that separate retrieval success from precision are capable of detecting subtle differences in mnemonic fidelity even when retrieval success could not. Nonetheless, Bayesian analyses found good evidence that ε3ε4 carriers did not remember fewer object locations [F(1, 42) = 0.450, P = 0.506, BF01 = 3.02], nor was their precision for the spatial position of objects reduced compared to ε3ε3 carriers [F(1, 42) = 0.12, P = 0.726, BF01 = 3.19]. Because the participants in the sample presented here were a subset of a study on apolipoprotein ε4-carrier status and spatial navigation in the Sea Hero Quest game [Coughlan et al., 2019. PNAS, 116(9)], we obtained these data to contrast genetic effects on the two tasks within the same sample (n = 33). Despite the smaller sample size, wayfinding deficits among ε3ε4 carriers could be replicated [F(1, 33) = 5.60, P = 0.024, BF10 = 3.44]. Object-location memory metrics and spatial navigation scores were not correlated (all r < 0.25, P > 0.1, 0 < BF10 < 3). These findings show spared object-location binding in the presence of a detrimental apolipoprotein ε4 effect on spatial navigation. This suggests that the sensitivity of memory fidelity and binding tasks may not extend to individuals with one ε4-allele in their early to mid-60s. The results provide further support to prior proposals that spatial navigation may be a sensitive marker for the earliest cognitive changes in Alzheimer's disease, even before episodic memory.


Biofilm formation of hypermucoviscous and non-hypermucoviscous Klebsiella pneumoniae recovered from clinically affected African green monkey (Chlorocebus aethiops sabaeus).
In recent years, an emergent Klebsiella pneumoniae hypermucoviscous (HMV) phenotype has been associated with increased invasiveness and pathogenicity in primates. The HMV phenotype is characterized by different capsular serotypes, associated with several genes including the rmpA (regulator of mucoid phenotype) and magA (mucoviscosity-associated) genes. In African green monkeys (AGM) (Chlorocebus aethiops sabaeus) serotypes K1 and K5 have been implicated in fatal multisystemic abscesses. In order to better understand the epizootiology of this pathogen, the capacity of biofilm production of K. pneumoniae isolates presenting the HMV was compared to non-HMV isolates at three different temperatures (25, 30 and 37 °C). The results indicate that HMV and non-HMV isolates display similar capacity to form biofilms at the three different evaluated temperatures. Temperature appears to play a role in the formation of biofilms by K. pneumoniae presenting the HMV phenotype, where larger biofilms were formed at 37 °C than at 25 °C. Knowledge regarding local environmental sources of K. pneumoniae and the possible role of wildlife in the maintenance of this agent in the area is necessary to develop effective recommendations for the prevention and management of this disease in captive AGM populations.


Cognitive rehabilitation for spatial neglect following stroke.
Unilateral spatial neglect causes difficulty attending to one side of space. Various rehabilitation interventions have been used but evidence of their benefit is lacking. To assess whether cognitive rehabilitation improves functional independence, neglect (as measured using standardised assessments), destination on discharge, falls, balance, depression/anxiety and quality of life in stroke patients with neglect measured immediately post-intervention and at longer-term follow-up; and to determine which types of interventions are effective and whether cognitive rehabilitation is more effective than standard care or an attention control. We searched the Cochrane Stroke Group Trials Register (last searched June 2012), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL (1983 to June 2011), PsycINFO (1974 to June 2011), UK National Research Register (June 2011). We handsearched relevant journals (up to 1998), screened reference lists, and tracked citations using SCISEARCH. We included randomised controlled trials (RCTs) of cognitive rehabilitation specifically aimed at spatial neglect. We excluded studies of general stroke rehabilitation and studies with mixed participant groups, unless more than 75% of their sample were stroke patients or separate stroke data were available. Two review authors independently selected studies, extracted data, and assessed study quality. For subgroup analyses, review authors independently categorised the approach underlying the cognitive intervention as either 'top-down' (interventions that encourage awareness of the disability and potential compensatory strategies) or 'bottom-up' (interventions directed at the impairment but not requiring awareness or behavioural change, e.g. wearing prisms or patches). We included 23 RCTs with 628 participants (adding 11 new RCTs involving 322 new participants for this update). Only 11 studies were assessed to have adequate allocation concealment, and only four studies to have a low risk of bias in all categories assessed. Most studies measured outcomes using standardised neglect assessments: 15 studies measured effect on activities of daily living (ADL) immediately after the end of the intervention period, but only six reported persisting effects on ADL. One study (30 participants) reported discharge destination and one study (eight participants) reported the number of falls.Eighteen of the 23 included RCTs compared cognitive rehabilitation with any control intervention (placebo, attention or no treatment). Meta-analyses demonstrated no statistically significant effect of cognitive rehabilitation, compared with control, for persisting effects on either ADL (five studies, 143 participants) or standardised neglect assessments (eight studies, 172 participants), or for immediate effects on ADL (10 studies, 343 participants). In contrast, we found a statistically significant effect in favour of cognitive rehabilitation compared with control, for immediate effects on standardised neglect assessments (16 studies, 437 participants, standardised mean difference (SMD) 0.35, 95% confidence interval (CI) 0.09 to 0.62). However, sensitivity analyses including only studies of high methodological quality removed evidence of a significant effect of cognitive rehabilitation.Additionally, five of the 23 included RCTs compared one cognitive rehabilitation intervention with another. These included three studies comparing a visual scanning intervention with another cognitive rehabilitation intervention, and two studies (three comparison groups) comparing a visual scanning intervention plus another cognitive rehabilitation intervention with a visual scanning intervention alone. Only two small studies reported a measure of functional disability and there was considerable heterogeneity within these subgroups (I² > 40%) when we pooled standardised neglect assessment data, limiting the ability to draw generalised conclusions.Subgroup analyses exploring the effect of having an attention control demonstrated some evidence of a statistically significant difference between those comparing rehabilitation with attention control and those with another control or no treatment group, for immediate effects on standardised neglect assessments (test for subgroup differences, P = 0.04). The effectiveness of cognitive rehabilitation interventions for reducing the disabling effects of neglect and increasing independence remains unproven. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. However, there is some very limited evidence that cognitive rehabilitation may have an immediate beneficial effect on tests of neglect. This emerging evidence justifies further clinical trials of cognitive rehabilitation for neglect. However, future studies need to have appropriate high quality methodological design and reporting, to examine persisting effects of treatment and to include an attention control comparator.


