Identification of multiple forms of membrane-associated neutral sphingomyelinase in bovine brain.
Many different stimuli such as bioactive agents and environmental stresses are known to cause the activation of sphingomyelinase (SMase), which hydrolyzes sphingomyelin to generate ceramide as a second messenger playing a key role in differentiation and apoptosis in various cell types. Here we identified multiple forms of the membrane-associated neutral SMase (N-mSMase) activity in bovine brain. They could be classified into two groups according to extracting agents: group T-mSMase, extracted with 0.2% Triton X-100, and group S-mSMase, extracted with 0.5 M (NH(4))(2)SO(4). Group T-mSMase: alpha, beta, gamma, and delta, which were extensively purified from 40,000-g pellets of bovine brain homogenates by 3,150-, 5,275-, 1,665-, and 2,556-fold over the membrane extracts, respectively, by sequential use of several column chromatographies. On the other hand, S-mSMase was eluted as two active peaks of S-mSMase epsilon and zeta in a phenyl-5PW hydrophobic HPLC column and further purified by 1,119- and 976-fold over 40,000-g pellets of the homogenates, respectively. These highly purified N-mSMase enzyme preparations migrated as several bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed many different features in biochemical properties such as pH dependence, Mg(2+) requirements, and effects of detergents. Taken together, our data strongly suggest that mammalian brain N-mSMase may exist as multiple forms different in both its chromatographic profiles and biochemical properties.


"Esophagomediastinal fistula presenting as drug resistant tuberculosis".
Esophageal tuberculosis is one of the rarest forms of tuberculosis with higher incidence in immunocompromised cases. In majority of cases it is seen associated with esophagomediastinal and esophagotracheal fistulas. Diagnosis is established with the help of esophagoscopy followed by histopathology and microbiological analysis of biopsy sample. Treatment with antituberculous therapy alone is sufficient in majority of cases, however surgical management is mandatory in severe and non resolving cases. We thereby report an interesting case of esophagomediastinal fistula presenting as drug resistant tuberculosis with retroviral disease.


Quantitative changes in amylase activity in the salivary glands, pancreas, saliva, and serum after administration of isoproterenol, pilocarpine, and acetylcholine.
Amylase activity in various tissues--i.e., submandibular/sublingual and parotid glands, the pancreas, saliva, and serum--in rats was measured after injection of isoproterenol, pilocarpine, and acetylcholine. All agents reduced amylase activity in the parotid gland and increased the enzyme activity in the submandibular/sublingual glands, in saliva and serum.


Entry into clinical trials in breast cancer: the importance of specialist teams. Scottish Breast Cancer Focus Group and Scottish Cancer Therapy Network.
The aim of this study was to identify the factors influencing entry of women with invasive breast cancer into clinical trials in Scotland. Women diagnosed during 1987 and 1993 were identified from cancer registry data records and their case notes reviewed. Entry into clinical trials was recorded, along with clinical and demographic data for 4688 patients. In 1987, the proportion of women entering clinical trials was 12.3% and, allowing for shorter follow-up, this appeared unchanged in 1993. Patients seen by surgeons with a high case load and those referred to an oncologist were approximately seven times and three times, respectively, more likely to enter a clinical trial (P < 0.0001). The area of Scotland (Health Board) where the woman was first treated also influenced study entry (P < 0.0001), whereas social deprivation had no effect (P = 0.93). Older women, especially those over 80 years of age, were less likely to enter studies (P = 0.05). Extending the management of patients by specialist multidisciplinary teams should increase recruitment into clinical trials and help to identify better treatments for women with breast cancer.


Projections to the ventral surface of the cat brainstem demonstrated by horseradish peroxidase.
Topical application of horseradish peroxidase (HRP) to the ventral surface of the medulla oblongata revealed various cells with axons terminating near this region. Fibers traced from the ventral surface originated in the nucleus of the tractus solitarius and the dorsal nucleus of the vagus, both near the dorsal surface of the medulla. Projections from the cochlear nucleus were also observed. Using short HRP contact time, fibers were shown which terminate at, or near, the ventral surface. The possible involvement of these projections in various responses mediated from the ventral surface is discussed.


Modulation of plasma antidiuretic hormone levels does not change the magnitude of the LPS-induced febrile response in Pekin ducks.
The objective of this study was to determine the effect of modulating the plasma concentrations of the avian antidiuretic hormone, arginine vasotocin (AVT), upon the febrile response to lipopolysaccharide (LPS) in Pekin ducks. LPS, intravenously administered into conscious control birds at a dose of 1 microg x kg(-1), caused a monophasic increase in body temperature of 0.85 +/- 0.12 degrees C associated with a Thermal Response Index of 2.5 +/- 0.6 C degrees h. Plasma AVT concentrations in the control birds also increased with the progression of the fever response, more than doubling from their basal values. Ducks in which the circulating level of AVT had either been elevated by the intravenous infusion of the peptide or dehydration, or reduced by the administration of a specific AVT antibody prior to LPS administration, produced body temperature profiles and Thermal Response Index values that did not differ significantly from those of the control birds. The lack of any direct effect of variations in plasma AVT concentrations upon the magnitude of the fever response indicates that the LPS-induced elevation in plasma AVT is not associated with modulating the rise in body temperature obtained in avian fever.


Body stuffing during apprehension resulting in distal esophageal impaction: a case report and review of the literature.
Body stuffing and body packing are two methods of concealing illicit drugs. Body stuffing is defined as the oral ingestion of illicit drugs, typically to avoid law enforcement detection or other consequences of possession, and may present a serious medical emergency in patients. Most commonly, body stuffers ingest possibly large or unknown quantities of illicit substances to avoid detection of the drugs during apprehension. This ingestion is typically hasty or impulsive, and therefore the substances ingested are rarely packaged in a way that would be considered safe for ingestion. This case highlights a series of rare complications of impacted esophageal foreign body including esophageal edema, pericarditis, and hydro-pneumothorax for a 16-year-old Hispanic male who was booked into a county juvenile detention and rehabilitation facility. He complained of persistent intractable epigastric pain, along with pleuritic chest pain with multiple episodes of vomiting over the previous 4 days. He denied swallowing any foreign body. He underwent esophagogastroduodenoscopy, and a plastic bag with content suspicious for marijuana was discovered in the distal esophagus and removed. Failure to consider body stuffing and foreign body impaction in individuals during medical evaluation in detention centers with complaints of chest pain, abdominal pain, dysphagia, and/or certain toxidromes can delay diagnosis and lead to a variety of medical complications.


Magnesium and zinc status during the menstrual cycle.
The effect of menstrual cycle phases on the indexes of magnesium and zinc status was assessed in five normally menstruating women. Plasma concentrations of magnesium and zinc and the magnesium and zinc content of red blood cells and peripheral blood mononuclear cells were measured for 3 or 5 days per week during three menstrual cycles. The cycles were divided into four phases: menses, follicular, ovulatory, and luteal. Plasma magnesium concentrations were highest during menses and then gradually declined, reaching the lowest point during the ovulatory phase. This was followed by a rise during the luteal phase. Plasma zinc concentrations were higher during menses and the follicular phase and then dropped during the ovulatory and luteal phases. Both the magnesium and zinc content of red blood cells and mononuclear cells remained constant over the course of the study and did not change significantly as a function of cycle phase. This study provides evidence that plasma magnesium and zinc concentrations fluctuate during the menstrual cycle in a phase-related fashion in normally menstruating women. Whether these changes are hormonally mediated or reflect metabolic changes will require further study.


Valuing non-marginal changes in mortality and morbidity risk.
Many stated-preference studies that seek to estimate the marginal willingness-to-pay (WTP) for reductions in mortality or morbidity risk suffer from inadequate scope sensitivity. One possible reason is that the risk reductions presented to respondents are too small to be meaningful. Survey responses may thus not accurately reflect respondents preferences for health and safety. In this paper we propose a novel approach to estimating the value per statistical life (VSL) or the value per statistical case (VSC) based on larger risk reductions measurable as percent changes. While such non-marginal risk reductions are easier to understand, they introduce well known biases. We propose a methodology to de-bias VSL and VSC estimates derived from the evaluation of non-marginal risk reductions and present a proof of concept using simulated stated preference data.


A system that delivers an antioxidant to mitochondria for the treatment of drug-induced liver injury.
Mitochondria, a major source of reactive oxygen species (ROS), are intimately involved in the response to oxidative stress in the body. The production of excessive ROS affects the balance between oxidative responses and antioxidant defense mechanisms thus perturbing mitochondrial function eventually leading to tissue injury. Therefore, antioxidant therapies that target mitochondria can be used to treat such diseases and improve general health. This study reports on an attempt to establish a system for delivering an antioxidant molecule coenzyme Q10 (CoQ10) to mitochondria and the validation of its therapeutic efficacy in a model of acetaminophen (APAP) liver injury caused by oxidative stress in mitochondria. A CoQ10-MITO-Porter, a mitochondrial targeting lipid nanoparticle (LNP) containing encapsulated CoQ10, was prepared using a microfluidic device. It was essential to include polyethylene glycol (PEG) in the lipid composition of this LNP to ensure stability of the CoQ10, since it is relatively insoluble in water. Based on transmission electron microscope (TEM) observations and small angle X-ray scattering (SAXS) measurements, the CoQ10-MITO-Porter was estimated to be a 50 nm spherical particle without a regular layer structure. The use of the CoQ10-MITO-Porter improved liver function and reduced tissue injury, suggesting that it exerted a therapeutic effect on APAP liver injury.


