The effect of chemotherapy in relation to pathohistological tumour grading in head and neck cancer.
Histological serial sections of resection specimens from 37 patients suffering from advanced squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, and supraglottic region of the larynx were examined after pre-operative chemotherapy with methotrexate (M), bleomycin (B), and cisplatin (P) - (MBP). Pathohistological grading criteria for SCC from various sources were used. Results were compared with initial biopsy specimens. Statistical interpretation was carried out with the sign test. Mode of growth, degree of keratinization, mode of invasion and cellular reaction showed a significant change towards more benign behaviour. However, the maturity of the remaining tumour cells showed a considerable tendency towards greater malignancy. Some grading criteria proved to be insufficient for the determination of statistically significant alterations, with the exception of keratinization, which showed a change towards benignity. Results obtained for the different mechanisms of action of drugs used in the MBP-combination and the different regression behaviour of variously differentiated squamous cell carcinomas under chemotherapy are discussed in this study.


[Retropharyngeal abscess revealing diabetes: a case report].
Retropharyngeal abscess, a rare event in adults, is usually observed in immunodeficient persons or subsequent to foreign bodies. We report a case of retropharyngeal abscess which revealed diabetes mellitus. A 47-year-old woman with an uneventful history complained of fever, dysphagia and trismus. Clinical findings were swelling of the pharyngeal posterior wall. The CT scan showed an abscess in the retropharyngeal space. Puncture revealed the purulent nature of the collection. The bacteriological study identified a Gram-negative aerobic germ (Citrobacter freundii). Laboratory tests disclosed diabetes mellitus with ketosis. The treatment consisted in surgical drainage and lavage of the retropharyngeal space using a saline solution with gentamycin associated with infusion of appropriate antibiotics. Abscess formation in the retropharyngeal space is a rare event in adults. The immunological status of the patient should be carefully explored. Management requires drainage of the collection and infusion of active antibiotics.


Electrophysiological study of transport systems in isolated perfused pancreatic ducts: properties of the basolateral membrane.
In order to study the mechanism of pancreatic HCO3- transport, a perfused preparation of isolated intra- and interlobular ducts (i.d. 20-40 microns) of rat pancreas was developed. Responses of the epithelium to changes in the bath ionic concentration and to addition of transport inhibitors was monitored by electrophysiological techniques. In this report some properties of the basolateral membrane of pancreatic duct cells are described. The transepithelial potential difference (PDte) in ducts bathed in HCO3(-)-free and HCO3(-)-containing solution was -0.8 and -2.6 mV, respectively. The equivalent short circuit current (Isc) under similar conditions was 26 and 50 microA . cm-2. The specific transepithelial resistance (Rte) was 88 omega cm2. In control solutions the PD across the basolateral membrane (PDbl) was -63 +/- 1 mV (n = 314). Ouabain (3 mmol/l) depolarized PDbl by 4.8 +/- 1.1 mV (n = 6) within less than 10 s. When the bath K+ concentration was increased from 5 to 20 mmol/l, PDbl depolarized by 15.9 +/- 0.9 mV (n = 50). The same K+ concentration step had no effect on PDbl if the ducts were exposed to Ba2+, a K+ channel blocker. Application of Ba2+ (1 mmol/l) alone depolarized PDbl by 26.4 +/- 1.4 mV (n = 19), while another K+ channel blocker TEA+ (50 mmol/l) depolarized PDbl only by 7.7 +/- 2.0 mV (n = 9). Addition of amiloride (1 mmol/l) to the bath caused 3-4 mV depolarization of PDbl. Furosemide (0.1 mmol/l) and SITS (0.1 mmol/l) had no effect on PDbl. An increase in the bath HCO3- concentration from 0 to 25 mmol/l produced fast and sustained depolarization of PDbl by 8.5 +/- 1.0 mV (n = 149). It was investigated whether the effect of HCO3- was due to a Na+-dependent transport mechanism on the basolateral membrane, where the ion complex transferred into the cell would be positively charged, or whether it was due to decreased K+ conductance caused by lowered intracellular pH. Experiments showed that the HCO3- effect was present even when the bath Na+ concentration was reduced to a nominal value of 0 mmol/l. Similarly, the HCO3- effect remained unchanged after Ba2+ (5 mmol/l) was added to the bath. The results indicate that on the basolateral membrane of duct cells there is a ouabain sensitive (Na+ + K+)-ATPase, a Ba2+ sensitive K+ conductance and an amiloride sensitive Na+/H+ antiport. The HCO3- effect on PDbl is most likely due to rheogenic anion exit across the luminal membrane.


The biology of aging, with particular reference to the musculoskeletal system.
A broad assessment of the current status of knowledge of biologic gerontology is presented. The extent to which the aging phenotype is due to primary aging processes, or to lifestyle, or to disease processes is discussed. Particular emphasis is placed on the aging of the musculoskeletal system. Both bone and skeletal muscle are discussed within the framework of our current knowledge of aging.


The expression of a viral microRNA is regulated by clustering to allow optimal B cell transformation.
The Epstein-Barr virus (EBV) transforms B cells by expressing latent proteins and the BHRF1 microRNA cluster. MiR-BHRF1-3, its most transforming member, belongs to the recently identified group of weakly expressed microRNAs. We show here that miR-BHRF1-3 displays an unusually low propensity to form a stem-loop structure, an effect potentiated by miR-BHRF1-3's proximity to the BHRF1 polyA site. Cloning miR-BHRF1-2 or a cellular microRNA, but not a ribozyme, 5' of miR-BHRF1-3 markedly enhanced its expression. However, a virus carrying mutated miR-BHRF1-2 seed regions expressed miR-BHRF1-3 at normal levels and was fully transforming. Therefore, miR-BHRF1-2's role during transformation is independent of its seed regions, revealing a new microRNA function. Increasing the distance between miR-BHRF1-2 and miR-BHRF1-3 in EBV enhanced miR-BHRF1-3's expression but decreased its transforming potential. Thus, the expression of some microRNAs must be restricted to a narrow range, as achieved by placing miR-BHRF1-3 under the control of miR-BHRF1-2.


Headache in African Americans: An Overlooked Disparity.
The persistence of health disparities in the U.S. has necessitated additional research on race-related health disparities among Americans. Remarkably little research has examined race differences in persons with headache disorders, even though 45 million Americans experience episodic or chronic headaches annually. This review paper examined peer-reviewed publication to examine potential race differences in persons with headache disorders in the areas of headache epidemiology, headache characteristics, psychiatric comorbidity, treatment utilization, and treatment outcomes. A multi-database search (PubMed, Web of Science, PsychlNFO) identified U.S. studies that enrolled racially diverse samples of persons with headache disorders and qualitatively examined potential race-related disparities. Compared to their Caucasian counterparts, African American headache patients are more likely to (i) be diagnosed with comorbid depressive disorders; (ii) report headaches that are more frequent and severe in nature, (iii) have their headaches under-diagnosed and/or undertreated; and (iv) discontinue treatment prematurely, regardless of socioeconomic status. State of the science treatments for chronic headaches are efficacious; unfortunately, race-related disparities prevent African American headache patients from benefiting from these treatments. Research is needed that enables African Americans with severe headaches to access current headache treatments to alleviate headache burden on the African American community.


Cardiopulmonary bypass without systemic heparinization. Performance of heparin-coated oxygenators in comparison with classic membrane and bubble oxygenators.
Performance characteristics of heparin-coated hollow-fiber membrane oxygenators (COATED HFMO, n = 5) were evaluated in an open-chest dog model without systemic heparinization. Four other oxygenators were evaluated with standard systemic heparinization (300 IU/kg, activated clotting time more than 400 seconds): a standard hollow-fiber membrane oxygenator (HFMO, n = 5), an inversed hollow-fiber membrane oxygenator (IHFMO, n = 5), a plate membrane oxygenator (PLATE MO, n = 5) and a bubble oxygenator (BUBBLE O, n = 5). The 25 dogs (36 +/- 12 kg) were perfused after cavo-aortic cannulation for 6 hours with a mean flow of 100 ml/kg body weight. At the end of perfusion without systemic heparin, heparin-coated equipment was replaced in three animals with standard uncoated equipment for control studies. Besides continuous hemodynamic evaluation with Mikro-Tip pressure transducers (Millar Instruments, Inc., Houston, Texas), a standard battery of analyses was performed before, after mixing, and every 30 minutes during bypass. All animals could be perfused in accordance with the protocol. Blood-gas values (pH, arterial oxygen tension, and arterial carbon dioxide tension) were maintained within physiologic ranges for all groups. After 6 hours of perfusion, plasma hemoglobin levels were as follows: 0.57 +/- 0.51 gm/L for COATED HFMO without systemic heparinization versus 2.65 +/- 1.02 gm/L for HFMO (p less than 0.05), 1.77 +/- 0.48 gm/L for IHFMO (p less than 0.05), 1.96 +/- 0.41 gm/L for PLATE O (p less than 0.05), and 1.5 +/- 0.40 gm/L for BUBBLE O (p less than 0.05) with systemic heparinization. Platelet levels were highest for COATED HFMO with 47% +/- 36% without systemic heparinization versus 33% +/- 9% for HFMO, 12% +/- 2% for IHFMO, 36% +/- 17% for PLATE O, and 19% +/- 12% for BUBBLE O with systemic heparinization. Activated clotting time for COATED HFMO without systemic heparinization was 135 +/- 75 seconds before bypass, 207 +/- 21 seconds after mixing, and 131 +/- 20 seconds after 4 hours of perfusion. There was no statistically significant increase of plasma heparin levels in the group perfused without systemic heparin. Determination of fibrin split products during perfusion without systemic heparinization did not show a significant increase. At the end of perfusion all devices were disconnected and gently rinsed with saline: There were no macroscopic clots in the COATED HFMO group perfused without systemic heparin. However, uncoated equipment introduced for control in animals perfused without systemic heparin showed major clotting.(ABSTRACT TRUNCATED AT 400 WORDS)


Amniotic fluid embolism. A case report.
Amniotic fluid embolism is a rare, yet catastrophic event. In the United States it occurs in 1 per 20,000 to 30,000 births. With an 86% maternal mortality rate, amniotic fluid embolism is responsible for 10-15% of all maternal deaths. This article presents a case study of a CNM's experience with a maternal and fetal death resulting from an amniotic fluid embolism. Pathogenesis and appropriate management are also presented.