Ribosomal heterogeneity - A new inroad for pharmacological innovation.
The paradigm of ribosome usage in protein translation has shifted from a stance proposed as scientists began to unpick the genetic code that each mRNA was partnered by its own, unique ribosome to a rapid reversal of this view that ribosomes are completely interchangeable and simply recruited to mRNAs from a completely homogenous cellular pool. Evidence that the ribosomal proteome, ribosomal gene transcriptome and ribosome protein and RNA modifications differ between cells and tissues points to the fact that ribosomes are heterogeneous in their composition and have a degree of specialisation in their function. It has also been posited that the tissue-specificity of ribosome diseases provides an indication of functional ribosome heterogeneity, but there are substantial caveats to this interpretation. Only now have proteomic technologies developed to a level enabling accurate stoichiometric comparison of the abundance of specific ribosomal proteins in actively translating ribosomes and to measure protein in non-denatured ribosomes. This poises the field for the provocation that ribosome heterogeneity offers a novel and powerful inroad for the pharmacological targeting of disease. Such ribosome-targeted treatments may extend beyond specific ribosomopathies through strategies such as targeting features of ribosomes that are unique to diseased cells, particularly cancer cells, or to activated immune cells, as well as augmenting the action of other drugs through weakening the production of new proteins in target tissues. We may also be able to harness the potential power in ribosome diversity and specialism to better tune synthetic biology for the production of pharmaceutical proteins.


Analysis of matched mRNA measurements from two different microarray technologies.
[corrected] The existence of several technologies for measuring gene expression makes the question of cross-technology agreement of measurements an important issue. Cross-platform utilization of data from different technologies has the potential to reduce the need to duplicate experiments but requires corresponding measurements to be comparable. A comparison of mRNA measurements of 2895 sequence-matched genes in 56 cell lines from the standard panel of 60 cancer cell lines from the National Cancer Institute (NCI 60) was carried out by calculating correlation between matched measurements and calculating concordance between cluster from two high-throughput DNA microarray technologies, Stanford type cDNA microarrays and Affymetrix oligonucleotide microarrays. In general, corresponding measurements from the two platforms showed poor correlation. Clusters of genes and cell lines were discordant between the two technologies, suggesting that relative intra-technology relationships were not preserved. GC-content, sequence length, average signal intensity, and an estimator of cross-hybridization were found to be associated with the degree of correlation. This suggests gene-specific, or more correctly probe-specific, factors influencing measurements differently in the two platforms, implying a poor prognosis for a broad utilization of gene expression measurements across platforms.


Circumferential skin folds in a child: a case of Michelin tire baby syndrome.
A six-month-old girl who presented with dermatitis was found to have multiple, symmetric, deep, gyrate skin folds involving her trunk and similar circumferential lesions on her extremities since birth. She had a characteristic round face with hypertelorism, depressed nasal bridge, thin, down-turned vermillion border of upper lip and short neck. Skin biopsy demonstrated increased smooth muscle fibers in the deeper dermis. A diagnosis of Michelin tire baby syndrome was made. Clinical features, histopathology, differential diagnosis and prognosis of this rare disorder have been discussed.