Role of Na+/H+ exchange and HCO3- transport in pHi recovery from intracellular acid load in cultured epithelial cells of sheep rumen.
This study sought to investigate effects of short-chain fatty acids and CO2 on intracellular pH (pHi) and mechanisms that mediate pHi recovery from intracellular acidification in cultured ruminal epithelial cells of sheep. pHi was studied by spectrofluorometry using the pH-sensitive fluorescent indicator 2',7'-bis (carboxyethyl)-5(6')-carboxyfluorescein acetoxymethyl ester (BCECF/AM). The resting pHi in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution was 7.37 +/- 0.03. In HEPES-buffered solution, a NH4+/NH3-prepulse (20 mM) or addition of butyrate (20 mM) led to a rapid intracellular acidification (P < 0.05). Addition of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA: 10 microM) or HOE-694 (200 microM) inhibited pHi recovery from an NH4+/NH3-induced acid load by 58% and 70%, respectively. pHi recovery from acidification by butyrate was reduced by 62% and 69% in the presence of EIPA (10 microM) and HOE-694 (200 microM), respectively. Changing from HEPES-(20 mM) to CO2/HCO3(-)-buffered (5%/20 mM) solution caused a rapid decrease of pHi (P < 0.01), followed by an effective counter-regulation. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 100 microM) blocked the pHi recovery by 88%. The results indicate that intracellular acidification by butyrate and CO2 is effectively counter-regulated by an Na+/H+ exchanger and by DIDS-sensitive, HCO3(-)-dependent mechanism(s). Considering the large amount of intraruminal weak acids in vivo, both mechanisms are of major importance for maintaining the pHi homeostasis of ruminal epithelial cells.


The scales of human mobility.
There is a contradiction at the heart of our current understanding of individual and collective mobility patterns. On the one hand, a highly influential body of literature on human mobility driven by analyses of massive empirical datasets finds that human movements show no evidence of characteristic spatial scales. There, human mobility is described as scale free1-3. On the other hand, geographically, the concept of scale-referring to meaningful levels of description from individual buildings to neighbourhoods, cities, regions and countries-is central for the description of various aspects of human behaviour, such as socioeconomic interactions, or political and cultural dynamics4,5. Here we resolve this apparent paradox by showing that day-to-day human mobility does indeed contain meaningful scales, corresponding to spatial 'containers' that restrict mobility behaviour. The scale-free results arise from aggregating displacements across containers. We present a simple model-which given a person's trajectory-infers their neighbourhood, city and so on, as well as the sizes of these geographical containers. We find that the containers-characterizing the trajectories of more than 700,000 individuals-do indeed have typical sizes. We show that our model is also able to generate highly realistic trajectories and provides a way to understand the differences in mobility behaviour across countries, gender groups and urban-rural areas.


Cardiac autonomic function in type 1 and type 2 myotonic dystrophy.
The aim of this study was to evaluate cardiac autonomic nervous system function using Holter-derived and standard electrocardiographic parameters in patients with myotonic dystrophy (dystrophia myotonica, DM) and no clinically overt heart involvement. Eighty-four DM patients without conditions potentially influencing cardiac autonomic function were enrolled in the study: 44 with DM type 1 and 40 with DM type 2 (mean age 34.9 ± 11.5 and 47.8 ± 13.5 years, respectively). Two corresponding control groups of aged-matched healthy subjects were selected for DM1 (n = 35) and for DM2 (n = 30). Standard electrocardiography for QT interval dispersion and 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence were performed. No significant differences in time-domain heart rate variability parameters between DM1 or DM2 subjects and controls were observed. However, heart rate turbulence parameters were significantly impaired in DM1 patients as compared to their controls: turbulence onset (p = 0.025), and turbulence slope (p = 0.018). Moreover, turbulence slope was also impaired in DM2 patients (p = 0.042). As compared to controls, we observed an increased QT dispersion, both in DM1 (p = 0.003) and also in DM2 patients (p < 0.0001). No relationship between disease duration or neurological status and time-domain heart rate variability, heart rate turbulence, and QT dispersion was observed. Despite normal time-domain heart rate parameters, impaired heart rate turbulence and increased QT dispersion may suggest cardiac autonomic nervous system dysfunction in DM patients. The present study is the first one in which heart rate turbulence and QT dispersion assessment were examined both in DM1 and DM2 patients.


Antibody-functionalized magnetic polymersomes: in vivo targeting and imaging of bone metastases using high resolution MRI.
Multifunctional polymersomes loaded with maghemite nanoparticles and grafted with an antibody, directed against human endothelial receptor 2, are developed as novel MRI contrast agents for bone metastasis imaging. Upon administration in mice bearing bone tumor grown from human breast cancer cells, MR images show targeting and enhanced retention of antibody-labeled polymersomes at the tumor site.


Clonal karyotypic abnormalities associated with reactive lymphoid hyperplasia.
Cytogenetic abnormalities are important in the diagnosis and prognosis of hematolymphoid neoplasms. Although many recurrent karyotypic abnormalities are well-defined and known to underlie pathophysiologic processes contributing to malignancy, the significance of other cytogenetic changes is less clear. This uncertainty reflects an incomplete understanding of the frequency with which karyotypic abnormalities arise in benign processes. Numerous case reports and a small number of retrospective series have noted clonal cytogenetic changes in association with reactive-appearing lymph nodes. However, the incidence of such abnormalities has varied widely in published series. Here, we report the largest retrospective series of karyotypic abnormalities in association with reactive lymphoid hyperplasia published to date. Clonal karyotypic abnormalities were present in 6.3% of reactive lymph nodes with informative karyotypes and 5.1% of all reactive lymphoid tissues. These data suggest that karyotypic abnormalities are less frequently found in association with reactive lymphoid tissue than previously reported and provide a clearer picture of the baseline incidence of cytogenetic changes in benign lymphoid processes.


Validity evidence based on internal structure of scores on the Spanish version of the Self-Description Questionnaire-II.
The aim of this study was to analyze the reliability and validity evidence of scores on the Spanish version of Self-Description Questionnaire II (SDQ-II). The instrument was administered in a sample of 2022 Spanish students (51.1% boys) from grades 7 to 10. Confirmatory factor analysis (CFA) was used to examine validity evidence based on internal structure drawn from the scores on the SDQ-II. CFA replicated the correlated II first-order factor structure. Furthermore, hierarchical confirmatory factor analysis (HCFA) was used to examine the hierarchical ordering of self-concept, as measured by scores on the Spanish version of the SDQ-II. Although a series of HCFA models were tested to assess academic and non-academic components organization, support for those hierarchical models was weaker than for the correlated 11 first-order factor structure. Results also indicated that scores on the Spanish version of the SDQ-II had internal consistency and test-retest reliability estimates within an acceptable range.


The role of natural gas as a primary fuel in the near future, including comparisons of acquisition, transmission and waste handling costs of as with competitive alternatives.
Natural gas comprises about a quarter of the United States' energy use. It is more environmentally friendly than oil and coal due to lower carbon dioxide (CO2) emissions per unit, less costly per unit of energy and more readily available domestically in abundant supply. However, due to a number of barriers in the political, infrastructural, pricing and other arenas, the use of natural gas as a significant energy source in the United States has been limited. In our paper, we highlight the favorable qualities of natural gas and its benefits for the consumer, producer, and environment, having compared the costs of the various components of the natural gas business such as drilling and transport to that of coal and oil. Moreover, we touch upon the major issues that have prevented a more prevalent use of the gas, such as the fact that the infrastructure of natural gas is more costly since it is transported though pipelines whereas other energy sources such as oil and coal have flexible systems that use trains, trucks and ships. In addition, the powerful lobbies of the coal and oil businesses, along with the inertia in the congress to pass a national climate change bill further dampens incentives for these industries to invest in natural gas, despite its various attractive qualities. We also include discussions of policy proposals to incentive greater use of natural gas in the future.


SolEmuls technology: a way to overcome the drawback of parenteral administration of insoluble drugs.
In this article, a nanosuspension of AmB was prepared and mixed with the preformed parenteral emulsion Lipofundin and subjected to high-pressure homogenization (SolEmuls technology). Characterization was performed by photon correlation spectroscopy (PCS), laser diffractometry (LD), and zeta potential measurements. Drug incorporation was studied by using light microscopy. The produced emulsions were further investigated by comparing them with the commercially available Fungizone in regard to antifungal efficiency and toxicity. Results suggest that through the SolEmuls process the AmB forms a reservoir, out of which it is released in such a manner that it is more efficient and less toxic than Fungizone.


Social Media Consequences of Pediatric Death.
Social media is an important access point for engagement of children and adolescents. For individuals with a life-limiting illness or serving as the caregiver for an ill child, social media can be a helpful outlet for support and information gathering. It has democratized the process of being remembered through providing an ongoing account of thoughts, pictures, and videos that theoretically live on forever via a digital legacy. Providers should be familiar with how this new generation uses social media during their illness, after death, and in the bereavement process.


Research policy and the mobility of US stem cell scientists.
State and national research policies governing human embryonic stem cell science are affecting the career plans of scientists in this exciting but controversial field.


Epidemiology of non-Hodgkin lymphoma.
Non-Hodgkin Lymphoma (NHL) occurs worldwide although there is notable geographical variation in incidence and subtype distribution. These differences are due to a combination of demographic, environmental and other unidentified factors. A dramatic increase in NHL incidence was seen starting around 1970, with subsequent stabilization 10 years ago. Despite this plateau, the number of new cases in many countries will increase significantly in coming years due primarily to aging populations. In the majority of cases, strong risk factors are not identifiable. There is significant epidemiological heterogeneity between NHL subtypes, yet cancer registries have tended to consider NHL as a single entity. This is one of several epidemiological obstacles discussed.


Development of biomimetic antimicrobial platelet-like particles comprised of microgel nanogold composites.
A blood clot is formed in response to bleeding by platelet aggregation and adherence to fibrin fibers. Platelets contract over time, stabilizing the clot, which contributes to wound healing. We have developed platelet-like particles (PLPs) that augment clotting and induce clot retraction by mimicking the fibrin-binding capabilities and morphology of native platelets. Wound repair following hemostasis can be complicated by infection; therefore, we aim to augment wound healing by combining PLPs with antimicrobial gold to develop nanogold composites (NGCs). PLPs were synthesized with N-isopropylacrylamide (NIPAm)/co-acrylic acid in a precipitation polymerization reaction and conjugated to a fibrin-specific antibody. Two methods were employed to create NGCs: 1) noncovalent swelling with aqueous gold nanospheres, and 2) covalent seeding and growth. Since the ability of PLPs to mimic platelet morphology and clot retraction requires a high degree of particle deformability, we investigated how PLPs created from NGCs affected these properties. Cryogenic Scanning Electron Microscopy (cryoSEM) and atomic force microscopy (AFM) demonstrated that particle deformability, platelet-mimetic morphology and clot retraction were maintained in NGC-based PLPs. The effect of NGCs on bacterial adhesion and growth was assessed with antimicrobial assays. These results demonstrate NGCs fabricated through noncovalent and covalent methods retain deformability necessary for clot collapse and exhibit some antimicrobial potential. Therefore, NGCs are promising materials for preventing hemorrhage and infection following trauma.