Medication use among older Australian veterans and war widows.
This study aimed to review the medications used by a group of Australian war veterans and widows, to identify type and number of medications used and potential inappropriate prescribing. Label details of 4304 medications used by 887 participants were recorded and classified according to the Anatomical Therapeutic Chemical code. The median number of regular medications being used was four (interquartile range 2-7), with a median of one other medication (interquartile range 1-2) being taken as needed. Over half (53%) the participants were taking four or more regular medications. There were 26 potential interactions among 25 people. Polypharmacy was a considerable problem for this group of older Australians.


Hedrocele: report of a case and review of the literature.
Hedrocele represents an unusual variant of the rare posterior perineal hernia and results from a defect in the rectogenital septum. In the male, because of the prostate gland and the resistance of the perineal body, a hernia through this defect is directed posteriorly through the anterior wall of the rectum. Diagnosis is based upon an awareness of the entity combined with the finding of an anterior intraluminal rectal mass. Correction requires celiotomy and closure of the anatomic defect.


Method validation, reference values, and characterization of acute-phase protein responses to experimentally induced inflammation and bluetongue virus infection in the Iberian ibex.
Acute phase protein (APP) concentrations can change due to inflammation and be used to monitor disease in the Iberian ibex (Capra pyrenaica). This study aimed to validate Haptoglobin (Hp) and serum amyloid A (SAA) analytes, establish reference values, and characterize Hp and SAA responses in the Iberian ibex after experimentally induced inflammation and experimental bluetongue virus (BTV) infection. Sera from 40 free-ranging box-trapped ibexes were used to establish Hp and SAA reference values. Six healthy ibexes were subcutaneously injected with 5 mL of turpentine, then, blood samples were taken, and clinical evaluations were performed on days 0, 1, 2, 3, 4, 7, and 14 postinjection. Another seven ibexes were challenged with BTV. Serum Hp and SAA concentrations were quantified using commercial assays following the manufacturer's instructions. Intra-assay precision and linearity were acceptable for both Hp and SAA. Intra-assay variation for high and low concentration of Hp and SAA were 9.74% and 17.31% and 16.49% and 12.89%, respectively. Inter-assay variation was higher for the low APP concentrations. Reference values for the healthy Iberian ibexes were (median, minimum, and maximum values) 0.2 (0.12-0.64) g/L for Hp and 4.74 (0.05-29.54) mg/L for SAA. Both Hp and SAA acted as a moderate and a major APP, respectively, and each could distinguish animals with turpentine-induced inflammation from those without. Hp and SAA did not change in asymptomatic BTV-infected animals. This study validated Hp and SAA analytes and provided basal reference values for these analytes in the Iberian ibex. Both APPs were able to discriminate between healthy and diseased Iberian ibexes animals during turpentine-induced inflammatory processes.


Progesterone withdrawal without parturition.
It has been demonstrated that administration of 100 mg of trilostane (an inhibitor of 3 beta-hydroxysteroid dehydrogenase) to late pregnant sheep will rapidly lower circulating levels of progesterone and that delivery ensues. Our intention was to reduce the dose of trilostane in order to separate the latter two sequelae and thereby obtain insight into the relationship between progesterone and prostaglandin biosynthesis. At the dose chosen (10 mg) the treatment did not induce parturition in 4 chronically catheterized sheep during late pregnancy. Circulating progesterone concentrations declined precipitously in all ewes but recovered to near basal values by 24 h after administration of trilostane. Circulating concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha rose slightly but significantly at 4-5 h after administration of trilostane but never reached values normally associated with labor. Plasma estradiol levels were unchanged by treatment. These results are consistent with the view that progesterone withdrawal must be of a critical magnitude and duration for prostaglandin biosynthesis to be sufficiently stimulated to induce labor in sheep during late gestation.


Individual and Household-Level Factors Associated With Caregivers' Intention to Keep Their Child Enrolled in WIC.
Identify factors associated with caregivers' intention to keep their child enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program until age 5 years. Baseline data from a longitudinal questionnaire aiming to assess the impact of a statewide intervention to increase WIC retention in Illinois were analyzed in 2018. Data on sociodemographics and household characteristics were collected in 2015 from 174 caregiver/child dyads. Logistic regression was used to identify factors associated with caregivers' intention to keep their child enrolled in WIC until age 5 years (ie, intention). A total of 66% of caregivers stated they were very likely to keep their child enrolled in the WIC program. Breastfeeding and homeownership status were associated with 58% (P =.03) and 72% (P =.02) lower odds of intention among caregivers, respectively. Significant inverse associations among breastfeeding, homeownership, and intention support the need for tailoring state-level WIC retention efforts to specific population characteristics and health behaviors.


Intermediate-term results of image-guided brachytherapy and high-technology external beam radiotherapy in cervical cancer: Chiang Mai University experience.
To evaluate the outcomes of image-guided brachytherapy combined with 3D conformal or intensity modulated external beam radiotherapy (3D CRT/IMRT) in cervical cancer at Chiang Mai University. From 2008 to 2011, forty-seven patients with locally advanced cervical cancer were enrolled in this study. All patients received high-technology (3D CRT/IMRT) whole pelvic radiotherapy with a total dose of 45-46 Gy plus image-guided High-Dose-Rate intracavitary brachytherapy 6.5-7 Gy × 4 fractions to a High-Risk Clinical Target Volume (HR-CTV) according to GEC-ESTRO recommendations. The dose parameters of the HR-CTV for bladder, rectum and sigmoid colon were recorded, as well as toxicity profiles. In addition, the endpoints for local control, disease-free, metastasis-free survival and overall survival were calculated. At the median follow-up time of 26 months, the local control, disease-free survival, and overall survival rates were 97.9%, 85.1%, and 93.6%, respectively. The mean dose of HR-CTV, bladder, rectum and sigmoid were 93.1, 88.2, 69.6, and 72 Gy, respectively. In terms of late toxicity, the incidence of grade 3-4 bladder and rectum morbidity was 2.1% and 2.1%, respectively. A combination of image-guided brachytherapy and IMRT/3D CRT showed very promising results of local control, disease-free survival, metastasis-free survival and overall survival rates. It also caused a low incidence of grade 3-4 toxicity in treated study patients.


Prospore membrane formation: how budding yeast gets shaped in meiosis.
During meiosis in Saccharomyces cerevisiae four daughter cells, called spores, are generated within the boundaries of the mother cell. This cell differentiation process requires de novo synthesis of prospore membranes (PSMs), which are the precursors of the spore plasma membranes. Assembly of these membranes is initiated at the spindle pole bodies (SPBs) during meiosis II. At this stage of the cell cycle, 4 SPBs are present. Two different meiosis-specific structures are known to be required for PSM formation. At the SPBs, specialized attachments, called the meiotic plaques, provide the required functionality necessary for the recruitment and assembly of the membranes. During subsequent membrane elongation, a second structure becomes important. This proteinaceous assembly forms a coat, called the leading edge protein coat (LEP coat), which covers the boundaries of the membranes. Assembly of the coat occurs at sites next to the SPBs, whereas its disassembly is concomitant to the closure of the membranes. This mini review discusses our current understanding of how the meiotic plaque and the LEP coat might function during biogenesis of the prospore membrane.


Distributed attentional deficits in chronic methamphetamine abusers: evidence from the Attentional Network Task (ANT).
The goal of the present study was to examine distributed attentional functions in long-term but currently abstinent methamphetamine (MA) abusers using a task that measures attentional alertness, orienting, and conflict resolution. Thirty currently abstinent MA abusers (1 month-5 years) and 22 healthy non-substance using adults were administered a multimodal version of the Attentional Network Task (ANT-I). In this task subjects identified the direction of a centrally presented arrow using a key press. Analyses examined the interaction between alerting tones, location cueing and congruency between the target arrows and flanking distractor stimuli. All participants were faster when an auditory tone preceded the trial onset (p<0.001), on trials in which a valid cue preceded the location of the target arrow (p<0.001), and on congruent trials (i.e., when all display arrows faced in the same direction) (p<0.001). Of primary interest was the finding that MA abusers were more influenced by the conflict between the peripheral arrows and the central target arrow (p=0.009). There were also correlations between length of drug sobriety and executive function as well as between drug-induced psychiatric symptoms and alertness. These results suggest that chronic MA abusers display cognitive deficits that may reflect a specific vulnerability to distraction on a task of executive function. These findings are consistent with other studies that have reported deficits in anterior attentional systems and top-down cognitive control.


Sustained ventricular tachycardia caused by anaphylactic reaction.
We report a 30-year-old man who developed severe anaphylactic reactions with sustained ventricular tachycardia after eating seafood. This case emphasizes the need for cardiac monitoring in patients with anaphylaxis to identify malignant ventricular arrhythmias early.


Kassinakinin S: a novel histamine-releasing heptadecapeptide from frog (Kassina senegalensis) skin secretion.
Amphibian defensive skin secretions remain a largely untapped resource for the peptide biochemist with an interest in the identification, structural characterization, and precursor cDNA cloning of novel bioactive peptides. Here we report the isolation, structural characterization, functional profiling, and nucleotide sequence of precursor cDNA of a novel histamine-releasing heptadecapeptide, FIPVTLLALHKIKEKLN-amide, from the defensive skin secretion of the African running frog, Kassina senegalensis. This peptide was found to be a potent histamine secretagogue (EC(50) = 6 microM; maximal release = 25 microM) in a rat peritoneal mast cell model system and was accordingly named kassinakinin S. The open-reading frame of the cDNA encoding prepro-kassinakinin S was found to consist of 71 amino acid residues containing a single copy of kassinakinin S and its glycyl residue amide donor at the C-terminus. Kassinakinin S can thus be added to the growing list of amphibian skin bioactive peptide prototypes.