Effects of dietary calcium, available phosphorus and vitamin D on growth rate, food utilisation, plasma and bone constituents and calcium and phosphorus retention of commercial broiler strains.
1. The effects of different dietary concentrations of calcium (Ca), available phosphorus (AP) and vitamin D (D) on 5- to 16-day growth performance, and aspects of calcium and phosphorus (P) metabolism of chickens from three commercial strains were studied in two experiments. 2. Increasing dietary Ca reduced weight gain, tibia Ca and P content and increased plasma total Ca, Ca consumption and excretion, whilst dietary Ca at 32 g/kg increased tibia Ca:P ratio, plasma ionized calcium and reduced plasma P, tibia ash, P excretion, excreta moisture and Ca retention. 3. Increasing dietary AP reduced plasma total and ionized Ca and excreta moisture and increased P consumption and excretion, plasma P and tibia ash. 4. The addition of vitamin D increased plasma total and ionized Ca, tibia Ca:P ratio and reduced plasma sodium and P concentrations. 5. Strains differed in their tibia contents of Ca and Ca:P ratios, in response to Ca, AP and vitamin D diets whilst they differed in Ca excretion and excreta moisture caused by feeding either dietary Ca or AP. 6. It was concluded that dietary Ca, AP, vitamin D and strain of broiler chickens influenced the metabolism of Ca and P and that, as a consequence, the tolerance to high dietary Ca. A lean strain of chickens tolerated high dietary calcium better than its fat counterparts.


Social Determinants of Suboptimal Cardiovascular Health Among Pregnant Women in the United States.
Background Suboptimal cardiovascular health (CVH) and social determinants of health (SDOH) have a significant impact on maternal morbidity and mortality. We aimed to evaluate the association of SDOH with suboptimal CVH among pregnant women in the United States. Methods and Results We examined cross-sectional data of pregnant women aged 18 to 49 years from the National Health Interview Survey (2013-2017). We ascertained optimal and suboptimal CVH based on the presence of 0 to 1 and ≥2 risk factors (hypertension, diabetes, hyperlipidemia, current smoking, obesity, and insufficient physical activity), respectively. We calculated an aggregate SDOH score representing 38 variables from 6 domains (economic stability; neighborhood, physical environment, and social cohesion; community and social context; food; education; and healthcare system) and divided into quartiles. We used Poisson regression model to evaluate the association of SDOH with suboptimal CVH and risk factors. Our study included 1433 pregnant women (28.8±5.5 years, 13% non-Hispanic Black). Overall, 38.4% (95% CI, 33.9-43.0) had suboptimal CVH versus 51.7% (95% CI, 47.0-56.3) among those in the fourth SDOH quartile. Risk ratios of suboptimal CVH, smoking, obesity, and insufficient physical activity were 2.05 (95% CI, 1.46-2.88), 8.37 (95% CI, 3.00-23.43), 1.54 (95% CI, 1.17-2.03), and 1.19 (95% CI, 1.01-1.42), respectively among those in the fourth SDOH quartile compared with the first quartile. Conclusions Over 50% of pregnant women with the highest SDOH burden had suboptimal CVH, highlighting the public health urgency for interventions in socially disadvantaged pregnant women with renewed strategies toward improving modifiable risk factors, especially smoking and insufficient physical activity.


Glucose production measured by tracer and balance data in conscious miniature pig.
The rate of glucose production was estimated in the conscious, unrestrained miniature pig during metabolic adaptation to starvation (up to 120 h) by the simultaneous use of three different techniques: 1) the isotopedilution technique, 2) the arteriohepatovenous catheter technique, and 3) the urinary nitrogen balance. During the experimental period 1) whole-body glucose turnover decreased, whereas the amount of glucose recycling increased; 2) splanchnic glucose output decreased, whereas the rate of splanchnic precursor extraction increased up to 48 h, followed by a decrease; 3) gut glucose consumption amounted to about 30% of splanchnic glucose output; and 4) urinary nitrogen excretion declined continuously. The comparison of the different methods revealed that during starvation 1) tracer-determined glucose production rate was within the range (+/- 10%) of the splanchnic glucose output; 2) mean hepatic glucose output overestimated the tracer data by about 30-40%; 3) splanchnic glucose output underestimated hepatic glucose production by the amount of gut glucose consumption; 4) tracer-determined glucose recycling corrected for isotope dilution and amino acid contribution was within the range of splanchnic gluconeogenic precursor extractions. Considering the limitations (e.g., gut glucose consumption, gut lactate and alanine release, blood flow measurement) and methodological problems of the different approaches applied, it is evident that each method reflects different events. It is suggested that the versatile tracer technique combined with nitrogen balance should be preferred for measurement of endogenous glucose production.