Soluble vascular cell adhesion molecule (VCAM)-Fc fusion protein induces leukotriene C4 secretion in platelet-activating factor-stimulated eosinophils.
Eosinophil adhesion to vascular cell adhesion molecule-1 (VCAM-1) is important for cellular recruitment into allergic inflammatory sites. To determine whether eosinophil adhesion to VCAM-1 affects cell function, leukotriene C4 (LTC4) was measured. Human eosinophils were incubated with platelet-activating factor (PAF) in the presence or absence of soluble VCAM-Fc fusion protein (sVCAM-Fc) or immobilized VCAM-Fc. sVCAM-Fc induced a concentration-dependent increase in LTC4 secretion, which was dependent on the presence of PAF and not blocked by cyclic peptides shown to inhibit alpha4beta1-dependent adhesion. Likewise, soluble ICAM-Fc induced a concentration-dependent LTC4 secretion. LTC4 secretion was induced by the calcium ionophore, A23187, and the combination of sVCAM-Fc and A23187 had synergistic properties. It is interesting to note that Mn2+ or anti-beta1 monoclonal antibody, TS2/16, inhibited LTC4 secretion induced by sVCAM-Fc and PAF. Eosinophil adhesion to VCAM-Fc or interleukin-1 beta-stimulated endothelial cells did not induce LTC4 secretion. These data suggest that sVCAM-Fc-induced LTC4 secretion depends on distinct signals from those of eosinophil adhesion.


Hyperventilation symptoms are linked to a lower perceived health in asthma patients.
Hyperventilation symptoms are among the sensations asthma patients tend to report during exacerbations of their disease. However, little is known about their importance for the patients' perceived well-being. We therefore studied the association of reported hyperventilation symptoms (Asthma Symptom Checklist) with perceived physical and mental health (36-item Short-form Health Survey) in a sample of primary care asthma patients (N = 190). We also studied the potential role of perceived control of asthma (Perceived Control of Asthma Questionnaire) in mediating any association between these variables. In hierarchical multiple regression analyses controlling for demographics, asthma severity, and other asthma symptoms (obstruction, congestion, panic-fear, irritation, and fatigue), hyperventilation symptoms were significantly associated with both physical and mental health status. This association was partially mediated by perceived control of asthma. It is possible that hypocapnia creates symptoms that asthma patients cannot control by using their antiasthmatic medication, thus compromising their perceived control over the management of their asthma, and consequently their perceived health. Behavioral interventions should address the problem of hyperventilation in asthma.


Landscape of neoadjuvant therapy in HER2-positive breast cancer: a systematic review and network meta-analysis.
The recommended preoperative approach for HER2-positive breast cancer is unclear. We aimed to investigate the following: i) what is the optimal neoadjuvant regimen and ii) whether anthracyclines could be excluded. A systematic literature search in Medline, Embase and Web of Science databases was performed. Studies had to satisfy the following criteria: i) randomised controlled trials (RCTs), ii) enroled patients treated preoperatively for HER2-positive BC (breast cancer), iii) at least one treatment group received an anti-HER2 agent, iv) available information of any efficacy end-point and v) published in English. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. Pathologic complete response (pCR), event-free survival (EFS) and overall survival (OS) were the efficacy end-points of interest, and selected safety end-points were also analysed. A total of 11,049 patients with HER2-positive BC (46 RCTs) were included in the network meta-analysis, and 32 different regimens were evaluated. Dual anti-HER2-therapy, with pertuzumab or tyrosine kinase inhibitors, combined with chemotherapy was significantly superior to trastuzumab and chemotherapy in terms of pCR, EFS and OS. However, a higher risk of cardiotoxicity was observed with dual anti-HER2-therapy. Anthracycline-based chemotherapy was not associated with better efficacy outcomes in comparison with non-anthracycline-based chemotherapy. In anthracycline-free regimens, the addition of carboplatin presented numerically better efficacy outcomes. Dual HER2 blockade with chemotherapy is the recommended choice as neoadjuvant therapy for HER2-positive breast cancer, preferably by omitting anthracyclines in favour of carboplatin.


Three novel B-type mannose-specific lectins of Cynoglossus semilaevis possess varied antibacterial activities against Gram-negative and Gram-positive bacteria.
Lectins are a group of sugar-binding proteins that are important factors of the innate immune system. In this study, we examined, in a comparative manner, the expression and function of three Bulb-type (B-type) mannose-specific lectins (named CsBML1, CsBML2, and CsBML3) from tongue sole. All three lectins possess three repeats of the conserved mannose binding motif QXDXNXVXY. Expression of CsBML1, CsBML2, and CsBML3 was most abundant in liver and upregulated by bacterial infection. Recombinant (r) CsBML1, CsBML2, and CsBML3 bound to a wide arrange of bacteria in a dose-dependent manner and with different affinities. All three lectins displayed mannose-specific and calcium-dependent agglutinating capacities but differed in agglutinating profiles. rCsBML1 and rCsBML2, but not rCsBML3, killed target bacteria in vitro and inhibited bacterial dissemination in fish tissues in vivo. These results indicate for the first time that in teleost, different members of B-type mannose-specific lectins likely play different roles in antibacterial immunity.


Introduction of the Modified Neuroanatomy Motivation Questionnaire and Its Role in Comparing Medical Student Attitudes Towards Learning Neuroanatomy Between Neuro-enthusiasts and Standard Students.
Neurophobia has been identified as a potential barrier to adequate knowledge of neurology in the medical community, and therefore to patient safety. There is a drive to identify the source of neurophobia, in the hope of tackling it. Comparing the learning motivations of standard medical students with those who enjoy neuroanatomy may be a way of doing this. The science motivation questionnaire (SMQ) was modified for neuroanatomy. It was distributed to three cohorts of second year medical students and students attending the extracurricular National Undergraduate Neuroanatomy Competition (NUNC). Cohen's D test for effect size was used to compare standard medical students and those attending the NUNC. Five hundred ninety-seven questionnaires were completed by second year students, and 320 by NUNC attendees. The differences in motivation to learn neuroanatomy between the 2 groups mainly fell into themes of career motivation, personal relevance, intrinsic motivation and assessment anxiety. This study has demonstrated the use of the SMQ in neuroanatomy, and found differences in motivators to learn neuroanatomy between self-selecting "neurophiles" and standard medical students, mainly relating to intrinsic motivation and its role in their lives. More research is needed to further explore these differences and how they might apply to interventions in medical school curricula.


Uterine artery embolization for symptomatic fibroids.
The aim of this study was to introduce uterine artery embolization (UAE) as an effective and safe treatment option in patients with symptomatic fibroids. Sixty-one patients underwent UAE with a 3- and 12-month follow-up. The procedure was well tolerated in all patients with the following symptoms improving: heavy bleeding [90% (95% CI 80.21%; 95.4%)]; dysmenorrhea [median -4 (95% CI -5; -4)]; feeling of a mass [74% (95% CI 57.9%; 85.8%)]; abdomino-pelvic discomfort [88% (95% CI 75.5%; 94.9%)]; and deep dyspareunia [90% (95% CI 71.1%; 97.3%)]. Uterine volume decreased by a median difference of 188 cm(3) (95% CI 146.5; 236), which related to a median % reduction of 37.7% (95% CI 32.4%; 45%) at 12-month follow-up. Most (91%) patients were satisfied with the procedure and only minor complications occurred. Uterine artery embolization can be performed effectively and safely at centers with the necessary expertise and can be used with success in Africa.


[Influence of obesity on urological malignancies].
Overweight presents a growing problem in our society; therefore, there is an increasing interest to understand the influence of obesity on urological forms of cancer. In prostate cancer the development of a more aggressive phenotype seems to correlate with obesity. In renal cell cancer (RCC) obesity is both, a risk factor for occurrence -and is also associated with an improved tumour-specific survival in patients with organ-confined disease following kidney surgery as well as overall survival of patients with advanced disease receiving VEGF(R)-targeted treatment. In contrast, even though an association between body mass index (BMI) and bladder cancer has been described the role of obesity in bladder cancer remains largely unclear as published data are contradictory. An update on currently available data focusing on the relationship between obesity and genitourinary malignancies is given in this review; however, basic research which is necessary to define the biological and metabolic effects associated with obesity and which might affect the development and progression of urological cancers, is indicated.


Static response of infrared neurons of crotaline snakes--normal distribution of interspike intervals.
Background discharges (static responses) of warm fibers in the pit organs (infrared receptive organs) of two species of crotaline snakes were recorded at various temperatures (water, 18-33 degrees C; air, 19-28 degrees C). Mean interspike intervals (means), standard deviations (SD), and coefficients of variation (CV) were calculated, and the goodness of fit of interspike interval histograms to a corresponding normal distribution (i.e., one having the same mean and SD) were tested. Means, SD, and CV were smallest at a certain temperature, which might be the optimum receptor temperature for the species. More than half of the histograms (22/42 for water, 7/10 for air) showed a normal distribution at a significance level of 0.01. This suggests that the spike intervals generated at the spike initiation site are constant, with some random error. Background discharges of three pure infrared secondary neurons from the lateral descending nucleus were analyzed in the same way and compared to the peripheral discharges. There were no histograms with a normal distribution in these central neurons, which might indicate that the constant interspike intervals which appear in the primary afferent fibers are not utilized for information processing at this level but occur only as part of a receptor mechanism which is still unknown. The discharge patterns of primary afferent fibers are also discussed in relation to the known discharge patterns of cold fibers in other animals.


Boundedness of the solutions for certain classes of fractional differential equations with application to adaptive systems.
This paper presents the analysis of three classes of fractional differential equations appearing in the field of fractional adaptive systems, for the case when the fractional order is in the interval α ∈(0,1] and the Caputo definition for fractional derivatives is used. The boundedness of the solutions is proved for all three cases, and the convergence to zero of the mean value of one of the variables is also proved. Applications of the obtained results to fractional adaptive schemes in the context of identification and control problems are presented at the end of the paper, including numerical simulations which support the analytical results.