[3H]forskolin binding to cardiac adenylate cyclase in guinea pigs chronically infused with isoproterenol.
Guinea pigs were infused with the beta-adrenoceptor agonist isoproterenol (400 micrograms/kg/hr, 7 days) and cardiac adenylate cyclase was detected using [3H]forskolin. Two populations of [3H]forskolin binding sites were present in heart, the affinities (KD 2 nM and 280 nM) and densities (Bmax 9 and 900 fmol/mg protein) of which were unchanged by isoproterenol infusion compared with vehicle (1 mM HCl). The autoradiographic localisation of [3H]forskolin binding was also unchanged. The G protein activators NaF 10 mM and 5'-guanylylimidodiphosphate (Gpp(NH)p) 10 microM increased [3H]forskolin binding in heart from vehicle-treated animals by 100% and 80% respectively. NaF-stimulated binding was unchanged in isoproterenol-treated animals, however, Gpp(NH)p-stimulated binding was reduced by 35% which may indicate an increased influence of Gi.


Use of 2-octyl cyanoacrylate together with a self-adhering mesh (Dermabond™ Prineo™) for skin closure following abdominoplasty: an open, prospective, controlled, randomized, clinical study.
Abdominoplasty is one of the most commonly performed procedures in plastic surgery. The appearance of the scar is a major factor that contributes to the aesthetic outcome of the procedure and depends largely on the technique of wound closure. The new Prineo™ wound closure system was introduced to combine the effectiveness of 2-octyl cyanoacrylate (Dermabond™) together with a self-adhering mesh. Fifty-two women and eight men aged between 21 and 65 years who were scheduled for abdominoplasty were included in the study. The total operating times after abdominoplasty of the traditional wound closure technique and the Prineo™-type wound closure technique were compared. Furthermore, an analysis comparing the cost of the two methods was performed. Two weeks after surgery the wounds were examined and graded using the Hollander Cosmesis Scale. At the 6- and 12-month follow-ups, the aesthetic outcome of the abdominal scar was evaluated using the Vancouver Scar Scale. Twelve months after surgery, the patients were asked to answer their part of the Patient Scar Assessment Scale. The mean total operating time for the new skin closure system was statistically significantly shorter than that of intradermal sutures. The mean price difference per patient was 104.27<euro> (134.79$) in favor of Prineo™. The Hollander Cosmesis Scale indicated a significantly more favorable overall result with Prineo™ at 2 weeks after surgery. The Vancouver Scar Scale demonstrated a better cosmetic outcome in favor of Prineo™ 6 and 12 months after surgery. The Patient Scar Assessment Scale scores 12 months after surgery indicated that the patients noted significantly less pain, thickness, and irregularity with Prineo™. Based on our results, we conclude that Prineo™ is a safe and effective substitute for superficial skin closure, with good cosmetic results and no increase in wound complications. The use of Prineo™ decreases operative time and cost and enhances the patient's postoperative comfort. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


COVID-19 infection in myasthenia gravis: Clinical course and outcomes.
Myasthenia gravis (MG) patients have been predicted to have high rates of coronavirus disease-2019 (COVID-19) complications due to frequent involvement of respiratory muscles in MG and frequent use of immunosuppressive therapies. We investigated outcomes of MG patients infected with SARS-CoV-2 to identify risk factors for exacerbation and severe disease. This was a retrospective analysis of 39 MG patients with SARS-CoV-2 infection from January March 1, 2020 to October 25, 2021 at Emory University. Patients' records were queried for demographic data, MG history, and COVID-19 treatments and hospitalizations. At the time of infection, 8 of 39 were vaccinated, 30 of 39 unvaccinated, and 1 unknown. Average age was 52.6 years. Twenty-seven patients were receiving immunomodulatory treatments at the time of infection. Thirty-five of 39 were symptomatic, 21 were hospitalized, and 7 required ventilations. MG exacerbations occurred in 5 and were treated with therapeutic plasma exchange (n = 1), intravenous immunoglobulin (IVIg) (n = 1), and prednisone taper (n = 5). Four hospitalized patients died from COVID-related lung injuries. No deaths were attributed to MG exacerbation; however, one patient receiving IVIg for MG exacerbation had a pulmonary embolism. There were no deaths in fully vaccinated patients, and only one vaccinated patient was admitted to the intensive care unit. High rates of COVID-19 complications and death were observed in this cohort of MG patients. Some patients with MG and COVID-19 also had an exacerbation during infection. Further studies are needed to determine whether MG patients are at higher risk for complications than the rest of the population.


Synergistic activation of phosphoinositide hydrolysis induced in brain slices by norepinephrine and the excitatory amino acid agonist, trans-ACPD.
Norepinephrine and trans-1-aminocyclopentyl-1,3-dicarboxylic acid (ACPD) each individually stimulated hydrolysis of phosphoinositides and when tested in combination caused a stimulation that was 50-90% greater than additive in hippocampal and cortical slices of the rat but not in striatal slices. This synergistic augmentation of hydrolysis of phosphoinositide was evident with all stimulatory concentrations of norepinephrine and of ACPD up to 1 mM, at which point ACPD was inhibitory. A time-course study revealed no lag in the synergistic interaction and no down-regulation through 60 min of incubation of the augmented response to the combined agonists. The synergistic reaction was mediated by alpha 1-adrenergic receptors and by metabotropic excitatory amino acid receptors. Increased intracellular calcium, but not activation of protein kinase C, may play a role in mediating the synergistic interaction. Thus, a unique synergistic stimulatory interaction was found between two receptors coupled with phosphoinositide metabolism, a finding which also supports the suggestion that these two systems are co-localized in some cells.


Solitary multinodular giant cell tumor of tendon sheath.
We present a 74 year old man with a solitary multinodular tumor of the right thumb and an adenocarcinoma of the prostate. Histologic examination of the hand tumor revealed a giant cell tumor of tendon sheath.


Differential induction of UDP glucuronosyltransferase activities towards various substrates after polycyclic aromatic hydrocarbon administration to rats.
Administration of the carcinogens, benzo[a]pyrene and 1,2-benzanthracene, increased UDP glucuronosyltransferase activities towards 4-nitrophenol, 3-hydroxybenzo[a]pyrene, 7-hydroxycoumarin and 1-naphthol to a greater extent than did pretreatment with the noncarcinogens, anthracene and phenanthrene. However, the activity towards morphine was preferentially increased by the noncarcinogens. Activities towards testosterone and oestrone were only slightly increased by the four hydrocarbons. The results suggest that even within a single class of inducer various compounds are capable of causing a differential stimulation of UDP glucuronosyltransferase activities towards certain substrates.


Epidural catheter direction and local anesthetic dose.
The volume of epidural local anesthetic required to achieve a particular dermatomal sensory level varies significantly between patients. Studies have demonstrated random cephalad or caudad migration and direction of the epidural catheter. However, no studies have investigated the relationship between catheter direction and total volume of local anesthetic. The study was approved by the Institutional Review Board for the Protection of Human Subjects. After obtaining informed consent, 28 patients (13 men, 15 women) scheduled for elective total knee or hip replacements were enrolled. The epidural catheter was inserted to a depth of 3 cm at L2-3 using a standard 18-gauge Tuohy needle with bevel directed either cephalad or caudad. After test dose, incremental volumes of 0.75% bupivacaine were injected to achieve a sensory anesthetic level of T6, and the total volume of drug was recorded. Immediately after surgery, 1 ml of omnipaque dye was injected through the catheter for x-ray determination of catheter-tip position. Statistical analysis used the Student's t-test and the Wilcoxon's rank sum test. Ages varied from 47 to 79 years (mean age, 66.5 +/- 8.51 years). Weight ranged from 51 to 125 kg (mean weight, 81.7 +/- 14.1 kg). Height ranged from 143 to 188 cm (mean height, 164.2 +/- 10.6 cm). All patients had good surgical anesthesia. Statistically significant differences (p < .001) were seen between average volumes necessary to achieve a T6 sensory level for catheters in the caudad direction (19.2 ml, n = 9) and in the cephalad direction (13.7 ml, n = 19). No statistical correlations could be demonstrated between total dose of local anesthetic and age, sex, weight, or height. The authors conclude that epidural catheter direction influences the total dose of local anesthetic required to achieve a specific sensory level in epidural anesthesia.


HNE--signaling pathways leading to its elimination.
The oxidation of polyunsaturated fatty acids results in the production of HNE, which can react through both non-enzymatic and enzyme catalyzed reactions to modify a number of cellular components, including proteins and DNA. Multiple pathways for its enzyme catalyzed elimination include oxidation of the aldehyde to a carboxylic acid, reduction of the aldehyde to an alcohol, and conjugation of the carbon-carbon double bond to glutathione (GSH). Interestingly, the enzymes that result in HNE elimination are induced by HNE itself although the chemical mechanism for signaling is not well understood. One of the striking effects of HNE is that after a transient decrease in GSH, synthesis of GSH is elevated through induction of glutamate cysteine ligase (GCL), which catalyzes the first step in de novo synthesis of GSH. GCL has two subunits, which are transcriptionally regulated by a wide variety of agents, including oxidants and electrophiles, such as HNE, which elevates both. The transcriptional regulation of GCL has been the subject of many investigations yielding a complex picture in which the pathways for up-regulation of the subunits appear to be independent and vary with inducing agent and cell type. We have found that in human bronchial epithelial cells, HNE acts through AP-1 activation with signaling through the JNK pathway, and that neither the ERK nor p38(MAPK) pathways is involved. With these results we review what is currently known about the signaling mechanisms for removal of HNE, focusing principally on conjugation mechanisms involving GSH.


Crystal structure of N-terminal degron-truncated human glutamine synthetase.
Glutamine synthetase (GS) is a decameric enzyme that plays a key role in nitrogen metabolism. Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N-degron is not essential for GS decamer formation. It is also shown that the N-degron can be exposed to a solvent region through a series of conformational adjustments upon ligand binding. In summary, this study elucidated the dynamic movement of the N-degron and the possible effect of glutamine in enhancing the acetylation process.