Vaccinium macrocarpon (Cranberry)-Based Dietary Supplements: Variation in Mass Uniformity, Proanthocyanidin Dosage and Anthocyanin Profile Demonstrates Quality Control Standard Needed.
Vaccinium macrocarpon (syn. American Cranberry) is employed in dietary supplements (DS) with the aim to improve urinary tract well-being. This property is linked to the antiadhesion-activity of proanthocyanidins (PACs) against uropathogenic-bacteria. However, the current European legislation has been criticized for being weak and ineffective. Indeed, recent scientific works report mislabeled, contaminated, and adulterated supplements containing dangerous or unknown compounds, or sold at toxic doses. In this work, we analysed 24 DS that claim to contain cranberry, and to have a specific dosage of PACs. Our tests included the control of the good manufacturing practice according to the European Pharmacopoeia, and the verification of the claimed dosage of PACs. Moreover, in order to confirm the real presence of cranberry in DS, chemical fingerprinting via HPLC-UV/Vis-MS/MS was employed. Our results showed that 17 DS did not comply with the uniformity test of dosage forms, and only five contained cranberry. Finally, 16 DS claimed an incorrect amount of PACs. These data suggest that several cranberry-based DS are present in the European market with insufficient quality controls. Considering that often DS are self-prescribed by consumer relying on their claim, the data obtained in this work should encourage more controls and stricter rules.


[Enteropathogens relating to diarrhea in HIV patients on antiretroviral therapy].
The etiology of the diarrheic process in AIDS may be caused by viruses, bacteria, fungi, protozoa or helminths, as well as HIV itself. This study evaluated enteropathogens relating to diarrhea in HIV patients who were on antiretroviral therapy. The parasitological methods used were Faust, Hoffmann and Kinyoun. Isolation and culturing of fungi were carried out in accordance with the methodology recommended by the NCCLS M27-A standard. The yeast species were identified using the polymerase chain reaction (PCR). Bacteria were isolated on MacConkey and SS agar and the species were identified using Enterokit B (Probac do Brasil) and biochemical methods. Forty-nine patients were evaluated: 44.89% presented enteroparasites and 48.1% presented Candida sp, of which 61.5% were Candida albicans, 7.6% were Candida sp and 30.7% were Candida non-albicans. Bacteria were isolated from 72% of the patients, of which 49% were Escherichia coli, 13% Salmonella parathyphi, Klebsiella sp or Proteus and 6% Citrobacter freundii or Yersinia sp. There was high prevalence of Candida sp in HIV patients with diarrhea and non-albicans species were isolated. Their presence could be taken to mean that they were accomplices in or causes of the infection.


Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants ubiquitously detectable in the environment and in the food chain. Prenatal exposure to PCBs negatively affects fetal development and produces long-term detrimental effects on child health. The present study sought to evaluate the cytotoxic and genotoxic effects of chronic PCB exposure on fetal cells during pregnancy. To this aim, sheep embryonic fibroblasts (SEF) and amniocytes (SA) were cultured in vitro in the presence of low doses of PCBs for a period of 120days, comparable to the full term of ovine pregnancy. Cellular proliferation rates, global DNA methylation, chromosome integrity, and markers of DNA damage were evaluated at different time points. Moreover, SEF treated with PCBs for 60days were left untreated for one further month and then examined in order to evaluate the reversibility of PCB-induced epigenetic defects. PCB-treated SEF were more sensitive than SA treated with PCBs, in terms of low cell proliferation, and increased DNA damage and global DNA methylation, which were still detectable after interruption of PCB treatment. These data indicate that chronic exposure of fetal cells to PCBs causes permanent genomic and epigenetic instability, which may influence both prenatal and post-natal growth up to adulthood. Our in vitro model offer a simple and controlled means of studying the effects of different contaminants on fetal cells - one that could set the stage for targeted in vivo studies.


Demographic features of subjects with congenital glaucoma.
Congenital glaucoma is a potentially blinding ocular disease of the childhood. Identification of the possible associated risk factors and may be helpful for prevention or early detection of this public health problem. To demonstrate the demographic features of congenital glaucoma subjects. The charts of congenital glaucoma patients referred to Tamcelik Glaucoma Center were retrospectively reviewed through the dates of 2000 and 2013. Analyzed data included diagnosis, age at first presentation, symptoms at first presentation, laterality of the disease, sex, presence of consanguinity, family history of congenital glaucoma, maturity of the fetus at delivery, and maternal age at conception. Statistical Package for Social Sciences (SPSS) version 19.0 by IBM (SPSS Inc, Chicago, Illinois, USA) was used to compare the mean of continuous variables with Student's t-test and analysis of variance (ANOVA) and χ2 test was used to test differences in proportions of categorical variables. The data of 600 eyes of 311 patients were analyzed. The distribution of primary and secondary congenital glaucoma among the patients were 63.3% (n = 197) and 36.7% (n = 114), respectively. Of the 311 patients, 57.2% (n = 178) were male and 42.8% (n = 133) were female. The overall frequency of bilateral disease was 92.3% (n = 287). Overall rate of consanguinity and positive family history was 45.3% (n = 141) and 21.2% (n = 66), respectively. Bilateral disease in this study was more common than previously reported studies. Positive family history was more frequent in primary congenital glaucoma although not statistically significant.