Dose finding study of erlotinib combined to capecitabine and irinotecan in pretreated advanced colorectal cancer patients.
This study evaluated the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine in pre-treated metastatic colorectal cancer patients. Five dose level combinations with irinotecan (from 180 to 240 mg/m(2), day 1, q21), capecitabine (1,500-2,000 mg/m(2) per day, days 2-15, q21) and erlotinib (50-150 mg per day, continuously) were planned. Patients were enrolled in cohorts of three, and evaluated for first cycle acute toxicity. Twenty-one patients were treated. In the first cohort, no DLT was reported, in the second: one DLT (G4 neutropenic fever associated with G3 cutaneous rash and mucositis); in the third dose level: two DLT (G3 diarrhea and G4 neutropenic fever). To confirm these results, other six patients were additionally included and no DLT was observed. The results documented that erlotinib at the dose of 100 mg per day, irinotecan 180 mg/m(2) and capecitabine 1,500 mg/m(2) per day for 14 days has an acceptable safety profile and appears suitable for further phase II studies.


CoQUAD: a COVID-19 question answering dataset system, facilitating research, benchmarking, and practice.
Due to the growing amount of COVID-19 research literature, medical experts, clinical scientists, and researchers frequently struggle to stay up to date on the most recent findings. There is a pressing need to assist researchers and practitioners in mining and responding to COVID-19-related questions on time. This paper introduces CoQUAD, a question-answering system that can extract answers related to COVID-19 questions in an efficient manner. There are two datasets provided in this work: a reference-standard dataset built using the CORD-19 and LitCOVID initiatives, and a gold-standard dataset prepared by the experts from a public health domain. The CoQUAD has a Retriever component trained on the BM25 algorithm that searches the reference-standard dataset for relevant documents based on a question related to COVID-19. CoQUAD also has a Reader component that consists of a Transformer-based model, namely MPNet, which is used to read the paragraphs and find the answers related to a question from the retrieved documents. In comparison to previous works, the proposed CoQUAD system can answer questions related to early, mid, and post-COVID-19 topics. Extensive experiments on CoQUAD Retriever and Reader modules show that CoQUAD can provide effective and relevant answers to any COVID-19-related questions posed in natural language, with a higher level of accuracy. When compared to state-of-the-art baselines, CoQUAD outperforms the previous models, achieving an exact match ratio score of 77.50% and an F1 score of 77.10%. CoQUAD is a question-answering system that mines COVID-19 literature using natural language processing techniques to help the research community find the most recent findings and answer any related questions.


Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase.
Beta-carotene 15,15'-monooxygenase (BCO), formerly known as beta-carotene 15,15'-dioxygenase, catalyzes the first step in the synthesis of vitamin A from dietary carotenoids. We have biochemically and enzymologically characterized the purified recombinant human BCO enzyme. A highly active BCO enzyme was expressed and purified to homogeneity from baculovirus-infected Spodoptera frugiperda 9 insect cells. The K(m) and V(max) of the enzyme for beta-carotene were 7 microm and 10 nmol retinal/mg x min, respectively, values that corresponded to a turnover number (k(cat)) of 0.66 min(-1) and a catalytic efficiency (k(cat)/K(m)) of approximately 10(5) m(-1) x min(-1). The enzyme existed as a tetramer in solution, and substrate specificity analyses suggested that at least one unsubstituted beta-ionone ring half-site was imperative for efficient cleavage of the carbon 15,15'-double bond in carotenoid substrates. High levels of BCO mRNA were observed along the whole intestinal tract, in the liver, and in the kidney, whereas lower levels were present in the prostate, testis, ovary, and skeletal muscle. The current data suggest that the human BCO enzyme may, in addition to its well established role in the digestive system, also play a role in peripheral vitamin A synthesis from plasma-borne provitamin A carotenoids.


Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes.
The objective of this study was to investigate the mechanisms by which tamoxifen modifies cholesterol metabolism in cellular models of liver metabolism, HepG2 cells and rat hepatocytes. The effect of tamoxifen on cholesterol and triglyceride-palmitate synthesis was measured using isotopomer spectral analysis (ISA) and gas chromatography-mass spectrometry (GC-MS) and compared with the effects of progesterone, estradiol, the antiestrogen ICI 182,780, and an oxysterol, 25-hydroxycholesterol (25OHC). Cholesterol synthesis in cells incubated in the presence of either [1-(13)C]acetate, [U-13C]glucose, or [4,5-(13)C]mevalonate for 48 hours was reduced in the presence of 10 micromol/L tamoxifen and 12.4 micromol/L 25OHC in both HepG2 cells and rat hepatocytes. The ISA methodology allowed a clear distinction between effects on synthesis and effects on precursor enrichment, and indicated that these compounds did not affect enrichment of the precursors of squalene. Progesterone was effective in both cell types at 30 micromol/L and only in HepG2 cells at 10 micromol/L. Estradiol and ICI 182,780 at 10 micromol/L did not inhibit cholesterol synthesis. None of the compounds altered the synthesis of triglyceride-palmitate in either cell type. Treatment of cells with tamoxifen produced accumulation of three sterol precursors of cholesterol, zymosterol, desmosterol, and delta8 cholesterol. This pattern of precursors indicates inhibition of delta24,25 reduction in addition to the previously described inhibition of delta8 isomerase. We conclude that tamoxifen is an effective inhibitor of the conversion of lanosterol to cholesterol in cellular models at concentrations comparable to those present in the plasma of tamoxifen-treated individuals. Our findings indicate that this mechanism may contribute to the effect of tamoxifen in reducing plasma cholesterol in humans.


Enriching rare variants using family-specific linkage information.
Genome-wide association studies have been successful in identifying common variants for common complex traits in recent years. However, common variants have generally failed to explain substantial proportions of the trait heritabilities. Rare variants, structural variations, and gene-gene and gene-environment interactions, among others, have been suggested as potential sources of the so-called missing heritability. With the advent of exome-wide and whole-genome next-generation sequencing technologies, finding rare variants in functionally important sites (e.g., protein-coding regions) becomes feasible. We investigate the role of linkage information to select families enriched for rare variants using the simulated Genetic Analysis Workshop 17 data. In each replicate of simulated phenotypes Q1 and Q2 on 697 subjects in 8 extended pedigrees, we select one pedigree with the largest family-specific LOD score. Across all 200 replications, we compare the probability that rare causal alleles will be carried in the selected pedigree versus a randomly chosen pedigree. One example of successful enrichment was exhibited for gene VEGFC. The causal variant had minor allele frequency of 0.0717% in the simulated unrelated individuals and explained about 0.1% of the phenotypic variance. However, it explained 7.9% of the phenotypic variance in the eight simulated pedigrees and 23.8% in the family that carried the minor allele. The carrier's family was selected in all 200 replications. Thus our results show that family-specific linkage information is useful for selecting families for sequencing, thus ensuring that rare functional variants are segregating in the sequencing samples.


Update on MR Contrast Agents for Liver Imaging: What to Use and When.
Contrast-enhanced liver MR imaging is an important diagnostic tool for many different liver diseases with the sensitivity and specificity in diagnosing liver diseases typically far exceeding other imaging modalities. The safety profile of GBCA is excellent with minimal adverse events. Both extracellular and hepatobiliary contrast agents offer unique advantages and potential limitations. ECA is excellent for obtaining high-quality arterial phase imaging and can be particularly useful for the evaluation of hepatocellular carcinoma (HCC) in cirrhotic patients. In contrast, hepatobiliary agent (HBA) can help distinguish FNH from adenomas, detect liver metastases, and provide biliary imaging due to their uptake within normal hepatocytes and biliary excretion.


Relationship between gut microbiota and colorectal cancer: Probiotics as a potential strategy for prevention.
Gut microbiota comprise microorganisms residing in the gastrointestinal tract. Some of these microbiota are implicated in the progression of colorectal cancer (CRC). Here, we highlight studies on the effects of meat intake and fermented foods on characteristics of gut microbiota that can influence colitis-associated factors underlying CRC. Gut microbiota can influence the development and progression of CRC, through influencing factors such as secretion of toxins; enzymes for activating carcinogenesis (including β-glucuronidase, β-glucosidase, azoreductase, nitroreductase, and alcohol dehydrogenase); hydrogen sulfide generation; generation of reactive oxygen species and inflammation; secondary bile salt transformation; and products of protein fermentation. Additionally, some studies that the composition of gut microbiota (probiotics) or prebiotics plays an important role in the production of short chain fatty acids, inactivation enzymes for carcinogenesis, antioxidant activities, and inhibition of pathogen colonization. In this review, we discuss various explanatory mechanisms of the relationship between the multifactorial role of the gut microbiota and the development of CRC. Moreover, this review provides fundamental information on dietary fermented food and the gut microbiota, which is helpful for healthy people and those with CRC alike.


Myopic extended wear with the Hydrocurve II soft contact lens.
One thousand ninety-nine patients were fitted by 42 investigators with a Hydrocurve II-55% contact lens for myopia extended wear. Five hundred thirty-three patients (48%) have successfully worn the lenses for 3 1/2 years. The major reasons for discontinuing extended wear were due to lack of interest or discontinuance of follow-up visits. Ninety-eight percent of all patients achieved a corrected acuity of better or equal to 20/30; 84% achieved an acuity better than or equal to 20/20. There was no permanent change in visual acuity in any patient during the study. Ocular complications forced 6.4% of patients to discontinue the study. It is clear from the results of this study that myopic extended wear is highly successful.