Neurogenesis and neuroadaptation.
Adult neurogenesis has been established as a further mechanism of neural plasticity in the adult nervous system, and numerous studies are beginning to provide insights into the functional purposes and consequences for this new mode of neuroadaptation. These studies have approached the problem from a molecular scale, attempting to identify signaling factors that regulate stem cell function, as well as a systems or behavioral level, attempting to establish correlative and potentially causal links between neurogenesis and behavior. These two approaches have begun to reveal several potential functions for adult hippocampal neurogenesis, including adaptive roles in learning and memory, adaptation to novel environments, potential links to depression and moods, and possible responses to injury. The further implementation and convergence of these two approaches and the development of new methods to study the problem will yield further insights into both what are the many neuroadaptive roles of neurogenesis and potential means to harness it for neuroregeneration.


Ochratoxin A triggered intracerebral hemorrhage in embryonic zebrafish: Involvement of microRNA-731 and prolactin receptor.
Ochratoxin A (OTA), a mycotoxin widely found in foodstuffs, reportedly damages multiple brain regions in developing rodents, but the corresponding mechanisms have not been elucidated. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to various concentrations of OTA and the phenomenon associated with intracerebral hemorrhage was observed at 72 hpf. Exposure of embryos to OTA significantly increased their hemorrhagic rate in a dose-dependent manner. Large numbers of extravagated erythrocytes were observed in the midbrain/hindbrain areas of Tg(fli-1a:EGFP; gata1:DsRed) embryos following exposure to OTA. OTA also disrupted the vascular patterning, especially the arch-shaped central arteries (CtAs), in treated embryos. Histological analysis revealed a cavity-like pattern in their hindbrain ventricles, implying the possibility of cerebral edema. OTA-induced intracerebral hemorrhage and CtA vessel defects were partially reversed by the presence of miR-731 antagomir or the overexpression of prolactin receptor a (prlra); prlra is a downstream target of miR-731. These results suggest that exposure to OTA has a negative effect on cerebral vasculature development by interfering with the miR-731/PRLR axis in zebrafish.


Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer.
The preparation of fairly strained carbocyclic ring systems by intramolecular 5-exo-trig ring closure has been well documented, and the absence of proton transfers that would compromise such cyclizations is a hallmark of this chemistry. In an effort to explore the limitations of this approach to more highly strained systems, the preparation of a stellane (tricyclo[18.104.22.168(3,7)]octane) framework by an intramolecular carbolithiation cascade involving three coupled 5-exo-trig cyclizations of the vinyllithium derived from 2-bromo-4-vinyl-1,6-heptadiene by lithium-bromine exchange was investigated. The cascade does not afford the stellane; rather, the cascade is terminated after two cyclizations by a proton transfer that occurs by an intermolecular process catalyzed by trace amounts of endo-5-methyl-2-methylenebicyclo[2.2.1]heptane present in reaction mixtures as a consequence of inadvertent quenching of an intermediate alkyllithium during prolonged reaction times at room temperature.


Low-dose megestrol acetate revisited: a viable adjunct to surgical sterilization in free roaming cats?
Approximately 2-3 million cats are euthanased in animal shelters across the United States annually. Preventing pregnancy in cats is a key step to reducing this number. While surgery is generally a safe and effective tool for curbing reproduction in cats, it is not a practical method to achieve the reduction in numbers required for an appreciable impact on the cat population as a whole. Low-dose megestrol acetate (MA) is a synthetic progestin that has been used for the management of reproduction in free roaming cat populations; however, there has been no regulatory oversight regarding the use of this product for this purpose. Additionally, there is a paucity of data regarding the safety and efficacy of the product for the management of reproduction in free roaming cats. The purpose of this review is: (1) to outline the need for a non-surgical contraceptive in cats; (2) to discuss the uses of MA in domestic cats; (3) to consider potential adverse effects of the drug, and (4) to discuss regulatory challenges associated with the use of MA in free roaming cat populations. In order to answer the questions posed in this review, more data will need to be collected in laboratory and field studies.


Phe-Met-Arg-Phe-amide (FMRFamide) stimulated growth hormone secretion in conscious OVX rats.
The presence of FMRFamide (Phe-Met-Arg-Phe-amide)-like immunoreactivity in neuronal elements in the hypothalamus suggested a role for this in the hypothalamic control of the anterior pituitary function. We report here the action of FMRFamide on growth hormone release following intracerebroventricular administration to rats. The injection of 200 ng (313.8 picomoles) of FMRFamide (in 2 ul) produced a significantly increased plasma GH 15 min after injection. The GH-increasing effect of 400-800 ng (627-1255 picomoles) of FMRFamide was already developed after 5 min and lasted up to 30 min. No change was detected in the plasma FSH, LH and prolactin levels at any time during the experimental period. The intravenous administration of 10, 30 or 100 ug of FMRFamide had no effect on the plasma GH level. We conclude that FMRFamide can act at low doses to increase GH release through the inhibition of somatostatin release or the stimulation of GRF. We could not exclude a direct site of action in the pituitaries.


Prevention of post-operative intra-nasal adhesions (a new material).
A new material, the wax paper enveloping the Fucidin gauze which is routinely used to pack the nose post-operatively, was utilized in 120 cases considered as 'high-risk' for the formation of post-operative nasal adhesions. This proved to be an inexpensive, simple and effective method when the prevention of the formation of nasal adhesions was the primary goal.


Chest Blunt Trauma: An Uncommon Cause of Aortic Stentless Bioprosthesis Dysfunction.
Acute leaflet rupture occurred in a Freedom Solo (Sorin Group, Milan, Italy) pericardial stentless aortic bioprosthesis after chest blunt trauma 8 years after valve replacement. Intraoperative findings revealed an acute tear of the right cusp at the level of the structural suture line. Pericardial leaflets were not degenerated at histologic analysis. Reoperation was easy, with simple removal of the prosthetic cusps, and a sutureless Perceval (Sorin Group) bioprosthesis was successfully implanted. This is the first reported case of an acute rupture of a stentless aortic bioprosthesis after a chest blunt trauma and the first histologic analysis of an 8-year-old Freedom Solo.


Prolonged contact with blood alters surgical gown permeability.
Surgical gowns are designed to prevent or minimize transmission of blood and pathogens between patients and hospital personnel. During prolonged procedures, a gown will probably be presented with repeated challenges of blood and other liquids. These multiple insults may alter the fabric's permeability to subsequent blood contact. In this study, a pressing-leaning simulator was used to quantify changes in fabric permeability to blood after surgical gowns were prewetted with anticoagulated or coagulating blood. Of the five commercially available gowns tested, contact with blood for 1 hr before application of an external pressure increased permeability for two gowns, decreased permeability for two gowns, and did not alter the permeability of one gown (as compared with test conditions in which the fabrics were not prewetted with blood). These data indicate that at least in some cases prolonged contact with blood increases the amount of blood penetration on application of an external pressure, such as may occur during a pressing or leaning motion. Because increased fabric permeability results in an increased risk of skin contact with liquid-borne pathogens for gown users, a major criterion in the design and selection of a gown should be its ability to resist blood penetration for prolonged periods.


[Adaptative immunity and pathophysiology of multiple sclerosis].
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The appearance of demyelinating patches in the CNS of patients with MS is associated with an inflammatory infiltrate mainly composed of macrophages and T lymphocytes. In this review, we focus on the evidence linking the development of the disease and the cell populations of the adaptative immune system. This evidence arises from anatomopathological, genetical and immunological studies, both on human and the animal model of the disease. Hence, we detail the implication of the effector lymphocytes, i.e. CD4(+) and CD8(+) T lymphocytes, but also B lymphocytes, in the disease. The implication of the regulatory T and B lymphocytes is also approached. Finally, the main hypotheses proposing an explanation to the development of MS are presented.


Correction: Graphene oxide-iron oxide and reduced graphene oxide-iron oxide hybrid materials for the removal of organic and inorganic pollutants.
[This corrects the article DOI: 10.1039/C2RA20885G.].


Prevalence of cardiac right left shunts in migraine: a population-based case-control study.
We aimed to investigate the prevalence of cardiac right left shunts (RLS) in population-based samples of subjects with migraine with aura (n = 42), migraine without aura (n = 44) and controls without headache (n = 41). Cardiac RLS was assessed with transcranial Doppler sonography with intravenous injection of saline. Prevalence of RLS was highest in migraineurs with aura (45.2%) compared to migraineurs without aura (34.1%) and controls (41.5%). Permanent as opposed to latent RLS was more common among patients with migraine with aura (40.5%) than in patients with migraine without aura (23.3%) or controls (24.4%). Differences did not reach statistical significance between the three groups (p = 0.564 for RLS prevalence, p = 0.349 for prevalence of permanent shunts). Our data implicate a trend towards higher prevalence of RLS with larger shunts in subjects with migraine with aura.


Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.
Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft. Notably, the residues on the cleft surface afford extensive interactions with the peptide substrate in a recognition mode that is distinct from that of its bacterial homologs. These structures represent the first model of eukaryotic enzymes in the glycoside hydrolase 84 (GH84) family and provide a crucial starting point for understanding the substrate specificity of hOGA, which regulates a broad range of biological and pathological processes.


Protective effect of high diastolic blood pressure during exercise against exercise-induced myocardial ischemia.
Hypertension is one of the risk factors for coronary artery disease. However, because most coronary blood flow to the left ventricle occurs during diastole, high diastolic blood pressure during exercise may have a protective effect against exercise-induced myocardial ischemia. The aim of the present study was to test this hypothesis. We identified 469 patients with sinus rhythm and known or suspected coronary artery disease who underwent exercise thallium-201 myocardial single-photon emission computed tomography and coronary arteriography. High diastolic blood pressure during exercise was defined as diastolic blood pressure at peak exercise > or = 90 mm Hg. There was no significant difference in medications, number of diseased vessels, or Gensini score between patients with high (n = 228) and normal (n = 241) diastolic blood pressure during exercise, whereas patients with high diastolic blood pressure during exercise exhibited a higher pressure-rate product during exercise than patients with normal diastolic blood pressure during exercise. The reversibility score on thallium-201 myocardial scan was significantly smaller in patients with high diastolic blood pressure during exercise than in patients with normal diastolic blood pressure during exercise (P = .021). High diastolic blood pressure during exercise has a potential protective effect against exercise-induced ischemia, although the mechanism of such effects remains to be determined.


Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences.
Six Clostridium botulinum isolates exhibiting type A toxicity as measured by the mouse bioassay were found to contain both type A and type B neurotoxin DNA sequences. The six strains were divided into three groups based on the DNA sequence of the type B neurotoxin gene. Members of each group exhibited 100% sequence identity over the 3876 bp type B toxin open reading frame. The type B toxin sequence of all groups differed at more than 60 positions when compared to the BGB control strain.


Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade.
Four different interventions were examined in dogs with cardiac tamponade. Infusion of 216 to 288 ml saline solution into the pericardium reduced cardiac output from 3.5 +/- 0.3 to 1.7 +/- 0.2 liters/min as systemic vascular resistance increased from 4,110 +/- 281 to 6,370 +/- 424 dynes . s . cm-5. Left ventricular epicardial and endocardial blood flows were 178 +/- 13 and 220 +/- 12 ml/min per 100 g, respectively, and decreased to 72 +/- 14 and 78 +/- 11 ml/min per 100 g with tamponade. Reductions of 25 to 65% occurred in visceral and brain blood flows and in a composite brain sample. Cardiac output during tamponade was significantly increased by isoproterenol, 0.5 microgram/kg per min intravenously; hydralazine, 40 mg intravenously; dextran infusion or combined hydralazine and dextran, but not by amrinone. Total systemic vascular resistance was reduced by all interventions. Left ventricular epicardial flow was increased by isoproterenol, hydralazine and the hydralazine-dextran combination. Endocardial flow was increased by amrinone and the combination of hydralazine and dextran. Right ventricular myocardial blood flow increased with all interventions except dextran. Kidney cortical and composite brain blood flows were increased by both dextran alone and by the hydralazine-dextran combinations. Blood flow to small intestine was increased by all interventions as was that to large intestine by all except amrinone and hydralazine. Liver blood flow response was variable. The most pronounced hemodynamic and tissue perfusion improvements during cardiac tamponade were effected by combined vasodilation-blood volume expansion with a hydralazine-dextran combination. Isoproterenol had as dramatic an effect but it was short-lived. Amrinone was the least effective intervention.


Ethanolic extract of red seaweed Gracilaria fisheri and furanone eradicate Vibrio harveyi and Vibrio parahaemolyticus biofilms and ameliorate the bacterial infection in shrimp.
Bacteria respond to host immunity for their proliferation and survival by cell-cell communications such as biofilm formation, bioluminescence, and secreting virulence factors. In the biofilm form, bacteria are more resistant to various antimicrobial treatments and withstand the host's immune system. The approaches of deciphering biofilm formation for treating bacterial infections are therefore highly desirable. Recently, we have reported that the ethanolic extract of the red seaweed Gracilaria fisheri (G. fisheri) enhanced immune activities and inhibited growth of the luminescent bacteria Vibrio harveyi in shrimp. We undertook the present research study in order to evaluate and compare the effectiveness of the ethanolic extract from G. fisheri and furanone, a known biofilm inhibitor, in inhibiting the formation of clinically important Vibrio biofilms. The results showed that sub-lethal concentrations of both the ethanolic extracts (5, 10 and 100 μg ml-1) and furanone (5 μM) inhibited biofilm formation by V. harveyi and Vibrio parahaemolyticus and also light production (luminescence) in V. harveyi. It is known that V. harveyi mediated light production via autoinducer AI-2 pathway, we further determined whether the inhibitory effect of the extract was involved the AI-2 signaling. The bioluminescence assay was conducted in an AI-2 deletion mutant V. harveyi. Supplementation of the AI-2 containing media with the extract or furanone impaired the light production in the mutant V. harveyi suggesting that the extract interfered AI-2 mediated light production similar to furanone. In vivo challenge study showed that the low concentrations (Sub MICs) of the ethanolic extract and furanone decreased bacterial adhesion and colonization in the surfaces of stomach lumen, down-regulated expression of a virulence factor, and protected shrimp against mortality from V. harveyi and V. parahaemolyticus infection. In conclusion, the present results suggest a potential application of the low concentrations of the ethanolic extract of G. fisheri as an efficient approach for treating biofilm-associated Vibrio diseases in aquacultures.


Library as place: results of a delphi study.
An expert consensus on the future of the library as place was developed to assist health sciences librarians in designing new library spaces. An expert panel of health sciences librarians, building consultants, architects, and information technologists was asked to reflect on the likelihood, desirability, timing, and impact on building design of more than seventy possible changes in the use of library space. An expert consensus predicted that the roles librarians play and the way libraries are used will substantially change. These changes come in response to changes in technology, scholarly communication, learning environments, and the health care economy. How health sciences library space is used will be far less consistent by 2015, as space becomes more tailored to institutional needs. However, the manner in which health sciences libraries develop and deliver services and collections will drastically change in the next decade. Libraries will continue to exist and will provide support for knowledge management and clinical trials, provide access to digital materials, and play a host of other roles that will enable libraries to emerge as institutional change agents.


Cytochrome b5 and cytochrome b5 reductase-phospholipid vesicles. Intervesicle protein transfer and oreintation factors in protein-protein interactions.
NADH-cytochrome b5 reductase readily binds to preformed phospholipid vesicles either below or above the phase transition temperature of the lipid and in the absence of detergents. The isolated vesicles are free of unbound reductase, and the lipid is present as small, closed bilayers (250 to 400 A in diameter) as indicated by gel filtration, density gradient centrifugation, and internal volume measurements with [3H]glucose. The order of substrate specificity of the bound reductase is: ferricyanide = cytochrome b5 bound to reductase vesicles (100%) greater than cytochrome b5 heme peptide (13%) greater than unbound cytochrome b5 (4.5%) greater than cytochrome b5 vesicles (0.1%). This indicates that a specific orientation of cytochrome b5 and reductase in the bilayer is required for optimal interaction. Protein transfer occurs between reductase vesicles and cytochrome b5 vesicles. The transfer is time-dependent (40 to 70% complete in 2 h), does not involve vesicle fusion, is most rapid at the phase transition temperature of the phospholipid, and appears to require a fluid bilayer.


An Innovative Scoring System to Select the Optimal Surgery in Breast Cancer after Neoadjuvant Chemotherapy.
The selection of surgery post-neoadjuvant chemotherapy (NACT) is difficult and based on surgeons' expertise. The aim of this study was to create a post-NEoadjuvant Score System (pNESSy) to choose surgery, optimizing oncological and aesthetical outcomes. Patients (stage I-III) underwent surgery post-NACT (breast-conserving surgery (BCS), oncoplastic surgery (OPS), and conservative mastectomy (CMR) were included. Data selected were BRCA mutation, ptosis, breast volume, radiological response, MRI, and mammography pre- and post-NACT prediction of excised breast area. pNESSy was created using the association between these data and surgery. Area under the curve (AUC) was assessed. Patients were divided into groups according to correspondence (G1) or discrepancy (G2) between score and surgery; oncological and aesthetic outcomes were analyzed. A total of 255 patients were included (118 BCS, 49 OPS, 88 CMR). pNESSy between 6.896-8.724 was predictive for BCS, 8.725-9.375 for OPS, and 9.376-14.245 for CMR; AUC was, respectively, 0.835, 0.766, and 0.825. G1 presented a lower incidence of involved margins (5-14.7%; p = 0.010), a better locoregional disease-free survival (98.8-88.9%; p < 0.001) and a better overall survival (96.1-86.5%; p = 0.017), and a better satisfaction with breasts (39.8-27.5%; p = 0.017) and physical wellbeing (93.5-73.6%; p = 0.001). A score system based on clinical and radiological features was created to select the optimal surgery post-NACT and improve oncological and aesthetic outcomes.


Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function.
Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 degrees C; the desired temperatures were achieved within one minute. Heating at 42 degrees C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 degrees C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injection of adriamycin given at a rate of 0.45mg/100gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents.


miR-223 and miR-142 attenuate hematopoietic cell proliferation, and miR-223 positively regulates miR-142 through LMO2 isoforms and CEBP-β.
miR-142 and miR-223 have been identified as hematopoietic specific microRNAs. miR-223 has crucial functions in myeloid lineage development. However, the function of miR-142 remains unclear. In this study, we found that both miR-142 and miR-223 attenuated the proliferation of hematopoietic cells, and that miR-223 up-regulated miR-142 expression through the LMO2-L/-S isoforms and CEBP-β. miR-223 negatively regulated both LMO2-L/-S isoforms and CEBP-β post-transcriptionally, while CEBP-β positively regulated the LMO2-L/-S isoforms and both of the LMO2-L/-S isoforms negatively regulated miR-142. These results reveal a novel miR-223--CEBP-β--LMO2--miR-142 regulatory pathway, which has pivotal functions in hematopoiesis.