[Chlamydia infections and sexual behavior among young women].
We wanted to determine the prevalence of Chlamydia trachomatis in a sample of young women and to assess risk factors related to sexual behaviour that are predictive of such infection. 898 healthy, non-pregnant women aged 16 to 24 years attending primary care centres over a two-year period (September 1998 to December 2000) were recruited for the study. Uterine cervix samples were tested for Chlamydia trachomatis and participants were interviewed about their sexual behaviour. Chlamydia test results from 881 samples were valid. The prevalence of genital Chlamydia trachomatis infection was 2.4% (21/881). In univariable analyses, a high number of lifetime partners (four or more), smoking, previous pregnancy and a previous positive chlamydia test were factors predictive of a positive Chlamydia test. In multivariable analyses, previous pregnancy and a previous positive Chlamydia test were the only significant factors. The number of lifetime partners was higher among women who had been pregnant or previously had tested positively for Chlamydia. The prevalence of Chlamydia was low in this population. Risk behaviour (frequent change of partners) can be expressed by teenage pregnancy and positive Chlamydia test results and these factors can be used for identification of women who should be tested more frequently than others for Chlamydia infection in a low-prevalence population.


Alprazolam-induced dyscontrol in borderline personality disorder.
The authors report a significant increase in dyscontrol in patients with borderline personality disorder who were taking alprazolam during a double-blind, placebo-controlled crossover study. They suggest that caution be used in prescribing alprazolam to patients with similar histories.


Application of temperature gradient gel electrophoresis to the study of yeast diversity in the estuary of the Tagus river, Portugal.
Temperature gradient gel electrophoresis (TGGE) was employed for the assessment of yeast diversity in the estuary of the Tagus river (Portugal). The molecular detection of yeasts was carried out directly from water samples and, in parallel, a cultivation approach by means of an enrichment step was employed. A nested PCR was employed to obtain a fungal amplicon containing the D2 domain of the 26S rRNA gene. For identification the TGGE bands were extracted, re-amplified, and sequenced. Fourteen fungal taxa were detected and all except one were yeasts. Most yeast sequences corresponded to members of the Ascomycota and only three belonged to the Basidiomycota. Five yeasts (four ascomycetes and one basidiomycete) could not be identified to the species level due to the uniqueness of their sequences. The number of species detected after enrichment was higher than the number of taxa found using the direct detection method. This suggests that some yeast populations are present in densities that are below the detection threshold of the method. With respect to the analysis of the yeast community structure, our results indicate that the dominant populations belong to Debaryomyces hansenii, Rhodotorula mucilaginosa, Cryptococcus longus, and to an uncultured basidiomycetous yeast phylogenetically close to Cr. longus. The combined analysis of direct detection and cultivation approaches indicates a similar community structure at the two sampled sites since nine species were present at both localities.


Sacroiliac Joint and Pelvic Dysfunction Due to Symphysiolysis in Postpartum Women.
Pregnancy-related pain in the sacroiliac joint (SIJ), lumbosacral region, pubic symphysis, or in any combination of these joints has been coined as pelvic girdle pain (PGP) and has been estimated to affect almost half of all pregnant women. SIJ dysfunction in pregnancy is due to multiple biomechanical mechanisms, such as increased weight, change in posture, increased abdominal and intrauterine pressure, and laxity of the spine and pelvic structures. Moreover, when compared to men, women have increased SIJ mobility due to increased pubic angle and decreased SIJ curvature. These differences may assist in parturition where hormones, such as relaxin and estrogen, cause symphysiolysis. A retrospective review of the literature was conducted in the PubMed database using the search term "pregnancy-related sacroiliac joint pain." All peer-reviewed studies were included. Around 8%-10% of women with PGP continue to have pain for one to two years postpartum. Patients that were treated with SIJ fusion show statistically significant improvement in pain scores when compared to patients that had non-operative treatment. Although we have a number of studies following patients after sacroiliac (SI) joint fusion for pelvic pain with SI joint dysfunction, further research is needed to study sacroiliac fusion for SI joint dysfunction in postpartum women to better tailor and optimize surgical outcomes for this patient population.


Adrenergic regulation of glucagon and insulin secretion during immobilization stress in normal and spontaneously diabetic BB rats.
To test for a possible role of adrenergic mechanisms in the altered glucagon secretion in the spontaneously diabetic "BB" rat, the responses of glucose, insulin, and glucagon to adrenergic blocking agents in diabetic and normal rats were compared at rest and during 2 h of immobilization stress. In unstressed normal rats, phentolamine alone caused a 20 mg/dl fall in glycemia, 1.2 ng/ml rise in insulin (IRI), and no change in glucagon (IRG), whereas the only effect of propranolol was a minor rise in glycemia. Stress caused increments in glycemia of 72 mg/dl and in IRG of 94 pg/ml, and no change in IRI. Phentolamine significantly attenuated the stress-related increments, and IRI increased by the same amount as in the unstressed state. Propranolol exhibited no statistically significant effects on the response to stress. These findings are consistent with alpha-adrenergic stimulation of IRG and suppression of IRI secretion. In unstressed diabetic rats (mean time 0 glycemia, 431 mg/dl), propranolol caused only a small rise in glycemia, whereas phentolamine induced marked increments of glycemia (131 mg/dl) and IRG (116 pg/ml). Stress alone did likewise (189 mg/dl, 122 pg/ml) as did stress with the phentolamine (271 mg/dl, 144 pg/ml). However propranolol significantly attenuated the stress-induced increments in glycemia (88 mg/dl) and IRG (82 pg/ml). Thus both alpha- and beta-adrenergic receptors influence IRG secretion in the diabetic rats. An in vivo model for elucidating neural control of glucoregulation has been developed that is independent of cardiovascular fitness.


Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling.
Lung development is mediated by assorted signaling proteins and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development. Moreover, evidence suggests that Notch signaling links embryonic lung development and asthmatic airway remodeling. Herein, we summarized all-recent advances associated with the mechanistic role of Notch signaling in lung development, consequences of aberrant expression or deletion of Notch signaling in linking early-impaired lung development and asthmatic airway remodeling, and all recently investigated potential therapeutic strategies to treat asthmatic airway remodeling.


Violence Against Widows in Nepal: Experiences, Coping Behaviors, and Barriers in Seeking Help.
Widows are a vulnerable population in Nepal. This study examined Nepalese widows' experiences of violence, their coping strategies, and barriers faced in seeking help. Study participants were recruited from Women for Human Rights, an NGO in Nepal. A stratified purposive sampling approach was used to select 51 widows and 5 staff members for in-depth interviews. Twenty-seven women who experienced violence were included in this analysis. Data were analyzed and synthesized using a thematic analysis procedure. Widows reported a range of violent experiences perpetrated by family and community members that spanned psychological, physical, and sexual abuse. Women dealt with abusive experiences using both adaptive (e.g., attempting to move ahead, seeking social support, using verbal confrontation) and maladaptive coping strategies (e.g., suicidal thoughts or self-medication). However, they faced barriers to seeking help such as insensitivity of the police, perceived discrimination, and general lack of awareness of widows' problems and needs. Findings highlight the need for interventions across the individual, family, community, and policy levels. Avenues for intervention include creating awareness about widows' issues and addressing cultural beliefs affecting widows' lives. Furthermore, efforts should focus on empowering widows, promoting healthy coping, and addressing their individual needs.


Dosimetric effects of manual cone-beam CT (CBCT) matching for spinal radiosurgery: our experience.
Radiosurgical treatment of cranial or extracranial targets demands accurate positioning of the isocenter at the beam and table isocenter, and immobilization of the target during treatment. For spinal radiosurgery, the standard approach involves matching of cone-beam CT (CBCT) in-room images with the planning CT (pCT) to determine translation and yaw corrections. The purpose of this study was to assess the accuracy of these techniques compared to advanced automatching using mutual information metrics, with consideration given to volume of interest (VOI) and optimizing translations and rotations in all axes. The dosimetric consequences of our current standard matching techniques were also evaluated. Ten consecutive spinal radiosurgery patients treated in the last year were subjected to analysis. For purposes of this analysis, the automatch using mutual information and a VOI was considered to create "the true isocenter" for positioning the patients. Review of the imaging from this automatch confirmed perfect superimposition of the two datasets within the VOI. Matching the CBCT to the pCT using the automatch allowed assessment of the rotations which had been previously ignored. Recalculation of the dose volume histogram was undertaken for each patient, assuming displacement of the true isocenter to the treated isocenter. Comparisons between the delivered doses and the intended doses were made. The mean absolute lateral/vertical/longitudinal translations and vector displacement between the manual CBCT-pCT matching isocenter and the true isocenter were 0.13, -0.05, and -0.39 mm, with a minimum and maximum individual pixel vector shift of 3.2 and 8.94 mm. The mean pitch, yaw, and roll correction for automatch was -0.30°, 0.25°, and 0.97° with a maximum of 1.65°, 2.92°, and 1.43°. Four of ten patients had a significant change in the coverage of the tumor due to lack of correction of translational and rotational errors. The largest errors were observed in patients with small and irregular target volumes. Our initial results show that precise positioning for spinal radiosurgery cannot be accomplished with manual pCT-CBCT matching without a clinical strategy to compensate for rotations. In the absence of this, significant underdosing of the tumor may occur.