The effect of surgical treatment of superior oblique muscle palsy on ocular torsion.
To compare the effectiveness of superior oblique tuck and inferior oblique weakening procedures on objective and subjective torsion in patients with superior oblique palsy. Patients with unilateral superior oblique palsy evaluated between September 2007 and October 2009 were treated with one of four surgical procedures on the basis of their preoperative findings: superior oblique tuck, anterior transposition of the inferior oblique muscle, inferior oblique recession, or inferior oblique myectomy. Subjective (double Maddox rods) and objective (fundus photography) torsion were measured pre- and postoperatively. A total of 28 patients were evaluated (mean age, 16.4 ± 12.4 years; range, 6-51 years). In 15 (53.6%) the superior oblique palsy was congenital; in 13 (46.4%) it was acquired. The mean decrease in subjective extorsion was 6.2° ± 2.3° after superior oblique tuck, 2.3° ± 2.4° after anterior transposition of the inferior oblique, 1.3° ± 2.7° after inferior oblique recession, and 2.6° ± 4.7° after inferior oblique myectomy. Objective extorsion decreased by 5.8° ± 0.8°, 4.4° ± 1.7°, 3.1° ± 3.2°, and 3.4° ± 4.7°, respectively. Superior oblique tuck appears to correct extorsion more effectively than inferior oblique surgery, but this may be an artifact of performing tucks in patients with greater initial extorsion. The small amount of extorsion correction was similar for all inferior oblique procedures.


Early changes in serum markers of cardiac extra-cellular matrix turnover in patients with uncomplicated hypertension and type II diabetes.
Extracellular matrix (ECM) turnover is a major determinant of diastolic dysfunction and pumping capacity, thus potentially contributing to the progression of congestive heart failure (CHF). Patients with both arterial hypertension and diabetes have a high risk of heart failure. Whether these patients have changes in cardiac ECM has not been studied previously. Our objective was to compare blood markers of collagen turnover among patients with CHF, patients with hypertension and type II diabetes (HD), and healthy individuals. Measurements were performed in 239 CHF patients; 64 HD patients and 92 healthy subjects. We showed by adjusted ANOVA that PIIINP levels were significantly higher in CHF and HD patients than in controls, and higher in CHF patients than in HD patients. MMP1 levels were significantly lower in CHF and HD patients than in controls. Collagen type I markers (PICP and PINP) were not influenced by CHF but were lower in HD patients as compared to controls (p<0.05 for all comparisons). In heart failure, markers of cardiac collagen synthesis are increased and markers of degradation are decreased, potentially contributing to cardiac fibrosis and thus to poor outcome. Changes in collagen turnover may also occur early in the disease process in high-risk patients before heart failure is clinically detectable.


Comparison of sperm separation methods: effect on recovery, motility, motion parameters, and hyperactivation.
To compare the Enhance (Percoll; Conception Technologies, San Diego, CA) and PureSperm (Gen X International, Madison, CT) sperm preparation methods with respect to recovery (percentage of motile sperm), motility (%), path and progressive velocities (microm/s), and hyperactivation (%). Comparison of sperm processing methods. University medical center-based clinical andrology laboratory and infertility program. Twenty-five men who presented for semen analysis. Each of 25 semen specimens were divided and each aliquot was prepared using two different density gradient centrifugation methods. The motile sperm recovery, percent motility, motion parameters, and percent hyperactivation were measured for each semen specimen (n=25) before and after separation with the use of the two methods. There was no difference in the percent motility and motile count between specimens prepared with Enhance (Percoll) and PureSperm and fresh specimens. Statistically significant differences were found (fresh versus test) in the velocities and in hyperactivation (PureSperm only), and no differences were found between the processing methods. PureSperm appears to be as effective as Percoll (Enhance) for the recovery of good, progressively motile sperm for use in IUI or other assisted reproductive techniques.


Clinical and field trials with attenuated Salmonella typhi as live oral vaccines and as "carrier" vaccines.
In recent years there has been a resurgence of research to develop new and improved attenuated strains of Salmonella typhi to function as live oral vaccines against typhoid fever and to serve as "carrier" vaccines to express foreign antigens of other pathogens and deliver them to the immune system. Strain Ty21a has served as a prototype in clinical and field trials to identify the optimal formulations and dosage schedules for live vaccines and to quantitate the duration of protection that can be achieved. Clinical trials with three new attenuated S. typhi candidate vaccines, a Vi+ variant of Ty21a, an aroC,aroD double mutant recombinant strain and a cya,crp double mutant, are underway or will be initiated shortly.


Differential binding patterns of anti-sulfatide antibodies to glial membranes.
Sulfatide is a major glycosphingolipid in myelin and a target for autoantibodies in autoimmune neuropathies. However neuropathy disease models have not been widely established, in part because currently available monoclonal antibodies to sulfatide may not represent the diversity of anti-sulfatide antibody binding patterns found in neuropathy patients. We sought to address this issue by generating and characterising a panel of new anti-sulfatide monoclonal antibodies. These antibodies have sulfatide reactivity distinct from existing antibodies in assays and in binding to peripheral nerve tissues and can be used to provide insights into the pathophysiological roles of anti-sulfatide antibodies in demyelinating neuropathies.


Continuous 14 Day Infusional Ifosfamide for Management of Soft-Tissue and Bone Sarcoma: A Single Centre Retrospective Cohort Analysis.
Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m2/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m2/14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated-46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1-24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.


Association between community-level political affiliation and peripartum vaccination.
Political affiliation has been associated with vaccine uptake, but whether this association holds in pregnancy, when individuals are recommended to receive multiple vaccinations, remains to be studied. This study aimed to examine the association between community-level political affiliation and vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19 in pregnant and postpartum individuals. A survey was conducted about tetanus, diphtheria, and pertussis and influenza vaccinations in early 2021, with a follow-up survey of COVID-19 vaccination among the same individuals at a tertiary care academic medical center in the Midwest. Geocoded residential addresses were linked at the census tract to the Environmental Systems Research Institute 2021 Market Potential Index, which ranks a community in comparison to the US national average. The exposure for this analysis was community-level political affiliation, defined by the Market Potential Index as very conservative, somewhat conservative, centrist, somewhat liberal, and very liberal (reference). The outcomes were self-reported vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19 in the peripartum period. Modified Poisson regression was used and adjusted for age, employment, trimester at assessment, and medical comorbidities. Of 438 assessed individuals, 37% lived in a community characterized by very liberal political affiliation, 11% as somewhat liberal, 18% as centrist, 12% as somewhat conservative, and 21% as very conservative. Overall, 72% and 58% of individuals reported receiving tetanus, diphtheria, and pertussis and influenza vaccinations, respectively. Of the 279 individuals who responded to the follow-up survey, 53% reported receiving COVID-19 vaccination. Individuals living in a community characterized by very conservative political affiliation were less likely to report vaccinations for tetanus, diphtheria, and pertussis (64% vs 72%; adjusted risk ratio, 0.83; 95% confidence interval, 0.69-0.99); influenza (49% vs 58%; adjusted risk ratio, 0.79; 95% confidence interval, 0.62-1.00); and COVID-19 (35% vs 53%; adjusted risk ratio, 0.65; 95% confidence interval, 0.44-0.96) than those in a community characterized by very liberal political affiliation. Individuals living in a community characterized by centrist political affiliation were less likely to report vaccinations for tetanus, diphtheria, and pertussis (63% vs 72%; adjusted risk ratio, 0.82; 95% confidence interval, 0.68-0.99) and influenza (44% vs 58%; adjusted risk ratio, 0.70; 95% confidence interval, 0.54-0.92) than those in a community characterized by very liberal political affiliation. Compared with pregnant and postpartum individuals living in communities characterized by very liberal political beliefs, those living in communities characterized by very conservative political beliefs were less likely to report vaccinations for tetanus, diphtheria, and pertussis; influenza; and COVID-19, and those in communities characterized by centrist political beliefs were less likely to report vaccinations for tetanus, diphtheria, and pertussis and influenza. Increasing vaccine uptake in the peripartum period may need to consider engaging an individual's broader sociopolitical milieu.


No deleterious effect of an additional pregnancy on glucose metabolism in women with previous gestational diabetes mellitus.
Women with gestational diabetes mellitus (GDM) often develop type 2 diabetes later in life. It remains unclear whether this results solely from a common underlying predisposition or, whether a pregnancy itself persistently impairs glucose metabolism in predisposed women. We therefore examined how an additional pregnancy affected different aspects of glucose metabolism in women with previous GDM. Nested case-control study within the prospective cohort study PPSDiab, recruited in Munich, Germany from 2011-16. Cases (n = 41): women with previous GDM who completed an additional pregnancy; controls: no additional pregnancy, pairwise matching. change of the area under the glucose curve (AUGC) of an oral glucose tolerance, of plasma glucose at 60' of the test (PG 60'), of the insulin sensitivity index (ISI) and of the disposition index (DI), all between before and after the additional pregnancy in cases/the corresponding observation period in controls. We observed no significant difference between cases and controls in the primary [ratio AUGC 1.05(0.92-1.15) vs. 0.97(0.85-1.14); p = 0.21] and in the secondary endpoints [difference PG 60', ratio ISI and ratio DI. We did not find a deleterious effect of an additional pregnancy on glucose metabolism in women with previous GDM.


Reduced immunoglobulin concentration and impaired macrophage function in mice due to diphenylhydantoin.
Diphenylhydantoin (DPH) depresses serum IgA and IgM concentrations and polyvinyl pyrrolidone (PVP) clearance in mice.


Enhancement of macromolecular ligand binding by rabbit alveolar macrophages by mannose oligosaccharides and related compounds.
When rabbit alveolar macrophages were incubated with 10 mM D-mannose, binding of macromolecular ligands containing D-mannose, such as bovine serum albumin modified with mannose (Man-BSA), was enhanced more than 100%, but was inhibited at higher concentrations [C.A. Hoppe and Y. C. Lee (1982) J. Biol. Chem. 257, 12831-12834]. This phenomenon was further investigated with ovalbumin-derived glycopeptide, Asn(GlcNA2,Man5), and with a wide variety of synthetic mannose oligosaccharides. The extent of enhancement is related to the fine structure of the oligosaccharide groups, but the results are complicated by concurrent inhibition exerted by these compounds. It appears that the more inhibitory a compound is, the less capable it is of exerting the enhancement effect. Thus, small mannose derivatives such as glycosides, including clustered mannosides based on tris(hydroxymethyl)aminomethane [Y. C. Lee (1978) Carbohydr. Res. 67, 509-514], and most of the biantennary mannose oligosaccharides were found to be effective in enhancing the binding of radiolabeled Man-BSA. Triantennary oligosaccharides, on the other hand, showed only a slight enhancement effect and a much stronger inhibitory effect. The effects of ligand size, valency, as well as the fine structure on enhancement are discussed.