Comparison of 6 and 7 French guiding catheters for percutaneous coronary intervention: results of a randomised trial with a vascular ultrasound endpoint.
To perform a randomized, ultrasound controlled trial to define the procedural and clinical advantages and limitations of 6 French (Fr) compared with 7 Fr transfemoral coronary intervention in the stenting era. The use of 7 Fr guiding catheters may facilitate Percutaneous Coronary Intervention (PCI), but may be associated with increased vascular complications when compared with 6 Fr catheters. Patients undergoing PCI considered suitable for either a 6 or 7 Fr sheath and guiding catheter system were included. All vascular sheaths were removed with assisted manual compression. Femoral vascular ultrasounds were performed prior to hospital discharge and interpreted by a vascular surgeon blinded to treatment assignment. The primary endpoint was a composite of significant vascular complications including major haematoma, retroperitoneal haematoma, pseudoaneurysm, arterio-venous fistula, or femoral venous or arterial thrombosis. During the study, 414 patients (mean age 61+/-11 years, 27% females) were randomly assigned to 6 Fr or 7 Fr sheath groups. The incidence of major vascular complications was 5.7% in the 6 Fr group and 3.9% in the 7 Fr group (P=0.383). There was no significant difference in procedural or angiographic success between the groups. The use of contrast volume was higher in the 7 Fr group (157+/-58 ml vs. 144+/-58 ml; P=0.029). There was a trend toward better operator satisfaction with the 7 Fr guide (P=0.08). This prospective, randomized trial indicates no reduction in major peripheral vascular complications with the use of smaller guiding catheters in PCI. There was less contrast used in the 6 Fr group, which may benefit some patient subsets, however operators tended to prefer the larger 7 Fr system. The target coronary anatomy and need for complex device intervention should mandate the choice of guiding catheter size, not a perceived impact on vascular complications.


Cobra cardiotoxin and phospholipase A2 as GAG-binding toxins: on the path from structure to cardiotoxicity and inflammation.
Glycosaminoglycans (GAGs) represent the sulfated carbohydrate moieties of proteoglycans which occur abundantly in tissues of the cardiovascular system. Many proteins bind specifically to GAGs and perform an important role in inflammation, cell proliferation, and blood coagulation processes. Recently, in vitro GAG-binding studies of cardiotoxins (CTXs) and basic phospholipase A(2) (PLA(2)) from cobra venom established the toxins as two new families of GAG-binding proteins. In particular, discontinuous basic residues in beta-sheet CTXs may form a cationic cradle suitable for heparin binding, as in the case of fibronectin module III-13. The binding specificity of beta-sheet proteins to different GAGs can be further enhanced by involving other cationic clusters near the flexible loop of the molecule. Since the three-dimensional structures of many CTXs and PLA(2) are available, these two toxins may serve as models for the elucidation of the molecular recognition of GAG-binding proteins and also as polypeptide templates for further improvement of the binding specificity suitable for future biomedical application. Research along the line of GAG-guided toxicity of cobra venom components may help us to understand the functional role of GAGs and the action mechanism of cobra venom components in the cardiovascular system.


Research progress on the effects of gut microbiome on lung damage induced by particulate matter exposure.
Air pollution is one of the top five causes of death in the world and has become a research hotspot. In the past, the health effects of particulate matter (PM), the main component of air pollutants, were mainly focused on the respiratory and cardiovascular systems. However, in recent years, the intestinal damage caused by PM and its relationship with gut microbiome (GM) homeostasis, thereby affecting the composition and function of GM and bringing disease burden to the host lung through different mechanisms, have attracted more and more attention. Therefore, this paper reviews the latest research progress in the effect of PM on GM-induced lung damage and its possible interaction pathways and explores the potential immune inflammatory mechanism with the gut-lung axis as the hub in order to understand the current research situation and existing problems, and to provide new ideas for further research on the relationship between PM pollution, GM, and lung damage.


Thrombosis prophylaxis in pregnancy with use of subcutaneous heparin adjusted by monitoring heparin concentration in plasma.
Twenty-six pregnant women were given prophylactic heparin treatment because of previous thromboembolic complications. The mean duration of treatment was 25 weeks (range, 6 to 32 weeks). The amount of heparin was adjusted to a plasma concentration of 0.08 to 0.15 IU/ml, measured as anti-factor Xa activity. This effect was compared with that on activated partial thromboplastin time. The average dose was 16,400 IU/24 hours or 225 IU/kg of body weight per 24 hours. When the plasma concentration was within the stipulated range, the dose was 234 IU/kg of body weight/24 hours. No significant prolongation of activated partial thromboplastin time was found in two thirds of the samples. Blood coagulation was either not activated or only slightly activated, as verified by a low level of fibrinopeptide A. Platelet counts and antithrombin III levels were generally not depressed. No thromboembolic complications occurred during the pregnancies or puerperium. Bleeding during delivery was not increased. No fractures of the spine caused by osteoporosis were found on radiologic examination post partum.


Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.
The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.


Sleeping respiratory rates in apparently healthy adult dogs.
Respiratory rate monitoring of cardiac patients is recommended by many cardiologists. However, little objective data exist about respiratory rates in apparently healthy dogs when collected in the home environment. We measured sleeping respiratory rates (SRR) in apparently healthy dogs and compared sleeping and resting respiratory rates (RRR) with a cross-sectional prospective study. Participants collected 12-14 one-minute SRR over a period ranging from 1 week to 2 months on 114 privately owned adult dogs. Selected participants simultaneously collected RRR. Mean within-dog average SRR (SRR(mean)) was 13breaths per minute (breaths/min). No dog had SRR(mean) >23 breaths/min; three dogs had instantaneous SRR measurements >30 breaths/min. Dogs had higher RRR(mean) (19 breaths/min) than SRR(mean) (15 breaths/min) (P<0.05). Canine SRR(mean) was unaffected by age, bodyweight or geographic location. Data acquisition was considered relatively simple by most participants. This study shows that apparently healthy adult dogs generally have SRR(mean) <30 breaths/min and rarely exceed this rate at any time.


Repeated low dose apomorphine induced subsensitivity of presynaptic dopamine receptors.
The influence of repeated administration of a low dose of apomorphine on presynaptic dopamine (DA) receptors was examined. (1) Male ddY mice were given a low dose of apomorphine (0.2 mg/kg) for 7 days. Following 2 drug-free days they were given apomorphine (0.2 mg/kg, IP), after which cage climbing behavior and the level of 3-methoxytyramine (3MT) in striatum was measured. Mice became tolerant to apomorphine's activity-depressing effect and 3MT-decreasing effect. (2) Mice were given haloperidol (1 mg/kg) for 7 days. Then after 2 drug-free days they were given 0.2 or 1.0 mg/kg of apomorphine, after which cage climbing behavior was measured. One mg/kg of apomorphine significantly increased cage climbing behavior, indicating that supersensitivity of postsynaptic DA receptors was induced by haloperidol, but the activity-depressing effect of 0.2 mg/kg of apomorphine was not modified. The results suggest that subsensitivity of presynaptic DA receptors participates in the tolerance to the activity-depressing effect of a low dose of apomorphine.


Comparison of brachial artery flow-mediated dilatation, uterine artery Doppler, and umbilical artery Doppler measurements in obese and normal pregnant women.
In this study, we aimed to compare vascular function at trimesters 1, 2, and 3 between obese and normal pregnant women through brachial artery flow-mediated dilatation (FMD), uterine artery Doppler, and umbilical artery Doppler measurements. Pregnant women between the ages of 18 and 40 who presented to our clinic were included. Brachial artery FMD, uterine and umbilical artery Doppler, and clinical parameters of 40 obese pregnant women from each trimester between 11 and 14 weeks, 24 and 28 weeks, 37 and 40 weeks and control pregnant group in the same number and gestational week were examined. In all three trimesters, the FMD value was lower in obese pregnant women compared to normal women with adequate weight (p < 0.001). In obese pregnant women, lower FMD values were observed in the second trimester compared to other trimesters (p = 0.011) Cut-off value of FMD below 14.35 in obese pregnant women was found to be associated with gestational diabetes mellitus. Uterine artery Doppler in obese pregnant women started to increase from the second trimester compared to normal women with adequate weight. Obese pregnant women have endovascular dysfunction compared to normal pregnant women and this becomes evident from the second trimester.


Effect of enhanced home support: a retrospective study of the « Ehpad-@-Dom » project
The growing needs related to the loss of autonomy of elderly people should be the opportunity to imagine alternatives to nursing homes. In this context, our study aimed to assess the effect of a reinforced home care model on the evolution of frailty in elderly people whose health conditions could have justified entering a nursing home. A retrospective observational study focusing on the evolution of the SEGA score and other variables reflecting the frailty of people over 75 years old according to classic home care, institutionalization, or reinforced home care. The average SEGA scores of the Ehpad-@-Dom (reinforced home care) and SAD (classic home care) groups are significantly better than that of the Ehpad group after 6 months (T6: Ehpad-@-Dom vs Ehpad, p =0.01 and SAD vs Ehpad, p=0.039) and 12 months (T12: Ehpad-@-Dom vs Ehpad, p=0.021). "Reinforced home care" seems to be an alternative to the classic nursing home model.


Society of Family Planning committee consensus on self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC).
Depot medroxyprogesterone acetate (DMPA) is a highly-effective, injectable contraceptive method that requires injections every 12 to 15 weeks. The need for return visits to a healthcare provider may present barriers to access, use, and continuation of DMPA. Studies demonstrate that self-administration of subcutaneous DMPA (DMPA-SC) outside clinical settings is safe, effective, feasible, acceptable, and can improve continuation. Based on existing evidence and potential to improve contraceptive access and autonomy, the Society of Family Planning recommends that DMPA-SC self-administration be made widely available as an additional option for patients. Provider-administered DMPA must also remain available to meet patients' individual needs and preferences.


Performance evaluation of non-porous versus porous ion-exchange packings in the separation of proteins by high-performance liquid chromatography.
The performance of a non-porous, anion-exchange packing was evaluated and compared with a number of similar porous high-performance liquid chromatography packings. The non-porous columns were found to be equally efficient for proteins spanning a wide range of molecular weights, while the porous columns exhibited decreasing efficiency as the proteins became larger. The porous materials also exhibited size exclusion effects that were not seen with the non-porous materials, which partially accounts for the loss of efficiency with large proteins. When increasingly steep gradients were employed, the loss of resolution was less with the non-porous materials.