An investigation of the molecular components of desmosomes in epithelial cells of five vertebrates.
We have shown previously, by fluorescent antibody staining, that desmosomal antigens are widely distributed in the tissues of vertebrate animals. Furthermore, we have demonstrated mutual desmosome formation between cells derived from man, cow, dog, chicken and frog. In this paper we have studied the components of desmosomes in a tissue or a cell line from each of these animals by immunoblotting with antibodies raised against the desmosomal components isolated from bovine nasal epithelium. Blotting was carried out on bovine nasal epithelial desmosomal cores, desmosome-enriched fractions derived from chicken and frog epidermis, nuclear matrix-intermediate filament scaffolds derived from Madin-Darby bovine and canine cells (MDBK and MDCK), and unextracted cultured human foreskin keratinocytes. The results show that desmosomes from all these sources contain high molecular weight proteins (desmoplakins) of similar or identical molecular weights (250 000 and 215 000). Antibodies against the two lower molecular weight desmosomal proteins (83 000 and 75 000) always recognized one or two bands in very similar molecular weight regions of the gels. The desmosomal glycoproteins were found to be much more variable than the proteins: they vary between sources in molecular weight, heterogeneity and antibody cross-reactivity. For instance, antibody specific for a group of glycoprotein bands of 175 000, 169 000 and 164 000 (Mr) in bovine nasal epithelium recognizes three bands of 245 000, 230 000 and 210 000 in MDCK cells but only a single band of 190 000 in keratinocytes. In mammals, the 175 000-164 000 glycoproteins and the desmosomal adhesion molecules, the desmocollins (Mr 130 000 and 115 000 in cow's nose), are immunologically distinct. In chicken and frog, however, there are glycoproteins that react with both anti-175 000-164 000 and anti-desmocollin antibodies, but there are also distinct desmocollin bands. The significance of these results is discussed in relation to conservation of desmosomal components and adhesion mechanisms. It is suggested that adhesion may be performed by a well-conserved protein domain and that the variation between desmosomal glycoproteins from different sources may be due to differences in their carbohydrate composition.


Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society.
The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control. Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4-6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function). Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.


A model-based method for assessing insulin sensitivity from the oral glucose tolerance test.
Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.


Extent of resection and lymphadenectomy in early Barrett's cancer.
The recognition of Barrett's esophagus as a premalignant condition has led to aggressive endoscopic screening protocols aimed at detecting adenocarcinoma in this organ. This policy has resulted in an increasing number of patients who present with 'early Barrett's cancer'. In the existing literature, very little data address patients with these lesions and, therefore, no consistent definition of early Barrett's cancer currently exists. Additionally, the extent of resection and lymphadenectomy that should be performed is not known. We define early Barrett's cancer as clinical T1N0M0 adenocarcinoma. We perform en bloc esophagectomy with radical lymphadenectomy for these lesions because current data suggest that a more radical operation may improve survival in patients with esophageal cancer. It is also the only way to stage adequately the tumour and is associated with morbidity and mortality rates comparable to less radical, 'standard' resections in experienced hands. Barrett's esophagus is associated with invasive adenocarcinoma in 40% of patients who undergo esophagectomy for the preoperative diagnosis of high-grade dysplasia. The existing literature suggests these lesions may represent the earliest subset of Barrett's cancer and that a standard, less radical resection may suffice for these patients.


[Role and mechanism of heat shock protein 70 in airway hypersecretion].
To explore the role and mechanism of heat shock protein 70 (HSP70) in airway hypersecretion. After a stimulation of 8% cigarette smoke extract (CSE), airway cells A549 were treated with HSP70 antibody and c-Jun N-terminal kinase (JNK) specific inhibitor SP600125 respectively. And the cells were divided into 4 groups of blank contrast (serum-free medium), CSE stimulation (8% CSE for 24 h), HSP70 antibody (30-min pre-treatment of HSP70 antibody and culturing in 8% CSE for 24 h) and SP600125 (30-min pre-treatment of SP600125 30 µmol/L and culturing in 8% CSE for 24 h). The relative expression levels of MUC5AC protein in various groups were determined by enzyme-linked immunosorbent assay (ELISA). And the relative transcription level of MUC5AC mRNA was detected by reverse transcription-polymerase chain reaction (PCR) while the synthesized levels of HS70 as well as the phosphorylation levels of JNK and activated protein-1 (mostly c-Jun) were measured by Western blot. As compared with those in blank contrast group (0.26 ± 0.10, 0.28 ± 0.06, 0.30 ± 0.05, 0.30 ± 0.08, 0.36 ± 0.08), HSP70 antibody group (0.30 ± 0.12, 0.29 ± 0.09, 0.34 ± 0.06, 0.47 ± 0.19, 0.39 ± 0.13) and SP600125 group (0.38 ± 0.06, 0.31 ± 0.14, 0.39 ± 0.04, 0.44 ± 0.12, 0.48 ± 0.11), the relative expression levels of MUC5AC protein and mRNA, phosphorylation JNK (p-JNK), c-Jun and p-c-Jun (0.52 ± 0.07, 0.64 ± 0.11, 0.73 ± 0.06, 0.67 ± 0.10, 0.67 ± 0.09) significantly increased in CSE stimulation group (all P < 0.05). And the synthesis levels of HSP70 (0.75 ± 0.09) in CSE stimulation group increased than blank contrast group (0.29 ± 0.03) and HSP70 antibody group (0.40 ± 0.11) (all P < 0.05). HSP70 may enhance the expression of MUC5AC in bronchial epithelial A549 cells via a signaling pathway of JNK/AP-1..