Glycoproteins of axonal transport: polypeptides interacting with the lectin from Aleuria aurantia.
The interaction between a new fucose-specific lectin from Aleuria aurantia and brain glycoproteins is described. It was found that several different glycoproteins could bind to a column of immobilized Aleuria lectin and that the bound material could be eluted with low concentrations of L-fucose. The polypeptide pattern of the bound glycoproteins differed markedly from that of unbound glycoproteins. A major portion of rapidly transported fucose-labelled glycoproteins from retinal ganglion cells bound to the Aleuria lectin. This chromatographic procedure led to a considerable purification of the rapidly transported glycoproteins. The major labelled, rapidly transported polypeptide which bound to the Aleuria lectin had an apparent mol. wt. of 114,000.


Interaction of cis-diamminedichloroplatinum and renal irradiation on renal function in the young and adult rat.
The interaction between single low doses of cis-diamminedichloroplatinum(II) (c-DDP) and renal irradiation (7.5, 10, 12.5 Gy) on renal function and systolic blood pressure (SBP) was investigated in young (3-4 weeks old, BW 45-65 g) and adult rats (over 12 weeks old, BW 230-290 g). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), plasma creatinine, urea and SBP were measured over 24 weeks. Changes in ERPF, plasma creatinine and urea concentrations paralleled GFR changes, but tended to be less pronounced. In young rats, BW and GFR were 10-20% below control values after c-DDP administration (5 mg/kg BW). Irradiation caused a dose-dependent drop in GFR, starting 4 weeks after irradiation in young rats. When c-DDP was given immediately after irradiation to the young rats, the loss of renal function was more pronounced than after either treatment modality alone. Dose-effect curves for a greater than 25% reduction of the GFR relative to controls (ml/min) after 24 weeks gave an ED50 of 9.8 Gy for irradiation alone and 4.6 Gy for irradiation followed by c-DDP. After correction for the drug effect, dose-effect curves were similar for renal irradiation given alone or followed by c-DDP administration in young rats. In adult rats, c-DDP (2.5 mg/kg BW) or irradiation alone did not significantly alter renal function during the follow-up period. Only 12.5 Gy in combination with c-DDP, caused a significant reduction in GFR after 16 weeks in adult rats. In adult rats data were too limited for probit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgical cardiac patient characteristics and the amount of analgesics administered in the intensive care unit after extubation.
The study investigated relationships between patient characteristics (desire for control, perceived control, perceived social support, state anxiety, gender, weight and age) and the amount of analgesics administered in the intensive care unit after extubation. Subjects included surgical cardiac patients (n = 56) who were predominantly male (75%), Caucasian (89%) and had a mean age of 59 years. The findings showed significant positive relationships between the amount of analgesics administered and state anxiety and weight. Significant negative relationships were found between the amount of analgesics administered and desire for control, perceived control and age. Desire for control, age and state anxiety predicted the amount of analgesics administered. The findings provided insight into analgesic requirement and nursing actions.


Proposals for quality control methods of bacterial vaccines for immunostimulation. II. In vivo and in vitro stimulation of lymphocytes by BCG.
An in vitro test for measuring the reaction of the draining lymph node after BCG vaccination and an in vitro test based on the stimulation of lymphocytes by concanavalin A were used to demonstrate immunostimulating properties of different BCG vaccines. A marked difference was seen between vaccines grown as a surface pellicle and ground in a ball mill, and those which were prepared from dispersed homogeneous cultures. In both systems the ball mill preparations were the less active.


Host-guest inclusion system of mangiferin with β-cyclodextrin and its derivatives.
The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of mangiferin (MGF) with β-cyclodextrin and its derivatives (hydroxypropyl-β-cyclodextrin (HPβCD), sulfobutyl ether β-cyclodextrin (SBEβCD) and mono (6-ethylene-diamino-6-deoxy)-β-cyclodextrin (ENβCD)) were investigated in both solution and solid state by means of PL spectroscopy, (1)H and 2D NMR, XRD, TG and DSC. The results showed that the water solubility and thermal stability of MGF were significantly increased in the inclusion complex with cyclodextrins. The MGF/CDs complexes will be potentially useful for the design of a novel formulation of mangiferin for herbal medicine.


Humanoid robot intervention vs. treatment as usual for loneliness in long-term care homes: Study protocol for a pilot randomized controlled trial.
Loneliness affects up to 42% of long-term care residents and is associated with poor health outcomes. Humanoid robot interventions hold promise for reducing loneliness and decreasing barriers to social interaction in long-term care settings, such as the current COVID-19 safety measures in many countries, limited mobility, and poor health. We present a protocol describing an assessor-blinded randomized controlled trial comparing the effects of a humanoid robot intervention to treatment as usual, on loneliness and mental health outcomes in long-term care residents. Seventy-four (n = 74) older adults experiencing loneliness in 3 long-term care homes will be randomized 1:1 to an 8-week, twice a week social intervention with the Grace humanoid robot vs. a treatment as usual active control. We will assess change (baseline to week 8) in (1) loneliness (primary outcome), (2) depression severity, and (3) stress (secondary outcomes), as well as (4) other exploratory outcomes: anxiety, quality of life and reduction in acute healthcare utilization. We will also assess the feasibility and acceptability of the intervention using qualitative methods. The proposed study will assess the effects of a social robot on loneliness and other mental health outcomes, as well as the feasibility of the intervention in older adults living in long-term care settings. NCT05423899.


Nitric oxide-mediated modification of the glycine binding site of the NMDA receptor during hypoxia in the cerebral cortex of the newborn piglet.
This study tested the hypothesis that cerebral hypoxia results in nitric oxide (NO)-mediated modification of the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. Glycine binding characteristics were determined in normoxic, hypoxic, and hypoxic with 7-nitroindazole (7-NINA)-pretreated newborn piglets. The role of nitration was evaluated by determining binding characteristics in non-nitrated and in-vitro nitrated membranes. Bmax and Kd values were 30% higher in the hypoxic group than the normoxic and 7-NINA pretreated hypoxic groups. Kd values in the in-vitro normoxic nitrated membranes were similar to the non-nitrated hypoxic group. Bmax values in the in-vitro) normoxic nitrated membrane samples were 16% lower than in the non-nitrated hypoxic group. We conclude cerebral hypoxia causes modification of the glycine-binding site of the NMDA receptor and this modification of the glycine-binding site may be NO mediated. We propose that NO-mediated modification of the glycine-binding site of the NMDA receptor regulates calcium influx through its ion-channel.


Role of hydration in the conformational transitions between unliganded and liganded forms of loop 13 of the Na+/glucose cotransporter 1.
SGLT1 as a Na+/glucose cotransporter is inhibited by phlorizin, a phloretin 2'-glucoside that has strong interactions with the C-terminal loop 13 (residues 541-638). Here we investigated the effect of a partial substitution of glycerol for water in the medium on the stability and phlorizin-binding function of loop 13 using fluorescence spectroscopy. Increasing the glycerol concentration promoted an increase in the stability of the protein to urea. The ability of loop 13 to expose hydrophobic surface promoted by phlorizin binding was partially lost in the presence of glycerol (20%). Glycerol also led to a decrease in the phlorizin affinity of loop 13 in solution. Approximately 15 molecules of water were taken up to cover additional surface area (137.7+/-27.9A(2)) upon formation of the loop 13-phlorizin complex. Together these results demonstrate quantitatively that the stability and phlorizin affinity of loop 13 are critically dependent on protein hydration.


Evaluation of Safety of Overhead Upper Extremity Positioning During Fenestrated-Branched Endovascular Repair of Thoracoabdominal Aortic Aneurysms.
Peripheral nerve and brachial plexus injury can occur from compression or stretching during positioning for operative procedures. The aim of this study was to evaluate the safety of overhead upper extremity positioning to optimize imaging during fenestrated-branched endovascular aortic repair (FB-EVAR) of pararenal (PRA) and thoracoabdominal aortic aneurysms (TAAAs). Forty-four consecutive patients enrolled in a prospective non-randomized study underwent FB-EVAR with overhead upper extremity positioning. Patients underwent intra-operative neuromonitoring of upper and lower extremities and neurological examination prior to discharge and at 2 months following the procedure. End points were peripheral or brachial plexus nerve injury, quality of lateral projection and cone beam computed tomography (CBCT) and major adverse event (MAEs). There were 28 (64%) male patients with mean age of 74 ± 8 years treated for 10 PRAs (23%) and 34 (78%) TAAAs. Mean body mass index was 29 ± 7 kg/m2, with 17 obese patients (39%). Open surgical upper extremity access was used in 19 patients (43%). Three patients (16%) had access-related complications, all focal brachial artery dissections treated by patch angioplasty. Two patients (5%) developed upper extremity changes in neuromonitoring, which immediately resolved with repositioning of the upper extremity. Technical success was 95%. Lateral projection and rotational CBCT were feasible in all patients with satisfactory imaging quality for catheterization and stenting of the celiac axis and superior mesenteric artery. There was one mortality (2%) at 30 days, and six patients (14%) had MAEs. There were no upper extremity neurological injuries. Overhead upper extremity position allows optimal imaging on lateral projections and rotational CBCT during FB-EVAR. There were no upper extremity neurological injuries in this study.


The influence of aging on the association between adiposity and bone mineral density in Jordanian postmenopausal women.
The objective of this study was to assess the relative association between body weight, body mass index (BMI), lean mass (LM) and fat mass (FM), and bone mineral density (BMD) in a group of Jordanian postmenopausal women and investigate if this possible association changes with age. A total of 3256 patients had dual-energy X-ray absorptiometry (DXA) scan in the period from January 2009 till January 2012 at the Radiology and Nuclear Medicine Department of Jordan University Hospital. Only 584 women met the selection criteria. Age has been recorded, and patients were divided into subgroups according to age. Body weight and height were measured, and BMI was calculated. Body composition (LM, FM, percentage of android fat, and percentage of gynoid fat) was assessed by DXA. BMD of the lumbar spine (L1-L4) and femoral neck was measured by DXA. Weight, BMI, FM, LM, percentage of android fat, and percentage of gynoid fat were positively correlated to BMD at both lumbar spine and femoral neck. However, this correlation disappeared at the age of 70 yr at lumbar spine and 75 yr at femoral neck. This study suggests that both FM and LM are important determinants of BMD in Jordanian postmenopausal women, and this correlation disappears after the age of 70 yr at lumbar spine and 75 yr at femoral neck.


Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: Results from the phase 2b TANDEM study.
With distinct mechanisms of action, the combination of tropifexor (TXR) and cenicriviroc (CVC) may provide an effective treatment for NASH. This randomized, multicenter, double-blind, phase 2b study assessed the safety and efficacy of TXR and CVC combination, compared with respective monotherapies. Patients (N = 193) were randomized 1:1:1:1 to once-daily TXR 140 μg (TXR 140 ), CVC 150 mg (CVC), TXR 140 μg + CVC 150 mg (TXR 140 + CVC), or TXR 90 μg + CVC 150 mg (TXR 90 + CVC) for 48 weeks. The primary and secondary end points were safety and histological improvement, respectively. Rates of adverse events (AEs) were similar across treatment groups. Pruritus was the most frequently experienced AE, with highest incidence in the TXR 140 group (40.0%). In TXR and combination groups, alanine aminotransferase (ALT) decreased from baseline to 48 weeks (geometric mean change: -21%, TXR 140 ; -16%, TXR 140 + CVC; -13%, TXR 90 + CVC; and +17%, CVC). Reductions in body weight observed at week 24 (mean changes from baseline: TXR 140 , -2.5 kg; TXR 140 + CVC, -1.7 kg; TXR 90 + CVC, -1.0 kg; and CVC, -0.1 kg) were sustained to week 48. At least 1-point improvement in fibrosis stage/steatohepatitis resolution without worsening of fibrosis was observed in 32.3%/25.8%, 31.6%/15.8%, 29.7%/13.5%, and 32.5%/22.5% of patients in the TXR 140 , CVC, TXR 140 + CVC, and TXR 90 + CVC groups, respectively. The safety profile of TXR + CVC combination was similar to respective monotherapies, with no new signals. TXR monotherapy showed sustained ALT and body weight decreases. No substantial incremental efficacy was observed with TXR + CVC combination on ALT, body weight, or in histological end points compared with monotherapy.


Histogenesis of Dupuytren's disease: an immunohistochemical study of 30 cases.
Thirty-seven specimens from the hands of 30 patients with Dupuytren's disease were examined by light microscopy after immunohistochemical staining for the presence of desmin intermediate filaments. Results indicated that desmin-positive cells were present in the proliferative Dupuytren's nodules, and that the number of desmin-positive cells decreased significantly in the fibrous phase of the disease. Also, on the basis of the pattern of distribution of the desmin-positive cells around vessels, we postulate that the desmin-positive cells in Dupuytren's nodules were migrating perivascular smooth muscle cells from the vessel wall. The exact fate of these cells is uncertain, but we hypothesize that these displaced perivascular smooth muscle cells are capable of transforming into collagen-producing, desmin-negative myofibroblasts that form the cellular basis of Dupuytren's lesions.


Lack of immune response to mouse IgG in hemophilia A patients treated chronically with Monoclate, a monoclonal antibody affinity purified factor VIII preparation.
Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (less than 50 ng/100 I. U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgM and IgE anti-mouse IgG antibody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate infusion. Data is presented demonstrating that induction of HAMA upon Monoclate treatment does not occur. The low level of mouse IgG contained in Monoclate appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate in these clinical studies.


A new class of ring avulsion injuries.
Sixteen patients with ring avulsion injuries treated at Loma Linda University over 10 years were reviewed. According to Urbaniak's classification scheme, there were two class I, seven class II, and seven class III injuries. Follow-up functional measurements showed that the grip strength of our class II patients were, on the average, no better than that of the class III patients, even though all of class III patients had amputation revisions. Five class II patients required only venous microvascular repair. We propose to modify Urbaniak's classification to IIC to include only ring avulsion injuries with venous compromise. These patients had excellent functional results, with an average total active motion of 224 degrees.


Identification of Benign and Malignant Lung Nodules in CT Images Based on Ensemble Learning Method.
Under the background of urgent need for computer-aided technology to provide physicians with objective decision support, aiming at reducing the false positive rate of nodule CT detection in pulmonary nodules detection and improving the accuracy of lung nodule recognition, this paper puts forward a method based on ensemble learning to distinguish between malignant and benign pulmonary nodules. Firstly, trained on a public data set, a multi-layer feature fusion YOLOv3 network is used to detect lung nodules. Secondly, a CNN was trained to differentiate benign from malignant pulmonary nodules. Then, based on the idea of ensemble learning, the confidence probability of the above two models and the label of the training set are taken as data features to build a Logistic regression model. Finally, two test sets (public data set and private data set) were tested, and the confidence probability output by the two models was fused into the established logistic regression model to determine benign and malignant pulmonary nodules. The YOLOv3 network was trained to detect chest CT images of the test set. The number of pulmonary nodules detected in the public and private test sets was 356 and 314, respectively. The accuracy, sensitivity and specificity of the two test sets were 80.97%, 81.63%, 78.75% and 79.69%, 86.59%, 72.16%, respectively. With CNN training pulmonary nodules benign and malignant discriminant model analysis of two kinds of test set, the result of accuracy, sensitivity and specificity were 90.12%, 90.66%, 89.47% and 88.57%, 85.62%, 90.87%, respectively. Fused model based on YOLOv3 network and CNN is tested on two test sets, and the result of accuracy, sensitivity and specificity were 93.82%, 94.85%, 92.59% and 92.31%, 92.68%, 91.89%, respectively. The ensemble learning model is more effective than YOLOv3 network and CNN in removing false positives, and the accuracy of the ensemble. Learning model is higher than the other two networks in identifying pulmonary nodules.


In vivo release of angiotensin II from the rat hypothalamus.
Recent studies suggest that angiotensin II is released from neuronal tissue in vitro, but the occurrence of this phenomenon in the intact brain has not yet been demonstrated. To characterize the in vivo release of immunoreactive angiotensin II, push-pull cannulas were positioned in the anterior hypothalamus in 47 Sprague-Dawley rats (200-250 g) anesthetized with Inactin (100 mg/kg i.p.). Artificial cerebrospinal fluid was perfused at 20 microliters/min, and effluent samples were collected for 15-minute periods over 2 hours. Angiotensin II was detectable (greater than 2.5 pg/ml) in the push-pull cannula perfusate of the majority (76%) of the rats. Spontaneous release of immunoreactive angiotensin II was constant for 2 hours in 11 rats at values averaging from 4.4 +/- 1.5 to 8.2 +/- 2.2 pg/ml. In addition, bilateral nephrectomy performed 48 hours before did not affect the detection of angiotensin II (n = 3). Angiotensin immunoreactivity in the rat hypothalamus was further characterized by high performance liquid chromatography. The analysis showed that the perfusate contained authentic angiotensin II as well as other angiotensin metabolites. The effect of beta-adrenergic modulation on the release of angiotensin II was assessed in 20 rats by adding isoproterenol (10(-10), 10(-8), and 10(-6) M), propranolol (10(-6) M), or a combination of both. Neither activation nor inhibition of hypothalamic beta-receptors altered the spontaneous release of angiotensin II. These data demonstrate that angiotensin II and congener peptides are detectable in the microenvironment of the anterior hypothalamus of the anesthetized rat and that the release of angiotensin II immunoreactivity in the anterior hypothalamus is not modified by beta-adrenergic receptors.


Teaching substance abuse screening, assessment, and brief intervention to vocational rehabilitation counselors.
Vocational rehabilitation counselors are in key positions to screen clients for alcohol and drug abuse. An educational program improved counselors understanding of this process.


Facial Nerve Schwannoma Complicated by Acute Hemorrhage After Treatment with Stereotactic Radiosurgery.
Facial nerve schwannomas (FNSs) are rare benign tumors that arise from Schwann cells of the facial nerve. FNSs are similar to vestibular schwannomas in many aspects, yet their infiltrative nature into the facial nerve fascicles warrants a more conservative management approach. In the last decade, stereotactic radiosurgery (SRS) has shown promise in stabilizing or shrinking FNSs. A 71-year-old woman presented with mild facial paresis. Tumor growth after a period of watchful waiting warranted treatment with SRS, which was complicated by an acute posterior fossa hemorrhage and brainstem compression, necessitating microsurgical hematoma evacuation, tumor resection, and facial nerve substitution. SRS has led to better facial nerve function and outcomes and is currently considered a reasonable alternative to microsurgical resection in patients with FNSs. This is the first report to our knowledge of an acute, life-threatening hemorrhage after SRS in a patient with FNS.


Inferring global surface HCHO concentrations from multisource hyperspectral satellites and their application to HCHO-related global cancer burden estimation.
Formaldehyde (HCHO) is a toxic and hazardous air pollutant that widely exists in atmosphere. Insufficient spatial and temporal coverage of surface HCHO measurements is limiting studies on surface HCHO-related air quality management and health risk assessment. This study develops a method to derive global ground-level HCHO concentrations from satellite-based tropospheric HCHO columns using TM5-simulated surface-to-column conversion factor with coarse spatial resolution. The method improves the factor more representative in finer grids by constraining TM5-simulated vertical profile shapes with satellite HCHO columns. The surface HCHO concentrations derived by the Ozone Mapping and Profiler Suite (OMPS) show good correlation with in situ HCHO measurements (R = 0.59) from the U.S. Environmental Protection Agency surface network. We investigated how surface HCHO relates to urbanization and population aggregation over seven regions with high HCHO pollution. The results show urban HCHO increases as a power function with population size in China, India, and West Asia. HCHO concentrations in rural aeras also present strong log-log relationship with population aggregation in China, India, the United States, and Europe. Moreover, OMPS-derived ground-level HCHO concentrations were used to estimate global cancer burden caused by long-term outdoor HCHO exposure. The results show that up to 418188 more people worldwide will develop this cancer during the human life cycle. The global cancer burden is mainly from the South-East Asia region (33.11 %) and the Western Pacific region (22.95 %). This cancer occurrence in India and China is ranked 1st and 2nd in the world due to the large population size and serious HCHO pollution. Besides, global surface HCHO concentrations and cancer burden derived from the Environmental Trace Gases Monitoring Instrument which is China's first hyperspectral space-based spectrometer are found similar patterns with that from OMPS. Our results provide new insight into the impact of population urbanization on HCHO pollution and global outdoor HCHO-caused health risks.


Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer.
We report the second interim analysis of data from a randomized prospective trial comparing the prophylactic effect of 15 courses of 50 mg. doxorubicin, 50 mg. thiotepa or 150 mg. bacillus Calmette-Guerin instilled intravesically against recurrences and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients 176 currently are evaluable with a mean follow-up of 3 years (range 3 to 97 months). The number of patients with recurrences was significantly lower in the bacillus Calmette-Guerin arm (9 of 67) compared to the doxorubicin (23 of 53, p equals 0.002) and thiotepa (20 of 56, p equals 0.003) arms. The over-all recurrence index per 100 patient-months also was lower for the bacillus Calmette-Guerin versus the thiotepa and doxorubicin groups (0.53 versus 1.55 and 1.7, respectively). Bacillus Calmette-Guerin also was superior in preventing recurrences and progression of high risk tumors, that is stage T1, grade 3 or multiple growths, associated or not with carcinoma in situ. In the stage T1 category 19 of 32 (60%) tumors recurred under treatment with doxorubicin, 11 of 33 (33%) with thiotepa and 6 of 49 (12%) with bacillus Calmette-Guerin. Toxicity to intravesical bacillus Calmette-Guerin was higher compared to the other drugs but it was not limiting: bladder irritability and malaise occurred in 42% of the patients, granulomatous cystitis in 16.4% and bladder contraction in 1.4% (1 of 64). The latter complication occurred in a patient whose stage T1m grade 2 tumors had recurred 3 times, who underwent 3 transurethral bladder resections within 15 months and who had received thiotepa for 4 months after having been removed from the study 11 months after entry. Three patients in the doxorubicin group (5.6%) underwent radical cystectomy for local urothelial progression. One patient (1.8%) in the same group died of distant progression. Our preliminary results suggest that at the dose, periodicity and duration used in the study bacillus Calmette-Guerin is significantly superior to the chemotherapeutic agents doxorubicin and thiotepa for the prophylaxis of recurrence and retardation of progression in superficial transitional cell bladder tumors.


[Pathophysiology, diagnosis and treatment of Zenker's diverticulum].
Zenker's diverticulum occurs at the dorsal pharyngoesophageal junction through Killian's dehiscence and is caused by increased intrabolus pressure. Symptomatic disease most frequently affects male elderly patients. Primary symptom is oropharyngeal dysphagia, as well as regurgitation of undigested food, halitosis, and chronic aspiration. A barium swallow study is performed to confirm diagnosis. Treatment options for symptomatic patients include open surgery, as well as transoral rigid or flexible endoscopic procedures. Transoral procedures have become the main treatment approach over the past year thanks to reduced intraoperative complication rates compared to open surgery. The septum dividing the diverticulum from the esophagus is most commonly divided by a stapler device, papillotome, or laser. For high-risk patients who are poor candidates for general anesthesia, the procedure can be performed via flexible endoscopy in awake patients, albeit at an increased risk of recurrence.


Vibrational spectroscopic analysis of 2, 3:4,5-Bis-O-(1-methylethylidene)beta-D-fructopyranose Sulfamate(Topiramate) by density functional method.
2,3:4,5-Bis-O-(1-methylethylidene)-beta-D- fructopyranose sulfamate otherwise called as Topiramate is a drug used for the treatment of alcohol dependence. Topiramate is a safe and consistently efficacious medication for treating alcohol dependence. The spectroscopic properties of Topiramate are investigated by Fourier Transform Infrared (FT-IR), Fourier Transform Raman (FT-Raman), Fourier Transform Nuclear magnetic Resonsnce(FT-NMR) andUltra Violet Visible (UV-visible) spectroscopic techniques. The FTIR, FT-Raman, FT-NMR and UV-visible spectra of Topiramate have been recorded and analyzed. Theoretical vibrational frequencies, geometric parameters, thermodynamic properties, Natural population analysis and Mulliken atomic charges of Topiramateare obtained by the Restricted Hartree-Fock (RHF) and density functional theory (DFT) using 6-31 + G(d,p) basis set. The calculated harmonic vibrational frequencies for Topiramate are compared with the experimental values of FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analysed using natural bond orbital (NBO) analysis. The first-order hyperpolarizability (βtot) and other related properties such as dipole moment(µ), polarizability(αo)values of the investigated molecule are computed using HF and DFT/B3LYP with 6-31 + G(d,p) basis set. The calculated results also show that the Topiramate molecule may have microscopic nonlinear optical (NLO) behaviour.


Clinical benefits of FOLFOXIRI combined with bevacizumab for advanced-stage primary signet ring cell carcinoma of the appendix: A case report.
Signet-ring cell carcinoma, which is an infrequent type of colorectal cancer. Abdominal pain is the primary presenting complaint of patients with acute appendicitis. It is difficult to diagnose patients with appendiceal carcinomas accompanying with symptoms of acute appendicitis. A 33-year-old female patient was admitted to our hospital, with chief complaints of "bilateral pelvic space-occupying lesions for 1 month, aggravated abdominal distension, and she accompanied with diarrhea for 3 days." The patient was with primary signet ring cell carcinoma of the appendix, presented with acute appendicitis, as well as bilateral ovarian metastasis and peritoneal implantation metastasis. She was then treated with irinotecan, oxaliplatin, calcium folinate, 5-FU combined with bevacizumab, surgical treatment, and postoperative adjuvant treatment with oxaliplatin, capecitabine regimen to consolidate the efficacy. The patient is in good conditions, and postoperative adjuvant chemotherapy is in progress as well. The outcomes highlighted the importance of strict histopathologic assessment for appendiceal adenocarcinoma, and provided new ideas for the diagnosis and treatment of advanced-stage signet ring cell carcinoma of the appendix.


Magnetic resonance imaging temporarily alters blood-brain barrier permeability in the rat.
Exposure to a short (23.2 min) standard clinical magnetic resonance imaging (MRI) procedure elicits a temporary dysfunction of the blood-brain barrier in rats. Monitoring of the increased permeability of rat brain frontal cortex microvessels with the protein tracer horseradish peroxidase and freeze-fracture electron microscopy, revealed an amplified vesicle-mediated transport of tracer across the microvessel endothelium to the albuminal basal lamina and extracellular compartment of the brain parenchyma. Recovery of normal blood-brain function, as evidenced by exclusion of protein tracer from subendothelial basal lamina and neuropil extracellular milieu, was complete 15-30 min following cessation of the MRI exposure. These findings raise the possibility that exposure to clinical MRI procedures may also temporarily alter central blood-brain permeability in human subjects.


Long Term Follow-up of Pulmonary Vein Isolation Using Cryoballoon Ablation.
Cryoballoon ablation is an established catheter-based approach to treating atrial fibrillation (AF). There is little data regarding the long-term efficacy of this approach. We enrolled 200 consecutive patients with symptomatic AF who had failed therapy with at least one anti-arrhythmic medication and followed them for five years. The primary efficacy endpoint was symptomatic recurrence of AF after a single cryoballoon ablation procedure. Two hundred patients formed the study group. Median follow-up was 56 months. Following a single procedure, 46.7% of patients with paroxysmal AF remained free of symptomatic recurrence of AF compared to 35.6% of patients with persistent AF. When allowing for repeat ablations, at the end of the follow-up period 53.3% of patients in the paroxysmal group remained free of symptomatic AF compared to 47.5% in the persistent group. The rate of complications was low. Cryoballoon ablation is an effective catheter-based approach for treating symptomatic AF with a low risk of complications.


Targeting Autophagy with Small-Molecule Modulators in Immune-Related Diseases.
Autophagy, a highly conserved and multistep lysosomal degradation process, plays a pivotal role in maintaining cellular and physiological homeostasis. Of note, autophagy controls intracellular homeostasis and cell responses to stresses by regulating the self-renewal, maturation, and survival of immune cells. And dysregulation of autophagy in immune cells may contribute to the inflammatory disorders and defect in immune responses against invasive pathogens. Accumulating evidence have indicated that dysregulated autophagy participates in the pathology of immune-related diseases. Therefore, targeting autophagy might represent a promising therapeutic strategy for treatment of immune-related diseases. In this chapter, we focus on discussing the link between autophagy and pathogenesis of immune-related diseases, as well as the dysregulation of autophagy-related signaling pathways, in different diseases. Moreover, we highlight the therapeutic potential of currently used small-molecule modulators of autophagy for treatment of immune-related diseases and illustrate the mechanisms of these small-molecule modulators.


Awareness, use, and consequences of evaluation data in a community mental health center.
A major aspect of the effort of the Mental Health Systems Evaluation Project of the Northwest Denver Community Health Center's has involved studying the utilization of program evaluation data by community mental health center managers and clinicians. The intent of this effort was twofold: to assess the impact of program evaluation feedback in the community mental health center per se; and to investigate factors that influenced this impact. The impact of such input was assessed initially at the level of "subjective utility." Later attempts involved more extended or interactive forms of input and impact assessment. Basic findings to date suggest that program evaluation data are most likely to have impact when directed at the managers most closely involved with the service at issue, and when presented, preferably simply and personally, in ways that insure an understanding of the data and its implications by those receiving it.


The effect of prolonged exercise and in vivo treatment with ACTH and norepinephrine on plasma cortisol and on the levels of energy metabolites in liver, muscle and blood of the guinea pig (Cavia porcellus).
1. Exercise and in vivo treatment with adrenocorticotrophic hormone (ACTH) showed a marked tendency to increase in vivo plasma cortisol levels in the guinea pig (Cavia porcellus). 2. However, in vivo norepinephrine (NE) treatment did not have any notable effect on plasma cortisol levels. 3. Metabolite levels (glycogen, glycerol and lactate) in liver and plantaris and soleus muscle, and the levels of glucose, glycerol and lactate in blood, were determined in response to the same treatments. 4. A number of statistically significant changes, as well as certain trends, in metabolite levels were observed in response to the treatments and are discussed.