The amino acid sequence of nucleoside diphosphate kinase I from spinach leaves, as deduced from the cDNA sequence.
The primary structure of nucleoside diphosphate (NDP) kinase from spinach leaves has been deduced from its cDNA sequence. A lambda gt 11 cDNA library derived from spinach leaves was screened using an antibody against NDP kinase I, which we previously purified to electrophoretic homogeneity (T. Nomura, T. Fukui, and A. Ichikawa, 1991, Biochim. Biophys. Acta 1077, 47-55). The cDNA sequences of positive clones contained the amino acid coding region (444 base pairs) for NDP kinase I as well as 5' and 3' noncoding regions of 33 and 361 base pairs, respectively. The cDNAs hybridized to a 1.1-kb mRNA. NDP kinase I contains 148 amino acid residues with a molecular mass of 16,305, which is in excellent agreement with that of the purified enzyme (16 kDa). Homology was found between the sequence of spinach NDP kinase I and those of the rat, Myxococcus xanthus, and Dictyostelium discoideum NDP kinases, as well as the human Nm23-gene product and the awd protein of Drosophila melanogaster.


Heart rate recovery after constant-load exercise tests is decreased in proportion to the importance (severity and diffusion) of exercise-induced lower-limb ischaemia.
Conditions that may influence heart rate recovery at 1 min of recovery from exercise (HRR1: end-exercise heart rate minus heart rate 1 min after exercise) are not fully understood. We hypothesized that the 'importance' (both local severity and regional diffusion) of peripheral skeletal muscle ischaemia is associated with low HRR1. In 529 patients with suspected or confirmed peripheral vascular disease not receiving beta-blockers (61·4 ± 11·3 years old), we retrospectively studied the relationship of HRR1 to exercise-induced changes in transcutaneous oxygen DROP index (limb changes minus chest changes from rest). The sum of DROP indices observed on both calves and both buttocks (DROPtot) provides the unique opportunity to estimate both the severity and the diffusion of exercise-induced ischaemia on the right and left side simultaneously. It was used during a constant-load treadmill test (3·2 km h(-1) ; 10% grade) to classify patients in quartiles, the fourth quartile representing the more 'important' ischaemias. There was an inverse relationship between quartiles of DROPtot and HRR1, even after adjustment for heart rate reserve (Delta HR: end-exercise minus resting heart rate), age (≤ or >60 years), gender, body mass index, treadmill maximal walking distance and ankle brachial index: adjusted R = 0·629; P<0·0001. During constant-load treadmill testing, DROPtot, an index of the 'importance' of exercise-induced lower-limb ischaemia, correlates with HRR1. Whether HRR1 is improved in proportion of DROPtot improvement in patients undergoing surgery or rehabilitation for peripheral artery disease is a fascinating issue for future studies.


Biomarkers of free radical damage applications in experimental animals and in humans.
Free radical damage is an important factor in many pathological and toxicological processes. Despite extensive research efforts in biomarkers in recent years, yielding promising results in experimental animals, there is still a great need for additional research on the applicability of, especially non-invasive, biomarkers of free radical damage in humans. This review gives an overview of the applications in experimental and human situations of four main groups of products resulting from free radical damage, these include: lipid peroxidation products, isoprostanes, DNA-hydroxylation products and protein hydroxylation products.


Perioperative subcutaneous emphysema: review of differential diagnosis, complications, management, and anesthetic implications.
Subcutaneous emphysema is not an uncommon anesthetic complication, but it often occurs unexpectedly. It is usually self-limited, but mediastinitis can occur with mortality as high as 50%. A case of subcutaneous emphysema occurring during dental surgery is reported here. The diagnosis, management, complications, and pathogenesis are discussed.


Properties of a tyrosine protein kinase from calf thymus. Response to ionic strength and divalent cations.
A tyrosine protein kinase activity has been partially purified from calf thymus using the phosphorylation of the tyrosine-containing peptide angiotensin I as an assay. Detergent extracts of calf thymus possessed only low levels of specific peptide phosphorylating activity when assayed at low ionic strength. The inclusion of NaCl at a concentration of 2 M stimulated endogenous tyrosine protein kinase activity, while the activity of other endogenous kinases was inhibited. This sensitivity to NaCl was retained following partial purification of the enzyme. The phosphorylation of other substrates such as casein or the R-R-SRC peptide (Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly) by the tyrosine protein kinase was less sensitive to NaCl. Phosphorylation of the PK-1 peptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) by the purified catalytic subunit of cAMP-dependent protein kinase was inhibited by NaCl. The effect of NaCl on angiotensin I phosphorylation could be mimicked by KCl or sodium acetate. The principal effect of NaCl was to increase the Vmax of the enzyme for the phosphorylation of angiotensin I. At low ionic strength, Mn2+ and Co2+ were the preferred required divalent cations. At elevated NaCl concentrations Mg2+ was preferred, with half-maximal activation occurring at 35 mM Mg2+. By conducting peptide phosphorylation assays in the presence of elevated levels of Mg2+ and NaCl, tyrosine protein kinase activity can readily be detected in extracts from cell lines that express low levels of the enzyme.


Speeding and maxillofacial injuries: impact of the introduction of penalty points for speeding offences.
On 31 October 2002 the Irish Government introduced a point demerit scheme for road speeding offences. To evaluate the impact of the scheme, we made a comparative assessment of the number of maxillofacial operations necessitated by road crashes at two tertiary surgical centres in the year before and the year after the introduction of penalty points. There were no significant differences in the composition of the groups between the two study periods. There were 57 operations in the year before and 22 in the year after for injuries caused by collisions (a 61% reduction). No changes were seen in the distribution or severity of maxillofacial injuries or in the pattern or severity of other injuries. Severity was assessed using the Abbreviated Injury Scale (AIS) and Maximum Abbreviated Injury Severity Scale (MAIS), and bodily injuries by the Injury Severity Scale (ISS). The number of patients requiring intensive care and the duration of admission to the unit were unchanged, as was the total duration of hospital admission. There were no differences in the requirement for other specialist management.


Inverse optimization of hydraulic, solute transport, and cation exchange parameters using HP1 and UCODE to simulate cation exchange.
Reactive transport modeling is a powerful tool to evaluate systems with complex geochemical relations. However, parameters are not always directly measurable. This study represents one of the first attempts to obtain hydrologic, transport and geochemical parameters from an experimental dataset involving transient unsaturated water flow and solute transport, using an automatic inverse optimization (or calibration) algorithm. The data come from previously published, controlled laboratory experiments on the transport of major cations (Na, K, Mg, Ca) during water absorption into horizontal soil columns that were terminated at different times. Experimental data consisted of the depth profiles of water contents (θ), Cl concentrations, and total aqueous and sorbed concentrations of major cations. The dataset was used to optimize several parameters using the reactive transport model, HP1 and the generic optimization code, UCODE. Although the soil hydraulic and solute transport parameters were also optimized, the study focused mainly on the geochemical parameters because the soil columns were constructed from disturbed soil. The cation exchange capacity and the cation exchange coefficients for two exchange models (Gapon and Rothmund-Kornfeld) were optimized. The results suggest that both calibrated models satisfactorily described the experimental data, although the Rothmund-Kornfeld model fit was slightly better. However, information content and surface response analyses indicated that parameters of the Gapon model are well identifiable, whereas those of the Rothmund-Kornfeld model were strongly correlated. The calibrated geochemical parameters were validated using an independent dataset. In agreement with the identifiability analysis, the Gapon approach was better than the Rothmund-Kornfeld model at calculating the observed concentrations of major cations in the soil solution and on the exchange sites.


[Comparative serologic proteome analysis of Staphylococcus aureus and S. epidermidis exoproteins in prosthetic joint infections].
Staphylococci such as Staphylococcus aureus and S. epidermidis are the most frequently pathogens associated to prosthesis joint infections (PJI), counting for 75% among the isolated bacteria. In this study, we identified PJI-related antigens using two-dimensional immunoblots of S. aureus and S. epidermidis exoproteins probed with serum samples from patients with confirmed PJIs. We further analysed by ELISA tests the response of patients to the identified proteins. Secreted proteins from Mu50 strain (S. aureus) and RP62A strain (S. epidermidis) were separated by 2D gel electrophoresis and analyzed by western blot with serum samples from patients with confirmed S. aureus and S. epidermidis PJIs. Recombinant proteins corresponding to the identified proteins were expressed and screened with an in-house ELISA to evaluate their interest for the diagnosis of S. aureus and S. epidermidis PJIs. Fifty-two antigenic exoproteins were identified: 42 belonging to Mu50 strain, and 10 to RP62A strain. Twenty-two proteins were identified as S. aureus specific. Among these proteins, five were most frequently recognized by patients with S. aureus PJI. Our results showed that few exoproteins were antigenic by RP62A strain compared to Mu50 strain. We identified five antigenic and S. aureus specific proteins, which may contribute to diagnosis, prevention and treatment of these infections.


The presence of vasotocin and mesotocin in serum and the hypothalamo-neurohypophyseal axis of chick embryos before hatching and in posthatch chicks.
Decreasing hematocrit values were observed in chick embryos, from Day 17 to 1 day posthatching. Arginine vasotocin (AVT) and mesotocin (MT) were determined radioimmunologically in serum, neural lobe, and hypothalamic tissue. Serum levels of AVT and MT were significantly increased on Day 18 of incubation compared to Day 17. Thereafter AVT levels decreased, reaching at hatching levels even below Day 17. Serum MT remained elevated on Day 19, but decreased thereafter to the concentration values of Day 17. The amount of AVT in the preoptic hypothalamus and infundibulum was maximal on Day 19, whereas in the neural lobe the maximum was attained on Day 20. The MT content of the infundibulum and neural lobe reached a maximum plateau on Day 18. These results suggest that a stimulation of the hypothalamo-neurohypophyseal axis in the chick embryo occurs at the end of incubation. A possible causal relation with the observed decreasing hematocrit values is discussed.