Hepatitis B antigen and viral hepatitis type B in India.
Surveys were conducted to determine the occurrence of overt hepatitis manifested by jaundice in groups of hospital patients who had survived their initial illness. Of those who had been given blood that had not been screened for the presence of hepatitis B antigen (HB Ag) 9.4% reported that they had had jaundice during the 6 months following transfusion. During a similar period jaundice was reported by only 1.1% of those who had received blood found to be negative for HB Ag by the cross-over electrophoresis test. This difference is highly significant. Jaundice was reported by 25.5% of recipients of HB Ag-positive blood. Of a control population of hospitalized but non-transfused patients 2.2% reported jaundice within 6 months of hospitalization. The risk of overt hepatitis from HB Ag in transfused blood is high in southern India and is similar to that in temperate countries where the occurrence of antigen carriers, and presumably of immune status, are lower than in the tropics.


[Therapy resistant leg ulcer caused by multiple myeloma].
The authors review an elderly woman suffering from leg ulcer with bad curability which was a consequence of a malignant haematologic disease. Multiple relapse of this ulcer was observed and did not react to usual conservative therapy. The only sign of multiple myeloma was the extremely high level of iron measured in the blood serum bound to a monoclonal paraprotein. Sternum aspiration was made and the sample showed presence of plasmoblasts supporting diagnosis of multiple myeloma. The poor therapeutical results were caused by hyperviscosity syndrome in consequence of the high level of the monoclonal component in the blood serum. The ulcer was cured within eight weeks by suppression of the monocloclonal component and thus, elimination of hyperviscosity. This case is a special one from several points of view. Leg ulcers not reacting to usual therapy may be caused by haematologic disease thus the physician should consider this and extend examinations as well and necessarily hospitalize patient. Appearance of multiple myeloma is unusual in this case. Hystology made from the skin excised from the periphery of the wound has not showed signs of pyoderma gangrenosum, which is known mostly being associated with multiple myeloma.


Melatonin attenuates the changes in polyamine levels induced by systemic kainate administration in rat brains.
Systemically administered kainate has been demonstrated to induce neuronal damage and changes of the levels of biochemical substances related to neurotoxicity. Polyamines are thought to be important in the generation of edema and neuronal cell loss associated with various type of excitotoxicity. Melatonin exerts potent free radical scavenging, antioxidant, and neuroprotective properties. This study was designed to estimate the effect of exogenous melatonin administration on the changes of polyamine levels in rat brains after systemic administration of kainate. Kainate [10 mg/kg, intraperitoneally (i.p.)] was injected into the rats to produce excitotoxicity. Melatonin (15 mg/kg, i.p.) was administered 1 h before, immediately after, and 1 h after kainate treatment. We examined the polyamine [putrescine (PU), spermidine (SD) and spermine (SM)] levels in the cerebral cortex and hippocampus and neuronal density in the hippocampal CA1 and CA3 subsectors in brain sections. PU levels were increased 8 and 24 h after kainate treatment and the administration of melatonin attenuated these changes. Only minor changes were noted in the levels of the polyamine SD and SM after the kainate treatment. In histology, neuronal injuries in the hippocampal CA1 and CA3 subsectors were examined 3 days after kainate treatment and melatonin reduced the kainate-induced neuronal injuries. Our results show that melatonin inhibits the polyamine responses in the cerebral cortex and hippocampus following kainate-induced excitotoxicity and PU may be responsible for the protective effect of melatonin against kainate-induced excitotoxicity.


3D video visualization employing wavelet multilevel decomposition.
This study analyzed the implementation and performance of a framework that can be efficiently applied to three-dimensional (3D) video sequence visualization. The proposed algorithm is based on wavelets and wavelet atomic functions used in the computation of disparity maps. The proposed algorithm employs wavelet multilevel decomposition and 3D visualization via color anaglyphs synthesis. Simulations were run on synthetic images, synthetic video sequences, and real-life video sequences. Results shows that this novel approach performs better in depth and spatial perception tasks compared to existing methods, both in terms of objective criteria such as quantity of bad disparities and similarity structural index measure and the more subjective measure of human vision.


Manufacture of PLGA multiple-channel conduits with precise hierarchical pore architectures and in vitro/vivo evaluation for spinal cord injury.
By the method of injection molding combined with thermally induced phase separation (TIPS), a novel nerve conduit with a plurality of channels and macro-/microporous architecture was fabricated using poly (lactide-co-glycolide) (PLGA, 75:25; Mn=1.22x10(5)). The diameter of the conduits and the number of channels could be regulated by changing the parameters of the mold, and the porosity of the conduit was as high as 95.4%. Meanwhile, the hierarchical pore architecture of the walls could be controlled through varying the solution concentration and the contents of porogen. The degradation study in vitro showed that 7-channel conduit could hold its apparent geometry for about 12 weeks in phosphate buffer solution (PBS) at 37degreesC, and the pH values of the degradation solution were detected in the range 4.1-4.5. The influences of the conduit architecture on the cell attachment, spreading, and proliferation were evaluated by culturing rat mesenchymal stem cells alone or together with Schwann cells in vitro. The implantation of the PLGA conduit in the spinal cord showed that it had good biocompatibility, and no obvious inflammatory response was detected. Therefore, the results implied that these PLGA multiple-channel nerve conduits have the potential use for spinal cord injury.