The influence of predation and conspecific adults on the abundance of juvenile Evechinus chloroticus (Echinoidea:Echinometridae).
Reefs dominated by red algae, associated with high echinoid densities, are consistent features of the shallow subtidal around northeastern New Zealand. Factors determining the abundance of juvenile Evechinus chloroticus were investigated in such a habitat. Using a factorial design, a field experiment was used to assess the influence of predators and adult E. chloroticus on juvenile abundance. The use of 2 m2 exclusion cages enhanced juvenile E. chloroticus abundance over a 16 month period, an effect independent of conspecific adults. We attributed this effect to the exclusion of benthic-feeding, predatory fish. Several species forage over the study area at high densities and are known from gut content analysis to prey on juvenile E. chloroticus in the field. Invertebrate predators are at very low densities in the area. The possibility of caging and site artefacts confounding this interpretation is discussed.Adult E. chloroticus did not directly affect conspecific juvenile densities during the experimental period. However their removal produced a significant change in community structure toward one dominated by macroscopic brown algae. Echinoid removal led to rapid recruitment of laminarian and fucoid algae, predominantly Ecklonia radiata and Sargassum sinclairii. In addition, densities of herbivorous gastropods, particularly the limpet Cellana stellifera decreased in the echinoid exclusion area, as did the feeding rates of predatory fish. The consequences of E. chloroticus removal may be dependent upon the size of the area from which they are excluded.Despite the high densities of predatory fish, a low though consistent number of juvenile E. chloroticus escape predation. We suggest that these represent sufficient input into the adult grazing population to maintain the habitat. This interpretation argues against a key role for predators in structuring shallow water reef communities in northeastern New Zealand.


Muscle Oxygenation of the Paretic and Nonparetic Legs During and After Arterial Occlusion in Chronic Stroke.
Oxygen delivery and demand are reduced in the paretic leg post-stroke, reflecting decreased vascular function and reduced muscle quantity and quality. However, it is unknown how muscle oxygenation, the balance between muscle oxygen delivery and utilization, is altered in chronic stroke during and after occlusion-induced ischemia. The objective was to determine muscle oxygen consumption rate, microvascular responsiveness and reactive hyperemia in the paretic and nonparetic legs during and after arterial occlusion post-stroke. Muscle oxygen saturation was measured with near-infrared spectroscopy on the vastus lateralis of each leg during 3-minute arterial occlusion and recovery (3 min). Muscle oxygen consumption was derived from the desaturation slope during ischemia, microvascular responsiveness was derived from the resaturation slope after ischemia and reactive hyperemia was derived from the area under the curve above baseline after ischemia. Eleven subjects (91% male; 32.2±6.1 months post-stroke; age 62.9±13.6 years) with a hemiparetic gait pattern participated. There was no significant between-leg muscle oxygenation difference at rest (paretic: 64.9±16.6%; nonparetic: 70.6±15.6%, p = 0.13). Muscle oxygen consumption in the paretic leg (-0.53±0.24%/s) was significantly reduced compared to the nonparetic leg (-0.70±0.36%/s; p = 0.03). Microvascular responsiveness was significantly reduced in the paretic leg compared to the nonparetic leg (paretic: 4.6±1.8%/s; nonparetic: 5.7±1.6%/s, p = 0.04). Reactive hyperemia was not significantly different between legs (paretic:4384±2341%·s; nonparetic: 3040±2216%·s, p = 0.07). Muscle oxygen consumption and microvascular responsiveness are impaired in the paretic compared to the nonparetic leg, suggesting both reduced skeletal muscle aerobic function and reduced ability to maximally perfuse muscle tissue.


Transcriptomic and hormonal analysis of the roots of maize seedlings grown hydroponically at low temperature.
Prolonged cold stress has a strong effect on plant growth and development, especially in subtropical crops such as maize. Soil temperature limits primary root elongation, mainly during early seedling establishment. However, little is known about how moderate temperature fluctuations affect root growth at the molecular and physiological levels. We have studied root tips of young maize seedlings grown hydroponically at 30 ºC and after a short period (up to 24 h) of moderate cooling (20 ºC). We found that both cell division and cell elongation in the root apical meristem are affected by temperature. Time-course analyses of hormonal and transcriptomic profiles were achieved after temperature reduction from 30 ºC to 20 ºC. Our results highlighted a complex regulation of endogenous pathways leading to adaptive root responses to moderate cooling conditions.


Initial tension loss in cerclage cables.
Cerclage cables, frequently used in the management of fractures and osteotomies, are associated with a high failure rate and significant loosening during surgery. This study compared the capacity to maintain tension of different types of orthopaedic cable systems. Multifilament Cobalt-Chrome (CoCr) cables with four different crimp/clamp devices (DePuy, Stryker, Zimmer and Smith&Nephew) and one non-metallic Nylon (Ny) cable from Kinamed were instrumented with a load cell to measure tension during insertion. Significant tension loss was observed with crimping for all cables (P<0.05). Removing the tensioner led to an additional unexpected tension loss (CoCr-DePuy: 18%, CoCr-Stryker: 29%, CoCr-Smith&Nephew: 33%, Ny: 46%, and CoCr-Zimmer: 52%). The simple CoCr (DePuy) cable system outperformed the more sophisticated locking devices due to its significantly better ability to prevent tension loss.


Langerhans cells are strongly reduced in the skin of transgenic mice overexpressing follistatin in the epidermis.
Activins are members of the transforming growth factor-beta (TGF-beta) family and are important for skin morphogenesis and wound healing. TGF-beta1 is necessary for the population of the epidermis with Langerhans cells (LC). However, a role for activin in LC biology is not known. To address this question, we analyzed skin from transgenic mice overexpressing the activin antagonist follistatin in the epidermis. Using immunofluorescence, we observed a striking decrease in the number of LC in the epidermis of transgenic mice in comparison to wild-type mice. Nevertheless, these LC expressed normal levels of major histocompatibility complex (MHC)-class II and Langerin/ CD207 in situ. In explant cultures of whole ear skin the number of dendritic cells (DC), which migrated into the culture medium, was reduced. This reduction was even more pronounced in cultures of epidermal sheets. Virtually all emigrated cutaneous DC displayed typical morphology with cytoplasmic "veils", showed translocation of MHC-class II to the surface membrane, and expressed the maturation marker 2A1. Thus, cutaneous DC from transgenic mice seemed to mature normally. These results demonstrate that overexpression of follistatin in the epidermis affects LC trafficking but not maturation and suggest a novel role of the follistatin-binding partner activin in LC biology.


Correlation between 3D ultrasound appearance and postnatal findings in bilateral malformations of the fetal hands.
Malformations of the hand have an incidence of 1 in about 1,500 births. Ultrasound diagnosis and classification of the anomaly is not always easy because of the various positions taken by the hand. We describe the case of a 23-year-old patient with a fetus affected by a symmetrical and bilateral hand oligodactyly associated with deformities of the other fingers. 3D ultrasound evaluation allowed an exact prediction of the malformation and showed perfect correspondence with postnatal findings. The case illustrates the contribution of 3D ultrasound to the evaluation of fetal limb anomalies.


[Findings in extracranial arteries ensuring cerebral blood supply in patients with peripheral and generalized disturbances of blood flow (author's transl)].
Attention is drawn to the incidence rate of the various types of obliterations of the carotid artery in the extracranial area. The evaluation is based on 242 carotid stenoses from a total of 1283 angiograms. Over and above this, the paper presents initial results of computertomography in 15 patients with obliterations of the carotid arteries in the cervical region.


Light-Induced Pulsed EPR Dipolar Spectroscopy on a Paradigmatic Hemeprotein.
Light-induced pulsed EPR dipolar spectroscopic methods allow the determination of nanometer distances between paramagnetic sites. Here we employ orthogonal spin labels, a chromophore triplet state and a stable radical, to carry out distance measurements in singly nitroxide-labeled human neuroglobin. We demonstrate that Zn-substitution of neuroglobin, to populate the Zn(II) protoporphyrin IX triplet state, makes it possible to perform light-induced pulsed dipolar experiments on hemeproteins, extending the use of light-induced dipolar spectroscopy to this large class of metalloproteins. The versatility of the method is ensured by the employment of different techniques: relaxation-induced dipolar modulation enhancement (RIDME) is applied for the first time to the photoexcited triplet state. In addition, an alternative pulse scheme for laser-induced magnetic dipole (LaserIMD) spectroscopy, based on the refocused-echo detection sequence, is proposed for accurate zero-time determination and reliable distance analysis.


Wastewater-based prevalence trends of gout in an Australian community over a period of 8 years.
Gout is a rheumatic arthritis disease which poses a health burden. Monitoring the prevalence of gout is key to reduce the community burden of gout disease and associated health costs. Allopurinol has been used as a first line gout preventive medication in Australia which is metabolised into oxypurinol and excreted in urine. Wastewater-based epidemiology (WBE) was applied to estimate temporal trends of gout prevalence in an Australian community over eight-years via the quantification of oxypurinol in wastewater. A total of 180 wastewater samples collected between 2012 and 2019 were analysed for oxypurinol to estimate allopurinol consumption in a community in South East Queensland, Australia. Annual gout prevalence was estimated by daily defined doses (DDD) consumed and ranged from 24 to 32 DDD/day/1000, an equivalent gout prevalence of 2.3 to 3.2% over the eight-year period. A statistically significant increase in allopurinol consumption was observed over the period (Slope = 0.094, p = 0.0001), equating to year-on-year increases in gout prevalence of 3.6% per year. To the best of our knowledge, this is the first long-term gout prevalence study using wastewater, adding epidemiological and public health insights in the gout research field.


Release of intact, monomeric cytochrome c from apoptotic and necrotic cells.
Cytochrome c (Cyt c) has been shown to translocate from mitochondria to the cytoplasm of cells early in apoptosis. In this study sandwich ELISAs for Cyt c were used to determine if Cyt c is ultimately released from apoptotic and necrotic cells. Gel-filtration and cation-exchange chromatographies, in conjunction with immunoreactivity in ELISA, and Western blotting were employed to examine the integrity of the released Cyt c. The results show that Cyt c is released from both apoptotic and necrotic cells in an intact, monomeric form. The release of Cyt c from apoptotic splenocytes began within 2 h following apoptotic insult, while Cyt c was immediately released following induction of necrosis by heat shock. These findings may be relevant to understanding how Cyt c becomes a target for antibody production in some patients with systemic autoimmune diseases.